2012 American Neuropsychiatric Association Annual Meeting Abstracts

Background: Most descriptions of psychogenic amnesia have been single-case reports. There have been very few recent investigations looking at larger groups. Objective: This investigation examined 53 cases of psychogenic amnesia: fugue cases, psychogenic focal retrograde amnesia (FRA), and patients with gaps in their memory. The hypothesis was that these groups would differ in terms of psychosocial associations, predisposing factors, and neuropsychological performance. Methods: We examined 16 patients with psychogenic fugue, 16 with a fugue-like onset developing into FRA, 16 with psychogenic FRA after (for example) minor head injury, and 5 with gaps in their memory. We examined case records and the pattern of performance on tests of anterograde memory, retrograde memory, and other cognitive function. Results: Results were examined using one-way or two-way repeated-measure ANOVAs. Fugue cases were characterized by loss of personal identity, whereas FRA patients commonly failed to recognize their family. We found a mild impairment on anterograde verbal and visual memory tests during psychogenic amnesia, as compared with post-amnesia scores. For past personal semantic information and recall of autobiographical episodes, we found that patients in “fugue” showed a “flat” uniform loss of remote memories across all time-periods, whereas patients with FRA showed a “reversed” temporal gradient. At follow-up, fugue patients had returned to normal performance for personal facts and near-normal performance for autobiographical episodes. FRA patients showed improvement, but less pronounced than in the fugue group. Conclusion: These findings suggest the operation of executive inhibitory control mechanisms, consistent with Anderson et al.’s (2004) model of memory suppression.

Background: Autoantibodies that cause neurological dysfunctions tend to have specific effects on susceptible tissue; yet there have been no cases associated with the exclusive presence of striational antibodies described. These are primarily detected in the sera of MG patients. In these patients, azythromycin (AZM) administration has a deleterious effect. Similar clinical presentations not associated with striational antibodies showed complete resolution of symptoms within 4 months, with no definitive diagnosis. Case History: A 7-year-old girl with previous medical history of migraine headaches presented with stereotypic movements, learning disabilities, and personality and affective changes after a severe neuropsychiatrc illness of acute onset. Neurological symptoms included loss of expressive language, emotional lability, paranoia, and self-injurious behavior. During the acute illness, CSF IgG was elevated, and the presence of striational antibodies was detected. EEG video monitoring showed multiple electrographic seizures originating from the right-posterior region. Dramatic clinical improvement followed a course of AZM indicated for a suspected coincidental upper respiratory infection. Treatment plan of 5-day on and off cycles of AZM have dramatically improved the patient’s functioning. Seven months after initial symptoms appeared, she is in good health and back to baseline functionality. The dramatic effect of AZM in this case might underline immunomodulating potential of the antibiotic. Conclusions: The neuropsychiatric symptoms experienced could be a result of the isolated antibodies’ effect on brain cells. Immunologic processes can modify neuronal functioning, altering the electrical activity of neurons, which could lead to behavioral changes.

Background: Dextromethorphan/quinidine (DMQ) is a recently-approved formulation for the treatment of pseudobulbar affect. Its mechanism of action is hypothesized to be agonism of the sigma-1 receptor (primarily concentrated in the cerebellum and brainstem) and antagonism of the NMDA receptor. Injury to the cerebellum can result in a pattern of behavioral abnormalities that has been termed the cerebellar cognitive affective syndrome (CCAS), which features deficits of executive function, spatial organization, personality, and language. No clear treatment strategy has yet been developed for the management of CCAS. Case History: We present the case of a man who developed symptoms consistent with CCAS after a PICA stroke. Trials of benzodiazepines and first- and second generation neuroleptics failed to ameliorate his symptoms. Given that sigma-1 receptors are highly concentrated in the cerebellum (his primary locus of injury), an off-label trial of DM/Q was attempted resulting in rapid improvement in his behavioral symptoms. His symptoms worsened after the medication was stopped, and rapidly improved again once it was reinitiated. Conclusions: Drugs with activity at the sigma-1 receptor have demonstrated efficacy in the management of a number of neuropsychiatric conditions, including pseudobulbar affect and delirium. This report describes a patient with another diagnostic entity associated with behavioral and affective changes (CCAS), who benefited from a sigma-1 agonist. More research is needed on the role of agents with sigma-1 activity (including DM/Q) in the management of CCAS and other conditions associated with agitation and other behavioral symptoms.

Background: Reversible cases of frontal temporal dementia (FTD) are linked to an identified etiology that is corrected. The authors report two cases that initially presented as FTD, not explained by secondary etiologies. Cognitive and behavioral improvement was significant with psychopharmacological treatment, and patients no longer met criteria for FTD 1 year later. Case History: Case #1: A 47-year-old male patient presented with insidious onset of personality change, including apathy, disinhibition, OCD-type behaviors, and lack of insight. Neuropsychological testing (NPT) identified impairment in executive function and memory. Behavioral symptoms improved over the course of 1 year with sertraline at a supratherapeutic dose. The patient’s wife reported a “75%” return to premorbid baseline, and the patient regained driving privileges. An updated NPT revealed improvement across several cognitive tasks, and no longer meeting criteria for FTD. In Case #2, a 58-year-old female patient presented with rapid onset of personality change, including apathy, changes in appetite and sleep, and lack of insight. NPT identified pronounced impairment in executive function and memory. Brain SPECT showed bilateral hypoperfusion of frontal lobes. Her behavioral changes improved over the course of 1 year with bupropion at maximum dose. Her husband reported a “100%” return to premorbid baseline, allowing the patient to care for her grandson during the day. An updated NPT revealed marked improvement across several cognitive tasks, no longer meeting criteria for FTD. Conclusions: These cases highlight the reversibility of cognitive and behavioral symptoms and functional impairment in syndromes initially presenting as FTD. Such improvements bring the initial diagnosis into question.

Background: Pathological hoarding can be a manifestation of primary psychiatric (e.g., obsessive-compulsive disorder) and neurological illnesses. Hoarding has been reported in neurodegenerative diseases such as frontotemporal dementia and in association with focal brain injuries due to tumors, cerebrovascular disease, and other causes. We report the first known case of hoarding related to a pituitary adenoma that was resected surgically. Case History: A 57-year-old teacher underwent right frontal resection of a growth hormone-secreting pituitary macroadenoma at age 41. Around age 45, she developed severe hoarding. Her husband reported hoarding of old school papers, books, periodicals, clothing, and household supplies that the patient did not use. Photographs showed objects and plastic containers filled with objects that were piled almost to the ceiling of the patient’s home. The patient insisted the objects might be useful in the future. Between ages 48 and 51, the patient had two manic episodes. At age 52, she was arrested after assaulting her husband when he tried to clear their home of some of the hoarded objects. At age 57, the patient developed complex partial seizures associated with right frontotemporal abnormalities on EEG. A brain MRI done at age 50 showed abnormalities in the right gyrus rectus and adjacent fronto-orbital gyrus. Conclusion: Case reports and neuroimaging studies of hoarding patients have highlighted dysfunction of the ventromedial prefrontal cortex and anterior cingulate cortex. We believe that, in keeping with the literature, our patient developed hoarding as well as mania and seizures as a result of right frontal lobe injury.

Background: Neurodegeneration with brain iron accumulation (NBIA), formerly known by the eponymous label Hallervorden-Spatz disease, is now known as a group of heterogenous disorders that include Friedrich ataxia, aceruloplasminemia, pantothenate kinase-associated neurodegeneration (PKAN), and neuroferritinopathy. Although most cases of inherited NBIA present early in life with extrapyramidal and corticospinal symptoms accompanied by cognitive impairment, they may also manifest with late-life Huntington-esque choreic movements. Characteristic findings on brain MRI scans include decreased T₂ signal intensity in the basal ganglia. Treatment with deferiprone, an iron-chelator, in a pilot study has been shown to reverse brain iron accumulation and related symptoms. Case History: The author presents a case of a 69-year-old man admitted to a general hospital for failure to thrive, who manifested confusion, agitation, and significant choreic movements of his limbs, trunk, and face. He reported a history of lupus-induced chorea, and his mother had a history of abnormal movements. Serologic work-up for causes of chorea was negative, including ceruloplasmin, antistreptolysin O titer, autoimmune markers for lupus, Sjogren’s syndrome, and antiphospholipid-antibody syndrome. Genetic testing for Huntington disease was negative. EEG was negative for epileptiform activity and encephalopathy. MRI brain scan revealed iron deposition in the lentiform nuclei, substantia nigra, and dentate nuclei bilaterally. Treatment for chorea was instituted with haloperidol 0.5 mg bid with good effect. Videographic and radiographic data will be reviewed. Conclusions: Brain iron accumulation disorders are a rare cause of neuropsychiatric symptoms in adults, and they may be misdiagnosed early in their course. Correct diagnosis of NBIA will allow for future effective treatments to halt or even reverse the disease process.

Background: Pervasive Refusal Syndrome (PRS) is a rare child psychiatric disorder characterized by refusal across multiple domains (especially food and school), active/angry resistance to help, and social withdrawal leading to an endangered state. Although most authors have used psychodynamic formulations that focus on learned helplessness and hopelessness as the etiology, Max Fink and Gabrielle Carlson first proposed in 1995 that PRS may be a form of pediatric catatonia. Even though later case series of PRS include catatonia in the differential diagnosis, no reports of treatment with ECT could be identified in the English-based literature, despite a 25%–30% rate of partial recovery from PRS. Case History: “D.O.” was a 16-year-old young man of mixed Native American/Hispanic ancestry, who was transferred from an outlying hospital because of refusal to eat. On examination, he presented with polite but firm refusals to all offers of food, liquid, and grooming in an automatic fashion, without thought. He also had brief episodes of stupor and verbal automatism that seemed to be triggered by excessive questioning, but no other signs of catatonia. After complete failure to respond to psychotherapy, multiple antipsychotics, antidepressants, mood stabilizers, and benzodiazepines, he received 20 ECT treatments, resulting in a full recovery from the PRS. Conclusion: This case supports the concept of a diagnostic overlap between Pervasive Refusal Syndrome and Pediatric Catatonia, as well as the potential effectiveness of ECT in treatment-resistant Pervasive Refusal Syndrome.

Background: Overlap syndromes between progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) have mixed motor phenotypes, and cognitive features similar to behavior variant frontotemporal dementia may occur in PSP-CBS. However, much less is known about specific neuropsychiatric phenotypes such as severe anxiety, which may be overlooked as uncommon initial manifestations of PSP-CBS, as in our case. Case History: Our patient is a 76-year-old woman without previous psychiatric history, who developed severe and constant ruminating anxiety and obsessive-compulsive features, including her enforcement of strict, rule-bound behavior for herself and family, self-harm threats if separated from her spouse, mental rigidity, and bizarre and time-consuming rituals. This was followed by impaired problem-solving and perspective-taking, childlike behavior, and pathological laughing and crying; 1½ years later, she showed repeated falls and axial-predominant parkinsonism and, later, asymmetric rigidity, myoclonus, and apraxia (videotaped). Brain MRI at 3 months and brain PET at 1 year after motor onset revealed mild left-sided predominant parietal, medial prefrontal, and anterior temporal atrophy and hypometabolism, respectively. Anxiety spectrum symptoms were somewhat responsive to sertraline. Conclusions: Severe anxiety with elements of a frontal cognitive syndrome may preceed a PSP-CBS overlap disorder but often go unrecognized, yet may benefit from pharmacotherapy and family education. This symptom cluster requires additional study to determine its utility early on in predicting PSP-CBS syndromes.

Background: Deep brain stimulation for Parkinson’s disease has been associated with a variety of neuropsychiatric complications, including delirium, personality changes (apathy; disinhibition, including aggression, emotional hyperreactivity, pathological gambling, etc.), mania, depression, executive problems, psychosis, and suicide. The rates of psychiatric complications may be higher with DBS of the subthalamic nucleus (STNDBS) as compared with Globus Pallidus Interna DBS (GPi DBS). Case History: We present the case of a 45-year-old man diagnosed with PD at age 32. He had no previous psychiatric illness. He underwent STN DBS placement in 2004, with revision in 2008, and GPi DBS in 2010. Over the years, he has shown an array of neuropsychiatric symptoms secondarily to PD, adjustment to illness, antiparkinsonian medications, and the three DBS surgeries. His symptoms have included severe depression, for which he received post-DBS ECT; anxiety; personality changes, hypersexuality, and compulsive buying; apathy; and mood lability, including irritability and giddiness. We will discuss the course of his neuropsychiatric symptoms and their management, with focus on the correlation of psychiatric manifestations after each DBS surgery and after variations in DBS settings. Conclusions: Psychiatric complications are a common occurrence of DBS surgery for Parkinson’s disease. Further research is needed to learn more about these psychiatric manifestations and to help in their prevention and management. The potential for psychiatric complications underscores the importance of obtaining fully-informed consent before these procedures are done.

Background: Parkinson’s disease (PD) is a neurodegenerative movement disorder frequently associated with neuropsychiatric symptoms. Electroconvulsive therapy (ECT) has been shown to be effective in treating depression and psychosis along with the simultaneous effect of improving parkinsonian motor symptoms. Despite its marked effectiveness in producing concurrent mood and motor recovery, there is reluctance to utilize ECT in PD patients with DBS implantation because of safety concerns regarding the DBS electrode. Case History: We present the case of a 76-year-old man with a history of psychotic depression and a >10-year history of PD s/p right STN DBS, with continued, significant tremor on the right side, who presented with psychosis in the context of the recent addition of amantadine. The patient’s planned, contralateral DBS (left STN) implantation was postponed, and he was admitted for psychiatric stabilization. He received an acute series of eight right-unilateral ultra-brief pulse ECT treatments (using Thymatron, Lake Bluff, IL). His psychiatric symptoms remitted, and there was a marked reduction in tremor. Amantadine and dopamine-agonist were discontinued, and levodopa was significantly reduced. He was able to sustain this medication-reduction while maintaining improved motor/mood functioning during the interval between his acute ECT course and STN DBS implantation. Conclusions: This is the first reported case of utilizing ECT as a bridge for contralateral DBS implantation in a patient with a previous unilateral DBS implantation. We discuss the functional neuroanatomy of mood- and motor-regulation, their overlap, and ECT’s putative shared mechanism on both networks.

Background: The high prevalence rates for catatonia among individuals with ASD suggest a neurobiological connection between these conditions. ASD is related to disorders of GABA and glutamate activity, both of which are also associated with epilepsy and mood disorders. Methods: This presentation includes a brief overview of the most recent basic neuroscience and genetic literature on ASD as it relates to an increased risk of catatonia. This risk appears independent of the level of intellectual disability (IDD), mood, and schizophrenia spectrum disorders. Results: The presence of catatonia among individuals with ASD suggests an endophenotype that may have a common neurobiological substrate with epilepsy and mood/anxiety disorders. These vulnerabilities may point to developmental disruptions in glutamate, GABA-ergic, and dopaminergic activity. Conclusion: Catatonia in individuals with ASD is a neuropsychiatric condition that is responsive to benzodiazepines, ECT, and antipsychotic medications. Part of the differential diagnosis of catatonia involves neuroleptic malignant syndrome (NMS), nonconvulsive status epilepticus (NCSE), and complex neuropsychiatric disorders (demyelinating, cerebrovascular, and possibly mitochondrial disorders). This degree of heterogeneity and the exquisite sensitivity of many individuals with ASD to most antipsychotic medications reinforces a measured approach to catatonia. The effectiveness of direct/indirect GABA agonists and glutamate (NMDA) antagonists will be discussed.

Background: ASD is a complex disorder that affects social communication, cognitive, and behavioral adaptive capacities, and a constricted repertoire of ritualistic behaviors. Recently, Pruett et al. (2011) reported the potential usefulness of a modified social-responsive scale for chimpanzees as a means of exploring the evolutionary neurobiology of ASD in humans. Additional work, using facial and postural cues to predict dominance among chimpanzees, raises interest in humans, suggesting shared processing of social behaviors. Methods: We will explore recent chimpanzee field work addressing attachment, social communication, and tool-making; communication among human-reared great apes, and evidence for variability between species (bonobos, common chimpanzees); variations in social and cultural behaviors among different chimpanzee groups. This review compares human and chimpanzee patterns of brain maturation, cognitive, and neurophysiological processing of social cues in terms of recent studies relying on mirror-neuron activity. Results: Chimpanzees live in complex and diverse social groups, making global comparisons risky. Even though we observe the precursors of complex social relationships, communication, tool use, and “culture,” we must account for the nearly 6 million years of divergent neurological evolution. Conclusion: It is risky to extrapolate the foundations of ASD among great apes. Recent studies human rating of social behaviors (Social Responsiveness Scale) and recognition of chimpanzee nonverbal cues of dominance provide an interesting insight into this facet of primate social behavior.

Background: Empirical evidence has suggested that sensory and motor deficits may present as consistent features of autism spectrum disorders in addition to the core traits of social impairment, communication difficulties, and restricted, repetitive, and stereotyped patterns of behavior. Objective: The study sought to identify differences in sensory functioning between autism and Asperger’s syndrome while also assessing diagnostic contribution of such assessment. Methods: A group of 16 individuals with autism and 10 with Asperger’s syndrome completed the Dean-Woodcock Sensory-Motor Battery. Outcomes on the primary sensory subtests were compared. This included performance in visual confrontation, palm writing, object identification, finger identification, and simultaneous localization. Results: A sole significant difference was found between groups, favoring Asperger’s over autism. Specifically, individuals with autism tended to demonstrate mild astereognosis (i.e., object identification) with the right hand, versus those diagnosed with Asperger’s syndrome. Differences approaching significance were noted in object identification with the right and simultaneous localization of right and left stimulation. Of particular interest, based on sensory outcomes alone, 100% of individuals were accurately differentiated. Conclusions: Findings support sensory dysfunction as a core feature of these presentations, while demonstrating the utility of sensory assessment in diagnostic practice. Discrepancies raise questions about the proposed combination of the two disorders.

Background: Bardet-Biedl Syndrome (BBS) is a genetic abnormality inherited in an autosomal recessive manner. The diagnosis of BBS is confirmed by clinical evaluation, but 14 genes are associated with this disorder. Related clinical findings include rod–cone dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotrophic hypogonadism, complex female genitourinary malformations, and renal abnormalities. Neuropyschiatric complications are common, and a majority of individuals have significant learning difficulties. A minority present with severe impairment on IQ testing. Case History: We present a case of a 10-year-old boy with Bardet-Biedl disease and will highlight the intriguing neuropsychiatric aspects of this presentation. We will review the genetic associations with other neuropsychiatric illness germane to this case, subtle features that suggest a unique presentation of comorbid attention and thought-processing problems. Neuropsychiatric assessments, including measures of executive functioning, will be presented, as well as longitudinal observation of treatment outcome. The literature on neuropsychiatric symptoms of Bardet-Biedl disease is quite sparse, and we hope to build on that limited body of knowledge. Conclusion: This patient has presented with an interesting clinical array of neuropsychiatric symptoms, including mood swings, arguing with peers, difficulty with social interactions, as well as problems with concentration, impulse control, and obsessive fears. Also, he has a voracious appetite and has gained considerable weight. He also has problems with conversation and cannot logically and sequentially connect his thoughts. This patient had initially been diagnosed with Major Depressive Disorder, as well as attention-deficit hyperactivity disorder (ADHD). He received fluoxetine; however, he became increasingly irritable and began to improve his flow of thought after taking mixed amphetamine salts. Bardet-Biedl is a genetic autosomal-recessive disease (previously grouped with Laurence-Moon-Biedl syndrome) that has a unique constellation of symptoms. It is a rare, severe disorder that is often diagnosed incorrectly. This disorder is relevant to neuropsychiatry because of associated visual impairment as well as the nonspecific behavioral problems that can result from this condition.

1. Pagon RA: Bardet-Biedl syndrome. GeneReviews. Sept. 2011

Background: Delayed neurological symptoms occur in approximately 3% of carbon monoxide (CO) poisoning cases. After a recovery period of 2–40 days, rapid deterioration can develop, which includes urinary incontinence, hallucinations, and disorientation. Case History: A 53-year-old, Hispanic man was found unresponsive while using a space heater. He was placed on 100% oxygen, intubated in the field, and transported to the ER. His carboxyhemoglobin was 28%. Hyperbaric oxygen chamber therapy (HBOT) with hypothermia was initiated. Approximately 17 days after CO exposure, the patient was medically stable and discharged to a post-acute rehabilitation facility. Examination revealed an MMSE score of 22/30, flattened affect, intermittent confusion, increased jaw and snout reflexes, and a shuffling gait. After 1 month of progressing in rehabilitation, the patient suffered a rapid deterioration in cognitive and physical functioning. He developed a parkinsonism-like gait, urinary incontinence, had increased confusion, and developed hallucinations. The patient’s CT scan and labwork was unremarkable. He was treated with a dopaminergic agonist, vitamin E, and melatonin. The patient experienced a reversal of neurological symptoms within 4 weeks. Conclusions: Delayed neurological symptoms after CO poisoning are a rare occurrence but may be reversed with combination therapy including HBOT, antioxidants, and dopaminergic agents.

Background: The experience of depressive symptoms in cognitively impaired older adults is complex and not well described, and characterizing this presentation can have implications for diagnosis and treatment. Objective: The authors describe the phenomenology of depressive symptoms in a sample of older adults with varying degrees of cognitive impairment. Specifically, they examined the differences in symptom endorsement between individuals diagnosed with Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD) by use of a self-report depression measure. Method: A group of 208 community-dwelling older adults diagnosed with MCI or AD completed the Beck Depression Inventory–II (BDI–II). Descriptive statistics were used to examine the frequency of endorsed items. Results: Overall, participants with MCI and AD endorsed a similar degree of depressive symptoms (mean AD: 7.5; mean MCI: 9.5). Both groups endorsed a similar profile of symptoms, with loss of energy, concentration difficulties, fatigue, changes in sleep patterns, and decreased libido the most frequently endorsed by both groups, symptoms that generally are not specific to depression. Within this cognitively impaired sample, clinically depressed individuals (BDI–II >13) also endorsed self-criticism, self-dislike, indecisiveness, anhedonia, and pessimism, symptoms that distinguished them from their non-depressed peers. Conclusion: In general, MCI and AD individuals endorsed similar level and types of depressive symptoms, which may at least partially reflect the direct neuropsychiatric effects of their degenerative disease. However, individuals who also report negative self-perception, such as decreased confidence and self-blame, are more likely to be clinically depressed, and report of these symptoms may raise a greater degree of concern for depression than in those who primarily report somatic concerns.

Background: Determining capacity for independent living is a common demand placed on clinicians within the neurosciences. Although loss of capacity is often associated with various neuropsychiatric presentations, whether a specific neurocognitive constellation underlies this type of functional defect is unknown. Objective: The current study sought to investigate to what degree various cognitive constructs contribute to particular skills for independent living. Methods: Participants included 134 individuals who completed various tasks of neurocognition, who were also administered the Independent Living Scales. Results: An individual’s capacity in visuospatial awareness and construction, confrontational naming and semantic fluency, and selective attention, as well as processing-speed, were significantly related to the individual’s abilities in managing money, managing home and transportation, and management of health and safety. Performance in single-trial learning of unrelated and contextual information was significantly to capacities in managing of home and transportation and health and safety. Interestingly, within the realm of delay memory, only delayed recall of contextual information demonstrated any significant relationship with skills of independent living. Specifically, this aspect of delayed recall was significantly related to capacities in managing home and transportation and health and safety. All noted correlations were low to low-moderate in strength. Conclusions: Although the findings demonstrate some reliance of independent living skills on particular aspects of neurocognition, in reality, the relationships were low to low-moderate. A significant amount of variance remains unexplained, suggesting that singular cognitive entities do not adequately predict outcomes within these capacities. Rather, it is likely the case that independence relies on their combination.

Background: Patients with neurodegenerative disorders may experience both anosognosia (lack of awareness) and depression. However, the relative contributions of objective memory performance and awareness of cognitive impairments on self-reported depressive symptoms have not been thoroughly explored. Objective: Authors examined the association between objective memory deficits, clinician-rated awareness of cognitive impairments, and patients’ self-reported depressive symptoms. Method: A group of 138 older adults diagnosed with Mild Cognitive Impairment and Alzheimer’s disease completed the Hopkins Verbal Learning Test–Revised (HVLT–R) and Beck Depression Inventory–II (BDI–II) as part of an outpatient neuropsychological evaluation. Ratings of patients’ awareness of cognitive deficits were completed by skilled clinicians. Results: Poorer memory performance, as measured by delayed recall of a word list, was correlated with lower levels of depression and awareness. However, when both clinician ratings of awareness and objective memory performance were used as predictors of self-reported depressive symptoms, only awareness remained a significant predictor, with individuals rated as aware reporting greater depressive symptoms. Conclusion: Results suggest that reporting of depressive symptoms is associated with objective memory performance. However, this relationship appears to be mediated by patients’ level of awareness. Overall, findings suggest that patients’ awareness of cognitive deficits and reported mood are closely related, and lack of awareness may potentially serve as a buffer against depression.

Background: Certain dementias (e.g., Huntington’s disease, Parkinson’s disease) impair both motor and cognitive functions, a combination that can accelerate functional decline. Medications may provide modest benefits, although results vary, depending on the underlying disorder, and side effects are an ever-present concern. New strategies are needed that provide tangible and clinically relevant results. This study reports results of a physical training regimen that included writing, which improved level of function and behavior. Case History: A 63-year-old African American man with Huntington’s disease-like disorder and chronic alcohol abuse, with an 8-year history of worsening movement disorders and progressive cognitive and behavioral decline, was admitted for placement because of verbally abusive and physically aggressive behaviors (e.g., kicking a door at home). Initial examination showed inability to feed himself, with intermittent irritable and agitated behavior when he was touched, even lightly. Involuntary movements included chorea and tremor with intention. He presented on antipsychotic therapy. Citalopram and propranolol were added, and gabapentin was increased. Physical therapy, using reciprocal exercise, was initiated. When the writing program began, his behavior became less restless, but some intention tremor remained. Results: Within 8 weeks, all movement-disorder symptoms improved, including chorea, with significant near-elimination of the intention tremor. Within 12 weeks, flexibility and hand dexterity improved, facilitating independent placement of shoes and return to self-feeding, and gait stability noticeably increased. Conclusions: Motor training can help improve functioning and independence in patients with dementia. Further attention to patient-centered protocols is needed.

Background/Objective: A recent provocative hypothesis links Alzheimer ’s disease with Fragile X and Autism (Sukol et al., Neurology 2011). This study investigates the frequency of family history by depth and serial inquiry for idiopathic dementia (ID) in a referred sample of child and young adult patients with DSM–IV confirmed Tourette Syndrome (TS), Pervasive Developmental Disorder (PDD), and Attention-Deficit Disorder (ADD), all similarly evaluated at the Institute for Developmental and Behavioral Neurology. Method: Retrospective chart analysis of 36 TS (26 men), 92 PDD (62 men), 372 ADD (265 men) seen and diagnosed between ages 4 and 25 years. Results: TS patients, n=7 (19%); PDD, n=24 (26%); ADD, n=82 (22%) had affected grandparent (GP) and/or great-grandparent (GGP); in paternal line: n=59; in maternal line: n=60; 6 patients had multiple affected family members (gender affected: 75 female, 44 male). Conclusions: There is no statistically significant different frequency of affected GP or GGP in these three developmental disorders. However, in each group, the frequency exceeds the estimated 13% in persons >65 years of age (Alzheimer’s Association: Alzheimer’s & Dementia, 2011) and was highest in the PDD population. Whether developmental disorders are linked with dementia in affected children or their families requires further investigation.

Background: The situation of children living at home with an early-onset dementia parent, especially if frontotemporal dementia, calls for unique support, yet no educational materials have existed. Objective: To create online access to materials crafted to meet child-caregiver needs as expressed in focus groups conducted in 2011. Methods: A total of 14 participants, ranging in age from 11 to 18 years and covering an average of 3 years of hands-on caregiving, connected to Skype for a semi-structured interview administered to small groups. A thematic-analysis approach toward the transcripts identified themes through a coding scheme. Also, consultants from the Young Carers Initiative and McMaster University’s Montessori Learning Program for the Aging provided input on the emerging themes to shape web content. Results: Young caregivers felt their roles positively affected their sense of self and maturation. They felt responsible for the well parent as much as the patient with dementia. They requested that well parents maintain some normal family activities and balance stressors so as not to appear overwhelmed in front of their children. Psychological caveats for child-caregivers included compulsive caregiving and false maturity. This information allowed the creation of a dual website, one side to advise well parents, and the other for teens who may be accessing information online themselves. Focus-group participant feedback for the resulting website was gratifying and supportive. Conclusion: www.lifeandminds.ca/research/whendementiaisinthehouse was launched on November 15, 2011, to meet an identified need. Ongoing feedback will help revise the site and add interactive materials to support families in crisis over early-onset dementias.

Background: Psychiatry and neurology have visible residency programs and are core clinical clerkships for most medical students. Combined psychiatry-neurology is an evolving specialty with few training programs. Objective: To compare resident matches in combined psychiatry-neurology, psychiatry, and neurology over the past 4 years. Methods: Data from the National Resident Matching Program (NMRP) were averaged from match years 2008 to 2011. Data consisted of the number of programs, positions, and applicants for the first 2 postgraduate years. Comparisons in unfilled residency positions among these disciplines were made using Fisher’s exact test. Results: Combined psychiatry-neurology has five or fewer programs nationally, with six or fewer total residency positions offered annually. There was a significantly higher (p <0.005) percentage of unfilled positions in combined psychiatry-neurology residency programs (21.7%), as compared with either neurology (3.8%) or psychiatry (2.7%) programs. Although not statistically significant, presumably because of small sample sizes, the percentage of positions filled by international medical graduates was lower in combined psychiatry-neurology (8.3%) than in neurology (29.8%) and psychiatry (25.1%). The ratio of applicants to residency position was similar between psychiatry (1.9), neurology (2.4), and combined psychiatry-neurology (3.7). Conclusions: Neuropsychiatry is an evolving specialty, with few combined psychiatry-neurology residency programs. This report, comparing resident matches in the three specialties encompassing psychiatry and neurology, will serve as a baseline for comparison as more students begin to graduate from U.S. medical schools.

Background: The American Association of Directors of Psychiatry Residency Training (AADPRT) Task Force on Neuroscience and Neuropsychiatry Education of Psychiatry Residents was established in 2011, with the charge of seeking information on what the field of psychiatry considers the core topics in neuroscience and neuropsychiatry to which psychiatry residents should be exposed, whether there are any “competencies” in this area on which the field agrees, whether psychiatry departments have the internal capacity to teach these topics if they are desirable, and what the reception would be for a series of neuroscience modules, such as those being developed by the National Institute of Mental Health (NIMH). Method: The task force reviewed the literature and developed a survey instrument for administration to all U.S. psychiatry residency program directors. The task force also partnered with Drs. Mayada Akil from NIMH and Amit Etkin from Stanford University, who, in parallel, developed an NIMH-sponsored survey directed at psychiatry residents and practicing psychiatrists . The Neuroscience domains included in the two surveys were harmonized to allow for comparison of data obtained from three distinct survey groups: 1) psychiatry residency program directors; 2) psychiatry residents; and 3) practicing psychiatrists. The AADPRT Executive Committee assisted with survey review, and their feedback was incorporated into the final instrument. The survey was sent to psychiatry residency program directors in the Fall of 2011, and the results of the survey will be presented in this poster. If data are available from the NIMH/Stanford Survey, our survey data will be compared with their findings.

Background: Older patients with major depression have been shown to have increased prevalence of white-matter (WM) hyperintensities. Cardiovascular disease can adversely affect long-term outcome of patients with depression and their response to antidepressant medication. Persistent depression can cause further ischemic changes. Presence or absence of WM hyperintensities have not shown to influence response to electroconvulsive therapy (ECT). However, the effect of severity and lesion location needs further assessment. Objective: We hypothesized that ECT response during treatment of mood disorder will be independent of presence, location, or severity of ischemic changes. Method: We performed a chart review of patients who received ECT from 2001 until the present at James Lovell Federal Health Care Center. Information collected included demographics, diagnosis, cardiovascular risk factors, brain imaging, and drug and alcohol history. We used pre-and post-ECT psychopathology rating scales to assess response to ECT. Brain imaging was evaluated with the ARWMC Rating Scale for MRI and CT. We evaluated location and severity of ischemic changes. Results: Using analysis of variance, we found no difference in response to ECT between those with WM hyperintensities (n=32) and those with normal imaging results (n= 31; p=0.493 [NS]). There was no difference in response between those with severe lesions and those with mild. Multiple-regression analysis looking at location of lesions and response revealed no significant statistical findings. Conclusions: Presence, location, or severity of WM lesions did not predict a poor response to ECT. We conclude that ECT is an effective treatment for mood disorders in patients with WM ischemic changes.

Background: Many studies have demonstrated successful management of explosive young people by use of antipsychotic medications, such as risperidone (DeDenn and Buitelaar, 2006; Pandina et al., 2006). However, these medications have significant risks of adverse events. Objective: The current study explores the ability to manage explosive young people without any antipsychotic medications, using an alternative protocol of anticonvulsant and dopaminergic medications. Methods: Subjects were 91 explosive young people (52 boys, 39 girls, ages 5–17, with diagnoses including Mood Disorder), discharged from residential treatment on the alternative-protocol medications (without antipsychotics). In each case, the admitting psychiatrist had classified the history of aggression as explosive (impulsive temper outbursts with physical assaults) rather than premeditated (assaults committed for a purpose). Outcomes were measured by a mail survey of caregivers at 6 months post-discharge (positive outcome operationally defined as 50%-or-better reduction in frequency and severity of aggression, as compared with pretreatment behavior. Results: Percent of positive outcome was computed separately for those whose aftercare doctors were compliant with the alternative-medication protocol and those whose aftercare doctors were noncompliant (e.g., personal preference for antipsychotics). For the compliant, percent of positive outcome was 78%; for the noncompliant, percent positive outcome was 44%. Outcomes were compared by chi square analysis that showed a significant relationship between positive outcome and compliance. Conclusion: Although this was not a controlled study, the data suggest that positive outcomes can be achieved with the alternative-medication protocol, without the use of antipsychotic medication.

Introduction: Since the days of Phineas Gage, we have known, through observation of what happens when this structure is damaged, that the prefrontal cortex plays an important role in mediating our social conscience. In this paper, we are presenting the cases of two patients who exhibited lying post-frontal lobe injury in situations in which they were observed performing the behavior that they then denied. Case Reports: The first case involves a gentleman with FTD who would deny drinking water on multiple occasions when he was caught drinking. The second involves a gentleman with frontal TBI who would deny urinating and defecating in his bed, despite having this behavior discussed with him on multiple occasions. This type of denial/lying was not present in each patient before their CNS injury. Discussion: Are these cases of amnesia where the patient simply does not recognize that they are performing the act, or were they unable to avoid lying despite or possibly without recognition that they would be immediately found out. A literature search revealed no previously published papers looking at this phenomenon. We propose that frontal lobe damage may cause lying in a twofold manner: it disinhibits the patient from lying and also destroys the executive function necessary to understand that they will be caught. It may also impair the memory of the event or, because of a decrease of recognition of social code, allow these events to be ignored as important, and thus be forgotten.

Background: The impact of caloric consumption on mild cognitive impairment (MCI) is unknown. Objective: The authors investigated whether daily total caloric intake is associated with MCI. Methods: This was a cross-sectional study derived from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota. A random sample of 1,233 study participants without dementia (N=1,070 cognitively normal persons; N=163 with MCI) ages 70 to 89 years, reported their caloric consumption within 1 year preceding the date of interview by completing a Food Frequency Questionnaire. On the basis of published criteria, a consensus panel classified each subject as either cognitively normal or having MCI. Results: We used multivariable logistic-regression analyses to compute odds ratios (OR) and 95% confidence interval (95% CI) in order to measure the association between caloric intake and MCI, after adjusting for age, sex, education, depression, APOE genotype, medical comorbidity, and BMI. Analyses were conducted in tertiles of caloric intake: 600 – <1,526 cal/day (lowest tertile; reference group); 1,526 – 2,142.5 cal/day (middle tertile); and >2,142.5 to 6,000 cal/day (highest tertile). There was no significant difference between the middle tertile and the reference group (OR: 1.05; 95% CI: 0.63 – 1.77; NS). However, daily energy consumption in the highest tertile was associated with a doubled odds of having MCI (OR: 2.41; 95% CI: 1.51 – 3.86; p <0.001). We also observed a dose–response pattern, that is, increasing caloric consumption was associated with increasing odds of having MCI (p for trend <0.001). Conclusions: In this population-based case–control study, increased caloric intake was associated with increased odds of having MCI.

Background: Dandy-Walker syndrome (DWS) is a congenital brain malformation characterized by partial or complete agenesis of the cerebellar vermis and cystic dilatation of the fourth ventricle. Dandy-Walker syndrome is a spectrum disorder, with varying levels of malformations and impairment. The term Dandy Walker Variant (DWV) refers to only partial absence of the vermis. A large majority of cases are diagnosed in infancy, and incidental adult findings are quite rare. We provide a unique case of an incidental finding of DWV late in life. The patient completed a neuropsychological evaluation for memory problems, and authors discuss his imaging and testing results. Case History: The patient was a 68-year-old man found to have previously unsuspected DWV variant on CT scan imaging. He was referred for neuropsychological testing for a new-onset cognitive disorder. He displayed normal functioning in most areas, with impairments in impulsivity and language. The test pattern did not suggest dementia. He was diagnosed with Cognitive Disorder, NOS, that was considered to be related to the findings on his CT scan. Those findings were thought to represent chronic microvascular changes and were unlikely to be unrelated to the preexisting DWV. Conclusions: This DWV case is one of the first to provide and discuss neuropsychological test results. The patient’s test results were consistent with the literature, which indicated that cognitive functioning among individuals with DWS can vary greatly, with a large percentage of cases exhibiting normal-range functioning, particularly among individuals with DWV, a less severe form of the disorder.

Background: The neural and genetic basis of social cognition is subject to intensive research nowadays. Breaking slightly away from autism as being the archetypal disorder of social-cognitive skills, we present three chromosome-deletion cases presenting with issues in social cognition. Case #1: A 21-year-old young woman with de-novo deletion on chromosome 18q23, presenting with seizures, anxiety exacerbated by amenorrhea of unknown etiology, and lack of social skills. Case #2: A 43-year-old man with Williams syndrome (delation at 7q11.23) and gifted musical aptitude; high sociability led the community to place multiple restraining orders against him. Case #3: A 24-year-old young man with velo-cardio-facial syndrome (deletion at 22q11) presented as Pervasive Developmental Disorder, NOS, with above-average IQ and severely compromised social skills. He is in a high-performance IT job, yet cannot leave his home for a simple errand. He lives with his parents and requires full attendance to his needs. We compare these cases with two autosomal dominant disorders with known mutations. Case #4: Tuberous Sclerosis (TSC-1 and TSC-2) in an 18-year-old patient with seizures, renal angiolipoma, normal IQ, tics, extreme agitation, self-mutilation, and absent social skills. Case #5: Noonan Syndrome (PTPN11, KRAS, and SOS1) in a 25-year-old man with mild mental retardation, neoplastic lesions, anxiety, apathy, and deficient social skills. Unable to live independently. Conclusion: We use the clinical neuropsychiatry cases to distinguish the several dimensions of sociability in neurodevelopmental disorders. We speculate on the genetic influences on social cognition focusing on the distinct behavioral and social phenotype related to each disorder.

Background: Prader-Willi syndrome (PWS) is a genetic disorder resulting from a microdeletion on chromosome 15q11-q13, causing multiple physical symptoms. Cognitive studies indicate intellectual abilities ranging from average to severe mental retardation, with impairments in executive functioning, short-term memory, expressive language, and auditory processing. Visual-spatial abilities and receptive language are more likely to be less impaired. The role of weight, behavioral problems, and sleep disorders has been examined. The importance of psychosocial factors has not been reported. The current case examines a complex case of a child with PWS whose father is in the military. Case History: The patient is a 7-year-old girl diagnosed with PWS, who is the result of a pregnancy complicated by a maternal fall, with possible injury to her mother’s abdomen. Delivered at 32 weeks by emergency caesarean section, she had a lengthy and complicated hospitalization. She has a medical history of sleep apnea, asthma, strabismus, frequent ear infections, and allergies. There has been inconsistency in her treatment, given her father’s military background and multiple family moves. A thorough neuropsychological evaluation was conducted, and she demonstrated significant delays in motor coordination, language, and memory, with moderate mental retardation. These results will be presented. Conclusions: Consideration of the combination of language, cognitive abilities, and medical comorbidities is important as it relates to treatment recommendations. This case highlights the impact of complicating factors such as psychosocial stressors and lack of consistency of treatment on the clinical presentation of a child with PWS.

Background: Evidence-based treatments for psychogenic non-epileptic seizures (PNES) are emerging but remain limited. Mindfulness-based psychotherapies may be well suited for this population, and their efficacy is unknown. Objective: Authors tested the efficacy of a mindfulness-based psychotherapeutic intervention. Methods: Efficacy of a mindfulness-based psychotherapeutic intervention was evaluated at 6 and 12 sessions. The primary outcome measure was mean weekly PNES count. Secondary outcome measures included psychopathology severity scales. Subjects included 6 adult female patients with PNES. They participated in a four-module mindfulness-based individual psychotherapeutic program to be completed in 12 sessions. Timing for completion of each of the four modules was flexible, depending on individual presentations. Weekly PNES counts were taken at every session. Psychopathology self-rating scales were analyzed at the 6th and 12th sessions. Concurrent psychopharmacological interventions were kept minimal. Results: Subjects completed 12 sessions, except for one patient who completed all modules in 10 sessions. The initial mean weekly count of PNES, based on the previous 2-month average was 17.98 (range: 0.25–70). The mean weekly PNES count was 2.25 (range: 0–7) on the sixth session and 3 (range: 0–11) at the 12th session. The average time to complete the 12 sessions was 26.33 weeks (range: 15–43). Depression and anxiety scores were reduced at 6th and 12th sessions. Most patients entered a maintenance-treatment phase after the 12th session. Conclusion: This case series constitutes preliminary evidence of the efficacy of mindfulness-oriented psychotherapy for the treatment of PNES. The intervention took place in a flexible clinical setting that allowed for individualized timing of psychotherapeutic interventions and concurrent psychopharmacological changes.

Background: A patient was initially misdiagnosed with a transient tic disorder, and, upon closer observation, new clinical manifestations eventually surfaced that provided key diagnostic information leading to the diagnosis of EMA. Case History: A 4-year-old girl with a family history of motor tics was referred to the clinic after assessment by Adult Neurology for eye fluttering and repetitive blinking, accompanied by a hand gesture described as a “brow-wipe,” which became more pronounced in sunlight; worsening when she was excited, anxious, or exposed to warm temperatures. Episodes were frequent and brief, happening throughout the day. She was diagnosed with a transient tic disorder and given a trial of low-dose clonazepam. The patient was stable able for months, until dramatically worsening. The patient showed tics non-stop when in the sun, and she was described as seeking light stimuli to tic. A combined aripiprazole and clonazepam treatment decreased tic intensity, but never resolved symptoms. Video EEG indicated features of self-induced photic photosensitive epilepsy, with evidence of benign focal epileptiform discharges of childhood as generalized seizure classification. The patient would stare at the light and move her left hand across her face; the spike was usually at the time the little finger cleared the left eye. Conclusions: Diagnosis of EMA is quite clear if the characteristic seizures are present. The appropriate next step in diagnosis will always be a photic-stimulation video EEG; the characteristic eye closure-related discharges and photosensitivity confirm the diagnosis. EMA is many times misdiagnosed for tics, so it is worthwhile to reassess the tic patient who presents with photosensitivity.

Background: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor and phonic tics and commonly associated with behavioral problems. It is estimated that the majority of patients with TS experience depressive symptoms. We set out to investigate the associations between tics and depressive symptoms in TS and to determine what clinical and demographic factors predict depression in patients with TS. Methods: Fifty-four patients were recruited from the specialist TS clinic at the Department of Neuropsychiatry, Birmingham, UK. In addition to clinical and demographic data, tic symptoms were evaluated with the clinician-rated Yale Global Tic Severity Scale (YGTSS). Depressive symptoms were measured with the Beck Depression Inventory, 2nd Edition (BDI-II), a 21-item, self-rated questionnaire addressing the cognitive, affective, and autonomic manifestations of depression. Results: Authors found a high prevalence of mood disorders in TS (major depression: 42.6%; bipolar affective disorder: 9.3%). Mean (SD) BDI-II scores were 17.3 (12.3), with relative prominence of cognitive and somatic symptoms. Interestingly, correlation analysis did not demonstrate any relationship between BDI-II and YGTSS scores (two-tailed, Spearman’s ρ <0.19; NS). However, female gender predicted higher BDI-II scores for the affective component of depression (β value = –1.47; β = –0.27; p=0.041). Discussion: Depression is confirmed as a prominent comorbidity of TS, especially in its cognitive and somatic components. Although the current study did not identify any significant associations between tic severity and depression ratings, the association between female gender and affective symptoms of depression warrants further investigations on larger samples in order to explore possible gender-specific risk factors.

Background: As a complex process involving several areas in the brain, consciousness can be intricate to assess through clinical observation when a patient presents an altered state of consciousness such as minimally conscious state (MCS). Through a specific approach and personalized musical interventions, the music therapist can facilitate patient's purposeful responses. Objective: The primary goal of the study was to determine whether music therapy assessment can provide significant information for a differential diagnosis between minimally conscious state and vegetative state within an interdisciplinary assessment. Methods: Music therapy assessment was performed on a 22-year-old man with minimally conscious state secondary to traumatic brain injury. This assessment provided crucial clinical data for the differential diagnosis between vegetative state and minimally conscious state. The Wessex Head Injury Matrix (WHIM) was used to compare the patient’s responses during neuropsychology (NPS) and music therapy (MT) assessments. Results: The patient’s responses to music stimuli were evidenced by observable purposeful movements and gestures. WHIM scores were significantly higher during MT assessments. Basal WHIM scores (pre-treatment): NPS: 9/62; MT: 20/62. Final WHIM scores (after 1 month of intensive interdisciplinary treatment): NPS: 19/62, MT: 26/62. Video excerpts will be available to illustrate baseline and final assessments. Conclusion: We hypothesize that meaningful emotional and personalized musical experiences foster the arousal of several neural networks related to consciousness operation, enabling the ability to recruit and coordinate brain regions in MCS. Personalized music-therapy interventions can contribute with significant data toward differential diagnosis by promoting observable cross-sectional integrated responses.

Background: Patients with childhood sexual trauma-related posttraumatic stress disorder (CST–PTSD) exhibit abnormal fear responses and demonstrate frontolimbic dysfunction in neuroimaging studies. Few studies have explored structural abnormalities in CST–PTSD. Objective: This study investigated frontolimbic gray-matter volumes in patients with CST–PTSD as compared with healthy subjects. We hypothesized diminished anterior cingulate cortex and hippocampal volumes, with amygdalar volume increases. Method: A sample of 28 women (mean age: 30.1 years; SD: 6.4) with CST–PTSD (clinician-administered PTSD scale mean score: 63.8; SD: 13.9) and 28 women (mean age: 29.1; SD: 6.5) with no known psychiatric history were recruited. High-resolution T₁ weighted scans (3T MRI) were analyzed with voxel-based morphometry with Jacobian modulation. Group effect was assessed by an ANCOVA model, with age and total intracranial gray-matter volume entered as covariates of no interest. Between-group differences were considered significant if the peak voxel-wise p value was <0.05, corrected for multiple comparisons. For a priori regions of interest, differences were considered significant if the peak voxel-wise p value was <0.05 in small volume correction. Results: In preliminary analyses, the CST–PTSD group showed increased left amygdalar volume (p=0.024) and a trend toward reduced right rostral anterior cingulate cortex volume (p=0.075) in region-of-interest analyses. There were no statistically significant whole brain-corrected group differences. Conclusion: This study identified increased amygdalar volume in a sample of female patients with CST–PTSD, and provides a potential analog for previously identified heightened amygdalar activity in patients with CST–PTSD.

Background: Apathy is a frequent symptom in Alzheimer’s disease (AD) that can be associated with additional functional disability. Thus far, apathy has most consistently been associated with atrophy of the left anterior cingulate, left superior frontal, and middle frontal gyri, and left and right orbitofrontal regions (N studies=16). Although apathy has already received attention from several studies, most (N=14) were relatively small (N ≤50) and most (N=13) did not used advanced neuroimaging techniques. Moreover, most (N=11) did not distinguish apathy from depression, two frequently related but distinct behavioral syndromes, with possibly different neuroanatomical correlates. Objective: To determine the neuroanatomical correlates of apathy, independent from depression, in a large sample of mild AD, using advanced volumetric techniques. Methods: Using advanced morphometric techniques, authors compared AD subjects in the Alzheimer’s Disease Neuroimaging Initiative with (N=58) and without (N=104) apathy. These subjects were all without significant depressive symptoms (Geriatric Depression Scale ≤5). A statistical surface map was generated, controlling for covariates. Results: AD subjects with and without apathy were comparable on age, gender, education, and global cognitive functioning (MMSE global score). As predicted, AD subjects with apathy presented with atrophy of the left lateral orbitofrontal cortex (OFC) as compared with AD subjects without. Conclusion: This study supports previously reported association between apathy and left OFC. This region has been involved in reward-processing and learning of stimulus–reinforcement associations, which suggests similar neural substrates for motivated behaviors in AD and normal subjects.

Background: Deep brain stimulation of the subthalamic nucleus (STN DBS) has become a widely accepted treatment option for selected patients with Parkinson’s disease (PD). However, in some cases, STN DBS can cause deleterious effects on cognition or emotion. Important research questions include precisely defining locations within, or near, the STN at which DBS is most likely to induce benefit and identifying locations at which DBS is most likely to cause side effects. Objective: For any quantitative measure of motor, cognitive, or emotional functioning, to create three-dimensional (3D) images of STN and nearby anatomical structures showing, at each voxel, 1) best-estimate effect of stimulation at that voxel, based on stimulation at or near that location; 2) the probability that the effect differs significantly from zero, and 3) correct the statistical inference for multiple comparisons. Methods: PD patients >2 months after STN DBS surgery were examined off medications in four conditions: no stimulation or DBS using the left or right electrode or both, using the contact(s) previously chosen clinically for chronic monopolar stimulation. Condition order was counterbalanced. Measures of motor function (UPDRS), response inhibition (Go/No-Go task), and emotion (Visual Analog Scales) were assessed in a double-blind fashion. Custom software created 3D images of weighted (for nearness to an active contact) mean effect, a weighted t statistic for difference from zero, and a probability (_log10 p) image based on the t image and the appropriate degrees of freedom (df) at each point (censoring data from contacts >3.1 mm away). Additional custom software implemented a permutation test to compute the probability that a _log10 p image with a given peak magnitude or cluster size could occur by chance, that is, by randomly assigning measured responses to the list of locations stimulated (without regard for which response was actually observed in which subject). This also corrects for any apparent but false association of precise location with response for outcome measures that respond similarly to DBS at any location (in or near STN) actually stimulated in at least 6 patients. Results: The most robust association of DBS location with any response was improvement in UPDRS score with stimulation in the zona incerta (dorsal to STN; peak [most significant] p <10⁻²⁰⁰). However, corrected p=0.165 [alternative methods yielded p of 0.02–0.35]). Conclusions: 1) The new visualization and statistical method can identify brain locations in or near STN that are associated with a behavioral response to “STN” DBS. 2) The multiple-comparisons correction method chosen here may be too conservative; alternatively, the specific location of stimulation in or near STN may not matter significantly for several clinically important outcomes.

Background: The precuneus is the default mode network (DMN) node with the greatest functional connectivity. Most of the energy consumed by the brain region is devoted to glutamatergic signaling, as modulated by GABA. Regional GABA has been correlated with fMRI within regions of interest, but never with whole-network activity. Objective: The authors tested the hypothesis that DMN functional connectivity correlates with MRS-measured neurotransmitters. Methods: Authors scanned 19 healthy men (age: 48 [SD: 15]) at rest using J-PRESS magnetic resonance spectroscopy (MRS) within a precuneus voxel (25 × 18 × 20 mm), followed by two-dimensional fitting (ProFit) to obtain glutamate and GABA spectra. They implemented group Independent Component Analysis (ICA) to resting fMRI to extract the DMN. The beta coefficient for the DMN was regressed by age and glutamate/GABA. Results: We obtained a good fit (Cramer-Rao lower bounds) for glutamate and GABA in 15/19 men. The regression was significant (F[2]=10.541; p=0.002). The ratio Glu/GABA correlated with DMN activity (R²=0.58; beta=0.722; p=0.001); but not age (β = –0.243; p=0.194). If we entered Glu and GABA as regressors separately, the model weakened (F[3]=2.568; p=0.108), although there was trend for GABA significance (β = –0.616; p=0.058). Conclusions: The balance between inhibition/excitation is more important than either one alone in determining DMN functional connectivity. Changes in DMN connectivity and Glutamatergic/GABAergic signaling occur in aging and Alzheimer’s disease. Combining resting fMRI and MRS may offer novel biomarkers for these conditions.

Background: The startle eyeblink reflex is modulated differently by positive and negative emotional pictures during anticipation versus perception. Non-depressed individuals with Parkinson’s disease (PD) show blunted responses during negative picture-viewing. Effects of PD depression on startle eyeblink responses are not known. Results of previous studies examining affective startle modulation in depressed adults without PD have been mixed. Objective: To test the hypothesis that PD depression would be associated with reduced modulation of the startle eyeblink reflex during both anticipation and perception of emotional pictures. Methods: A group of 30 individuals with PD (10 with DSM-IV depression) and 20 non-depressed healthy controls participated in a cued picture paradigm using the International Affective Picture System. Eyeblinks were elicited by white noise bursts during either anticipation or perception and measured by electromyography. Results: Groups did not differ in age, education, cognitive status, sex distribution, baseline startle eyeblink responses, or subjective ratings of picture valence and arousal. As expected, healthy controls showed enhanced responding during emotional picture anticipation and a linear pattern of responding during emotional picture perception. Non-depressed individuals with PD showed similar patterns, with the exception of blunted responding during negative picture-viewing, as previously reported. In contrast, depressed individuals with PD showed flattened responses during anticipation (p=0.83; ηp²=0.01) and potentiation of startle during negative picture viewing (p<0.01; ηp²=0.64). Hyper-startle responding in this condition correlated with specific depressive symptoms of dysphoria and anxiety. Conclusions: In PD, depression is associated with reduced emotional expectancy and exaggerated threat-responding. These physiologic responses may be modifiable with targeted behavioral treatment.

Background: There is a suggestion that self-reported depressive syndromes can independently manifest in the general population as cognitive/affective or somatic/vegetative. However, this finding has not been examined in an older adult memory-disorder sample. Objective: To determine whether older adults with cognitive impairments also exhibited independent cognitive/affective and somatic/vegetative depressive syndromes, the authors explored the factor structure of the Beck Depression Inventory, 2^nd Edition (BDI–II) in this population. Methods: Participants were 208 older adults (mean age: 74; SD: 7.7) diagnosed with Mild Cognitive Impairment (N=131) or early Alzheimer’s disease (N=77), who completed the BDI–II as part of an outpatient neuropsychological evaluation. Results: Exploratory principal-component factor analysis with direct Oblimin rotation was conducted. A two-factor solution was specified, based on our theoretical conceptualization of the cognitive/affective and somatic/vegetative items from the scale. The first factor represented cognitive/affective symptoms of depression (e.g., self-dislike, pessimism, worthlessness), and accounted for 33% of the variance. Adding the second factor, reflecting somatic/vegetative items (e.g., sleep and appetite changes, loss of energy) accounted for an additional 6.9% of the variance. Conclusion: Results supported the presence of two distinct depressive syndromes, cognitive/affective and somatic/vegetative, on a self-report measure of depression. Thus, cognitively impaired older adults report mood symptoms relatively similarly to the general population. This may have implications for psychiatric treatment in this population. The effects of awareness in this sample also will be discussed.

Background: Purpose in life (PIL) is associated with decreased incidence of dementia. PIL has been hypothesized to be potentially neuroprotective, but this idea has not been empirically validated. Objective: We examined 1) the relationship between midlife PIL and cognitive functioning in later life; 2) whether engagement in stimulating leisure activities (physical, social, and cognitive activities) mediated the relationship between PIL and cognitive functioning. Methods: A historical cohort study derived from the Midlife Development in the United States (MIDUS) is an NIH-funded, nationwide community-based sample that investigates midlife exposure and cognitive outcomes in late life. The sample for this study constituted 1,003 participants, age 51 to 75 at baseline (in 1995). A sense of direction in life at baseline was measured by a Purpose-in-Life questionnaire. Other measures included demographic and health information (at baseline and follow-up), a self-report questionnaire of leisure activities (follow-up), and telephone-administered composite measures of episodic memory and executive functioning (follow-up). Results: Baseline PIL score significantly predicted follow-up episodic memory and executive functioning. Multiple mediating modeling indicated that leisure activities jointly or individually mediated the effect of PIL on follow-up episodic memory and executive functioning. Conclusions: Results support both a total effect of PIL and indirect effects through the engagement in stimulating leisure activities on episodic memory and executive functioning in old age.

Background: In Huntington’s disease (HD), striatal dysfunction could affect the functioning of the prefrontal cortex, leading to changes in social reasoning and higher cognitive abilities, such as decision-making. Objective: We investigated whether individuals with HD exhibit impairments in moral judgment and decision-making and whether any deficits were related to executive dysfunction and difficulties with Theory of Mind (ToM): the ability to reason about mental states. Methods: A group of 16 patients with HD and 16 control subjects took part. They completed a task that involved judging how wrong a list of acceptable and immoral behaviors were, and a version of the Ultimatum Game (UG), an economic decision-making task involving social reasoning. Two ToM tasks were used, which involved judging people’s mental states from photographs of pairs of eyes, and understanding socially inappropriate remarks. Participants also completed measures of verbal fluency, working memory, and inhibition. Results: Patients with HD exhibited a tendency to rate the severity of immoral behaviors below that of controls, but this difference did not reach significance. However, HD was associated with significantly more “irrational” rejections of offers of money on the UG. Patients with HD also exhibited significant deficits on both ToM tasks and executive function. However, there were no significant correlations between moral judgments or UG decisions and performance on the ToM and executive tasks. Conclusions: HD is associated with impairments in decision-making, deficits in ToM, and executive dysfunction. These difficulties could be linked to some of the problematic social behaviors seen in HD.

Background: The mechanism of how physical symptoms become the focus of suffering in somatizing conditions is poorly understood. Objective: Authors tested the hypothesis that when comparing outpatients with Conversion Disorder (CD), functional somatic syndromes (FSS), and non-somatizing medical patients (MC), the greatest deficits in the mental representation of emotions are associated with CD. Methods: In this case–control study at Mayo Clinic in Arizona and University of Arizona, authors administered measures of Theory of Mind (ToM), emotional awareness, positive and negative affect, depression, anxiety, physical symptoms, and psychiatric diagnoses to consecutive outpatients, age 19–60, with complaints of physical symptoms and diagnosed with either CD (n=29), FSS (n=28), or MC (n=30). The main outcome measure was the Animations–L score, that is, use of emotion-related words while describing a non-verbal stimulus of moving geometric shapes. Results: Groups did not differ in level of physical symptoms, negative emotions, performance on the Levels of Emotional Awareness Scale (LEAS), or cognitive ToM. However, as in a previous study of German somatoform-disorder inpatients, Animations–L scores, that is, measures of “emotional ToM,” were significantly lower in both the CD and FSS groups than in MC (contrary to expectations of CD <FSS). Both the CD and FFS groups also endorsed significantly fewer positive emotions, scored lower on a self-report measure of alexithymia, and higher on depression and anxiety measures than MC. Conclusions: Our results reflect impairment in “conversion” from implicit to explicit processing of emotions, as well as reduced focus on positive emotions and emotional expression, in the somatizing groups.

Background: This case series represents treatment of 17 bipolar spectrum-disordered patients with low-dose Abilify, Saphris, Latuda, and Geodon in augmentation of mood-stabilizers. Case Histories: Many people who have comorbid neurologic challenges, such as closed head injury and exposure to toxic level of alcohol in the past may be sensitive to the atypical antipsychotics at usual recommend doses when used as augmentation of mood-stabilizers. The objective of this case study was to evaluate mood stability after low-dose atypical antipsychotic augmentation of mood-stabilizers by use of a brief cognition screen and the Hamilton Rating Scale for Depression. Patients who have been stable psychiatrically in an outpatient private practice for 5 to 20 years were used in the study. Patients had subtle signs of toxicity on average doses of mood-stabilizers. Previous attempts to reduce cognition-impairing mood stabilizers were not tolerated, as mood instability and depression recurred. Low-dose atypical augmentation enabled dose reductions of lithium, Tegretol, and Depakote without mood instability or depression over 3 years. Conclusion: In my case series, low-dose Abilify, Geodon, Saphris, and Latuda augmentation prevented recurrence of symptoms of depression and enabled dose reductions of mood-stabilizers by about 25% and stopping Depakote in one case. Quantifiable improvements in cognition were noted in all people as a likely result of reduction of mood-stabilizer levels, although improvement in attention due to Abilify itself could not be ruled out. An improvement in the quality of life was noted in study subjects.

Background: The Clock-Drawing Test (CDT) is a commonly used and easily administered test to assess cognitive function. Most variations involve drawing a clock-face, adding all the numbers, and placing the hands to indicate a specific time. The CDT is utilized as a bedside test and in neuropsychological testing batteries. There is evidence that this test can help differentiate between the subtypes of dementia and detect the presence of neuroanatomical lesions. Objective: The objective of this review is to create teaching materials that present a color-coded functional neuroanatomic map of brain areas involved in the CDT. Method: The relevant scientific literature was reviewed and synthesized for information related to CDT errors and anatomy, dementia, and functional imaging (fMRI, SPECT, PET). Results: Multiple brain regions and networks are required to complete an accurate clock-face and hand placement. The CDT requires primary sensory and motor areas to coordinate with higher-order association areas in several brain regions. Dysfunction in these areas can result in different types of errors in the CDT, such as comprehension of the test, perseveration, visuospacial planning, and hand placement. Thus, the CDT has some specificity for the different subtypes of dementia and different focal lesions of the brain. Conclusion: The CDT is an effective tool for cognitive testing because of the utilization of multiple functional brain areas. It is important to understand the functional areas involved when using this test for neuropsychiatric evaluation.

Background: Patients often react to cancer diagnosis with anxiety. Psychological adaptive mechanisms theoretically manage symptoms of anxiety, but this thesis has not been tested in cancer patients. Objective: This study hypothesized that frequencies of anxiety symptoms would correlate neither with Immature nor Mature adaptive styles, since, in theory, both cap anxiety equally well. A secondary hypothesis proposed that depression symptom frequency, by contrast, would be significantly associated with Immature adaptation. Methods: With IRB approval, consenting cancer outpatients undergoing infusion chemotherapy (n=31) completed two symptom severity scales (Beck Depression Inventory and Hamilton Rating Scale for Anxiety) and a measure of adaptive mechanism maturity (Defense Style Questionnaire). The final sample included 14 women and 17 men, ranging in age from 27 to 81 years (mean: 59; SD: 11.9). Pearson’s r assessed the scale scores for association (p <0.05). Results: As hypothesized, anxiety symptom frequency did not correlate with Immature adaptive mechanism frequency (Immature: r=0.27; NS). Frequency of depression symptoms correlated only with Immature adaptive mechanism endorsement (r=0.36; p=0.04). Conclusions: Adaptive mechanisms appeared to control anxiety irrespective of adaptive maturity. The secondary hypothesis correctly predicted a significant relationship between depression symptom frequency and Immature adaptive styles. These data suggest that targeted interventions towards cancer patients with Immature adaptive styles could potentially ease depression severity.

Background: Paraneoplastic neurological syndromes are defined as remote effects of cancer that are not caused by the tumor and its metastasis, or by infection, ischemia, or metabolic disruptions. In most patients, the neurological disorder develops before the cancer becomes clinically overt, and further follow-up reveals the presence of a malignancy. Case History: A 63-year-old Caucasian woman with slowly-progressing cognitive deficits presented for the evaluation of her functional decline. Initial work-up failed to reveal any obvious cause of her cognitive deficits. Retrospective medical data review revealed a pulmonary nodule which had not been previously evaluated. Further evaluation revealed pulmonary adenocarcinoma with metastatic spread to liver and spine. MRI of brain did not reveal any metastatic lesion. CSF analysis revealed presence of anti-Hu antibody, and a diagnosis of limbic encephalitis was made. Chemotherapy was initiated for the patient; however, she died before any cognitive improvement could be noted. Conclusions: Limbic encephalitis is an inflammatory process, localized to structures of the limbic system, that produces cognitive impairment, along with disordered perception, mood changes, and sleep disturbances. Association with small-cell lung cancer has been most frequent; however, cases with other types of lung cancer have been reported. Anti-Hu antibody is most frequently found in CSF analysis of such patients. In a patient work-up for cognitive deficits, detection of paraneoplastic antibodies could facilitate early diagnosis and better treatment outcome for the occult malignancy.

Background: Dengue fever is a potentially lethal infection, little acknowledged in the United States, but common elsewhere and expected to become increasingly more so in the U.S., in part because of climate change and increasing global travel. This flavivirus infection, transmitted by Aedes mosquitoes, may be frequently overlooked. It has recently been demonstrated to be a neurotrophic virus, with possible neurologic sequelae including Guillain-Barre syndrome, intracranial hemorrhage, ischemic stroke, isolated nerve palsies, and encephalopathy. However neuropsychiatric sequelae remain little acknowledged. We present a case of apparent manic reaction after dengue fever and conduct a literature review for similar cases. This is the first case of mania after dengue fever documented in the American literature, and the first in the literature to include longitudinal follow-up after the initial episode. Case History: A 48-year-old man with a history of dengue virus infection in 2008, followed by mood changes and lability, presented for management of insomnia, anxious ruminations, and impulsive angry outbursts. Immediately after the dengue fever, he described feeling “elated” and “ecstatic,” being extremely talkative and energetic, thinking more quickly and writing more, and being told to “slow down.” His ideas were coming so quickly that he recalled asking his wife to write them down. He was unsure whether he had been given mood stabilizers during that period, but was treated for insomnia with an anticholinergic agent. By time of presentation, in 2010, the patient had endured a suicidal depression and was being maintained on citalopram 10 mg alone, with the residual symptoms described above. Although he had a previous history of depression for which he had had numerous unsuccessful medication trials, the episode of hypomanic symptoms after dengue viral infection was the only one of its kind in his history. He did report a family history of mood disorder with possible suicidality in his father. Results: The patient was started on lamotrigine for mood stabilization, with subsequent improvement in mood, irritability, and impulsive outbursts. However while abroad, shortly after a dose increase to 175 mg, the patient developed a rash accompanied by fever, neck stiffness, and oral ulcerations, and lamotrigine was discontinued. He tolerated a 10-day course of oral steroids without overt manic symptoms, although he did complain of feeling “hyper,” and thereafter was maintained off mood-stabilizer without ill effect. Even after an increase in antidepressant to citalopram 20 mg, he retained some residual depressive symptoms but no evidence of mania. Conclusion: This case demonstrates the need for awareness of possible neuropsychiatric sequelae of arboviral infections. In particular, it shows that mania is a rare but possible consequence of dengue fever. A literature review, consisting of a MEDLINE search for similar cases expanded to include the reference lists of relevant publications, revealed three other pertinent cases. All three cases involved known dengue fever with subsequent neuropsychiatric disturbance involving symptoms of a manic state, including elevated or expansive mood, irritable or expansive affect, new psychosis, increased goal-directed activity, and decreased need for sleep. In all three cases, recovery from manic and psychotic features was complete and episodes appeared isolated and time-limited. However, longitudinal follow-up data were not provided, so the need for ongoing management remained unclear. The case presented here is unique in that it provides over 2 years of follow-up data. These data suggest that patients may be safely maintained on antidepressant monotherapy after manic reaction to dengue, unlike in idiopathic mania.

Background: The experience of depressive symptoms in cognitively impaired older adults is complex and not well described, and characterizing this presentation can have implications for diagnosis and treatment. Objective: The authors describe the phenomenology of depressive symptoms in a sample of older adults with varying degrees of cognitive impairment. Specifically, they examined the differences in symptom endorsement between individuals diagnosed with Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD) by use of a self-report depression measure. Method: A group of 208 community-dwelling older adults diagnosed with MCI or AD completed the Beck Depression Inventory–II (BDI–II). Descriptive statistics were used to examine the frequency of endorsed items. Results: Overall, participants with MCI and AD endorsed a similar degree of depressive symptoms (mean AD: 7.5; mean MCI: 9.5). Both groups endorsed a similar profile of symptoms, with loss of energy, concentration difficulties, fatigue, changes in sleep patterns, and decreased libido the most frequently endorsed by both groups, symptoms that generally are not specific to depression. Within this cognitively impaired sample, clinically depressed individuals (BDI–II >13) also endorsed self-criticism, self-dislike, indecisiveness, anhedonia, and pessimism, symptoms that distinguished them from their non-depressed peers. Conclusion: In general, MCI and AD individuals endorsed similar level and types of depressive symptoms, which may at least partially reflect the direct neuropsychiatric effects of their degenerative disease. However, individuals who also report negative self-perception, such as decreased confidence and self-blame, are more likely to be clinically depressed, and report of these symptoms may raise a greater degree of concern for depression than in those who primarily report somatic concerns.

Background: Medical management of congestive heart failure (CHF) has improved survival; however few transplantable hearts are available. Therefore, many patients are receiving ventricular-assist devices (VAD) to relieve symptoms and prolong life. Once used as a bridge to transplant, VADs are being used for heart recovery and as permanent use. These devices require good cognition to be operative and may lead to postoperative neuropsychiatric complications. Case History: With VADs becoming a realistic option for many CHF patients, it is important for physicians to assess baseline cognitive functioning and appreciate the post-operative complications to provide the best quality of care. One study found that 70% of CHF patients had some form of cognitive impairment (CI). The Montreal Cognitive Assessment (MoCA) is a good tool and is more sensitive to CI than the Mini-Mental State Exam in CHF patients. Unrecognized CI can be problematic because caring for a VAD is complex. Patients may have difficulty following commands such as how to take anticoagulants and how to charge batteries. Post-operatively, cognition may not improve; one study found the VAD may induce executive cognitive dysfunction without stroke. Theories for this CI include: cerebral hypoperfusion, cerebral microembolization, and cerebral hyperperfusion. Conclusions: More research is needed to understand the neuropsychiatric complications of heart failure pre- and post-VAD implantation. At Christ Medical Center in Chicago, IL, our neuropsychiatric team and Cardiology Dept. just started a protocol to evaluate neuropsychiatric conditions in VAD patients at baseline and again at 6 months, 1 year, and 2 years post-op.

Background: Current research is looking into new targets for the treatment of bipolar disorder. One of them happens to be the glutamate system. There is, however, little research into the use of glutamate antagonists in the treatment of bipolar disorder. This is a report on a patient whose mania, which was not responding to treatment, appeared to respond immediately to a glutamate antagonist. Case Report: This is a case of a young gentleman with developmental delay who was admitted to the hospital with mania and destructive behavior. The patient had been treated in the hospital with lithium, tegretol, klonopin, and Geodon, without any change in his behavior. He was then placed on Cardizem and Neurontin and then Minocin. Within 2–3 days of starting the minocycline (an NMDA antagonist and antibiotic), he calmed significantly, almost to the point of being asymptomatic. He remained so and was able to be discharged 1 week later, without symptoms. Conclusion: NMDA antagonists are currently getting attention for efficacy in depression with rapid results. The literature is sparse on such treatment in bipolar disorder. This case would be the first noted on the treatment of mania with minocycline, and, thus, an NMDA antagonist. It could be argued that the response was not due to minocin alone, because of the Neurontin and Cardizem, but the known efficacy of these drugs in mania is anecdotal and usually not this rapid. We would hope that this case will spark interest in research on NMDA antagonists for the treatment of mania.

Background: Minocycline is a broad-spectrum tetracycline antibiotic that is used mostly for acne. New research has discovered multiple actions of minocycline, including inhibition of microglia, antiinflammatory, antioxidant, and N-Methyl-D-aspartic acid (NMDA) as an NMDA antagonist. Minocycline has been found to attenuate diabetic neuropathic pain in rats in 28 days, working through down-regulating inflammatory cytokines. Furthermore, research has shown that NMDA antagonists may have a role in improving depression. We present a case of a gentleman who could not tolerate many antineuropathic pain medication, who responded to minocycline addition to nortriptyline. Case History: An elderly male patient presented with depression secondary to neuropathic pain that was poorly controlled. The patient could not tolerate multiple anti-pain medications, including gabapentin, venlafaxine, and duloxitine. The patient was prescribed nortriptyline but also found this to be ineffective. He was depressed, denied suicidal ideation, but was “okay with dying.” He was prescribed 100 mg minocycline 2 times/day and had his nortriptyline raised to 25 mg. The patient described relief of pain after 24 hours of minocycline. After 72 hours, he had continued to have relief of pain. He denied feeling depressed. The patient was discharged at that time and lost to follow-up. Conclusions: Minocycline is possibly an effective medication for patients who have uncontrolled neuropathic pain. Indeed, it may have greater use in combination therapy. We also wonder about its antidepressant effects, given the recent effectiveness of NMDA antagonists such as ketamine in depression.

Background: The relationship between epilepsy and behavioral disorders is well known. “Forced normalization” is a phenomenon where there is a worsening of the patient’s behavioral disorder when a better seizure control has been obtained. Complications of anti-epileptic treatment worsening the behavioral disorder are proposed mechanism. Case History: A 24-year-old white man with temporal-lobe epilepsy has had poor seizure control for the past 12 years. He had failed various trials of anti-epileptic medications, and seizure control was not obtained even after a vagal-nerve stimulator placement. MRI had demonstrated left mesial-temporal sclerosis, and intracranial EEG recording located seizure foci in the left medial-temporal lobe. The patient underwent left-temporal lobectomy for seizure control, with partial success. However, he developed postoperative complications, including infection of the overlying skull tissue. The patient later presented with frontal-lobe syndrome even after treatment of the previous complication. Conclusion: The above illustrates a case where partial seizure control was obtained with surgical procedure, however resulting in worsening of the patient’s behavioral disorder. This could be an example of forced normalization, where the patient presented with frontal-lobe syndrome as a complication of the epilepsy surgery.

Background: The concurrent rise of undertreated pain and opiate abuse poses a unique challenge to physicians and researchers alike. A focal, non-invasive form of brain stimulation called repetitive transcranial magnetic stimulation (rTMS) has been shown to produce acute and chronic analgesic effects when applied to dorsolateral prefrontal cortex (DLPFC), but the anatomical and pharmacological mechanisms by which prefrontal rTMS induces analgesia remain unclear. Data suggest that DLPFC mediates top-down analgesia via gain-modulation of the supraspinal opioidergic circuit (SOC). This potential pathway might explain how prefrontal rTMS reduces pain. Objective: The purpose of this double sham-controlled, double-blind, crossover study was to determine whether left DLPFC rTMS induces analgesia by releasing endogenous opioids. Methods: A group of 24 healthy volunteers were randomized to receive real or sham TMS after either intravenous saline or naloxone pretreatment. Acute hot and cold pain via quantitative sensory testing (QST) and chronic hot pain via block testing on capsaicin-treated skin was assessed at baseline and at 0, 20, and 40 minutes after TMS treatment. Results: When compared with sham, real TMS produced analgesia. Naloxone pretreatment significantly reduced the analgesic effects of real TMS on acute and chronic hot pain. Conclusion: These results demonstrate that DLPFC rTMS-induced analgesia requires opioid activity and suggest that TMS drives endogenous opioidergic pain relief in the human brain via DLPFC. Further studies with chronic dosing regimens of drugs that block or augment the actions of opiates are needed to determine whether TMS can augment opiates in chronic or postoperative pain-management.

Background: The incidence and prevalence of cognitive impairment and dementia are higher in patients with Parkinson’s disease (PD) than in healthy elderly, but research investigating the risk factors for cognitive impairment is limited. Vascular risk factors (VRF) are involved in the development of vascular dementia and Alzheimer’s disease, but little is known about their contribution in PD cognition. Objectives: To clarify the association between VRF and cognition and to investigate the possible biological mechanisms underlying the presence of VRF and cognitive dysfunctions in PD. Method: A search for studies assessing both VRF and cognition in PD was conducted in several databases. Results: The analysis of 18 articles (1990–2011) revealed a consistent relationship between cognitive impairment in PD and hyperhomocysteinemia (9 articles), and a more controversial association between smoking (9 articles), heart disease, and cognition. No evidence of any relationship between cognition and diabetes, hypertension, alcohol intake, stroke history, transient ischemic attack, or hypercholesterolemia were found. Conclusion: Hyperhomocysteinemia in PD is most likely a consequence of levodopa metabolism and is associated with brain atrophy by several vascular and neurotoxic mechanisms, which could both explain the relationship found between hyperhomocysteinemia and cognitive impairment in PD. Regarding smoking, even if nicotine may protect against nigral neuronal losses, side effects from the other compounds of cigarette smoke may be deleterious for the vascular system and consequently for cognition. However, there is a lack of studies regarding the other VRF, thus preventing any firm conclusion about their impact on cognition in PD.

Background: Parkinson’s disease (PD) patients often experience compromised quality of life (QoL), previously associated with motor, cognitive, and depression symptoms. Current controversy exists as to whether “apathy,” a highly prevalent motivational disorder in PD, also influences quality of life. Objective: To learn whether apathy uniquely contributes to overall or specific components of QoL. Methods: Participants included 107 PD patients (69% men) without dementia from the UF Center for Movement Disorders and Neuro-restoration. All completed a Parkinson-specific QoL scale (PDQ–39) and self-report measures of apathy (AS), depression (BDI–II), and anxiety (STAI–Trait). Following Kirsch-Darrow et al. (2011), we computed four factor-based scores from the BDI–II and AS: pure dysphoria, pure apathy, somatic symptoms, and decreased interest. Stepwise regressions investigated the unique contribution of each factor and anxiety on overall and domain-specific PDQ–39 scales. Results: Overall PDQ–39 was best predicted by three mood components: anxiety (β=0.4; p=0.002), dysphoria (β=0.316; p=0.012), and decreased interest (β = –0.247; p=0.027; adjusted R²=0.341; F[6, 100]=8.616; p <0.001). Different patterns emerged with respect to domain-specific QoL. Anxiety significantly predicted six domains: ADL, Emotion, Stigma, Communication, Discomfort, Mobility. Decreased Interest significantly predicted ADL and Emotion. Dysphoria significantly predicted Social and Cognition. Apathy significantly predicted Communication. Somatic Symptoms significantly predicted Social. Conclusions: The current study demonstrates that QoL is a construct that contains several factors, and various mood components (anxiety, dysphoria, apathy, somatic concerns, decreased interest) influence distinct aspects of QoL. Even so, Anxiety and Dysphoria were greater contributors to overall QoL than Apathy. Future research should examine the relationship with caregiver burden.

Background: Although psychiatric symptoms are frequently seen in Huntington’s disease (HD), there are few reports of psychosis as a first manifestation. Case History: “Mr. Y,” a 42-year-old teacher from Moho-Puno-Peru (a population without reported cases of HD), over a 7-year span, developed behavioral changes, including irritability, ambivalence, depression, delusions, and hallucinations. He also showed dysarthria and ataxia. One month before admission, he became grossly psychotic, with paranoid ideation, thought-blocking, apathy, mutism, and psychomotor agitation. He was admitted under the working diagnosis of schizophrenia with extrapyramidal side effects. On the unit, subtle choreic movements of the shoulders and arms were observed. As psychosis remitted, the patient reported that his father and grandfather developed abnormal movements at age 65. Results: An MRI revealed caudate atrophy with ventricular enlargement. A tentative diagnosis of HD with secondary psychosis was proposed, and genetic testing confirmed the diagnosis. The patient was discharged on haloperidol. However, 2 months later, he discontinued his medication, and psychosis recurred. He was then readmitted and treated with olanzapine. On follow-up 1 year later, the patient remained compliant with treatment, and he was free of psychosis. He had also resumed his teaching position. At this time, a semi-quantitative H-MRS revealed abnormalities in the creatine and N-acetylaspartate ratios in the anterior cingulate cortex and caudate nucleus, suggesting an impaired neuronal metabolism. Conclusions: HD can present with psychotic features as an early manifestation and therefore should be suspected when psychosis is seen in the presence of involuntary choreic movements.

Background: Pathological crying is distinguishable from depression by a lack of emotional context, or crying out of proportion with experienced emotion. There are many possible etiologies for this condition, including pseudobulbar affect, dycastic seizures, and drug-withdrawal syndromes. This particular patient is unique in that her history and diagnostic testing results lead to the possibility that her symptoms could result from any of these three etiologies. Case Report: In this case, we report on a woman with previously diagnosed and treated pseudobulbar affect, consulted for uncontrollable crying episodes after a knee replacement. An EEG was done because of her unresponsiveness during the crying episodes that revealed a possible seizure focus in the right temporal lobe. She had also had her SSRI medication reduced abruptly on admission before the episodes. This created the dilemma of whether this was the re-emergence of pseudobulbar affect, seritonin withdrawal symptoms, or new-onset dycrastic epilepsy. Since SSRIs had effectively treated these symptoms previously, she was changed to sertraline, eventually with the dose increased to 100 mg, which stopped the crying. In this poster session, we will discuss the differentiation between these three conditions and provide a review of the literature. Conclusion: Although our case most likely turned out to be the recurrence of PBA, we still cannot rule out that the crying was not mood instability from the reduction in SSRI dose. Also, even though the likelihood of dycrastic seizures is low, we would need at least a 24-hour EEG to completely rule them out.

Background: Traumatic brain injury (TBI) is a “signature injury” of the wars in Afghanistan and Iraq. There is growing evidence of comorbid conditions in many combat veterans, creating the need for teaching materials to improve understanding of these complex cases. Educational research strongly supports use of guided experiences in which experts explicitly draw attention to key connections to promote the creation of active (useable) knowledge in learners. Methods: Clinical and research findings relevant to functional neuroanatomy of blast-related TBI with comorbidities were reviewed, synthesized, and summarized into graphic-rich original teaching materials in which color carries a significant portion of the new information. This approach allows large volumes of new information to be presented without overwhelming the learner. Results: In Part I of this series (2009), teaching examples combining new educational materials with clinical cases of blast-injured war fighters were created, presented, and published. These have been used both in preparing learners prior to patient exam and in follow-up discussion afterwards. Evaluations have been very positive. Incorporation of new cases and new research findings will further facilitate establishment of connections between functional neuroanatomy and clinical practice, deepen interest in the individual patient, and enhance appreciation of co-occurring pathologies and prognosis. Conclusion: These newly-revised tools support guiding learners’ through the intricacies of this complicated field. Use of guided experiences strongly promotes the development of the active, integrated knowledge of functional anatomy required for the practice of neuropsychiatry as it relates to the assessment and treatment of blast-injured war-fighters with comorbidities.

Background: Exposure to an explosion (blast) is a major cause of injury during deployment. There is no question that secondary and tertiary blast-related forces can injure the brain. The potential for traumatic brain injury (TBI) caused by primary blast forces remains controversial. Objective: Post-deployment veterans with and without mild TBI after exposure to primary blast forces were compared. Methods: Performance on computer-based neurocognitive tests from the Cambridge Neuropsychological Test Automated Batteries (CANTAB) were compared from groups of post-deployment veterans who differed on presence/absence of psychiatric diagnoses and mild TBI due to primary blast exposure. Results: All veterans with confirmed mild TBI (n=7) were comorbid for posttraumatic stress disorder (PTSD). Veterans with no psychiatric diagnosis (n=19) performed better (group mean Z scores 0.10 – 0.74) than age-matched civilians on all measures, indicating that use of CANTAB’s norms may be misleading when applied to this cohort. Veterans without mild TBI but with PTSD (n=15) had longer response latencies on the Affective Go/No-Go, greater delay aversion in the Cambridge Gambling Task, and impaired Rapid Visual Information-Processing performance, a test requiring sustained attention. Among veterans with PTSD, those with mild TBI performed worse on Delayed Matching to Sample, a test requiring visual working memory. Conclusion: These results suggest that PTSD may be associated with deficits in sustained attention, whereas primary blast-related mild TBI may be associated with impaired visual working memory. Further investigation is necessary to further differentiate the effects of primary blast-related mild TBI and associated psychiatric symptoms.

Support: This material is based on work supported in part by a grant from the Department of Defense Joint Improvised Explosive Device Defeat Organization (JIEDDO), with resources of the VISN 6 Mental Illness Research Education and Clinical Center (MIRECC), and with resources and the use of facilities at the W.G. Hefner VA Medical Center (AMSRD-ARL-RO-SI Grant 51467-EG-JDO).

Background: In recent years, there have been a number of case reports demonstrating an association between marijuana-smoking and onset of atrial fibrillation.¹ The exact mechanism by which marijuana may induce atrial fibrillation remains unclear. Hypotheses focus on the well-documented role of the autonomic nervous system in the pathogenesis of atrial fibrillation. Low-to-moderate levels of Δ-9-tertrahydrocannabinol (THC), the bioactive component of marijuana, increase heart rate, blood pressure, and plasma catecholamine levels in humans.² Data suggest that these effects are mediated by cannabinoid-1 receptor regulation of the autonomic nervous system.³ Stimulation of the adrenergic system is potentially pro-arrhythmic, as it reduces action potential duration and favors automaticity, triggered activity, and re-entry. The increase in sympathetic tone after marijuana use may contribute to the development of atrial fibrillation, especially in patients with preexisting cardiovascular complications. Case History: The patient is a 40-year-old Hispanic man who has a history of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI), which he sustained from three military tours in Iraq and Afghanistan. The patient’s PTSD symptoms are being treated with diazepam 5 mg po bid as well as remeron 15 mg po qhs. He presented to the emergency department complaining of nausea and vomiting. He reported that these symptoms began after ingesting a brownie that may have contained cannabis at a housewarming party the night before. His presenting symptoms included diarrhea, diffuse abdominal pain, and chest discomfort. In the course of his emergency department visit, he developed tachycardia in the 140–150 range. An EKG revealed atrial fibrillation, with rapid ventricular response, premature ventricular or aberrantly conducted complexes, and nonspecific ST segment and T-wave abnormalities. Urine toxicity was positive for benzodiazepines, cannabinoids, methadone, and opioids, but negative for salicylates and acetaminophen. A repeat EKG showed atrial fibrillation, but the nonspecific ST segment and T-wave abnormalities were no longer evident in the inferior leads. Chest X-ray, echocardiogram, and CT thorax without contrast were all within normal limits. He was administered diltiazem, and central access was placed in the femoral vein for adequate fluid administration. He was admitted to the hospital with a diagnosis of atrial fibrillation and gastroenteritis secondary to cannabinoid use. The patient improved after 3 days and was discharged for outpatient follow-up. Conclusion: The presence of TBI in this patient may have made him more susceptible to cardiovascular complications. Furthermore, marijuana induces alterations in coronary vasculature that may contribute to the development of atrial fibrillation.¹ More research is necessary to elucidate the precise mechanism involved in marijuana-induced atrial fibrillation.

1. Korantzopoulos P, Liu T, Li G, et al: Atrial fibrillation and marijuana smoking. Int J Clin Pract 2007; 62:308–313

2. Beaconsfield P, Ginsburg J, Rainsbury R: Marijuana smoking: cardiovascular effects in man and possible mechanisms. N Engl J Med 1972; 287:209–212

3. Huestis MA, Gorelick DA, Heishman SJ, et al: Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry 2001; 58:322–328

Background: Patients with mild traumatic brain injury (TBI) are often misdiagnosed, and their treatment is characterized by a number of previous therapeutic failures. Diagnosis of mild TBI is difficult because structural imaging studies do not provide supportive evidence for this condition. A method that utilizes quantitative EEG and TBI discriminant function allows for more objective assessment of these difficult cases. Objective: Based on clinical data, our hypothesis is that patients with TBI are difficult to treat, and patients who present with additional EEG findings characterized by sharp wave patterns are more complex than patients who do not present in this way. Methods: We analyzed archived qEEG data of 136 psychiatric patients at an outpatient clinic; 47% were women (n=64), and 53% were men (n=72). Ages ranged from 7 to 64 years old. Patient who reported a history of head trauma (n=63) were compared with a normative database. Results: Of patients reporting a history of head trauma, 33 (52%) were classified with mild TBI on the severity index. Of these patients, 11 (33%) showed signs of abnormality characterized by sharp waves, which were generally distributed bilaterally (64%) and localized to the frontotemporal regions (66%). Correlational data based on additional imaging modalities will be presented based on individual cases. Conclusion: Relying on quantitative EEG in conjunction with other functional imaging such as PET or SPECT may enhance the identification of neuronal networks involved in individual cases presenting with mild TBI, leading to more precise therapeutic interventions.

Background: Traumatic brain injury (TBI) can cause cognitive impairments in arousal, attention, memory, processing speed, and executive functioning. These symptoms drive treatment choices and can pose pharmacological challenges. They can be conceptualized differently diagnostically: dementia or amnestic disorder due to TBI; or cognitive disorder, NOS, are used, but these may warrant different medications. Objective: Case-derived data available within the TBI patient population are sparse. This case series serves to demonstrate how TBI patients in our specialty neuropsychiatry clinic have been diagnosed and treated. Methods: This retrospective case study was conducted on adult TBI patients who regularly attend our outpatient neuropsychiatry clinic. All subjects (N=83) had sustained a moderate-to-severe head injury and have been followed regularly for ongoing follow-up and treatment. Results: Each case was analyzed according to the patient’s demographic information, diagnosis, impairments (cognitive, behavioral, mood, and thought disorders) and pharmacological treatments. Overall, the majority of patients (95%) were diagnosed with a cognitive disorder. However, only 33% were prescribed medicines traditionally aimed at posttraumatic cognitive impairments (psychostimulants for attentional deficits, for example). Specifically, cholinesterase inhibitors (19%), psychostimulants (12%), modafinil (2%), atomoxetine (2%), and memantine (1%) were utilized. Conclusion: Cognitive disorders that result from TBI require psychopharmacological treatments that include a variety of agents for focused cognitive symptom-management. Iatrogenic behavioral deterioration, problematic side effects, or a lack of treatment response are just a few challenging treatment issues. This case series highlights prescribing trends in the neuropsychiatric management of TBI and attempts to demonstrate some of the complexities of neuropsychiatric psychopharmacology.

Background: Lithium is an effective primary or adjunctive treatment for many primary psychiatric disorders, including some resembling the neuropsychiatric complications of TBI. However, lithium use is often avoided in persons with TBI because of concerns about neurotoxicity. Whether or not this avoidance is justified is not clear. Objective: Through a literature review, authors evaluated the neurotrophic and neurotoxic effects of lithium, and assessed the state of the evidence describing lithium use among persons with TBI. Method: Authors performed a PubMed search anchored to the terms “lithium” and “traumatic brain injury,” “neurotrophic,” and “neurotoxic” and reviewed studies reporting neurotrophic or neurotoxic effects. Results: Lithium confers neurotrophic effects in humans, with magnetic resonance imaging studies suggesting functionally important benefits on dorsolateral prefrontal cortex, cingulate cortex, the hippocampus, and cerebral white matter—areas relevant to TBI, given their vulnerability to biomechanical neurotrauma. Experimental injury models suggest that lithium may be neuroprotective and may attenuate the cognitive and behavioral consequences of TBI. Few studies describe lithium use among persons with TBI, and there are no studies demonstrating neuroprotective or neurorestorative effects of lithium on these brain areas in persons with such injuries. Conclusion: The role of lithium in the treatment, as well as the possible prevention, of the neuropsychiatric sequelae of TBI remains almost entirely unexplored. Converging evidence from experimental-injury models and from investigations of the neurotrophic effects of lithium suggests that this may be a useful and underutilized treatment among persons with TBI. Further investigation along these lines is needed.