The American Journal of Psychiatry Current Issue

Suicidal Behavior and Severe Neuropsychiatric Disorders Following Glucocorticoid Therapy in Primary Care

Fri, 17 Feb 2012 00:00:00 GMT

Objective:

The incidence and the risk of suicidal behaviors and severe neuropsychiatric disorders in people treated with systemic glucocorticoids are poorly known. The authors assessed the incidence rates of depression, mania, delirium, panic disorder, and suicidal behaviors in patients treated with glucocorticoids in primary care settings and the risk factors for developing these outcomes.

Method:

Data were obtained for all adult patients registered between 1990 and 2008 at U.K. general practices contributing to The Health Improvement Network (THIN) primary care database. The incidence rates for the outcomes of interest were assessed in patients who received prescriptions for oral glucocorticoids and compared with those in patients who did not receive such prescriptions. The predictors of these outcomes in exposed patients were ascertained using Cox proportional hazards models.

Results:

Overall, 786,868 courses of oral glucocorticoids were prescribed for 372,696 patients. The authors identified 109 incident cases of suicide or suicide attempt and 10,220 incident cases of severe neuropsychiatric disorders in these patients. The incidence of any of these outcomes was 22.2 per 100 person-years at risk for first-course treatments. Compared to people with the same underlying medical disease who were not treated with glucocorticoids, the hazard ratio for suicide or suicide attempt in exposed patients was 6.89 (95% CI=4.52–10.50); for depression, 1.83 (95% CI=1.72–1.94); for mania, 4.35 (95% CI=3.67–5.16); for delirium, confusion, or disorientation, 5.14 (95% CI=4.54–5.82); and for panic disorder, 1.45 (95% CI=1.15–1.85). Older men were at higher risk of delirium/confusion/disorientation and mania, while younger patients were at higher risk of suicide or suicide attempt. Patients with a previous history of neuropsychiatric disorders and those treated with higher dosages of glucocorticoids were at greater risk of neuropsychiatric outcomes.

Conclusions:

Glucocorticoids increase the risk of suicidal behavior and neuropsychiatric disorders. Educating patients and their families about these adverse events and increasing primary care physicians' awareness about their occurrence should facilitate early monitoring.

Auditory Emotion Recognition Impairments in Schizophrenia: Relationship to Acoustic Features and Cognition

Fri, 17 Feb 2012 00:00:00 GMT

Objective:

Schizophrenia is associated with deficits in the ability to perceive emotion based on tone of voice. The basis for this deficit remains unclear, however, and relevant assessment batteries remain limited. The authors evaluated performance in schizophrenia on a novel voice emotion recognition battery with well-characterized physical features, relative to impairments in more general emotional and cognitive functioning.

Method:

The authors studied a primary sample of 92 patients and 73 comparison subjects. Stimuli were characterized according to both intended emotion and acoustic features (e.g., pitch, intensity) that contributed to the emotional percept. Parallel measures of visual emotion recognition, pitch perception, general cognition, and overall outcome were obtained. More limited measures were obtained in an independent replication sample of 36 patients, 31 age-matched comparison subjects, and 188 general comparison subjects.

Results:

Patients showed statistically significant large-effect-size deficits in voice emotion recognition (d=1.1) and were preferentially impaired in recognition of emotion based on pitch features but not intensity features. Emotion recognition deficits were significantly correlated with pitch perception impairments both across (r=0.56) and within (r=0.47) groups. Path analysis showed both sensory-specific and general cognitive contributions to auditory emotion recognition deficits in schizophrenia. Similar patterns of results were observed in the replication sample.

Conclusions:

The results demonstrate that patients with schizophrenia show a significant deficit in the ability to recognize emotion based on tone of voice and that this deficit is related to impairment in detecting the underlying acoustic features, such as change in pitch, required for auditory emotion recognition. This study provides tools for, and highlights the need for, greater attention to physical features of stimuli used in studying social cognition in neuropsychiatric disorders.

Neural Mechanisms Underlying 5-HTTLPR-Related Sensitivity to Acute Stress

Fri, 17 Feb 2012 00:00:00 GMT

Objective:

Many studies have shown that 5-HTTLPR genotype interacts with exposure to stress in conferring risk for psychopathology. However, the specific neural mechanisms through which this gene-by-environment interaction confers risk remain largely unknown, and no study to date has directly examined the modulatory effects of 5-HTTLPR on corticolimbic circuit responses during exposure to acute stress.

Method:

An acute laboratory stressor was administered to 51 healthy women during blood-oxygen-level-dependent functional magnetic resonance imaging. In this task, participants were threatened with electric shocks of uncertain intensity, which were unpredictably delivered to the wrist after a long anticipatory cue period of unpredictable duration.

Results:

Relative to women carrying the L allele, those with the SS genotype showed enhanced activation during threat anticipation in a network of regions, including the amygdala, hippocampus, anterior insula, thalamus, pulvinar, caudate, precuneus, anterior cingulate cortex, and medial prefrontal cortex. Individuals with the SS genotype also displayed enhanced positive coupling between medial prefrontal cortex activation and anxiety experience, whereas enhanced negative coupling between insula activation and perceived success at regulating anxiety was observed in individuals carrying the L allele.

Conclusions:

These findings suggest that during stress exposure, neural systems that enhance fear and arousal, modulate attention toward threat, and perseverate on emotional salience of the threat may be engaged preferentially in individuals with the SS genotype. This may be one mechanism underlying the risk for psychopathology conferred by the S allele upon exposure to life stressors.

Naltrexone Implant for the Treatment of Polydrug Dependence: A Randomized Controlled Trial

Fri, 17 Feb 2012 00:00:00 GMT

Objective:

The majority of drug addicts are polydrug dependent, and no effective pharmacological treatment is currently available for them. The authors studied the overall real-world effectiveness of naltrexone implant in this patient population.

Method:

The authors assessed the effectiveness of a naltrexone implant in the treatment of coexisting heroin and amphetamine polydrug dependence in 100 heroin- and amphetamine-dependent outpatients in a 10-week randomized, double-blind, placebo-controlled trial. The main outcome measures were retention in the study, proportion of drug-free urine samples, and improvement score on the Clinical Global Impressions Scale (CGI). Analyses were conducted in an intent-to-treat model.

Results:

At week 10, the retention rate was 52% for patients who received a naltrexone implant and 28% for those who received a placebo implant; the proportions of drug-free urine samples were 38% and 16%, respectively, for the two groups. On the CGI improvement item, 56% of the patients in the naltrexone group showed much or very much improvement, compared with 14% of those in the placebo group (number needed to treat=3).

Conclusions:

Naltrexone implants resulted in higher retention in the study, decreased heroin and amphetamine use, and improved clinical condition for patients, thus providing the first evidence of an effective pharmacological treatment for this type of polydrug dependence.

Differences in White Matter Fiber Tract Development Present From 6 to 24 Months in Infants With Autism

Fri, 17 Feb 2012 00:00:00 GMT

Objective:

Evidence from prospective studies of high-risk infants suggests that early symptoms of autism usually emerge late in the first or early in the second year of life after a period of relatively typical development. The authors prospectively examined white matter fiber tract organization from 6 to 24 months in high-risk infants who developed autism spectrum disorders (ASDs) by 24 months.

Method:

The participants were 92 high-risk infant siblings from an ongoing imaging study of autism. All participants had diffusion tensor imaging at 6 months and behavioral assessments at 24 months; a majority contributed additional imaging data at 12 and/or 24 months. At 24 months, 28 infants met criteria for ASDs and 64 infants did not. Microstructural properties of white matter fiber tracts reported to be associated with ASDs or related behaviors were characterized by fractional anisotropy and radial and axial diffusivity.

Results:

The fractional anisotropy trajectories for 12 of 15 fiber tracts differed significantly between the infants who developed ASDs and those who did not. Development for most fiber tracts in the infants with ASDs was characterized by higher fractional anisotropy values at 6 months followed by slower change over time relative to infants without ASDs. Thus, by 24 months of age, those with ASDs had lower values.

Conclusions:

These results suggest that aberrant development of white matter pathways may precede the manifestation of autistic symptoms in the first year of life. Longitudinal data are critical to characterizing the dynamic age-related brain and behavior changes underlying this neurodevelopmental disorder.