• Adding atomoxetine to antipsychotic drug therapy provided no significant benefits in reducing schizophrenia-related cognitive impairments compared with placebo in a randomized, double-blind, exploratory study. From April 2004 to December 2006, 30 patients with schizophrenia or schizoaffective disorder taking antipsychotic monotherapy were randomly assigned to either 80 mg/day atomoxetine (n=14) or placebo (n=16). After eight weeks of treatment, the patients' overall performance on neuropsychological tests did not differ significantly between the two groups. In addition, there was no significant difference on specific test results, including measurements of attention, motor speed, executive function, processing speed, verbal and visual memory, and working memory between the groups. The study was supported by grants from the Veterans Affairs Capitol Health Care Network, Stanley Medical Research Institute, and National Institute of Mental Health.

• Healthy children without a diagnosis of attention-deficit/hyperactivity disorder (ADHD) or other neurodevelopmental disorders may exhibit ADHD-like behavioral symptoms when they do not get enough sleep, according to a study conducted in Finland. A group of 7- and 8-year-olds, including 146 girls and 134 boys, were monitored for sleep quality using actigraphs, a device that measures the sleep/wake cycle and sleep quality at home. Participants wore the device on the nondominant wrist continuously for seven or more days. Their sleep duration and quality were measured by a 26-item questionnaire, the Sleep Disturbance Scale for Children (SDSC). The participating mothers rated the presence and extent of their children's behavioral symptoms such as inattention and impulsivity on an 18-item standard ADHD rating scale. Short sleep duration was significantly associated with a higher hyperactivity/impulsivity score. A higher overall level of sleeping difficulty, defined as elevated total SDSC score, was associated with hyperactivity/impulsivity, inattention, and total ADHD rating scores. The study was funded by grants from the Academy of Finland, European Science Foundation, Juho Vainio Foundation, John D. and Catherine T. MacArthur Foundation, and Finnish Foundation for Pediatric Research.

A Web-based self-assessment tool can help some heavy drinkers reduce excessive drinking, a study conducted in Finland found. The online assessment tool, known as Drinking Habit Test, was modified from a Canadian self-assessment service and was launched in Finland in 2003. In 2004 researchers invited online users of the tool to participate in the study. Participants (n=343) filled out a questionnaire about their drinking habits at three, six, and 12 months after the initial assessment. The response rates at three, six, and 12 months were 78 percent, 69 percent, and 61 percent, respectively. More women (n=208) participated in the study than men (n=135). Using intent-to-treat analysis, the researchers found that self-reported drinking levels and harmful consequences of drinking were significantly reduced from baseline at the three-month follow-up. The self-assessment questionnaire included the Alcohol Use Disorders Identification Test (AUDIT) and other questions about psychosocial consequences. This reduction was maintained at the six-month and 12-month follow-ups. The study was funded by the Finnish Foundation for Alcohol Studies.

• Donepezil given to patients which mild cognitive impairment (MCI) produced a small but statistically significant improvement in cognition in a randomized, placebo-controlled clinical trial. However, the change in global functioning, as measured by the Clinical Dementia Rating Scale–sum of boxes (CDRS-SB), did not differ from that of patients taking placebo. From December 2003 to March 2007, 821 patients aged 45 to 90 with MCI were randomly assigned to either donepezil treatment (n=409) or placebo (n=412) for 48 weeks. The modified Alzheimer Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) scores decreased by 1.0 point from baseline in the donepezil group compared with 0.13 point from baseline in the placebo group (p<0.01). Most other secondary measures of global impairment, cognition, and functioning did not differ significantly between the two groups. The study was sponsored by Esai Inc. and Pfizer Inc.

• Acid-sensing ion channel-1a (ASIC1a), a protein widely expressed in the nervous system and particularly concentrated in the amygdala, plays an important role in mood regulation and may be an effective target for future antidepressants, according to findings in a mouse study. After applying several methods of inhibiting ASIC1a in mice, researchers saw consistent evidence of antidepressant-like effects in standard behavioral stress tests that simulate human depression. Disruption of the ASIC1a gene expression, as well as chemical inhibition of the protein, led to similar antidepressant effects. Although the pathophysiology is not yet understood, amygdala hyperactivity has been long linked to depression. Under stress, ASIC1a-gene knockout mice did not show a decrease in the level of brain-derived neurotrophic factor. This phenomenon is similar to the neurological action of other antidepressants. Moreover, the antidepressant effects of ASIC1a inhibition appeared to be independent of the serotonin, norepinephrine, and dopamine reuptake pathways, suggesting that ASIC1a inhibition may provide an additive therapeutic effect to currently available antidepressants.

• Oxytocin, a neuropeptide attracting growing attention in neuropsychiatric research, reduces the brain's immediate reactions to potentially threatening social stimuli and increases the tendency to interpret ambiguous signals (photos of facial expressions) as friendly or positive, a recent U.K. study found. Researchers gave 29 healthy male volunteers one dose of oxytocin through nasal spray, followed by a battery of psychological tests intended to measure their reaction to and memory of positive and negative emotional cues.

In the past, antidepressant and anxiolytic drugs have been shown to alter numerous neuropsychiatric pathways for emotional-processing of external stimuli. The effects of oxytocin seen in this study were not as broad as those of antidepressants and anxiolytics, but appear to be subtle changes in the emotion processing pathways. The single dose of oxytocin appeared to gently“ push” the volunteers to perceive external stimuli in a less alarming manner. The authors suggested that this effect may have potential clinical application in improving social functioning in certain psychiatric disorders such as autism, social anxiety, and depression.

• A genomic study provides new evidence to support the notion that narcolepsy is an autoimmune disease involving genetic variations in a T lymphocyte receptor and a human leukocyte antigen (HLA). Previous genetic studies have found that narcolepsy is strongly associated with a variant in the gene encoding for an HLA known as DQ0602. A subunit of a T-cell receptor, expressed from the T-cell receptor alpha (TRA@) locus, is known to interact with a class of HLA including DQ0602. The researchers scanned the genome of 807 Caucasian patients with narcolepsy and more than 1,000 healthy controls, all carrying the HLA variant, and found a significant association between narcolepsy and a specific variant in TRA@. This genomic association was replicated in three additional samples including Asian and African-American patients and controls. Normally, HLAs help the body's immune system recognize“ self,” so that one's own cells and tissues are not mistaken by the immune system for invading organisms. The authors believe that a mismatched interaction between the T-cell receptor subunit and HLA variants may be responsible for autoimmune attacks that kill hypocretin-producing cells in the hypothalamus, which causes narcolepsy and cataplexy (sudden loss of muscle tone).

Hallmayer J, Faraco J, Lin L, et al. Narcolepsy Is Strongly Associated With the T-Cell Receptor Alpha Locus. Nature Genetics. Published online May 3, 2009. ▪