Randomized controlled trial of adjunctive Valproate for cognitive remediation in early course schizophrenia.

BACKGROUND: Schizophrenia (SZ) is associated with cognitive impairment that contributes to disability, but the cognitive dysfunction is relatively refractory to pharmacologic intervention. Though Valproate augmentation is reported to improve psychopathology among patients with SZ, its effects on cognitive functions have not been investigated systematically. METHODS: Using a randomized double blind placebo controlled design, the effects of Valproate or placebo as adjuncts to risperidone (RISP) treatment were evaluated among patients with early course SZ (N = 109). Domains of cognitive function, estimated using the Arabic version of the Penn Computerized Neurocognitive Battery, were the prime outcomes. Clinical severity and social function were secondary outcomes. We also explored the effects of valproate treatment on serological responses to Toxoplama Gondii (TOXO), a putative risk factor for cognitive dysfunction in SZ. RESULTS: There were no significant differences between Valproate and placebo (PLA) treated groups with respect to changes in cognitive functions, positive or negative symptom scores or daily function scores at the beginning and end of the study. No significant Valproate/PLA differences were noted on TOXO serostatus or TOXO-related cognitive dysfunction. CONCLUSION: Valproate treatment may not be beneficial for cognitive dysfunction in SZ or for TOXO infection.

The association of BDNF gene polymorphism with cognitive impairment in insomnia patients.

BACKGROUND: Reductions in BDNF activity have shown associations with depressed mood. Other evidence has demonstrated that the BDNF Val66Met polymorphism (rs6265) appears to reduce neural plasticity. A limited number of studies have investigated the influence of these genetic polymorphisms in insomnia. The present study sought to confirm the presence of associations between BDNF Val66Met polymorphism (rs6265) occurrence in normal sleepers and those with insomnia. METHOD: The study subjects consisted of a patient group (n = 199) complaining of insomnia and a control group (n = 51). Each subject was clinically interviewed using questions taken from the Brief Insomnia Questionnaire. After the interview, the subjects were asked to complete the Insomnia Severity Index, The Hamilton Depression Rating Scale, and the Montreal Cognitive Assessment Test. An overnight polysomnography test was also administered. Blood samples were collected for genetic study. RESULTS: The insomnia patients showed a greater prevalence of heterozygous (A/G) VAL/MET polymorphism than the normal controls (p = ≤ 0.0001). This finding confirmed that this genetic polymorphism, which impairs BDNF activity, is an important correlate of disturbed sleep. Further, the finding of significantly greater (p = ≤ 0.0001) depression scores among the insomnia group suggested that BDNF is an important factor in the development of depressive symptoms. CLINICAL IMPLICATIONS: The results of the present study indicate that BDNF gene polymorphism plays a prominent role in the variation of symptoms among insomnia patients and, further, that this polymorphism is strongly related to the severity of depression.