Alon Reshef

Family-based and case-control study of catechol-O-methyltransferase in schizophrenia among Palestinian Arabs

COMT is a ubiquitous enzyme crucial to catechol metabolism. The molecular basis of COMT thermolability, that leads to three to fourfold differences in enzyme activity, is due to a substitution of valine with methionine in the Val158/108Met polymorphism. Of special interest is the role of this gene in major psychoses especially since a microdeletion (22q11) containing the COMT gene (velo‐cardio‐facial syndrome) also carries with it several types of behavioral disorders, including an increased prevalence of schizophrenia. Almost 20 genetic studies have examined the role of COMT in schizophrenia with ambiguous results. Towards clarifying the role of this polymorphism in conferring risk for psychosis, we examined a large group of culturally and ethnically akin Palestinian Arab schizophrenic triads (N = 276) using both a case–control and family‐based study. In 194 informative triads with at least one heterozygote parent, no preferential transmission of either COMT allele was observed in this sample (TDT statistic chi‐square = 0.14 NS; 131 COMT valine alleles were transmitted and 125 alleles not transmitted). However, using a case–control design a significant increase (Likelihood ratio = 3.935, P = 0.047) in the valine allele was observed in the group of schizophrenic patients (N = 276) compared to an ethnically matched control group (N = 77). The association was stronger in female patients (P = 0.012) similar to other studies showing that some COMT behavioral effects are gender sensitive. In summary, by case–control design but not by a family‐based study, there is a weak effect in female patients of the high activity COMT allele in conferring risk for schizophrenia.

Mitochondrial DNA HV lineage increases the susceptibility to schizophrenia among Israeli Arabs

Haplotypes and haplogroups are linked sets of common DNA variants, acting as susceptibility or protective factors to complex disorders. Growing evidence suggests that dysfunction of mitochondrial bioenergetics contributes to the schizophrenia phenotype. We studied mitochondrial DNA haplogroups in schizophrenia patients. Since mitochondria are inherited from the mothers, we used healthy fathers as an ideal case-control group. Analysis of the distribution of mitochondrial haplogroups in schizophrenia patients compared to their healthy fathers (202 pairs) resulted in an over-representation of the mtDNA lineage cluster, HV, in the patients (p=0.01), with increased relative risk (odds ratio) of 1.8. Since mitochondrial DNA is small relative to nuclear DNA, a total mitochondrial genome analysis was possible in a hypothesis-free manner. However, mitochondrial DNA haplogroups are highly variable in human population and it will be necessary to replicate our results in other human ethnic groups.

Preliminary effects of bupropion and the promoter region (HTTLPR) serotonin transporter (SLC6A4) polymorphism on smoking behavior in schizophrenia

In the current study, we investigated how individual variants in the serotonin promoter gene, previously associated with smoking cessation and linked to anxiety-related personality traits, were associated with individual differences in responsiveness to bupropion and cognitive behavioral therapy (CBT) in a clinical population. We hypothesize that subjects with the long allele may be less responsive to treatment. Altogether 61 schizophrenic patients (46 M, 15 F) on stable neuroleptic medication were initially enrolled in a smoking reduction program (prospective, double-blind, placebo-controlled) including cognitive behavioral therapy plus placebo or CBT plus bupropion. Additionally, subjects were genotyped for a polymorphism in the serotonin transporter (SLC6A4). Thirty-two subjects (23 M, 9 F) completed a 14-week course of treatment. While both groups of subjects demonstrated significant reductions in smoking behavior due to CBT, subjects receiving bupropion did not show significant differences in smoking behavior when compared to placebo. In addition, analysis by SPSS repeated measures multivariate showed a significant sex by SLC6A4 genotype interaction on the number of cigarettes smoked. Only male subjects with at least one short promoter region allele (short/short and short/long combined) showed a reduction in cigarette consumption as a result of treatment. This study provides preliminary evidence of how polymorphisms in the serotonin transporter can be informative in predicting individual responses to smoking reduction therapy.

The Effects of Acupuncture Treatment on Sleep Quality and on Emotional Measures among Individuals Living with Schizophrenia: A Pilot Study.

Purpose. To examine the effects of acupuncture on sleep quality and on emotional measures among patients with schizophrenia. Methods. Twenty patients with schizophrenia participated in the study. The study comprised a seven-day running-in no-treatment period, followed by an eight-week experimental period. During the experimental period, participants were treated with acupuncture twice a week. During the first week (no-treatment period) and the last week of the experimental period, participants filled out a broad spectrum of questionnaires and their sleep was continuously monitored by wrist actigraph. Results. A paired-sample t-test was conducted comparing objective and subjective sleep parameters manifested by participants before and after sequential acupuncture treatment. A significant effect of acupuncture treatment was observed for seven objective sleep variables: sleep onset latency, sleep percentage, mean activity level, wake time after sleep onset, mean number of wake episodes, mean wake episode and longest wake episode. However, no significant effects of acupuncture treatment were found for subjective sleep measures. Likewise, the results indicate that acupuncture treatment improved psychopathology levels and emotional measures, that is, depression level and anxiety level. Conclusions. Overall, the findings of this pilot study suggest that acupuncture has beneficial effects as a treatment for insomnia and psychopathology symptoms among patients with schizophrenia.

A Pilot Study of Possible Easy-to-Use Electrophysiological Index for Early Detection of Antidepressive Treatment Non-Response

Introduction The evaluation of response to pharmacological treatment in MDD requires 4–8 weeks. Therefore, the ability to predict response, and especially lack of response to treatment, as early as possible after treatment onset or change, is of prime significance. Many studies have demonstrated significant results regarding the ability to use EEG and ERP markers, including attention-associated markers such as P300, for early prediction of response to treatment. But these markers are derived from long EEG/ERP samples, often from multiple channels, which render them impractical for frequent sampling. Methods and results We developed a new electrophysiological attention-associated marker from a single channel (two electrodes), using 1-min samples with auditory oddball stimuli. This work presents an initial evaluation of the ability to use this marker’s dynamics between repetitive measures for early (<2 weeks) differentiation between responders and non-responders to antidepressive treatment, in 26 patients with various levels of depression and heterogeneous treatment interventions. The slope of change in the marker between early consecutive samples was negative in the non-responders, but not in the responders. This differentiation was stronger for patients suffering from severe depression (p < 0.001). Conclusion This pilot study supports the feasibility of the EEG marker for early recognition of treatment-resistant depression. If verified in large-scale prospective studies, it can contribute to research and clinical work.