It is believed that dopamine and alterations of energy metabolism in cortical and subcortical structures are involved in the pathophysiology of schizophrenia. Recently, we and others have shown that dopamine may affect energy metabolism by interacting with mitochondrial complex I activity in rats both in vivo and in vitro. In this study activity of complexes I and IV was assessed in mitochondria isolated from blood platelet of schizophrenic patients and compared to patients with affective disorders and healthy control subjects. Seventy-seven in-patients who met DSM-IV criteria for schizophrenia (in acute exacerbation), bipolar disorder depressed type (BP), or recurrent major depressive disorder (MDD) and 24 control subjects participated in the study. A highly significant increase (240%, p < 0.001) in complex I activity but not in complex IV, was detected in medicated and unmedicated schizophrenic patients compared to controls. No such change was observed in patients with affective disorders. The data demonstrate a specific and selective, alteration in platelet complex I activity in schizophrenic patients, which is not related to medication. If this abnormality in platelet mitochondria reflects brain alterations, it may further support the relevance of alterations in energy metabolism to the pathophysiology of schizophrenia. Finally in the lack of any clinically relevant biological marker for schizophrenia, complex I activity in platelets might become a useful peripheral marker for this disorder.

There was a highly significant association between SERT and the categorical definition of smoking, irrespective of dependence level, suggesting that this gene influences the initiation of smoking. Mediation analysis failed to substantiate the hypothesis that novelty seeking partially mediates the effect of SERT on smoking. SERT appears to independently contribute to novelty seeking and smoking.

Dysfunction of glutamatergic neurotransmission may be relevant to the pathogenesis of post-traumatic stress disorder (PTSD). Preclinical and clinical evidence suggests that PTSD symptoms could be alleviated following enhancement of neurotransmission mediated at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Eleven patients with chronic PTSD participated in a double-blind, placebo-controlled, cross-over trial with 50 mg/d D-cycloserine which acts as a partial agonist at the glycine regulatory site on the NMDA receptor. D-cycloserine treatment resulted in significant improvements in numbing, avoidance, and anxiety symptoms; however, similar effects were also observed during placebo treatment. In addition, D-cycloserine treatment resulted in a significant (p=0.03), reduction in the perseverative error scores as measured by the Wisconsin Card Sorting Test. This pilot study is the first to assess the efficacy of a NMDA receptor modulator for PTSD treatment and its results warrant further, larger-scale investigation.

IntroductionThe 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 resultsWe 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).ConclusionThis 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.