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Obsessive-compulsive symptoms (OCS) in patients with schizophrenia are a common co-occurring condition, often associated with additional impairments. A subgroup of these patients develops OCS during treatment with second-generation antipsychotics (SGAs), most importantly clozapine and olanzapine. So far, little is known about possible neural mechanism of these SGAs, which seem to aggravate or induce OCS. To investigate the role of SGA treatment on neural activation and connectivity during emotional processing, patients were stratified according to their monotherapy into two groups (group I: clozapine or olanzapine, n = 20; group II: amisulpride or aripiprazole, n = 20). We used an fMRI approach, applying an implicit emotion recognition task. Group comparisons showed significantly higher frequency and severity of comorbid OCS in group I than group II. Task specific activation was attenuated in group I in the left amygdala. Furthermore, functional connectivity from left amygdala to right ventral striatum was reduced in group I. Reduced amygdala activation was associated with OCS severity. Recent literature suggests an involvement of an amygdala-cortico-striatal network in the pathogenesis of obsessive-compulsive disorder. The observed differential activation and connectivity pattern of the amygdala might thus indicate a neural mechanism for the development of SGA-associated OCS in patients with schizophrenia. Further neurobiological research and interventional studies are needed for causal inferences.

Background: Cognitive impairment in schizophrenia is highly disabling and remains one of the major therapeutic challenges. Agomelatine (AGO), an agonist at melatonergic MT1/MT2 receptors and antagonist at 5-HT2C receptors, increases dopamine and norepinephrine in the prefrontal cortex and may therefore have the potential of improving neurocognition in patients with schizophrenia., Methods: Twenty-seven patients with schizophrenia and comorbid depression were treated with AGO in addition to stable doses of antipsychotic drugs. Cognitive abilities were assessed with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) at study entry and after 12 weeks of AGO treatment after the intention-to-treat principle., Results: We observed statistically significant yet clinically negligible increases of the MCCB composite score and the reasoning/problem solving subscore. Patients with unimpaired sleep at baseline showed greater improvements over time than those with sleep disturbances. Changes on the MCCB were not correlated with other psychometric variables., Conclusions: Despite statistically significant, cognitive improvements after 12 weeks of AGO treatment were clinically irrelevant. Our findings may be limited by baseline properties of the study sample and the study design. In particular, lacking a control group, it cannot be ruled out that improvements were unrelated to AGO treatment. That is why randomized controlled trials are needed to validate the relevance of AGO as a cognitive enhancer in schizophrenia.

Background: Depressive episodes in schizophrenia constitute a major clinical problem, and treatment success is often limited by treatment-emergent side effects. Agomelatine, an agonist at melatonergic MT1/MT2 receptors and 5-HT2C receptor antagonist, is a new antidepressant with a novel mode of action which constitutes a potential therapeutic option for depression in schizophrenia., Methods: Twenty-seven patients with lifetime diagnoses within the schizophrenia spectrum and comorbid depression were treated with agomelatine in addition to stable doses of antipsychotic agents. Severity of depression and other psychopathological domains (positive/negative symptoms, general psychopathology, psychosocial performance) was assessed regularly by means of standardized rating scales during a 6-week acute treatment phase as well as after a 6-week extension phase. Moreover, safety measures (electrocardiograms, laboratory counts, neurological and non-neurological side effects, sleep quality, sexual functioning) were monitored on a regular basis., Results: Depressive symptoms improved significantly during the 6-week acute treatment phase. In parallel, a significant improvement of negative symptoms, global psychopathology, and psychosocial performance was observed, whereas positive symptoms remained stable. Agomelatine was mostly well tolerated with predominantly mild and self-limiting side effects. However, pharmacokinetic interactions with antipsychotic agents were observed. Interestingly, the quality of sleep did not improve significantly, pointing toward mechanisms that do not depend on resynchronization of circadian rhythms., Conclusions: Agomelatine appears to be safe and efficacious in treating depressive symptoms in patients with schizophrenia. The risk of pharmacokinetic interactions with antipsychotic agents warrants the need of therapeutic drug monitoring, and regular recording of vital signs seems necessary. Further randomized trials will have to confirm these findings.