The relationship between plasma levels of clozapine and N-desmethyclozapine as well as M1 receptor polymorphism with cognitive functioning and associated cortical activity in schizophrenia.

Studies that examined the effect of clozapine on cognitive functions in schizophrenia provided contradictory results. N-desmethylclozapine (NDMC) is the major metabolite of clozapine and have procognitive effects via agonistic activity in the M1 cholinergic receptors. The rs2067477 polymorphism in the M1 receptors may play role in cognitive profile in schizophrenia. We investigated the association of plasma clozapine (PClz), NDMC (PNdmc) levels and the rs2067477 polymorphism with cognitive functions and cortical activity measured by functional near infrared spectroscopy during the N-Back task in subjects with schizophrenia (N = 50) who are under antipsychotic monotherapy with clozapine. We found that PClz and PNdmc levels were negatively, PNdmc/PClz ratio was positively correlated with immediate recall score in the Rey Auditory Verbal Learning Test. PNdmc/PClz ratio was positively correlated with cortical activity during the N-back task. M1 wild-type group (CC: wild-type) produced higher cortical activity than M1 non wild-type group (CA: heterozygote / AA: mutant) in cortical regions associated with working memory (WM). These results suggest that individual differences in clozapine's effect on short term episodic memory may be associated with PClz and PNdmc. Higher activity in the M1 wild-type group may indicate inefficient use of cortical resources and/or excessive use of certain cognitive strategies during WM performance.

[Prefrontal Cortex Activity During Facial Affect Processing in Schizophrenia: Association with Clinical Symptoms and Social Cognitive Functions]. / Sizofrenide Yüzdeki Duygu Ifadelerini Tanima Sirasindaki Prefrontal Korteks Aktivitesinin Klinik Belirtiler ve Sosyal Bilis Islevleriyle Iliskisi.

OBJECTIVES: In the present study, we aimed to investigate the prefrontal cortex (PFC) activity during facial affect recognition in schizophrenia, as well as the association of this activity with symptom severity and with the higher order social cognitive functions, namely recognition of false beliefs, faux-pas and hinting. METHOD: Functional near infrared spectroscopy (fNIRS) was used to measure frontal cortical activity during a neuroimaging task prepared with a standard set of pictures of facial affect. The data of the Index Group (IG) consisting of 27 subjects with DSM-IV based diagnoses of schizophrenia and schizophreniform disorder and control group (CG) (N=25) were compared. The control condition was to detect nonaffective changes on a neutral face. Associations with frontal activity during affect recognition and clinical symptoms, false belief recognition, hinting and faux-pas were investigated. RESULTS: Prefrontal activity during both affective and non-affective conditions was higher in the IG than the CG. The IG performed worse than the CG in social cognitive tests. Social cognitive test performance was not correlated with cortical activity. There were no correlations between education status, age and PFC activity in both groups. In the IG, right ventral prefrontal cortex (VPFC) and right medial prefrontal cortex (mPFC) activities were associated with hallucination severity. CONCLUSION: These results suggest the presence of hyperfrontality during face processing in schizophrenia. Results also suggest that schizophrenia patients require more frontal resources to achieve a performance comparable to that of healthy controls in order to detect both affective and non-affective changes on a face. There might be a relationship between facial processing and hallucinations.