Vjekoslav Peitl

Platelet serotonin concentration and depressive symptoms in patients with schizophrenia

Depressive symptoms seem to be frequent in schizophrenia, but so far they have received less attention than other symptom domains. Impaired serotonergic neurotransmission has been implicated in the pathogenesis of depression and schizophrenia. The objectives of this study were to investigate platelet serotonin concentrations in schizophrenic patients with and without depressive symptoms, and to investigate the association between platelet serotonin concentrations and symptoms of schizophrenia, mostly depressive symptoms. A total of 364 patients were included in the study, 237 of which had significant depressive symptoms. Significant depressive symptoms were defined by the cut-off score of 7 or more on Calgary Depression Rating Scale (CDSS). Platelet serotonin concentrations were assessed by the enzyme-linked immunosorbent assay (ELISA). Prevalence of depression in patients with schizophrenia was 65.1%. Schizophrenic patients with depressive symptoms showed lower platelet serotonin concentrations (mean±SD; 490.6±401.2) compared to schizophrenic patients without depressive symptoms (mean±SD; 660.9±471.5). An inverse correlation was established between platelet serotonin concentration and depressive symptoms, with more severe symptoms being associated with lower platelet serotonin concentrations. Depressive symptoms in schizophrenic patients may be associated with reduced concentrations of platelet serotonin.

Depressive symptoms in schizophrenia and dopamine and serotonin gene polymorphisms

ABSTRACT Although depressive symptoms seem to be frequent in schizophrenia they have received significantly less attention than other symptom domains. As impaired serotonergic and dopaminergic neurotransmission is implicated in the pathogenesis of depression and schizophrenia this study sought to investigate the putative association between several functional gene polymorphisms (SERT 5‐HTTLPR, MAO‐A VNTR, COMT Val158Met and DAT VNTR) and schizophrenia. Other objectives of this study were to closely examine schizophrenia symptom domains by performing factor analysis of the two most used instruments in this setting (Positive and negative syndrome scale ‐ PANSS and Calgary depression rating scale ‐ CDSS) and to examine the influence of investigated gene polymorphisms on the schizophrenia symptom domains, focusing on depressive scores. A total of 591 participants were included in the study (300 schizophrenic patients and 291 healthy volunteers). 192 (64%) of schizophrenic patients had significant depressive symptoms. Genotype distribution revealed no significant differences regarding all investigated polymorphisms except the separate gender analysis for MAO‐A gene polymorphism which revealed significantly more allele 3 carriers in schizophrenic males. Factor analysis of the PANSS scale revealed the existence of five separate factors (symptom domains), while the CDSS scale revealed two distinct factors. Several investigated gene polymorphisms (mostly SERT and MAO‐A, but also COMT) significantly influenced two factors from the PANSS (aggressive/impulsive and negative symptoms) and one from the CDSS scale (suicidality), respectively. Depressive symptoms in schizophrenic patients may be influenced by functional gene polymorphisms, especially those implicated in serotonergic neurotransmission. HIGHLIGHT3 repeat allele of MAO‐A gene polymorphism was significantly more prevalent in male schizophrenic patients.Five separate PANSS and two CDSS symptom factors were identified.Investigated SERT and MAO‐A gene polymorphisms seem to influence several schizophrenia symptom domains.Negative symptoms of schizophrenia seem to be influenced by the investigated COMT gene polymorphism.

S115. SYMPTOM DOMAINS IN SCHIZOPHRENIA AND GENE POLYMORPHISMS

Abstract Background Dopamine and serotonin neurotransmission relies mostly on the action of four factors: serotonin and dopamine transporters (SERT and DAT) and enzymes monoaminooxidase A (MAO-A) and catechol-O-mehtyltransferase (COMT). The goal of this research was to closely examine schizophrenia symptom domains in relation to the investigated polymorphisms. Methods Study group was composed of 300 schizophrenic patients. Severity of schizophrenia was assessed by the Positive and negative syndrome scale (PANSS), depressive symptoms were assessed with Calgary depression scale for schizophrenia (CDSS). SERT (5-HTTLPR), DAT (VNTR), COMT (Val158Met) and MAO-A (VNTR) gene polymorphisms were analyzed. Schizophrenia symptom dimensions were determined with multivariate statistical methods, while logistic regression and ANOVA were used to investigate the influence of a genotype on a symptom domain. Results Factor analysis of PANSS scale retained all 30 items and identified 5 separate factors (aggressive/impulsive, affective/depressive, cognitive, negative and positive symptoms). Analysis of CDSS scale revealed 2 separate factors (depression and suicidality). Statistically significant PANSS variables were those of aggressive/impulsive and negative symptoms, while suicidality was the only significant CDSS variable. Discussion Our PANSS scale factor analysis established 5 distinct factors. Previous factor analyses provided from 3, up to 7 different factors, but mostly 5 distinct ones: negative symptoms, positive symptoms, depressive symptoms, excitement and disorganization. That factor distribution corresponds to our findings in terms of identified number of factors, but seems to differ in terms of item distribution within those factors. When testing the influence of investigated gene polymorphisms on the variable of total PANSS score and five distinct factors we did not establish significant findings regarding four variables: total PANSS score, positive, cognitive and affective/depressive symptoms. While that is in line with majority of other investigations, SERT promoter polymorphism and COMT Val158Met gene polymorphism have been previously associated with depressive and positive symptoms. SERT and MAO-A polymorphisms separately had a significant effect on the variable of aggressive/impulsive symptoms, which has not been reported earlier. Furthermore, significant influence of COMT gene polymorphism was established for the variable of negative symptoms, which is a confirmation of some earlier reports, although there have been contrary findings. Previous reports of CDSS scale factor structure are limited to data from its initial validation to the few recent findings of its three-factor structure (depression, cognition and melancholy). We identified 2 separate factors using factor analysis, “depression” (which included seven out of nine items) and “suicidality”. To the best of our knowledge this is the first investigation of the putative association between any of the four investigated polymorphisms and depressive symptoms of schizophrenia measured by the CDSS scale. Ultimately, we did not establish a significant association of investigated gene polymorphisms and total CDSS score, as well as the “depression” factor. However, there was a significant association between the “suicidality” factor and SERT and MAO-A gene polymorphisms, as well as their interaction. The fact that the significant association was established for only one of the two obtained CDSS factors suggests that the association is subtle and, at least partially, explains rarely reported associations between investigated gene polymorphisms and schizophrenia symptom domains, which is especially true for depressive symptomatology.