The relationship between self-reported childhood adversities, adulthood psychopathology and psychological stress markers in patients with schizophrenia.

BACKGROUND: Childhood adversity is a well-established risk factor for the development of schizophrenia. In particular, there is evidence that childhood adversity increases the occurrence of positive symptoms, possibly through glucocorticoid influences on dopaminergic neurotransmission. AIMS: To compare levels of childhood trauma in schizophrenia patients vs. healthy control persons, and to study the association between childhood adversity and the symptomatology of adulthood schizophrenia, as well as subjective and biological markers of psychological stress. METHODS: Thirty-seven patients fulfilling ICD-10 criteria for schizophrenia and 39 healthy control persons filled out the comprehensive Childhood Abuse and Trauma Scale (CATS). Data were analyzed after a data-driven dichotomization into two groups of either high or low CATS score in patients and controls, respectively. The psychopathology of the patients was measured by the Positive and Negative Syndrome Scale (PANSS) and analyzed by a five-factor PANSS model. Measures of perceived stress (Perceived Stress Scale) and hypothalamic-pituitary-adrenal (HPA)-axis activity (9AM plasma cortisol and daytime salivary cortisol output) were recorded. RESULTS: As expected, patients had significantly higher total CATS scores than the control persons (>3-fold, P<0.001), reflecting significantly higher scores across all subscales of the CATS. In patients, the total PANSS score did not significantly differ between the high and the low CATS score group (P=0.2). However, there was a statistically significant higher level of positive symptoms in the high CATS group (P=0.014), and no difference in other psychopathological domains. Correspondingly, when using the CATS score as a continuous variable, a strong association with positive PANSS scores was found (P=0.009). The high CATS score group showed higher levels of perceived stress (P=0.02), but there was no difference between the high vs. low CATS group in HPA-axis activity. CONCLUSION: Although causal inferences cannot be made from this cross-sectional study, the study adds support to the suggestion that childhood adversity specifically increases the occurrence of positive symptoms in adulthood schizophrenia in a manner that appears to leave HPA-axis activity unaltered.

Asymmetric dimethylarginine in somatically healthy schizophrenia patients treated with atypical antipsychotics: a case-control study.

BACKGROUND: Schizophrenia is associated with increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, and the L-arginine:ADMA ratio are markers of endothelial dysfunction that predict mortality and adverse outcome in a range of cardiovascular disorders. Increased ADMA levels may also lead to increased oxidative stress. We hypothesized that ADMA and the L-arginine:ADMA ratio are increased in somatically healthy schizophrenia patients treated with atypical antipsychotics (AAP), and that the ADMA and the L-arginine: ADMA ratio are positively correlated to measures of oxidative stress. METHODS: We included 40 schizophrenia patients treated with AAP, but without somatic disease or drug abuse, and 40 healthy controls. Plasma concentrations of ADMA and L-arginine were determined by high-performance liquid chromatography. Data were related to markers of systemic oxidative stress on DNA, RNA and lipids, as well as measures of medication load, duration of disease and current symptomatology. RESULTS: Plasma ADMA and the L-arginine:ADMA ratio did not differ between schizophrenia patients and controls. Furthermore, ADMA and the L-arginine:ADMA ratio showed no correlations with oxidative stress markers, medication load, or Positive and Negative Syndrome Scale scores. CONCLUSIONS: Schizophrenia and treatment with AAP was not associated with increased levels of plasma ADMA or the L-arginine:ADMA ratio. Furthermore, plasma levels of ADMA were not associated with levels of systemic oxidative stress in vivo.