A longitudinal study on the impact of antipsychotic treatment on serum leptin in schizophrenia.

OBJECTIVE: The study objective was to explore the biological basis for link between antipsychotic-induced weight gain and therapeutic response in schizophrenia by examining longitudinal changes in serum leptin level after antipsychotic treatment. METHODS: We examined serum leptin in schizophrenia patients at antipsychotic-naive baseline status as well as after 3 months of antipsychotic treatment. For baseline analyses, the patients were compared with healthy controls matched for anthropometric measures and physical activity. RESULTS: At baseline, schizophrenia patients had significantly lower levels of leptin in comparison with controls. After treatment, body mass index and levels of leptin increased significantly in patients. The magnitude of increase in leptin had a significant positive correlation with magnitude of increase in body mass index; the magnitude of reduction in SANS total score showed significant positive correlation with the magnitude of increase in leptin level. CONCLUSION: The study findings suggest a potential role for leptin to mediate the link between antipsychotic-induced weight gain and beneficial therapeutic response in schizophrenia.

Effect of antipsychotic treatment on Insulin-like Growth Factor-1 and cortisol in schizophrenia: a longitudinal study.

Neurodevelopmental pathogenesis of schizophrenia might be mediated by abnormalities in Insulin-like Growth Factor-1 (IGF-1). Developmental disturbances like obstetric complications, by themselves, as well as through the resultant hypercortisolemia due to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, can lead to deficient IGF-1 level. The relevance of IGF-1-Cortisol interactions in schizophrenia, especially in the context of antipsychotic treatment, is yet to be explored. In this study, thirty-three antipsychotic-naïve schizophrenia patients (13-men) were examined for serum IGF-1 and cortisol levels at baseline and after 3months of antipsychotic treatment. For baseline analyses, the patients were compared with 33 healthy controls matched for age, sex, socio-economic status, and physical activity. Symptoms were assessed using Scale for Assessment of Positive Symptoms (SAPS) and Scale for Assessment of Negative Symptoms (SANS). At baseline, schizophrenia patients had significantly lower levels of IGF-1 [t=4.6; p<0.0001] and higher levels of cortisol [t=3.9; p=0.0002] in comparison with healthy controls. Following treatment, IGF-1 level increased significantly [t=4.5; p<0.0001] whereas cortisol decreased significantly [t=2.5; p=0.02] in patients. There was a significant positive correlation between magnitude of increase in IGF-1 level and the magnitude of reduction in cortisol level [r=0.52; p=0.002]. Also, the greater the increase in IGF-1 the greater was the reduction in SAPS score [r=0.39; p=0.02]. Our study findings demonstrate that antipsychotic treatment can result in significant elevation of serum IGF-1 possibly mediated by reduction in cortisol levels. These observations suggest a possible link between HPA axis abnormalities and IGF-1 deficits in the neurodevelopmental pathogenesis of schizophrenia.

Oxidative stress and neopterin abnormalities in schizophrenia: a longitudinal study.

Oxidative stress abnormalities have been proposed to explain the pathogenesis of schizophrenia. The present study examined neopterin and oxidative stress abnormalities in schizophrenia patients before and after treatment. Serum neopterin, total anti-oxidants, nitrites and thiols in antipsychotic-naïve schizophrenia patients (n=45) were assessed at baseline before treatment in comparison with healthy controls (n=43). The schizophrenia patients on treatment were followed up for 3months and these parameters were reassessed (n=32). In comparison to healthy controls, schizophrenia patients had significantly higher levels of neopterin and nitrites and significantly lower levels of anti-oxidants before treatment. During follow-up assessments in schizophrenia patients after treatment with antipsychotics, there was a significant decrease in the neopterin levels and significant increase in anti-oxidant levels. Our study observations support increased oxidative stress in schizophrenia that improves with antipsychotic treatment.

Longitudinal study of beta2-microglobulin abnormalities in schizophrenia.

In an earlier cross-sectional study, we reported antipsychotic-naive schizophrenia patients to have significantly elevated beta2-microglobulin (beta2M) level suggestive of its potential association with the pathogenesis of schizophrenia. In this study, we present the follow-up analyses of beta2M in 31 patients from the previous study who were re-assessed after 92.1+/-7.2 days of antipsychotic treatment. Compared to baseline, there was a further significant elevation of beta2M in schizophrenia patients following treatment, especially in those who were treated with risperidone. Also, there was a significant negative correlation between beta2M level and total psychopathology score during follow-up in risperidone group. The study findings extend further support the role for beta2M in the pathogenesis of schizophrenia strengthening the case for immune dysregulation. Moreover, the observations suggest the possibility that the mechanism of action of antipsychotics might involve alteration of immune parameters.

Beta2-microglobulin abnormalities in antipsychotic-naïve schizophrenia: evidence for immune pathogenesis.

Studies examining immune dysfunction in schizophrenia have reported decreased type-1 T-helper cell specific immunity (Th1) and increased type-2 T-helper cell specific immunity (Th2) and related abnormalities in inflammatory system. Beta2-Microglobulin (beta2M) influences the development of dendritic cells, which play a significant role in regulating the differentiation of naive CD4+ T cells into Th1 or Th2 lineages. The present study examined serum beta2M in antipsychotic-naïve schizophrenia patients (n=43) in comparison with age, sex, handedness and socioeconomic status matched healthy controls (n=43). Serum beta2M was significantly higher in schizophrenia patients (1692.6+/-354.4 ng/mL) than healthy controls (1409.6+/-246.9 ng/mL) (t=4.3; p<0.0001). There was a significant positive correlation between beta2M level and total psychopathology score (r=0.32; p=0.035). These novel observations suggest that beta2M abnormalities might have a potential association with the pathogenesis of schizophrenia.

Insulin and insulin-like growth factor-1 abnormalities in antipsychotic-naive schizophrenia.

OBJECTIVE: The purpose of this study was to examine the evidence for the insulin-like growth factor-1 (IGF-1) deficiency hypothesis in the pathogenesis of schizophrenia. METHOD: The authors examined the fasting plasma levels of glucose, insulin, IGF-1, and cortisol in antipsychotic-naive schizophrenia patients (N=44) relative to age- and sex-matched healthy comparison subjects (N=44). Patients and comparison subjects were also matched for anthropometric measures and physical activity. RESULTS: Schizophrenia patients had a significantly higher mean plasma insulin level as well as a significantly higher mean insulin resistance score relative to healthy comparison subjects. The mean plasma IGF-1 level was significantly lower in patients. IGF-1 levels had a significant negative correlation with plasma insulin levels. The total positive symptoms score as well as the hallucinations subscore had a significant inverse relationship with IGF-1 levels. CONCLUSIONS: Deficient IGF-1 might underlie insulin resistance in schizophrenia. The IGF-1 deficit in antipsychotic-naive schizophrenia patients and its significant correlation with psychopathology scores suggest that IGF-1 might be potentially involved in the pathogenesis of schizophrenia.