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.

Antidepressant efficacy and hormonal effects of Sudarshana Kriya Yoga (SKY) in alcohol dependent individuals.

BACKGROUND: Sudarshana Kriya Yoga (SKY) has demonstrable antidepressant effects. SKY was tested for this effect in inpatients of alcohol dependence. METHODS: Following a week of detoxification management consenting subjects (n=60) were equally randomized to receive SKY therapy or not (controls) for a two-week study. SKY therapy included alternate day practice of specified breathing exercise under supervision of a trained therapist. Subjects completed the Beck Depression Inventory (BDI) before and after the two weeks of this intervention. Morning plasma cortisol, ACTH and prolactin too were measured before and at the end of two weeks. RESULTS: In both groups reductions in BDI scores occurred but significantly more so in SKY group. Likewise, in both groups plasma cortisol as well as ACTH fell after two weeks but significantly more so in SKY group. Reduction in BDI scores correlated with that in cortisol in SKY but not in control group. LIMITATIONS: Antidepressant effects of SKY were demonstrated in early abstinence that also had substantial spontaneous improvement. It is not known if this effect contributes to sustained abstinence. CONCLUSION: Results extend the antidepressant effects of SKY in alcohol dependence subjects. Reduction in stress-hormone levels (cortisol and ACTH) along with BDI reductions possibly support a biological mechanism of SKY in producing beneficial effects.

Nuclear localization of Munc18-1 (p67) in the adult rat brain and PC12 cells.

Munc18-1, also referred to as p67, co-purifies with Cdk5 and has an important role in neurotransmitter release. The role of Munc18-1 for functional connectivity of the nervous system was demonstrated by gene knockout experiments in mice, wherein accumulation of neurotransmitter and silencing of synaptic activity was observed. Our earlier studies have shown that both Munc18-1 and Cdk5 co-purify and co-localize with cytoskeletal components, implying that apart from having a regulatory role in vesicle docking and fusion, Munc18-1 could also affect the dynamics of neuronal cytoskeleton. In the present study we have shown the presence of Munc18-1 in nuclear rich fraction from rat brain and confirmed the nuclear localization of this protein in PC12 cells and adult rat brain neurons by immunofluorescence and immunoelectron microscopy. We also demonstrate the binding of Munc18-1 to double stranded (ds) DNA. The ability of Munc18-1 to bind dsDNA, albeit the lack of DNA binding domains, suggests that the binding may be mediated through protein-protein interaction through some other DNA-binding proteins. The presence of both nuclear import and export signals in Munc18-1 primary structure corroborates its nuclear localization and makes it a putative shuttle protein between nuclear and cytoplasmic compartments, the precise physiological relevance of which needs to be elucidated.