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1
Multiple Complement Pathway-related Proteins Might Regulate Immunopathogenesis of Major Depressive Disorder

Preethi V. Reddy(Preethi V. Reddy ),Pinku Mani Talukdar(Pinku Mani Talukdar ),Manjula Subbanna(Manjula Subbanna ),Praerna H. Bhargav(Praerna H. Bhargav ),Rashmi Arasappa(Rashmi Arasappa ),Ganesan Venk 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.2
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  KCI
  
  스콜라
Objective: Exacerbated inflammatory pathway has emerged as a predominant etiological construct of major depressive disorder (MDD). Innate immune molecules like complement proteins induce inflammatory responses and also regulate key neurobiological processes. However, there is a dearth of literature on the impact of critical complement proteins in MDD. Herein, plasma profiling of seven complement proteins was carried out to obtain a better insight into the role of the complement pathway in MDD. Methods: Plasma levels of C1q, C3, C3b/iC3b, C4, Factor B, Factor H, and properdin were assayed in 22 patients with MDD and 27 healthy controls by multiplex suspension assay. The patients with MDD were diagnosed as per DSM IV-TR. Hamilton Depression Rating Scale (HAM-D), Montgomery Depression Rating Scale and Clinical Global Improvement were used for clinical assessments of the patients. The plasma levels of these complement proteins were also correlated with various clinical scores and phenotypes of MDD. Results: The patients with MDD and healthy controls did not differ in terms of age and gender (p > 0.1). The patients with MDD had a mean duration of illness of around 3 years, with average number of depressive episodes being 6 and the mean HAM-D score was 19. Of the seven complement components, the plasma levels of C1q, Factor B, and Factor H (p ≤ 0.05) were significantly elevated in MDD patients compared to healthy controls. However, the plasma levels of these complement proteins were not found to correlate with the clinical profile of MDD patients. Conclusion: Both Factor B and Factor H are crucial in the induction and regulation of the alternative pathway of complement activation. The alternative pathway also plays a critical role in inflammation. These findings suggest an important role of the alternative complement pathway in immuno-inflammation in MDD.
2
A Longitudinal Study of Relation between Side-effects and Clinical Improvement in Schizophrenia: Is There a Neuro-metabolic Threshold for Second Generation Antipsychotics?

Ganesan Venkatasubramanian,Naren P. Rao,Rashmi Arasappa,Sunil V. Kalmady,Bangalore N. Gangadhar 대한정신약물학회 2013 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.11 No.1
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Objective: Classical studies demonstrated Neuroleptic Induced Extrapyramidal Side-effects (NIES; Neuroleptic threshold) to correlate with the efficacy of first generation antipsychotics. Second generation antipsychotics (SGAs), in addition to the extrapyramidal side effects, are also associated with metabolic side effects. This prospective study on antipsychotic-naïve schizophrenia patients, for the first-time, examined concurrently the relationship between clinical improvement and these side-effects NIES and Neuroleptic Induced Metabolic Side-effects. Methods: Thirty six-antipsychotic-naïve schizophrenia (DSM-IV) patients were examined at baseline and after 5 weeks of treatment with antipsychotics. At baseline and follow-up, we recorded the body mass index (BMI) and assessed psychopathology using Scale for Assessment of Positive-symptoms (SAPS) and Scale for Assessment of Negative-symptoms (SANS), extrapyramidal symptoms using Simpson-Angus Extra Pyramidal Scale (SAEPS) and improvement using Clinical Global Impression Improvement (CGI). Results: After treatment, patients showed significant reduction in SAPS (baseline, 27.97±14.47; follow-up, 14.63±13.25; p<0.001)and SANS total scores (baseline, 63.77±28.96; follow-up, 49.30±28.77; p=0.001) and a significant increase in BMI (baseline,18.5±3.37; follow-up, 19.13±3.17; p<0.001). At follow-up CGI-Improvement score was (2.55±0.65) and SAEPS score was (0.8±1.32). CGI-Improvement score had a significant negative correlation with magnitude of increase in BMI (rs=-0.39; p=0.01)and SAEPS symptom score at follow-up (rs=-0.58; p<0.001). In addition, magnitude of increase in BMI showed positive correlation with the magnitude of reduction in SAPS total score (rs=0.33; p=0.04). Conclusion: The study findings suggest a possible relation between clinical improvement and antipsychotic-induced neuroleptic as well as metabolic side-effects in schizophrenia. Though the mechanism of this relation is yet to be elucidated, insulin signaling pathways and lipid homeostasis are potential mechanisms in addition to the established neurotransmitter hypothesis. Theoretically findings support the novel hypothetical construct of ‘Neuro-Metabolic threshold’ in the treatment of schizophrenia.