Effects of antipsychotic medications in glucose and lipid metabolism at the fasted state in drug-naïve first episode patients with psychosis after six months and three years of treatment.

Diabetes and dyslipidemia are common in patients with psychosis and may be related to adverse effects of antipsychotic medications. Metabolic disturbances in first-episode patients with psychosis are common, even prior to any antipsychotic treatment, and antipsychotic medications are implicated in the development of metabolic syndrome, at least in the long run. We therefore aimed to follow a group of drug-naïve, first-episode patients with psychosis at different time points (baseline, six months, and 36 months after the initiation of antipsychotic treatment) in order to evaluate the progression of metabolic abnormalities after antipsychotic therapy and the time-course of their onset. We assessed glucose and lipid metabolism during the fasted state in 54 drug-naïve patients with first-episode psychosis (FEP) before the initiation of any antipsychotic treatment and compared them with matched controls. The same parameters were assessed in the patient group (n=54) after six months of antipsychotic treatment and in a subgroup of patients (n=39) after three years of continuous and stable treatment in comparison to baseline. Measurements were obtained for fasting serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL), glucose, insulin, connecting peptide (C-peptide), homeostatic model assessment index (HOMA-IR), glycated hemoglobin (HbA1c) and body mass index (BMI). Insulin, C-peptide, triglyceride levels, and HOMA-IR index were significantly higher compared to controls. Total cholesterol, triglyceride levels and BMI, increased significantly in the patient group after six months of antipsychotic treatment. After three years of continuous antipsychotic treatment, we found statistically significant increases in fasting glucose, insulin, total cholesterol, triglyceride levels, HbA1c, HOMA-IR index, and BMI compared to baseline. In conclusion, FEP patients developed significant increases in BMI and serum lipid levels as soon as six months after antipsychotic treatment. These metabolic abnormalities persisted following 36 months of treatment and in addition, increases in fasting glucose, insulin, HbA1c and HOMA-IR were observed compared to baseline.

GSK3ß and mTORC1 Represent 2 Distinct Signaling Markers in Peripheral Blood Mononuclear Cells of Drug-Naive, First Episode of Psychosis Patients.

BACKGROUND AND HYPOTHESIS: Schizophrenia is characterized by a complex interplay between genetic and environmental risk factors converging on prominent signaling pathways that orchestrate brain development. The Akt/GSK3ß/mTORC1 pathway has long been recognized as a point of convergence and etiological mechanism, but despite evidence suggesting its hypofunction, it is still not clear if this is already established during the first episode of psychosis (FEP). STUDY DESIGN: Here, we performed a systematic phosphorylation analysis of Akt, GSK3ß, and S6, a mTORC1 downstream target, in fresh peripheral blood mononuclear cells from drug-naive FEP patients and control subjects. STUDY RESULTS: Our results suggest 2 distinct signaling endophenotypes in FEP patients. GSK3ß hypofunction exhibits a promiscuous association with psychopathology, and it is normalized after treatment, whereas mTORC1 hypofunction represents a stable state. CONCLUSIONS: Our study provides novel insight on the peripheral hypofunction of the Akt/GSK3ß/mTORC1 pathway and highlights mTORC1 activity as a prominent integrator of altered peripheral immune and metabolic states in FEP patients.

Adiponectin, leptin and resistin levels in first-episode, drug-naïve patients with psychosis before and after short-term antipsychotic treatment.

OBJECTIVE: There is increasing evidence that adiponectin, resistin and leptin may be implicated in the pathophysiology of neuropsychiatric disorders, including schizophrenia. The results of the studies so far remain controversial. Our aim was to compare serum adiponectin, leptin and resistin levels between drug-naïve, first -episode patients with psychosis and healthy controls and in the same group of patients after six weeks of antipsychotic treatment. METHODS: Forty first-episode patients with psychosis and 40 matched controls were included in the study. Serum levels of adiponectin, resistin and leptin were measured by enzyme linked immunosorbent assay (ELISA) in both groups. In the patient group, the same adipokines were also measured six weeks after the initiation of antipsychotic treatment. RESULTS: Log-transformed serum levels of adiponectin (mean difference = 1.68, 95% confidence interval [CI] = 1.30 to 2.06, U = 157, p < 0.0001), resistin (0.48, 95% CI = 0.36 to 0.59, t = 8.00, p < 0.0001) and leptin (0.66, 95% CI = 0.52 to 0.80, U = 160, p < 0.0001) were significantly higher to the patient group compared to controls. Leptin levels were significantly decreased in the patient group six weeks after the initiation of antipsychotic treatment (mean change = -0.40, 95% CI = -0.59 to -0.21, W = 666; p < 0.0001) while those of adiponectin and resistin levels did not change significantly. CONCLUSION: In our study we found higher levels of adiponectin, leptin and resistin in drug-naïve, first-episode patients with normal Body Mass Index (BMI) compared to controls. After six weeks of antipsychotic treatment, there was no change in adiponectin and resistin levels, while leptin levels were reduced compared to baseline.

Sex hormone levels in drug-naïve, first-episode patients with psychosis.

Aim: Sex differences have long been reported in schizophrenia leading to the hypothesis that sex hormones may be implicated in the pathophysiology of the disorder. We assessed gonadal hormones during the fasted state in drug-naïve patients with psychosis.Method: Fasting serum concentrations of follicular-stimulating hormone (FSH) and luteinizing hormone (LH), testosterone, free-testosterone, Sex Hormone Binding Globulin (SHBG) and oestradiol (E2) were compared between a group of 55 newly diagnosed, drug-naïve, first-episode men with psychosis and a group of 55 healthy controls, matched for age, smoking status and BMI. Testosterone, free-testosterone and SHBG were compared between a group of 32 drug-naïve, first-episode females with psychosis and a group of 32 healthy controls matched for age, smoking status and BMI.Results: Testosterone and free-testosterone levels were significantly lower in the patients' group and SHBG levels significantly higher in the patients' group compared to those in healthy controls. The two female groups had similar values in the hormones which were measured.Conclusion: Our findings provide evidence of lower testosterone and free-testosterone levels and increased SHBG levels in drug-naïve, first-episode males with psychosis.KEY POINTSReduced testosterone and free-testosterone levels in drug-naive, first-episode males with psychosis.Increased SHBG levels in drug-naive first-episode males with psychosis.No difference in FSH, LH and E2 levels between drug-naive first episode males with psychosis and controls.No difference in testosterone, free-testosterone and SHBG levels between drug-naive, first-episode women with psychosis and controls.

Prevalence, comorbidity, quality of life and use of services of obsessive-compulsive disorder and subthreshold obsessive-compulsive symptoms in the general adult population of Greece.

Objective: We aimed to describe the epidemiology of obsessive-compulsive disorder (OCD) and related subthreshold symptoms in the general population of Greece and to assess the comorbidity, use of health services and impact on quality of life of these syndromes in the general population. Methods: This was a secondary analysis of the 2009-2010 general population Greek psychiatric morbidity survey (4902 participants living in private households, response rate 54%). Psychiatric disorders were assessed with the revised Clinical Interview Schedule (CIS-R). Quality of life was assessed with the EuroQoL EQ-5D. Results: 1.69% of the participants (95% confidence interval [CI]: 1.33%-2.05%) met criteria for current OCD while 2.79% met criteria for subthreshold obsessive-compulsive symptoms (95%CI: 2.33%-3.26%). In the adjusted analysis few sociodemographic associations remained statistically significant. Although the full-blown syndrome was more severe in terms of comorbidity and quality of life our results showed that even subthreshold obsessive-compulsive symptoms were associated with significant comorbidity and reductions in quality of life. Use of mental health services was small. Conclusions: OCD is an under-treated public health problem that needs more attention in Greece and elsewhere. Provision of specialised mental health services should be a priority for publicly funded national health systems. Keypoints OCD is common in the general population of Greece with few sociodemographic associations apart from subjective financial difficulties. The comorbidity pattern of the full-blown syndrome versus the subthreshold obsessive-compulsive symptoms is similar and differs in magnitude in the expected way. Quality of life in OCD is greatly reduced especially when there is chronicity and/or comorbidity with depression. Use of services is limited but comorbidity with depression may increase the chances of consultation with a mental health professional.