Metabolomics-based understanding of the olanzapine-induced weight gain in female first-episode drug-naïve patients with schizophrenia.

Previous studies have demonstrated that patients with schizophrenia (SZ) have greater rate of metabolic disorder as compared with the control population, which likely be the consequence of use of atypical antipsychotics. Olanzapine is a widely used antipsychotic, which increases the weight of SZ patients. However, the underlying mechanism remains poorly understood. Here we report the metabolomics-based understanding of the weight gain induced by olanzapine. 57 first-episode drug-naïve patients (FEDN) were recruited, of whom 27 patients completed a 4-week clinical trial. We then profiled the metabolomes of their plasma with the LC-MS-based nontargeted metabolomics approach at the baseline and after olanzapine monotherapy for 4 weeks. We observed that the plasma of the olanzapine-treated patient had significantly higher lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE) and lower carnitine as compared with that of the baseline plasma samples. Moreover, regression analyses indicated that the change of LysoPC(14:0) level was an independent contributor to the olanzapine-induced weight gain. Our study suggests that the metabolomics-based approach may facilitate the identification of biomarkers associated with the metabolic disorder causing by antipsychotic in schizophrenia patients.

Therapeutic Response Is Associated With Antipsychotic-Induced Weight Gain in Drug-Naive First-Episode Patients With Schizophrenia: An 8-Week Prospective Study.

BACKGROUND: Some previous studies have shown that weight gain is associated with greater improvement in psychopathology during antipsychotic treatment in patients with chronic schizophrenia. However, the results are mixed due to many confounding factors. The current study aimed to investigate whether weight gain was associated with antipsychotic response in patients with antipsychotic-naive and first-episode (ANFE) DSM-IV--diagnosed schizophrenia. METHODS: 526 ANFE patients and 313 healthy controls were enrolled in this study, which was conducted from January 2012 to December 2018. Treatment outcome was measured by the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up. Weight was measured at baseline and at the end of 8 weeks. RESULTS: After treatment, PANSS scores were significantly reduced as follows: positive symptoms (-10.40; 95% CI, -9.31 to -10.60), negative symptoms (-5.01; 95% CI, -4.43 to -5.54), general psychopathology (-13.01; 95% CI, -12.01 to -14.01), and PANSS total score (-28.53; 95% CI, -26.73 to -30.33). In addition, the average weight of ANFE patients increased by 2.89 kg (95% CI, 2.55 to 3.22), although it was still lower than the average weight of healthy controls. The proportion of patients with weight gain ≥ 7% after treatment was 38.2%. Weight gain was positively associated with decrease of PANSS positive symptoms, general psychopathology, and total score (all P < .05). Multiple linear regression analysis showed that baseline weight, decrease of PANSS total score, and sex were significantly associated with weight gain after treatment. CONCLUSIONS: Our findings suggest that there is a significant association between weight gain and improvement of clinical symptoms after 8 weeks of antipsychotic treatment in patients with ANFE schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04076371.

Altered Antioxidant Defenses in Drug-Naive First Episode Patients with Schizophrenia Are Associated with Poor Treatment Response to Risperidone: 12-Week Results from a Prospective Longitudinal Study.

Abnormal redox regulation is thought to contribute to schizophrenia (SCZ). Accumulating studies have shown that the plasma antioxidant enzyme activity is closely associated with the course and outcome in antipsychotics-naïve first-episode (ANFE) patients with SCZ. The main purpose of this study was to investigate the effect of risperidone on oxidative stress markers in ANFE patients and the relationship between risperidone response and changes in oxidative stress markers. Plasma activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) enzyme, total antioxidant status (TAS), and malondialdehyde (MDA) levels were measured in 354 ANFE patients and 152 healthy controls. The clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Patients received risperidone monotherapy for 12 weeks and oxidative stress markers and PANSS were measured at baseline and at follow-up. Compared with healthy controls, the patients exhibited higher activities of SOD, CAT, and TAS levels, but lower MDA levels and GPx activity. A comparison between 168 responders and 50 non-responders at baseline and 12-week follow-up showed that GPx activity decreased in both groups after treatment. Moreover, GPx activity decreased less in responders and was higher in responders than in non-responders at follow-up. These results demonstrate that the redox regulatory system and antioxidant defense enzymes may have predictive value for the response of ANFE patients to risperidone treatment.

Sex-specific Association of Antipsychotic-induced Weight Gain and Treatment Response for Antipsychotic-Naive First Episode Schizophrenia Patients: A Prospective 8-week Longitudinal Study.

BACKGROUND: Patients with antipsychotic-naïve first-episode (ANFE) schizophrenia (SZ) can help clarify many confounding factors in determining sex differences in antipsychotic drug induced weight gain and its association with symptom improvement. METHODS: This 8-week longitudinal trial of ANFE patients with SZ enrolled 526 patients and 313 healthy controls. We evaluated bodyweight and the efficacy of antipsychotics on the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 8. RESULTS: Males and females after treatment showed no sex difference in weight gain, BMI increase, and percentage of weight gain. However, at baseline, male patients had more positive symptoms than female patients, and decreases in positive symptoms, general psychopathology, and total PANSS scores were less in male than female patients. Adjusting for confounding factors using multiple linear regression confirmed that weight gain was significantly associated with these decreases in PANSS symptoms only in men not women. CONCLUSIONS: The relationship between weight gain and symptom reduction after 8 weeks of antipsychotic treatment exists only in male patients with ANFE SZ and not in female patients.