Weight gain and lipid metabolic abnormalities induced by olanzapine in first-episode, drug-naïve patients with psychotic disorders

AbstractPatients with schizophrenia have a lower than average life span, largely due to the increased prevalence of cardiometabolic co-morbidities. Identification of individuals with psychotic disorders with a high risk of rapid weight gain, and the associated development of metabolic complications, is an unmet need as regards public health. Here, we applied mass spectrometry-based lipidomics in a prospective study comprising 48 controls (CTR), 44 first-episode psychosis (FEP) patients and 22 individuals at clinical-high-risk (CHR) for psychosis, from two study centers (Turku/Finland and London/UK). Baseline serum samples were analyzed by lipidomics, while body mass index (BMI) was assessed at baseline and after 12 months. We found that baseline triacylglycerols with low double bond counts and carbon numbers were positively associated with the change in BMI at follow-up. In addition, a molecular signature comprised of two triacylglycerols (TG(48:0) and TG(45:0)), was predictive of weight gain in individuals with a psychotic disorder, with an area under the receiver operating characteristic curve (AUROC) of 0.74 (95% CI: 0.60–0.85). When independently tested in the CHR group, this molecular signature predicted said weight change with AUROC = 0.73 (95% CI: 0.61–0.83). We conclude that molecular lipids may serve as a predictor of weight gain in psychotic disorders in at-risk individuals, and may thus provide a useful marker for identifying individuals who are most prone to developing cardiometabolic co-morbidities.

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Exploring Patterns of Disturbed Eating in Psychosis: A Scoping Review

Nutrients ◽

10.3390/nu12123883 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3883

Author(s):

Nicolette Stogios ◽

Emily Smith ◽

Roshanak Asgariroozbehani ◽

Laurie Hamel ◽

Alexander Gdanski ◽

...

Keyword(s):

Weight Gain ◽

Scoping Review ◽

Psychotic Disorders ◽

Self Report ◽

First Episode ◽

Eating Patterns ◽

Eating Behaviours ◽

Qualitative Synthesis ◽

Early 19Th Century ◽

Disturbed Eating

Disturbed eating behaviours have been widely reported in psychotic disorders since the early 19th century. There is also evidence that antipsychotic (AP) treatment may induce binge eating or other related compulsive eating behaviours. It is therefore possible that abnormal eating patterns may contribute to the significant weight gain and other metabolic disturbances observed in patients with psychosis. In this scoping review, we aimed to explore the underlying psychopathological and neurobiological mechanisms of disrupted eating behaviours in psychosis spectrum disorders and the role of APs in this relationship. A systematic search identified 35 studies that met our eligibility criteria and were included in our qualitative synthesis. Synthesizing evidence from self-report questionnaires and food surveys, we found that patients with psychosis exhibit increased appetite and craving for fatty food, as well as increased caloric intake and snacking, which may be associated with increased disinhibition. Limited evidence from neuroimaging studies suggested that AP-naïve first episode patients exhibit similar neural processing of food to healthy controls, while chronic AP exposure may lead to decreased activity in satiety areas and increased activity in areas associated with reward anticipation. Overall, this review supports the notion that AP use can lead to disturbed eating patterns in patients, which may contribute to AP-induced weight gain. However, intrinsic illness-related effects on eating behaviors remain less well elucidated, and many confounding factors as well as variability in study designs limits interpretation of existing literature in this field and precludes firm conclusions from being made.

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Antipsychotic-Induced Weight Gain in Chronic and First-Episode Psychotic Disorders

CNS Drugs ◽

10.2165/00023210-200822070-00002 ◽

2008 ◽

Vol 22 (7) ◽

pp. 547-562 ◽

Cited By ~ 161

Author(s):

Mario Álvarez-Jiménez ◽

César González-Blanch ◽

Benedicto Crespo-Facorro ◽

Sarah Hetrick ◽

Jose Manuel Rodríguez-Sánchez ◽

...

Keyword(s):

Weight Gain ◽

Psychotic Disorders ◽

First Episode

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Association Between Circulating Lipids and Future Weight Gain in Individuals With an At-Risk Mental State and in First-Episode Psychosis

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa087 ◽

2020 ◽

Cited By ~ 1

Author(s):

Santosh Lamichhane ◽

Alex M Dickens ◽

Partho Sen ◽

Heikki Laurikainen ◽

Faith Borgan ◽

...

Keyword(s):

At Risk ◽

Weight Gain ◽

High Risk ◽

Psychotic Disorders ◽

First Episode Psychosis ◽

Molecular Signature ◽

First Episode ◽

Baseline Serum ◽

Average Life Span ◽

Episode Psychosis

Abstract Patients with schizophrenia have a lower than average life span, largely due to the increased prevalence of cardiometabolic comorbidities. There is an unmet public health need to identify individuals with psychotic disorders who have a high risk of rapid weight gain and who are at risk of developing metabolic complications. Here, we applied mass spectrometry-based lipidomics in a prospective study comprising 48 healthy controls (CTR), 44 first-episode psychosis (FEP) patients, and 22 individuals at clinical high risk (CHR) for psychosis, from 2 study centers (Turku, Finland and London, UK). Baseline serum samples were analyzed using lipidomics, and body mass index (BMI) was assessed at baseline and after 12 months. We found that baseline triacylglycerols (TGs) with low double-bond counts and carbon numbers were positively associated with the change in BMI at follow-up. In addition, a molecular signature comprised of 2 TGs (TG[48:0] and TG[45:0]) was predictive of weight gain in individuals with a psychotic disorder, with an area under the receiver operating characteristic curve (AUROC) of 0.74 (95% CI: 0.60–0.85). When independently tested in the CHR group, this molecular signature predicted said weight change with AUROC = 0.73 (95% CI: 0.61–0.83). We conclude that molecular lipids may serve as a predictor of weight gain in psychotic disorders in at-risk individuals and may thus provide a useful marker for identifying individuals who are most prone to developing cardiometabolic comorbidities.

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Peripheric Metabolic Abnormalities in Schizophrenia Patients

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1549 ◽

2017 ◽

Vol 41 (S1) ◽

pp. s802-s802

Author(s):

M. Amorim ◽

A. Moreira ◽

A. Marques ◽

T. Summavielle

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Fasting Blood Glucose ◽

Disease Onset ◽

First Episode ◽

Metabolic Abnormalities ◽

Metabolic Disturbances ◽

Antipsychotic Therapy ◽

Glucose Levels ◽

Drug Naïve

IntroductionSchizophrenia (SCZ) is frequently associated with metabolic symptoms including dyslipidaemia, hyperinsulinemia, type 2 diabetes and obesity. In fact, SCZ patients have been reported to present higher prevalence of these conditions than general population, commonly associated to second generation antipsychotic therapy. Recent studies, however, have demonstrated that peripheral metabolic disturbances can appear at disease onset or drug-naïve patients.Objectives/aimsTo assess metabolic disturbances in first episode and/or drug-naïve SCZ patients.MethodsWe conducted a literature review through Pubmed search for MeSH: schizophrenia, metabolism, glucose, insulin. Controlled studies on first episode and/or drug-naïve SCZ patients were included.ResultsSeveral studies showed no change in SCZ patients’ fasting blood glucose, while others found increased glucose levels and impaired glucose tolerance in SCZ patients compared to healthy controls in several recent studies. Hyperinsulinemia and insulin resistance have also been identified in antipsychotic-naïve SCZ patients and it has been suggested that early onset patients are more likely to present insulin resistance. In addition, there's evidence of increased circulating levels of chromogranin A, pancreatic polypeptide, prolactin, cortisol, progesterone, thus emphasising that multiple components of the hypothalamic-pituitary-adrenal-gonadal axis may be affected in SCZ. These elevations were associated to normal glycaemia suggesting there may be insulin intolerance during early stages of SCZ, requiring an increased secretion from pancreatic Bcells to maintain normal glucose levels.ConclusionsRecent studies of first onset and/or drug-free schizophrenia patients have shown impaired fasting glucose tolerance, hyperinsulinemia and insulin intolerance, suggesting that metabolic abnormalities may play a role in SCZ onset and pathophysiology.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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

Journal of Psychiatric Research ◽

10.1016/j.jpsychires.2021.06.001 ◽

2021 ◽

Author(s):

Jia Hong Liu ◽

Nan Chen ◽

Yan Hong Guo ◽

Xiao Ni Guan ◽

Jun Wang ◽

...

Keyword(s):

Weight Gain ◽

First Episode ◽

Drug Naïve

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Probiotic supplements reduce antipsychotic-induced metabolic disturbances in drug-naïve first-episode schizophrenia

10.1101/2021.02.16.21251872 ◽

2021 ◽

Author(s):

Dongyu Kang ◽

Fengyu Zhang ◽

Ye Yang ◽

Chenchen Liu ◽

Jingmei Xiao ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Metabolic Disturbance ◽

First Episode ◽

Controlled Clinical Trial ◽

Fasting Insulin ◽

Metabolic Disturbances ◽

Drug Naïve ◽

Level Of Significance ◽

First Episode Schizophrenia

ABSTRACTProbiotic supplements have demonstrated efficacy in improving metabolic abnormalities and may prevent antipsychotic-induced metabolic disturbance and weight gain. A few studies in rodents have found that antipsychotic-induced metabolic dysfunctions are associated with the altered composition of gut microbiota. Here, we conducted a randomized-controlled clinical trial to determine the effectiveness and safety of probiotic supplements on antipsychotic-induced metabolic disturbance and weight gain. Patients with drug-naïve first-episode schizophrenia were randomized to receive either olanzapine plus probiotics or olanzapine monotherapy and scheduled to evaluate with follow-ups for clinical and metabolic profiles. After a treatment of 12 weeks with addition of probiotics, the increase of mean fasting insulin was significantly lower than olanzapine monotherapy. Insulin resistance increased considerably in the olanzapine plus probiotics, but also significantly lower than olanzapine monotherapy. We noted a difference in the increase in body mass index and body weight between treatments at a nominal level of significance, but it became non-significant after adjusting for appetite increase. Probiotics concurrently used with olanzapine is effective and safe in attenuating antipsychotic-induced elevation of fasting insulin and insulin resistance, but not the weight gain in drug-naïve first-episode schizophrenia. Further study is warranted to assess the longer-term maintenance of efficacy and safety.

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Therapeutic Response Is Associated With Antipsychotic-Induced Weight Gain in Drug-Naive First-Episode Patients With Schizophrenia

The Journal of Clinical Psychiatry ◽

10.4088/jcp.20m13469 ◽

2021 ◽

Vol 82 (3) ◽

Author(s):

Ying Qi Chen ◽

Xi Rong Li ◽

Lie Zhang ◽

Wei Bo Zhu ◽

Ya Qing Wu ◽

...

Keyword(s):

Weight Gain ◽

Therapeutic Response ◽

First Episode ◽

Drug Naïve

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Cigarette smoking, psychopathology and cognitive function in first-episode drug-naive patients with schizophrenia: a case-control study

Psychological Medicine ◽

10.1017/s0033291712002590 ◽

2012 ◽

Vol 43 (8) ◽

pp. 1651-1660 ◽

Cited By ~ 20

Author(s):

X. Y. Zhang ◽

D. C. Chen ◽

M. H. Xiu ◽

C. N. Haile ◽

S. C. He ◽

...

Keyword(s):

Cognitive Function ◽

General Population ◽

Psychotic Disorders ◽

Chronic Schizophrenia ◽

Case Control ◽

Mental Illnesses ◽

Positive Symptom ◽

First Episode ◽

Healthy Controls ◽

Drug Naïve

BackgroundAlthough patients with chronic schizophrenia have substantially higher smoking rates than either the general population or patients with other mental illnesses, drug-naive patients with a first episode of schizophrenia have received little systemic study. This study examined smoking rates, the association between smoking and symptom severity and cognitive function in Chinese first-episode schizophrenia (FES) patients using cross-sectional and case-control designs.MethodTwo hundred and forty-four drug-naive FES patients and 256 healthy controls matched for gender, age and education completed the Fagerström Test for Nicotine Dependence (FTND) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Patients were also rated on the Positive and Negative Symptom Scale (PANSS).ResultsThe rate and quantity of smoking were not significantly higher among FES patients compared to the general population. Among patients, smokers scored higher than non-smokers on the total PANSS and the positive symptom subscale scores. There were no significant associations between cognitive function and smoking in either FES patients or healthy controls.ConclusionsIn contrast to studies in patients with chronic schizophrenia, drug-naive FES patients did not smoke more frequently than the general population. Furthermore, patients with psychotic disorders who smoked did not exhibit significant cognitive differences compared with those who did not smoke. However, smoking may have other detrimental effects on physical and mental health, for example on positive symptoms.

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