Blood and Urinary Biomarkers of Antipsychotic-Induced Metabolic Syndrome

Khasanova, Aiperi K.; Добродеева, В. С.; Shnayder, Natalia A.; Петрова, М. М.; Pronina, Elena; Bochanova, E. N.; Lareva, N.V.; Гарганеева, Н. П.; Smirnova, Daria; Насырова, Р. Ф.

doi:10.3390/metabo12080726

Cited by 14 publications

(36 citation statements)

References 283 publications

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“…One study reported elevated levels even in first‐onset patients with schizophrenia 65 . Although the FGF system is considered a potential target in schizophrenia, 66 there are no data on the effect of antipsychotics on FGF‐21 67 . FGF‐21, as a mediator of energy homeostasis, represents a target for emerging new potentially beneficial therapies for obesity, dyslipidemia, and glucose dysregulation 68–70 and possibly in the development of strategies in prevention or treatment of adverse metabolic effects of antipsychotics.…”

Section: Discussionmentioning

confidence: 99%

Olanzapine, but not haloperidol, exerts pronounced acute metabolic effects in the methylazoxymethanol rat model

Horska,

Skrede,

Kucera

et al. 2024

CNS Neurosci Ther

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AimWidely used second‐generation antipsychotics are associated with adverse metabolic effects, contributing to increased cardiovascular mortality. To develop strategies to prevent or treat adverse metabolic effects, preclinical models have a clear role in uncovering underlying molecular mechanisms. However, with few exceptions, preclinical studies have been performed in healthy animals, neglecting the contribution of dysmetabolic features inherent to psychotic disorders.MethodsIn this study, methylazoxymethanol acetate (MAM) was prenatally administered to pregnant Sprague–Dawley rats at gestational day 17 to induce a well‐validated neurodevelopmental model of schizophrenia mimicking its assumed pathogenesis with persistent phenotype. Against this background, the dysmetabolic effects of acute treatment with olanzapine and haloperidol were examined in female rats.ResultsPrenatally MAM‐exposed animals exhibited several metabolic features, including lipid disturbances. Half of the MAM rats exposed to olanzapine had pronounced serum lipid profile alteration compared to non‐MAM controls, interpreted as a reflection of a delicate MAM‐induced metabolic balance disrupted by olanzapine. In accordance with the drugs' clinical metabolic profiles, olanzapine‐associated dysmetabolic effects were more pronounced than haloperidol‐associated dysmetabolic effects in non‐MAM rats and rats exposed to MAM.ConclusionOur results demonstrate metabolic vulnerability in female prenatally MAM‐exposed rats, indicating that findings from healthy animals likely provide an underestimated impression of metabolic dysfunction associated with antipsychotics. In the context of metabolic disturbances, neurodevelopmental models possess a relevant background, and the search for adequate animal models should receive more attention within the field of experimental psychopharmacology.

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Section: Discussionmentioning

confidence: 99%

Olanzapine, but not haloperidol, exerts pronounced acute metabolic effects in the methylazoxymethanol rat model

Horska,

Skrede,

Kucera

et al. 2024

CNS Neurosci Ther

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“…Reduced level of central serotonin is consistently linked to heightened impulsivity [24]. In obese individuals, insulin resistance is associated with elevated postprandial free fatty acid (FFA) level [25]. These FFAs compete with tryptophan, the precursor of serotonin, for binding to serum albumin.…”

Section: Discussionmentioning

confidence: 99%

Body Weight Variability and Risk of Suicide Mortality: A Nationwide Population-Based Study

Lee,

Jung,

Kang

et al. 2024

Depression and Anxiety

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Background. Suicide is a pressing global health concern, and identifying its risk factors is crucial for prevention. Body weight variability (BWV) has been increasingly recognized as a potential factor impacting physical and mental health outcomes. We aimed to explore the relationship between BWV and the risk of suicide mortality using a nationally representative database. Methods. This population-based cohort study used data from the Korean National Health Insurance Database and included a total of 1,983,701 subjects. BWV was assessed using at least three health examination datasets and validated variability indices (variability independent of the mean (VIM), average successive variability, and coefficient of variation), and patients were divided into BWV quartiles (Q1–Q4). The primary endpoint was suicide-related death. Results. During a median of 11.3 years of follow-up, 5,883 suicide deaths occurred. A higher baseline body weight was associated with a lower risk of suicide. However, greater BWV (VIM) was associated with a significantly greater risk of suicide (adjusted hazard ratio [95% confidence interval], 1.35 [1.26–1.45] in the Q4 group), even after adjusting for baseline body mass index (BMI). Similar results were observed regardless of obesity or BMI category. Consistent findings were observed when using different variability indices. Subgroup analyses according to sex, age, diabetes, and depression also supported these findings. Conclusion. Our study highlights the importance of considering BWV as a potential risk factor for suicide.

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“…Antipsychotic drugs are the main form of treatment for schizophrenia, and long-term maintenance antipsychotic treatment can protect against all-cause mortality (RR = 0.71, 95% CI: 0.59-0.84, n = 11) compared with no use of anti-psychotics [4]. However, almost all antipsychotic drugs lead to the development of metabolic syndrome (MetS) [5].…”

Section: Introductionmentioning

confidence: 99%

Association Between Prolactin, Estradiol, and Testosterone Levels and the Development of Metabolic Syndrome in Female Inpatients with Schizophrenia: A Case–Control Study

2023

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This study was to investigate the association between sex hormone levels and metabolic syndrome (MetS) risk in female schizophrenia inpatients. In total, 93 female schizophrenia patients were enrolled based on their electronic medical records of hospitalization at the Zigong Psychiatric Research Center, China, between August 2022 to September 2022. Baseline information was collected retrospectively from medical records 6 months before. Logistic regression analysis was applied to assess the potential relationship between sex hormone levels and the risk of developing MetS. 31.2% (29/93) of the total patients, 25.5% (12/47) of the 18–49 age group, and 37.0% (17/46) of the ≥ 50 age group had a history of MetS; the newly-developed MetS prevalence among all female schizophrenia patients was 15.05% (14/93), which was slightly higher but not statistically significant in older patients (age ≥ 50) than in younger patients (age 18–49) (≥ 50 vs. 18–49, 21.74% vs. 8.5%, p = 0.074). Univariate analysis of sex hormone levels and developed MetS discovered that only high prolactin levels correlated with developed MetS in total participants ( p = 0.006), especially in older patients ( p = 0.004), while estradiol and testosterone levels were not associated. Furthermore, univariate logistic regression analysis of the total participants and with an adjusted model of the ≥ 50 age group confirmed the association of prolactin with MetS in all (OR = 1.016, 95%CI:1.002–1.029, p = 0.023), and older female schizophrenia patients (OR = 1.04, 95%CI: 1.01–1.07, p = 0.008). High serum levels of prolactin in older patients (age ≥ 50) were strongly correlated with the risk of developing MetS among female schizophrenia patients.

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Blood and Urinary Biomarkers of Antipsychotic-Induced Metabolic Syndrome

Cited by 14 publications

References 283 publications

Olanzapine, but not haloperidol, exerts pronounced acute metabolic effects in the methylazoxymethanol rat model

Olanzapine, but not haloperidol, exerts pronounced acute metabolic effects in the methylazoxymethanol rat model

Body Weight Variability and Risk of Suicide Mortality: A Nationwide Population-Based Study

Association Between Prolactin, Estradiol, and Testosterone Levels and the Development of Metabolic Syndrome in Female Inpatients with Schizophrenia: A Case–Control Study

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