Inflammatory Cytokines and Antipsychotic-Induced Weight Gain: Review and Clinical Implications

Fonseka, Trehani M.; Müller, Daniel J.; Kennedy, Sidney H.

doi:10.1159/000441521

Cited by 52 publications

(31 citation statements)

References 171 publications

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“…15 Cytokines in peripheral blood access the CNS through numerous hormonal pathways acting in parallel. 16 suggested a systemic cause for elevated levels of IL-6 and TNF-α, contributing to psychopathological symptoms in earlyonset schizophrenia. 17 Our results showed that patients after treatment had lower peripheral levels of IL-2 and IFN-γ compared with the before treatment and healthy control groups.…”

Section: Discussionmentioning

confidence: 99%

Alteration of Serum Levels of Cytokines in Schizophrenic Patients before and after Treatment with Risperidone

Azizi¹,

Hosseini²,

Soudi³

et al. 2019

IJAAI

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A growing body of evidence suggests the existence of abnormalities in the immune system of schizophrenic patients. The current study examined serum levels of interleukin (IL) -1β, IL-6, IL-2,interferon(IFN) -γ, and tumor necrosis factor(TNF)-α in schizophrenic patients before and after treatment with risperidone and correlated levels of these cytokines with symptomatology. The study group consisted of 24 schizophrenic patients as defined by Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria and 24 healthy controls. Serum cytokine levels were examined using enzyme-linked immunosorbent assay (ELISA). Schizophrenic symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS) questionnaire. The serum levels of TNF-α, IL-1β and IL-6 were significantly higher in participants before treatment compared with the healthy controls and after treatment (p<0.001). IFN-γ and IL-2 levels were significantly lower in participants after treatment compared with before treatment and the healthy controls (p<0.001). Except for IL-6 (p<0.05), there was no significant difference in the levels of TNF-α and IL-1β between the patients receiving treatment and the healthy subjects. Moreover, there was no significant difference in levels of IFN-γ and IL-2 between patients before treatment and the healthy subjects. There were no significant correlations between the concentration of cytokines studied and the PANSS. Positive intercorrelations between the production of IFN-γ and IL-2 were detected for sums of all groups(r=0.33, p=0.005). Clinical improvement of treated patients was associated with a reduction in the studied cytokines. It seems that changes in the cytokines level may play a significant role in the psychopathology of these patients.

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Section: Discussionmentioning

confidence: 99%

Alteration of Serum Levels of Cytokines in Schizophrenic Patients before and after Treatment with Risperidone

Azizi¹,

Hosseini²,

Soudi³

et al. 2019

IJAAI

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“…Fonseka et al [98] have proposed that antipsychotics with a high propensity for weight gain, such as clozapine and olanzapine, influence the expression of immune genes, and induce changes in serum cytokine levels to ultimately down-regulate neuroinflammation. Inflammatory cytokines are normally involved in anorexigenic responses and reduced inflammation has been shown to mediate changes in feeding behaviours and other metabolic parameters, resulting in obesity.…”

Section: Discussionmentioning

confidence: 99%

Haloperidol affects bones while clozapine alters metabolic parameters - sex specific effects in rats perinatally treated with phencyclidine

Nikolić

Petronijević

Sopta

et al. 2017

BMC Pharmacol Toxicol

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BackgroundThe presentation of schizophrenia (SCH) symptoms differs between the sexes. Long-term treatment with antipsychotics is frequently associated with decreased bone mineral density, increased fracture risk and metabolic side effects. Perinatal phencyclidine (PCP) administration to rodents represents an animal model of SCH. The aim of this study was to assess the effects of chronic haloperidol and clozapine treatment on bone mass, body composition, corticosterone, IL-6 and TNF-α concentrations and metabolic parameters in male and female rats perinatally treated with PCP.MethodsSix groups of male and six groups of female rats (n = 6-12 per group) were subcutaneously treated on 2nd, 6th, 9th and 12th postnatal day (PN), with either PCP (10 mg/kg) or saline. At PN35, one NaCl and PCP group (NaCl-H and PCP-H) started receiving haloperidol (1 mg/kg/day) and one NaCl and PCP group (NaCl-C and PCP-C) started receiving clozapine (20 mg/kg/day) dissolved in drinking water. The remaining NaCl and PCP groups received water. Dual X-ray absorptiometry measurements were performed on PN60 and PN98. Animals were sacrificed on PN100. Femur was analysed by light microscopy. Concentrations of corticosterone, TNF-α and IL-6 were measured in serum samples using enzyme-linked immunosorbent assay (ELISA) commercially available kits. Glucose, cholesterol and triacylglycerol concentrations were measured in serum spectrophotometrically.ResultsOur results showed that perinatal PCP administration causes a significant decrease in bone mass and deterioration in bone quality in male and female rats. Haloperidol had deleterious, while clozapine had protective effect on bones. The effects of haloperidol on bones were more pronounced in male rats. It seems that the observed changes are not the consequence of the alterations of corticosterone, IL-6 and TNF-α concentration since no change of these factors was observed. Clozapine induced increase of body weight and retroperitoneal fat in male rats regardless of perinatal treatment. Furthermore, clozapine treatment caused sex specific increase in pro-inflammatory cytokines.ConclusionTaken together our findings confirm that antipsychotics have complex influence on bone and metabolism. Evaluation of potential markers for individual risk of antipsychotics induced adverse effects could be valuable for improvement of therapy of this life-long lasting disease.Electronic supplementary materialThe online version of this article (10.1186/s40360-017-0171-4) contains supplementary material, which is available to authorized users.

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“…According to this analysis, olanzapine, clozapine, and quetiapine produced moderate leptin elevations; meanwhile, haloperidol and risperidone were associated with small and non-significant leptin changes [72]. Since leptin is released by the adipocyte and is therefore proportional to fat mass and stores, its increase in blood of patients with antipsychoticinduced weight gain could be the result of the increased weight itself suggesting that hyperleptinemic state could be more a consequence than a cause of antipsychotics-induced weight gain (AIWG) [14,[72][73][74]. Greater leptin elevation with olanzapine, clozapine, and quetiapine can be explained by the higher affinity of these drugs for muscarinic M3 receptors, which are known to be the underlying source of large differences concerning weight gain and other side effects [72].…”

Section: Leptin and Antipsychotics-induced Weight Gainmentioning

confidence: 99%

Leptin and psychiatric illnesses: does leptin play a role in antipsychotic-induced weight gain?

et al. 2020

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Antipsychotic-induced weight gain is the most prevalent somatic adverse event occurring in patients treated by antipsychotics, especially atypical antipsychotics. It is of particular interest because of its repercussion on cardiovascular morbidity and mortality especially now that the use of second-generation antipsychotics has been extended to other mental health illnesses such as bipolar disorders and major depressive disorder. The mechanism underlying antipsychotics-induced weight gain is still poorly understood despite a significant amount of work on the topic. Recently, there has been an ongoing debate of tremendous research interest on the relationship between antipsychotic-induced weight gain and body weight regulatory hormones such as leptin. Given that, researchers have brought to light the question of leptin's role in antipsychotic-induced weight gain. Here we summarize and discuss the existing evidence on the link between leptin and weight gain related to antipsychotic drugs, especially atypical antipsychotics.

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Inflammatory Cytokines and Antipsychotic-Induced Weight Gain: Review and Clinical Implications

Cited by 52 publications

References 171 publications

Alteration of Serum Levels of Cytokines in Schizophrenic Patients before and after Treatment with Risperidone

Alteration of Serum Levels of Cytokines in Schizophrenic Patients before and after Treatment with Risperidone

Haloperidol affects bones while clozapine alters metabolic parameters - sex specific effects in rats perinatally treated with phencyclidine

Leptin and psychiatric illnesses: does leptin play a role in antipsychotic-induced weight gain?

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