Roles of inflammation in intrinsic pathophysiology and antipsychotic drug-induced metabolic disturbances of schizophrenia

Prestwood, Tyler R.; Asgariroozbehani, Roshanak; Wu, Sally; Agarwal, Sri Mahavir; Logan, Ryan W.; Ballon, Jacob S.; Hahn, Margaret; Freyberg, Zachary

doi:10.1016/j.bbr.2020.113101

Cited by 37 publications

(30 citation statements)

References 264 publications

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“…LPS has been shown to be an effective neurodevelopmental model of SCZ in rodents [71][72][73]. In addition, to LPS, SCZ patients have been shown to have increased inflammatory cytokines which may contribute to the change in gut permeability and development of a "leaky gut" [74]. Notably, SCZ patients were reported to have lower levels of the family Lachnospiraceae, which has been reported to be beneficial in health such as butyrate and other short-chain fatty acid production.…”

Section: Evidence For Psychobiotic Intervention In Schizophreniamentioning

confidence: 99%

The Gut Microbiome in Schizophrenia and the Potential Benefits of Prebiotic and Probiotic Treatment

et al. 2021

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The gut microbiome (GMB) plays an important role in developmental processes and has been implicated in the etiology of psychiatric disorders. However, the relationship between GMB and schizophrenia remains unclear. In this article, we review the existing evidence surrounding the gut microbiome in schizophrenia and the potential for antipsychotics to cause adverse metabolic events by altering the gut microbiome. We also evaluate the current evidence for the clinical use of probiotic and prebiotic treatment in schizophrenia. The current data on microbiome alteration in schizophrenia remain conflicting. Longitudinal and larger studies will help elucidate the confounding effect on the microbiome. Current studies help lay the groundwork for further investigations into the role of the GMB in the development, presentation, progression and potential treatment of schizophrenia.

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Section: Evidence For Psychobiotic Intervention In Schizophreniamentioning

confidence: 99%

The Gut Microbiome in Schizophrenia and the Potential Benefits of Prebiotic and Probiotic Treatment

et al. 2021

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“…Several included papers have investigated the pathophysiological basis of this relationship. The role of inflammation in the etiopathogenesis of SMI and metabolic dysfunction and the effect of antipsychotics on these processes is an area of active inquiry, and articles in this issue reflect this (17)(18)(19). For example, Reponen, Dieset, et al investigated the correlation between markers of systemic inflammation and dyslipidemia in patients with schizophrenia and bipolar disorder.…”

Section: Cardiovascular and Physical Health In Severe Mental Illnessmentioning

confidence: 99%

Editorial: Cardiovascular and Physical Health in Severe Mental Illness

et al. 2021

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“…Beyond affecting adipokine release, APs may also directly disrupt lipid metabolism in adipose tissue by increasing the expression of lipogenic genes involved in fatty acid synthesis 86–90 . Furthermore, both pre‐clinical and clinical findings suggest that APs may increase expression of pro‐inflammatory cytokines such as interleukins, tumor necrosis factor‐α, and monocyte chemoattractant protein‐1 in adipose tissue, although whether this is a cause or consequence of AP‐associated adiposity is unclear 67,91–93 . As shown in this study, these effects are likely to be especially prominent in young patients most vulnerable to AP effects 50 …”

Section: Discussionmentioning

confidence: 74%

“…Abnormalities in glucose regulation, lipid metabolism, feeding and energy sensing, have been reported from the earliest stages of illness, including the prodrome, and in unaffected siblings 4,43 . Furthermore, behavioral factors such as smoking, poor dietary habits, and low‐physical activity 59–65 ; biological factors such as increased inflammation, disruptions in the hypothalamic‐pituitary‐adrenal (HPA) axis, aberrant adipose tissue homeostasis, and brain insulin resistance 66–70 ; and systemic factors such as low socioeconomic status and barriers to care 71–73 interact and overlap to drive metabolic dysfunction, including the adiposity changes reported in the present study 8 …”

Section: Discussionmentioning

confidence: 99%

Adiposity in schizophrenia: A systematic review and meta‐analysis

Smith

Singh

Lee

et al. 2021

Acta Psychiatr Scand

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Objective Although a relationship between schizophrenia (SCZ), antipsychotic (AP) medication, and metabolic dysregulation is now well established, the effect of adiposity is less well understood. By synthesizing findings from imaging techniques that measure adiposity, our systematic review and meta‐analysis (PROSPERO CRD42020192977) aims to determine the adiposity‐related effects of illness and treatment in this patient population. Methods We searched MEDLINE, EMBASE, PsychINFO and Scopus for all relevant case‐control and prospective longitudinal studies from inception until February 2021. Measures of adiposity including percent body fat (%BF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were analyzed as primary outcomes. Results Our search identified 29 articles that used imaging methods to quantify adiposity among patients with SCZ spectrum disorders. Analyses revealed that patients have greater %BF (mean difference (MD) = 3.09%; 95% CI: 0.75–5.44), SAT (MD = 24.29 cm2; 95% CI: 2.97–45.61) and VAT (MD = 33.73 cm2, 95% CI: 4.19–63.27) compared to healthy controls. AP treatment was found to increase SAT (MD = 31.98 cm2; 95% CI: 11.33–52.64) and VAT (MD = 16.30 cm2; 95% CI: 8.17–24.44) with no effect on %BF. However, change in %BF was higher for AP‐free/AP‐naïve patients compared to treated patients. Conclusion Our findings indicate that patients with SCZ spectrum disorders have greater adiposity than healthy controls, which is increased by AP treatment. Young, AP‐naïve patients may be particularly susceptible to this effect. Future studies should explore the effect of specific APs on adiposity and its relation to overall metabolic health.

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Roles of inflammation in intrinsic pathophysiology and antipsychotic drug-induced metabolic disturbances of schizophrenia

Cited by 37 publications

References 264 publications

The Gut Microbiome in Schizophrenia and the Potential Benefits of Prebiotic and Probiotic Treatment

The Gut Microbiome in Schizophrenia and the Potential Benefits of Prebiotic and Probiotic Treatment

Editorial: Cardiovascular and Physical Health in Severe Mental Illness

Adiposity in schizophrenia: A systematic review and meta‐analysis

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