Crosstalk between Schizophrenia and Metabolic Syndrome: The Role of Oxytocinergic Dysfunction

Abstract

The high prevalence of metabolic syndrome in persons with schizophrenia has spurred investigational efforts to study the mechanism beneath its pathophysiology. Early psychosis dysfunction is present across multiple organ systems. On this account, schizophrenia may be a multisystem disorder in which one organ system is predominantly affected and where other organ systems are also concurrently involved. Growing evidence of the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, such as an association with cognitive dysfunction, altered autonomic nervous system regulation, desynchrony in the resting-state default mode network, and shared genetic liability, suggest that metabolic syndrome and schizophrenia are connected via common pathways that are central to schizophrenia pathogenesis, which may be underpinned by oxytocin system dysfunction. Oxytocin, a hormone that involves in the mechanisms of food intake and metabolic homeostasis, may partly explain this piece of the puzzle in the mechanism underlying this association. Given its prosocial and anorexigenic properties, oxytocin has been administered intranasally to investigate its therapeutic potential in schizophrenia and obesity. Although the pathophysiology and mechanisms of oxytocinergic dysfunction in metabolic syndrome and schizophrenia are both complex and it is still too early to draw a conclusion upon, oxytocinergic dysfunction may yield a new mechanistic insight into schizophrenia pathogenesis and treatment.

Schizophrenia and cardiometabolic abnormalities: A Mendelian randomization study

“…Aside from the aforementioned risk factors, the use of secondgeneration antipsychotics by patients with schizophrenia have been shown to lead to key features of metabolic syndrome, including weight gain, obesity, impaired glucose tolerance, and dyslipidaemia (Henderson et al, 2015;Goh et al, 2022;Richards-Belle et al, 2023).…”

“…Schizophrenia is a psychiatric disorder affecting approximately 1% of the world population ( Goh et al, 2022 ). Compared to the general population, individuals with schizophrenia have significant reductions in average life expectancy by 14.5 years; this premature mortality is primarily attributed to physical illness, including type 2 diabetes mellitus and cardiovascular disease ( Papanastasiou, 2013 ; Afzal et al, 2021 ; Goh et al, 2022 ).…”

“…Schizophrenia is a psychiatric disorder affecting approximately 1% of the world population ( Goh et al, 2022 ). Compared to the general population, individuals with schizophrenia have significant reductions in average life expectancy by 14.5 years; this premature mortality is primarily attributed to physical illness, including type 2 diabetes mellitus and cardiovascular disease ( Papanastasiou, 2013 ; Afzal et al, 2021 ; Goh et al, 2022 ). In addition, a systematic review and meta-analysis by Afzal et al (2021) of 120 studies from 43 countries demonstrated that people with severe mental illness have a drastically higher prevalence and odds of obesity than the general population.…”

Impact of SGLT2 inhibitors on metabolic status in patients with psychiatric disorders undergoing treatment with second‑generation antipsychotics (Review)

“…A systematic review and meta-analysis showed that several pharmacogenetic studies found that single nucleotide polymorphisms in adrenergic α2, dopaminergic D2, serotonergic 5HT2C and melanocortin-4 receptor genes were significantly associated with antipsychotic-related weight gain ( 13 ). Dysregulation of insulin, cortisol, glucagon, cholecystokinin, adiponectin, ghrelin, leptin, orexin, prolactin and oxytocin has also been reported during treatment with antipsychotic agents ( 14 , 15 ). The possible impairment of the mitochondrial dynamics in the pathogenesis of metabolic syndrome in patients undergoing antipsychotic treatment has been suggested, although data to support this hypothesis are still insufficient ( 16 ).…”

Association between Insertion-Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene and Treatment Response to Antipsychotic Medications: A Study of Antipsychotic-Naïve First-Episode Psychosis Patients and Nonadherent Chronic Psychosis Patients

“…We also investigated whether ACE-I/D polymorphism might influence plasma lipid and glucose levels among schizophrenia patients receiving antipsychotic treatment [ 14 ]. Schizophrenia patients (specifically those taking antipsychotic medication) are more likely to exhibit weight gain, lipid disturbance, and glucose dysregulation, which makes them an interesting group in which to study the genetic basis of dyslipidemia and diabetes [ 15 , 16 ]. Furthermore, among individuals from the general population, ACE-I/D polymorphism has been extensively linked to dyslipidemia, diabetes, and metabolic syndrome [ 17 , 18 , 19 , 20 ].…”