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Brain-Metabolic Crossroads in Severe Mental Disorders – Focus on Metabolic Syndrome

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Highly replicated evidence shows that mental illnesses are strongly associated with metabolic syndrome. Patients with schizophrenia or bipolar disorder are more frequently affected with metabolic syndrome than the general population. Metabolic syndrome and resulting cardiovascular deaths are among the ...

Highly replicated evidence shows that mental illnesses are strongly associated with metabolic syndrome. Patients with schizophrenia or bipolar disorder are more frequently affected with metabolic syndrome than the general population. Metabolic syndrome and resulting cardiovascular deaths are among the strongest contributors to increased mortality in psychiatric disorders. The comorbidity between mental illnesses and metabolic syndrome is only partially due to pharmacological treatment, as it is found already in young, drug-naïve patients and in those at risk for the illness.

Cognitive impairment, especially in the domains of attention, processing speed, working and verbal memory, executive functions, is typically present in patients with severe mental illnesses such as schizophrenia or bipolar disorders. Patients with metabolic syndrome appear to display cognitive impairments similar to those found in major psychiatric disorders and are at an increased risk for accelerated aging and dementia. Consequently, it is not surprising that metabolic syndrome and cognitive impairments seem to frequently co-occur in patients with severe mental illness. There is a number of mechanisms through which the metabolic syndrome might affect the brain, including insulin resistance, obesity, inflammation.

Insulin resistance, a key feature of metabolic syndrome, may play a particularly important role. Insulin acts not only peripherally but also contributes to memory formation and brain plasticity. Indeed, both type 2 diabetes and insulin-resistance are associated with specific cognitive impairment in memory, processing speed and executive functions and with reduced hippocampal volume. Peripheral insulin-resistance was also associated with poor psychiatric outcomes in bipolar disorders, resistance to treatment with lithium salts, and with greater severity of positive symptoms in schizophrenia. Several studies reported beneficial effects of intra-nasal insulin administration on verbal and working memory, and there is evidence that rosiglitazone, liraglutide, and to some extent metformin independently improve cognitive function in mice models and possibly also in humans.

Abdominal obesity, one of the most common features of metabolic syndrome, has pathoplastic effects on psychiatric morbidity and negative effects on brain structure and function. One of the main reasons for this may be the presence of systemic, low grade inflammation, which is often found in obesity or metabolic syndrome. Patients with metabolic syndrome typically demonstrate high levels of inflammatory markers, such as IL-1, IL-6, TNF-alpha, IL-1b and hs-CRP. Inflammation is associated with cognitive impairment in several cognitive domains, including working memory, processing speed, both in bipolar disorders and schizophrenia.

In light of these potentially translational findings, we intend to collect papers investigating the complex interplay between the metabolic syndrome, severe mental disorders and brain/cognitive/psychopathological outcomes. Submitted manuscripts should be either original research reports, conducted on animal models or human subjects, or review articles.


Keywords: insulin-resistance, inflammation, severe mental illness, Metabolic syndrome, cognitive


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