Concomitant pathologies and their impact on schizophrenia: a narrative overview of current evidence

Schizophrenia is a complex, heterogeneous, and disabling psychiatric disorder that disrupts cognitive, perceptual, and emotional functioning. In over 70% of patients, it is associated with multiple psychiatric and somatic comorbidities that, together with lifestyle and substance abuse, contribute to lower quality of life and reduced life expectancy. Other major psychiatric comorbidities, such as anxiety, depression, and bipolar disorder, often show considerable overlap with schizophrenic symptoms and are difficult to differentiate. The substrate of dementia in older schizophrenics and co-existing Alzheimer disease is a matter of discussion. Other common comorbidities like obsessive-compulsive and personality disorders predominate, while prenatal risk factors such as dysmorphologies, hypoxia, and infections may occur premorbidly or at illness onset. Among somatic comorbidities, cardiovascular and cerebrovascular diseases, metabolic syndrome, and diabetes are most frequent and show some genetic overlap with schizophrenia. Clinical and research interests in the co-occurring issues of schizophrenia are caused by the presence of multiple coexisting psychopathologies as well as comorbid medical conditions that may increase mortality. Current evidence suggests involvement of multiple neurotransmitter systems (dopaminergic, glutamatergic, and GABAergic), prefrontal cortical involvement, and corticostriate-thalamo-cortical circuit dysfunctions in the pathogenesis of both schizophrenia and many key psychiatric comorbidities, while the evidence implicating biological pathways affecting both body and brain is increasing for most somatic comorbidities. Although environmental bias increases throughout the disease course, the pathogenic factors for the majority of concurrent pathologies and their clinical implications warrant further attention.