SCHIZOPHRENIA COMORBIDITIES AND PATHOPHYSIOLOGY
Not an actual patient.
Common physical comorbidities and behavioral risk factors in schizophrenia
Dysregulation of neural systems in schizophrenia has been hypothesized to result in behavioral risk factors that may contribute to a range of comorbidities.1
Pathophysiology of schizophrenia may involve dysfunction across several neurotransmitter systems
Historically, core symptoms of schizophrenia have been attributed to dysregulation of the dopaminergic system, but others have also been implicated. Neurotransmitters proposed to play a role in schizophrenia pathophysiology include, but are not limited to, dopamine, glutamate, serotonin, acetylcholine, and γ-amino-butyric acid (GABA).11-13
Two prominent hypotheses of schizophrenia pathophysiology are the revised dopamine hypothesis and the N-methyl-d-aspartate (NMDA) hypothesis.
Dopamine hypothesis of schizophrenia11,12
in the mesolimbic
regions of the brain
the prefrontal cortex
NMDA hypothesis of schizophrenia13,14
& cognitive impairment
Schizophrenia may involve dysfunction across several systems
In addition to dysfunction of the central nervous system (CNS), schizophrenia may involve cardiometabolic disturbance, immune system disturbance, and endocrine disturbances. This was observed in a systematic meta-review from 165 case-control studies, including 6 studies of first-episode, antipsychotic-naive patients with schizophrenia.15
Dysregulation across these systems has been observed in several additional studies of patients with schizophrenia:
Reduced adiponectin levels have been observed in patients with schizophrenia.16
- Adiponectin, an adipokine hormone produced primarily by fat cells in adipose tissue, makes tissues more sensitive to insulin, while low levels of adiponectin are associated with insulin resistance, as reported in reviews from 2003, 2012, and 2017.16-18 Several studies have shown an association between low serum adiponectin levels and insulin resistance, type 2 diabetes, and cardiovascular disease in humans19
- The association between adiponectin and antipsychotic-naive schizophrenia is still unclear. Lower serum adiponectin levels have been detected in this subpopulation compared with healthy controls16,20
- Lower adiponectin levels have also been observed in antipsychotic-prescribed patients with schizophrenia16,20
Elevated blood cytokine levels have been observed in antipsychotic-naive first-episode patients with schizophrenia, according to a 2018 systematic meta-review from 165 case-control studies, including 4 studies that examined immune profile in antipsychotic-naive patients.15
- Elevated pro-inflammatory cytokines have been differentially associated with regional brain volume alterations, although correlations are inconsistent and further studies are required to clarify these alterations in the context of systemic inflammation in first-episode psychosis15
- Adipose tissue also releases pro-inflammatory cytokines (IL-6 and TNF-α), which may contribute to insulin resistance,21 and antipsychotic-naive patients with schizophrenia who have higher BMI have been observed to have increased levels of C-reactive protein, a biomarker of inflammation directly modulated by IL-622
A 2016 meta-analysis of 208 antipsychotic-naive patients, including patients with schizophrenia, reported elevated prolactin levels in male and female patients compared with matched controls.23
- Prolactin is a polypeptide hormone secreted from the anterior pituitary gland. It is believed that prolonged elevations in prolactin may be associated with certain health effects, including amenorrhea, galactorrhea, osteoporosis, low libido, erectile dysfunction, and breast cancer, as reported in a 2016 study23
- Prolactin release may be increased in response to stress and be associated with HPA activity15,23
BMI=body mass index; IL-6=interleukin six; TNF-α=tumor necrosis factor alpha.
Stay informed on Keep the Body in Mind
Continue to receive information on the pathophysiology of and comorbidities associated with bipolar disorder or schizophrenia from KEEP THE BODY IN MIND.