Overlapping mechanisms linking insulin resistance with cognition and neuroprogression in bipolar disorder

Cognitive impairment is highly prevalent in the progression of both diabetes mellitus and bipolar disorder. The relationship between insulin resistance in diabetes and the risk of developing major neurocognitive disorders such as Alzheimer’s disease has been well described. Insulin resistance and the associated metabolic deficiencies lead to biochemical alteration which hasten neurodegeneration and subsequent cognitive impairment. For bipolar disorder, some patients experience a cyclical, yet progressive course of illness. These patients are also more likely to have medical comorbidities such as cardiovascular disease and diabetes, and insulin resistance in particular may precede the neuroprogressive course. Diabetes and bipolar disorder share epidemiological, biochemical, and structural signatures, as well as cognitive impairment within similar domains, suggesting a common mechanism between the two conditions. Here we describe the association between insulin resistance and cognitive changes in bipolar disorder, as well as potential implications for therapeutic modulation of neuroprogression.