Shared neurobiological pathways between type 2 diabetes and depressive symptoms: a review of morphological and neurocognitive findings.

Type 2 diabetes (T2D) patients are twice as likely to experience depressive symptoms than people without T2D, resulting in greater economic burden, worse clinical outcomes, and reduced quality of life. Several overlapping pathophysiological processes including hypothalamic-pituitary-adrenal axis hyperactivity, sympathetic nervous system activation, and elevated pro-inflammatory biomarkers are recognized as playing a role between T2D and depressive symptoms. However, other neurobiological mechanisms that may help to further link these comorbidities have not been extensively reviewed. Reduced neuroplasticity in brain regions sensitive to stress (e.g., hippocampus) may be associated with T2D and depressive symptoms. T2D patients demonstrate reduced neuroplasticity including morphological/volumetric abnormalities and subsequent neurocognitive deficits, similar to those reported by patients with depressive symptoms. This review aims to summarize recent studies on morphological/volumetric abnormalities in T2D and correlated neurocognitive deficits. Modifying factors that contribute to reduced neuroplasticity will also be discussed. Integrating reduced neuroplasticity with other biological correlates of T2D and depressive symptoms could enhance future therapeutic interventions and further disentangle the bidirectional associations between these comorbidities.