Depression Associated with Diabetes: From Pathophysiology to Treatment

Abstract

Diabetes is a chronic and progressive syndrome commonly associated with several neuropsychiatric comorbities, of which depression is the most studied. The prevalence of depression is about two or three times higher in diabetic patients compared to the general population. It is believed that the diabetes - depression relation may be bidirectional, i.e., the depression can lead to diabetes and conversely diabetes could facilitate the emergence of depression. Depression is one of the most neglected symptoms in diabetic patients and is directly linked with lowering of quality of life. The treatment of depression in these patients is still quite ineffective and in many cases treatmentrefractory. Furthermore, some of the first choice drugs used to treat the depression affect the blood glucose control, aggravating the hyperglycemic state. These issues underscore the urgency in studies searching for new pharmacological targets for the treatment of depression associated with diabetes. For this, a better understanding of the pathophysiology that relates this comorbidity becomes critical. In this respect, this review will focus on some hypotheses that have been proposed to explain the mechanisms underlying depression associated with diabetes, highlighting the treatment options currently available and their limitations. Among these hypotheses, we will point out the hyperglycemia as a primary metabolic cause of the depression development, the involvement of the dysregulation of hypothalamic pituitary-adrenal (HPA) axis and of neurotransmitter systems, specially monoaminergic system. Besides, the role of oxidative stress, neuroinflammation and cell death, especially in hippocampus and prefrontal cortex, brain areas important for the mediation and modulation of emotional behavior will also be discussed. Finally, we will bring up the influence of the epigenetic regulation with respect to neuropsychiatric disorders.

Caracterização de pacientes diabéticos tipo 2 em uso recente de insulina: estilo de vida e sintomas depressivos

“…Ainda no que diz respeito aos sintomas depressivos, apresentaram maior prevalência os pacientes que relataram mudança da alimentação após o diagnóstico de DM. Estudos indicam que os sintomas depressivos podem influenciar negativamente na adesão ao tratamento da doença e no controle glicêmico, o que pode ser explicado por sentimentos de ansiedade, medo e dificuldade de aceitação da doença em pacientes que possuem uma doença crônica, principalmente nas fases iniciais onde o paciente terá que se adaptar a mudanças na alimentação e demais práticas de estilo de vida, além de questões fisiológicas e de interação medicamentosa [10,11,17]. Da mesma forma, esse dado sugere que a necessidade de restrição alimentar devido à doença pode desencadear sentimentos de negação e frustração nessa população.…”

Histone Lysine Methylation: A Potential New Treatment Target with Respect to BDNF Gene in Type 2 Diabetic Retinopathy

“…These receptor proteins are induced by BDNF and are essential for protection of the retinal cells. This difference along with epigenetic modification, genetic variations bring to the platform that somewhere BDNF could also be concerned in hypoglycemic agent (insulin) resistance and within the pathological process of T2DR, altering TrKB receptor [37] . A study in animal model demonstrated that during initial stage of T2DR, necrobiosis of retinal ganglion cells (RGCs) occur and at the same time lack of BDNF is associated with retinal neuro-degeneration.…”

The “A to Z” of Managing Type 2 Diabetes in Culturally Diverse Populations

“…The prevalence of depression among patients with diabetes is two to three times higher than in the general population ( 42 ). The diabetes—depression relation is usually bidirectional, with diabetes increasing the likelihood of depression and depression contributing to type 2 diabetes, usually through the presence of a lifestyle leading to obesity as well as through other mechanisms ( 42 ).…”

“…The prevalence of depression among patients with diabetes is two to three times higher than in the general population ( 42 ). The diabetes—depression relation is usually bidirectional, with diabetes increasing the likelihood of depression and depression contributing to type 2 diabetes, usually through the presence of a lifestyle leading to obesity as well as through other mechanisms ( 42 ). It is believed that dysregulation of the hypothalamic pituitary-adrenal axis and of neurotransmitter systems, especially the monoaminergic system, oxidative stress and neuroinflammation may influence this relationship ( 42 ).…”