The Neurobiological Pathogenesis of Poststroke Depression

Abstract

Poststroke depression (PSD) is an important consequence after stroke, with negative impact on stroke outcome. The pathogenesis of PSD is complicated, with some special neurobiological mechanism, which mainly involves neuroanatomical, neuron, and biochemical factors and neurogenesis which interact in complex ways. Abundant studies suggested that large lesions in critical areas such as left frontal lobe and basal ganglia or accumulation of silent cerebral lesions might interrupt the pathways of monoamines or relevant pathways of mood control, thus leading to depression. Activation of immune system after stroke produces more cytokines which increase glutamate excitotoxicity, results in more cell deaths of critical areas and enlargement of infarctions, and, together with hypercortisolism induced by stress or inflammation after stroke which could decrease intracellular serotonin transporters, might be the key biochemical change of PSD. The interaction among cytokines, glucocorticoid, and neurotrophin results in the decrease of hippocampal neurogenesis which has been proved to be important for mood control and pharmaceutical effect of selective serotonin reuptake inhibitors and might be another promising pathway to understand the pathogenesis of PSD. In order to reduce the prevalence of PSD and improve the outcome of stroke, more relevant studies are still required to clarify the pathogenesis of PSD.

Efficacy and feasibility of antidepressant treatment in patients with post-stroke depression

“…[1] Patients with PSD usually present with a wide range of symptoms, including apathy, weight changes, sleep disturbances, feelings of worthlessness, and fatigue. [2] It is already well documented that PSD impedes rehabilitation and reduces the quality of life in majority of stroke survivors. [3] However, up to now, the pathophysiological mechanisms of PSD are still not fully illuminated.…”

Sevoflurane prevents stroke‐induced depressive and anxiety behaviors by promoting cannabinoid receptor subtype I‐dependent interaction between β‐arrestin 2 and extracellular signal‐regulated kinases 1/2 in the rat hippocampus

“…Previous studies have suggested that alterations in neurotransmission during and after stroke may contribute to the development of depression (Whyte and Mulsant 2002). To support this hypothesis, studies using animal models of PSD have shown that several brain regions including the hippocampus, frontal cortex, and hypothalamus are critically involved in the development of PSD (Wang et al , 2010bFeng et al 2014;Shao et al 2015). Furthermore, various signaling molecules and neurotransmitters as well as their receptors have been shown to be involved in the development of PSD (Wang et al , 2010bFeng et al 2014;Shao et al 2015).…”

“…To support this hypothesis, studies using animal models of PSD have shown that several brain regions including the hippocampus, frontal cortex, and hypothalamus are critically involved in the development of PSD (Wang et al , 2010bFeng et al 2014;Shao et al 2015). Furthermore, various signaling molecules and neurotransmitters as well as their receptors have been shown to be involved in the development of PSD (Wang et al , 2010bFeng et al 2014;Shao et al 2015). However, few studies have been conducted to investigate the role of cannabinoid receptors in the development of PSD, even though increasing evidence suggests that cannabinoid receptor subtype 1 (i.e., CB1 receptor) is one of the critical substrates underlying the pathogenesis of depression (Aso et al 2011).…”

The factors related to early‐onset depression after first stroke

“…Large infarction may result in severe damage to the critical areas associated with modulating emotional behaviour and biochemical change . According to this hypothesis, cerebral lesions interrupt the projections ascending from the midbrain and brainstem, passing through the thalamus and basal ganglion, and reaching the frontal cortex; this then results in a decrease in the bioavailability of biogenic amines, including serotonin, dopamine, and noradrenaline, and thus in depressive symptoms .…”