Post‐stroke depression: mechanisms, translation and therapy

Abstract

The interaction between depression and stroke is highly complex. Post-stroke depression (PSD) is among the most frequent neuropsychiatric consequences of stroke. Depression also negatively impacts stroke outcome with increased morbidity, mortality and poorer functional recovery. Antidepressants such as the commonly prescribed selective serotonin reuptake inhibitors improve stroke outcome, an effect that may extend far beyond depression, e.g., to motor recovery. The main biological theory of PSD is the amine hypothesis. Conceivably, ischaemic lesions interrupt the projections ascending from midbrain and brainstem, leading to a decreased bioavailability of the biogenic amines – serotonin (5HT), dopamine (DA) and norepinephrine (NE). Acetylcholine would also be involved. So far, preclinical and translational research on PSD is largely lacking. The implementation and characterization of suitable animal models is clearly a major prerequisite for deeper insights into the biological basis of post-stroke mood disturbances. Equally importantly, experimental models may also pave the way for the discovery of novel therapeutic targets. If we cannot prevent stroke, we shall try to limit its long-term consequences. This review therefore presents animal models of PSD and summarizes potential underlying mechanisms including genomic signatures, neurotransmitter and neurotrophin signalling, hippocampal neurogenesis, cellular plasticity in the ischaemic lesion, secondary degenerative changes, activation of the hypothalamo-pituitary-adrenal (HPA) axis and neuroinflammation. As stroke is a disease of the elderly, great clinical benefit may especially accrue from deciphering and targeting basic mechanisms underlying PSD in aged animals.

Poststroke Depression: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

“…12,17,18 Fourth, poststroke depressive-like symptoms have been noted in several animal models. 19,20 Last, depression has been reported after transient ischemic attack and minor stroke (National Institutes of Health Stroke Scale score ≤5 at discharge). 21,22 Proposed biological factors contributing to PSD include lesion location, genetic susceptibility, inflammation, PSD and functional outcomes PSD is associated with poorer functional outcomes after stroke.…”

Effect of Fluoxetine on Motor Improvement in Ischemic Stroke Patients: A Double Blind Clinical Trial Study

“…In the acute phase of recovery, post-stroke depression can impress functional recovery of physical therapy outcome in short-term and long-term and initiation of antidepressant drugs as soon as possible after stroke may preclude the appearance of post-stroke depression [1][2][3]. Selective serotonin reuptake inhibitors (SSRIs) have been prescribed for many years to treat post-stroke depression [1,2]. Good functional recovery has been reported with prescription of antidepressant drugs in some studies [1][2][3][5][6][7].…”

“…Selective serotonin reuptake inhibitors (SSRIs) have been prescribed for many years to treat post-stroke depression [1,2]. Good functional recovery has been reported with prescription of antidepressant drugs in some studies [1][2][3][5][6][7]. Furthermore SSRIs may be effective in post-stroke emotional incontinence [3,4].…”

“…Recently, the increasing amount of remaining impairments and disabilities has focused concern in interpolations that might precipitate rehabilitation [3,4]. In the acute phase of recovery, post-stroke depression can impress functional recovery of physical therapy outcome in short-term and long-term and initiation of antidepressant drugs as soon as possible after stroke may preclude the appearance of post-stroke depression [1][2][3]. Selective serotonin reuptake inhibitors (SSRIs) have been prescribed for many years to treat post-stroke depression [1,2].…”

“…According to the WHO report in the year 2004 it causes significant physical, emotional and cognitive disabilities among survivors, accounting for 3.6% of the total disability-adjusted life years [1][2][3]. Few patients will recover completely (10%) and some of them die shortly after the stroke (15%), therefore a lot of patients recover with any impairment or need to home nursing [1,2]. Recently, the increasing amount of remaining impairments and disabilities has focused concern in interpolations that might precipitate rehabilitation [3,4].…”