Molecular mechanisms underlying major depressive disorder and post-stroke affective disorders

Two of the most common and incapacitating mental health disorders around the world are major depressive disorder (MDD) and post-stroke depression (PSD). MDD is thought to result from abnormal connectivity between the monoaminergic, glutamatergic, GABAergic, and/or cholinergic pathways. Additional factors include the roles of hormonal, immune, ageing, as well as the influence of cellular, molecular, and epigenetics in the development of mood disorders. This complexity of factors has been anticipated by the Swiss psychiatrists Paul Kielholz and Jules Angst who introduced a multimodal treatment of MDD. Depression is the predominant mood disorder, impacting around one-third of individuals who have experienced a stroke. MDD and PSD share common underlying biological mechanisms related to the disruption of monoaminergic pathways. The major contributor to PSD is the stroke lesion location, which can involve the disruption of the serotoninergic, dopaminergic, glutamatergic, GABAergic, or cholinergic pathways. Additionally, various other disorders such as mania, bipolar disorder, anxiety disorder, and apathy might occur post-stroke, although their prevalence is considerably lower. However, there are differences in the onset of MDD among mood disorders. Some mood disorders develop gradually and can persist for a lifetime, potentially culminating in suicide. In contrast, PSD has a rapid onset because of the severe disruption of neural pathways essential for mood behavior caused by the lesion. However, PSD might also spontaneously resolve several months after a stroke, though it is associated with higher mortality. This review also provides a brief overview of the treatments currently available in medical practice.