Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The biological mechanisms proposed to underlie primary mood disorder do not usually include a neuropathological component. However, a significant MRI literature attests to structural abnormalities in regions and has encouraged neuropathological investigations from which candidate histological correlates have begun to emerge. In particular, there are several reports of cytoarchitectural alterations in anterior cingulate and prefrontal cortices, characterized by a decrease in the number or density of glia. Reductions in the size and density of some neuronal populations have also been described, accompanied by alterations in indices of synaptic terminals and dendrites. This form of pathology putatively reflects aberrant neurodevelopment or impaired cellular plasticity. A separate pathological process is suggested by the excess of subcortical focal lesions seen on MRI, especially in elderly patients; these probably reflect white matter damage of vascular origin. Both types of pathology have been observed, to a greater or lesser extent, in unipolar as well as bipolar mood disorders. None of the findings appear attributable to treatment with antidepressants, mood stabilizers or electroconvulsive therapy (ECT). However, all findings remain preliminary due to a lack of unequivocal replication and the failure to control fully for other potential confounders and co-morbid conditions. There are also basic questions to be answered concerning the clinical correlates, magnitude, progression and heterogeneity of the pathology. Nevertheless, it must now be considered likely that changes in brain structure, both macroscopic and microscopic, are a feature of primary mood disorder, a fact to be taken into account when interpreting functional imaging, neuropsychological and neurochemical data. The neuropathology is postulated to contribute to the pathophysiology and dysfunction of the neural circuits which regulate mood and its associated cognitions, behaviours and somatic symptoms.


Journal article



Publication Date





1428 - 1449


Brain, Brain Stem, Electroshock, Frontal Lobe, Hippocampus, Humans, Lithium, Mood Disorders