Where in the Brain Is Depression?

Abstract

Major Depressive Disorder is a serious medical illness which is responsible for considerable morbidity and disability. Despite decades of research, the neural basis for depression is still incompletely understood. In this review, evidence from neuroimaging, neuropsychiatric and brain stimulations studies are explored to answer the question regarding the localization of depression in the brain. Neuroimaging studies indicate that although many regions of the brain have been repeatedly implicated in the pathophysiology of depression, not many consistent findings have been found until present. In recent times, the focus of neuroimaging has shifted from regional brain abnormalities to circuit level connectivity abnormalities. However, connectivity models are inherently more complicated, and the validity of these models remains to be tested. Neuropsychiatric studies of illnesses such as Parkinson’s Disease and stroke provide promising clues regarding areas involved in depression, but again consistent findings are rare. Similarly, stimulation of a variety of brain regions and circuits has been reported as being effective in depression. Therefore, the current knowledge indicates that the pathophysiology of depression may be distributed across many brain regions and circuits. In future studies, this distributed nature of depression needs to be further investigated, primary and secondary areas affected need to be identified, and new paradigms to explain complex mental functions need to be explored.

Cerebral microbleeds and neuropsychiatric symptoms in an elderly Asian cohort

“…The various parts of the brain involved in depression include the cortex (dorsal and medial prefrontal cortex, dorsal and ventral anterior cingulate cortex, orbital frontal cortex and the insula), subcortical limbic regions (amygdala, hippocampus, dorsomedial thalamus) and basal ganglia (striatum) 24. Orbitofrontal circuit lesions lead to personality changes that are characterised by disinhibition 25.…”

Depression: Discrete or Continuous?

“…A prominent difference consists of depressive inhibition being quite resilient to BIS/BAS-relevant stimuli: while a state of high BIS and low BAS can resolve quite rapidly with stimuli favoring high behavioral activation and low behavioral inhibition, as evidenced by the response of seasonal affective disorder (SADS) to bright sunny conditions, depressive inhibition tends to persist [60]. This occurrence suggests that other factors play a major role in depressive inhibition, the contributors including genetic, epigenetic, and neural influences [61,62,63,64]. …”

Biophysical changes in subcortical nuclei: the impact of diabetes and major depression

“…[10][11][12][13] Multiple neuroimaging modalities including structural, functional and microstructural approaches have been used to characterize the integrity of specific circuits in psychiatric disorders. [11][12][13] The neural substrates underlying mood disorders are widely distributed in the brain 14 and connectomicsbased approaches, using diffusion tensor imaging, have identified the default mode network and the cortical-subcortical network as being particularly impaired in a sample of patients with unipolar depression when compared with controls. [15][16][17][18] Magnetization transfer (MT) is a noninvasive magnetic resonance-related approach that permits us to examine the biophysical status of macromolecular proteins in cortical and subcortical regions.…”