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Major Depressive Disorder - Brain Regions and their Dysfunctions


"Mood abnormalities related to major depressive disorder (MDD) seem to result from disturbances in pathways connecting the fronto-limbic and subcortical, both regions known to be involved in the processing of emotional information." S
Affected Region Dysfunctions
Insular lobe Right: Lower activation to negative pictures S

Left: Greater activation to negative and lower activity to positive pictures S

Greater activation during successful inhibitory events S
Orbitofrontal Cortex Bilateral inferior OFC: Greater activation to negative pictures S

Bilateral inferior and medial OFC: Lower activation to pictures of sad faces S
Ventromedial PFC Lack of engagement of left lateral-ventromedial prefrontal circuitry important for the downregulation of amygdala responses to negative stimuli S
Dorsolateral PFC Bilateral: Lower activation to pictures of sad faces S
Temporal lobe Frontal and anterior temporal areas: Greater activation during correct rejections (inhibition) S
Hippocampus Right: Lower activation to negative affective pictures S

Bilateral: Lower activation to pictures of sad faces S
Dentate gyrus Inhibition of neurogenesis in the DG due to stress (via the release of glucocorticoids and activation of the sympathetic division of the ANS) may lead to a failure to modulate symptoms of stress and depression S, S, S

Dysregulation of synaptic consolidation (BDNF synthesis and Arc function) is linked to behavioral symptoms and cognitive deficits in animal models of depression S
Amygdala Left: Greater activation to sad faces and negative pictures S,

greater activation during successful inhibitory events S
Anterior Cingulate Cortex Right: Lower activation to positive pictures S

Rostral: Greater activation during unsuccessful inhibition (commission errors) S

Subgenual cingulate (Brodmann area 25) is metabolically overactive in treatment-resistant depression S and might benefit most from deep brain stimulation S
Striatum Greater activation to expressions of happiness S

Dysfunctional connections of the basal ganglia with the limbic system might contribute to depression S

Striatal (learning) deficit in depression S
Caudate nucleus Bilateral: Lower activation to pictures of sad faces S

Left: accelerated membrane turnover and impaired metabolism S
Globus pallidus Bilateral lesions might cause anhedonia and a loss of drug cravings S
Nucleus accumbens Greater activation during successful inhibitory events S

Dysfunctions might be responsible for impaired reward processing, as evidenced by anhedonia, and patients with refractory major depression might benefit from deep brain stimulation of the nucleus accumbens S
Hypothalamus, Pituitary, HPA axis Mediates the stress response (and with it depression) via CRH neuron activity in the hypothalamus (PVN) and the subsequent ACTH release from the pituitary followed by a cortisol release from the adrenal cortex S
Posterior pituitary AVP and oxytocin, originating from the hypothalamic-neurohypophysial system (HNS), might directly affect HPA axis activity and therefore contribute to stress and depression S, S
Periaqueductal gray Elevated 5-HTT binding-potential in the vicinity of the periaqueductal gray S
Locus caeruleus "The parallel engagement of the locus coeruleus-norepinephrine system with the HPA axis serves to coordinate endocrine and cognitive limbs of the stress response." S

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