Table 1 Brain region involved in Major Depressive Disorder (MDD).
REGION | ROLE | ALTERATIONS DETECTED IN NEUROIMAGING STUDIES | CLINICAL CORRELATIONS |
|---|---|---|---|
Frontal lobea | -The ACC has an anatomical connection with dorsal neocortical and ventral paralimbic regions and plays a role in cognitive processes and mood regulation -The OFC is involved in inhibiting background-independent, redundant, or uncomfortable neural activity, feelings, and behaviours and also plays a crucial role in emotional/motivational management and decision making -The DLPFC plays an essential role in emotional, motivational, attentional, and executive functions | -Decreased magnetization transfer ratio in the right ACC in patients with treatment-refractory MDD, which increased after electroconvulsive therapy -Reduction in thickness of prefrontal areas are associated with poor clinical outcomes -The ACC has increased functional correlations with the DLPFC and the amygdala in MDD patients - Structural (reduced thickness of the right medial orbital cortex, and during treatment increased cortical thickness in the OFC in MDD patients) and functional changes (reduced brain activity) in the bilateral OFC may contribute to the reduced inhibition of negative stimuli in depressive patients -The volume of grey matter in the left middle frontal gyrus was found to be decreased in untreated depressive patients and to increase after drug treatment (and associated with emotional bias, apathy, and loss of motivation) -Reduced grey matter volume and brain activity in the DLPFC of depressed patients; they could be increased to the average level after antidepressant treatment | -The fibres in the medial frontal cortex are part of the DMN and play an essential role in the execution of long-term mental plans from immediate environmental or internal demands -Transcranial magnetic stimulation of the left DLPFC induces morphological increases in the left ACC and the middle frontal OFC, indicating that the DLPFC has connections with the ACC and the OFC |
Hippocampus | -It is associated with memory recall and the rules of reward | -Volume reduction in depressed patients; on the other side, after antidepressant treatment and electroconvulsive therapy an increased grey matter volume in the hippocampus in MDD patients were found -Reduced volume of hippocampus may be associated with illness duration in MDD -Reduced functional activity in the hippocampus would lead to negative emotion and the inability of cognitive processing in depressive patients | -Stress via the hypothalamic-pituitary-adrenal axis can result in elevated glucocorticoid levels in patients with MDD and can act on the glucocorticoid receptors in the hippocampus, resulting in its atrophy, while increased hippocampal volume was associated with clinical improvement |
Parietal lobe | -Parietal lobe is involved in the organization, decision making, and predictions of rewards during conditioning that evaluates outcomes for future response choices that are uncertain. It is also related to emotional processing and cognitive changes and is part of the DMNb which has a functional connection with the caudate via dopaminergic projections (striatal dopaminergic circuits may regulate cognition and emotion by modulating the DMN in MDD) | -Increased cortical thickness in the left inferior parietal gyrus and in the left superior parietal lobule and increased grey matter volume in the right postcentral gyrus in MDD patients | -Increased thickness and correlations indicate compensatory mechanisms associated with inflammation or other aspects of the pathophysiology of depression |
Striatuma (basal ganglia): it contains the putamen, the caudate, and the VST | -Putamen plays a key role in mood, cognitive processes, motivation, and regulation of movement - The caudate nucleus is a critical component of the reward system in the brain | -Decreased grey matter intensity in the VST -Decreased volume of the bilateral putamen in MDD patients -Reduced volume and activity of the caudate in MDD patients | -Disruptions in striatal output may lead to impulsive and suicidal behaviour -Striatal activity plays an essential role in disease progression: it is reduced in reward system defects, and decreased reward network connections were found to be associated with depression severity -Dysfunction of the caudate nucleus may lead to a disruption in dopaminergic signalling in MDD patients, explaining the core features of depression or even the lack of responsiveness to positive stimuli or reward constituents |
Thalamusa: the subthalamic nuclei accept fibres from the pallidum and motor cortex and send out fibres to the substantia nigra. The lateral dorsal thalamic nucleus sends out fibres to the parietal lobe, and the ventral lateral thalamic nucleus has connections with the cerebellum and the brainstem. | -It is considered a complicated sensory information node that controls emotion, memory, and arousal | -Volume reductions and changes in shape in the both the right and left thalamus of patients with MDD | -Dysfunction and structural disruptions in the thalamus can lead to an amnestic syndrome due to impairments in recall and recognition -As the anterior thalamic nuclei form a key region involved in emotional regulation, the decreased functional activity in these regions in MDD might contribute to emotional deregulation and could be a target for diagnostic assessments and therapies |
