Volumetric changes in subcortical structures following repeated ketamine treatment in patients with major depressive disorder: a longitudinal analysis

Abstract

Abnormal subcortical structures have been associated with major depressive disorder (MDD) and could be reversed by antidepressant treatment. To date no study has examined the relationship between subcortical volumes and repeated ketamine treatment. The current study investigated volume changes in specific subcortical structures and hippocampal subfields after six ketamine infusions. Forty-four patients with MDD received six subanesthetic dose infusions of ketamine. Depressive symptoms were assessed and magnetic resonance imaging scans were performed before and after six ketamine infusions. FreeSurfer software was used to process the T1 images and analyze the volumes of the subcortical regions and hippocampal subfields. After six ketamine infusions, increases were observed in the volumes of the left amygdala; the right hippocampus; the cornu ammonis 4 body, granule cell and molecular layer of the dentate gyrus body in the left hippocampus; and the cornu ammonis 4 head and molecular layer head in the right hippocampus. Positive correlations were found between symptom improvement and the pretreatment volumes of the right thalamus (r = 0.501; P = 0.001) and left subiculum head of the hippocampus (r = 0.471; P = 0.002), and changes in the volumes of the left amygdala (r = −0.452; P = 0.003) and the left cornu ammonis 4 body (r = −0.537; P < 0.001). Our findings provided evidence for critical roles of the amygdala and specific hippocampal subfields in the antidepressant effect of repeated ketamine treatment. Relatively larger volumes in right thalamus and left subiculum head in the hippocampus can predict a superior clinical outcome of ketamine treatment in MDD patients.

An Integrative Approach to Ketamine Therapy May Enhance Multiple Dimensions of Efficacy: Improving Therapeutic Outcomes With Treatment Resistant Depression

“…This process is an elementary component of neuroplasticity (30,84). Research supports the proposition that functional and structural changes at spines and synapses are the basis of learning, memory, and cognitive flexibility (30,85,86).…”

Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia

“…Alternatively, the differences may have arisen due to the heavier use of other drugs in the ketamine users in our study. In contrast, a group studying the effect of intermittent ketamine for treatment of major depressive disorder reported increases in grey matter volume in amygdala and hippocampus (Zhou et al 2020). It is likely that the processes occurring when ketamine is used intermittently for the treatment of depression differ from chronic ketamine use in the setting of dependence or harmful use and may reflect the increases in dendritic spine formation that are hypothesised to underlie the antidepressant effects of ketamine, as supported by data from pre-clinical studies (Li et al 2010).…”

Severe Encephalatrophy and Related Disorders From Long-Term Ketamine Abuse: A Case Report and Literature Review

“…The side-effects of ketamine abuse or misuse (23), except addiction, include neurotoxicity, cognitive dysfunction, adverse events associated with mental status, psychotomimetic effects, uropathy effects, liver-gallbladder effects and cardiovascular events. Research has shown that chronic ketamine use may lead to brain atrophy, particularly during the time of brain development (24,25), and the anti-depressive effects may be associated with increases in brain area volume (20). But to our knowledge, we are the first to report a young adult suffering from severe brain atrophy after long-term abuse of ketamine.…”

“…Ketamine addiction is related to the interference of glutamate neurotransmission, which influences the establishment of the subcortical regions, such as nucleus accumbens, which is associated with addictive behaviours (18). Studies also show that there are specific antidepressant properties of glutamatergic medications targeting NMDA receptors (19,20) and effective reduction of suicidal ideation (5). Furthermore, a small dose of ketamine can relieve pain in advanced tumour patients (14,21,22), but side effects must be considered.…”