Default mode network functional connectivity following treatment with conventional antidepressants and (es)ketamine in major depressive disorder: A systematic review.
Juliana Lima Constantino, Jesca E de Jager, Jasper O Nuninga et al.
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In 30 seconds
This systematic review examined changes in default mode network resting-state functional connectivity (DMN rsFC) after conventional antidepressants or (es)ketamine in people with major depressive disorder, including links with clinical outcomes. Nineteen studies were included: 13 of conventional antidepressants (N = 546) and six of intravenous ketamine (N = 247). Conventional antidepressants were associated with heterogeneous DMN connectivity changes, some related to clinical improvement; ketamine was mostly associated with reduced DMN connectivity, particularly between DMN and limbic regions. Overall, the review suggests largely distinct patterns of DMN modulation, while noting substantial heterogeneity across studies.
Key findings
- The review included 19 studies: 13 of conventional antidepressants (N = 546) and six of intravenous ketamine (N = 247).
- Conventional antidepressants were associated with heterogeneous changes in DMN rsFC, some of which related to clinical improvements.
- Ketamine was mostly associated with reductions in DMN rsFC, particularly in DMN-limbic connectivity.
Why it matters
The review brings together evidence on how different antidepressant approaches relate to brain-network connectivity and clinical outcomes. The contrasting patterns may help frame hypotheses about treatment-related neural mechanisms in major depression, including possible differences between depression populations. However, the findings are not sufficiently consistent to establish a single connectivity signature of response.
What to keep in mind
Interpretation is limited by heterogeneity in study populations, treatment regimens, and timing of assessments.