Cognitive impairments are a core feature of several neuropsychiatric disorders. A common biomarker for pro-cognitive effects may provide a much-needed tool to select amongst candidate treatments targeting cognition. The hippocampus is a promising biomarker for target-engagement due to the illness-associated morphological hippocampal changes across unipolar disorder (UD), bipolar disorder (BD) and schizophrenia (SCZ). Following the PRISMA guidelines, we searched PubMed and Embase, for clinical trials targeting cognition across neuropsychiatric disorders, with longitudinal structural magnetic resonance imaging (MRI) measures of the hippocampus. Five randomized and three open-label trials were included. Hippocampal volume increases were associated with treatment-related cognitive improvement following treatment with erythropoietin across UD, BD and SCZ, lithium treatment in BD and aerobic exercise in SCZ. Conversely, an exercise intervention in UD showed no effect on hippocampal volume or cognition. Together, these observations point to hippocampal volume change as a putative biomarker-model for cognitive improvement. Future cognition trials are encouraged to include MRI assessments pre- and post-treatment to assess the validity of hippocampal changes as a biomarker for pro-cognitive effects.
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