Abstract
The recent Global Burden of Disease Study demonstrates how mental disorders such as dementia and depression are a leading source of medical disability in the world. However, in the past decade few compounds have shown truly new mechanisms of action, even fewer represent breakthroughs in efficacy. Genome-wide association studies in neuroscience have yielded little clear-cut drug-target association and have been plagued by a lack of replicability. This situation derives from the heterogeneity of mental disorders and the lack of biomarkers for stratification by their distinct subtypes.
Neuroimaging technologies have the potential to identify the dysfunctional brain circuits and objective neurobiological markers reflecting the underlying pathophysiological process in mental disorders, and can ultimately facilitate the development of personalized treatments. In this lecture, current research findings of structural and functional neuroimaging studies on depressive disorders including our recent fMRI research results will be introduced. In our recent resting fMRI study on the functional connectivity (FC) in patients with depressive disorders, it is suggested that the FC between left dorsolateral prefrontal cortex and posterior cingulate cortex may be a possible biomarker and a target of neuro-feedback treatment for melancholic type of depression.
To refine our understanding of the underlying pathophysiology and provide more reliable markers to guide treatment, instead of seeking for a single clinical or biological measure, a multi-scale, systems biology approach using analysis by artificial intelligence (AI) technology such as machine learning combined with human genetic, molecular and imaging studies is needed. Our recent multi-dimensional analysis can predict poor treatment responders of escitalopram, one of SSRI antidepressants, by co-clustering method of psychological examination, possible blood biomarkers and the FC of resting fMRI which demonstrated the high score of child abuse trauma scale and the high FC between angular gyrus and default mode network.
Finally, the precompetitive public-private partnerships (PPPs) that share data between academic and industry scientists for the development of psychotropic drugs were proposed by the International College of Neuropsychopharmacology (CINP) and followed by the Japanese Society of Neuropsychopharmacology (JSNP). The activity of the JSNP PPPs taskforce team will be also introduced in this lecture.
