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Whereas peaks in steady state levels may be associated with drug adverse effects, troughs may be associated with loss of efficacy

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Epidemiological studies showed that genes contribute to the vulnerability of multiple CNS disorders, such as major depressive disorders (MDD), schizophrenia and substance use disorders with heritability respectively of 3142%, 6480%, and 2379% [10,11,12,13]

There are also preexisting health conditions that can create cause it as well

Bibcode:2015PhRvB..92b0104H

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