Methods and compositions are disclosed to treat neuropsychiatric disorders based upon a new framework of diagnosis. Axis I biomarkers include genes related to prefrontal dopamine synthesis and/or dopamine degradation. Axis II includes genes related to re uptake of dopamine, norepinephrine and serotonin and autonomic hyperactivity. Axis III includes genes relates to impairments in inflammatory pathways, glutamate neurotransmission and/or neurotrophic factors. Axis IV includes genes related to glutamate reuptake and predisposition to addictive behavior, and obsessive compulsions.