Cyclin-dependent kinase-5 and p35/p25 activators in schizophrenia and major depression prefrontal cortex: basal contents and effects of psychotropic medications

Cyclin-dependent kinase-5 (CDK5) and p35/p25 activators, interacting with the exocytotic machinery (e. g. munc18-1 and syntaxin-1A), play critical roles in neurosecretion. The basal status of CDK5/p35/p25 and the effect of psychotropic drugs (detected in blood/urine samples) were investigated in post-mortem prefrontal cortex (PFC)/Brodmann's area 9 of schizophrenia (SZ) and major depression (MD) subjects. In SZ (all subjects, n=24), CDK5 and p35, but not p25, were reduced (-28 to -58%) compared to controls. In SZ antipsychotic-free (n=12), activator p35 was decreased (-52%). In SZ antipsychotic-treated (n=12), marked reductions of CDK5 (-47%), p35 (-76%) and p25 (-36%) were quantified. In MD (n=13), including antidepressant-free/treated subgroups, CDK5, p35 and p25 were unaltered. In SZ (n=24), CDK5, p35 or p25 correlated with munc18-1a, but not with syntaxin-1A. The results demonstrate reduced p35 basal content and down-regulation of CDK5/p35/p25 by antipsychotics in SZ. The suggested CDK5/munc18-1a functional interaction may lead to dysregulated neurosecretion in SZ PFC.