Molecular and topographic mapping of antipsychotic effects: a meta-analysis of postsynaptic density proteins in animal models with translational implications

We included 81 studies (n = 2542; rodents=2510; monkeys=26), resulting in 226 meta-analyses. Both typical and atypical antipsychotics modulated PSD molecules albeit with different degree due to the drug receptor profile, dose, specific protein detected, brain region, and administration regimen. Haloperidol, amisulpride, and aripiprazole significantly increased PSD protein expression in the striatum. Acute olanzapine increased PSD molecules levels in striatal regions, reducing Arc expression in frontal cortex (SMD [95%CIs]=-2.15 [-2.7;-1.61], p < 0.0001); chronic treatment had opposite effects. Clozapine increased Homer1a levels in dorsal (1.13 [0.41;1.86], p = 0.002) and ventral striatum (1.48 [0.72;2.24], p = 0.0001), and cingulate cortex (2.12 [1.12;3.12], p < 0.0001), as well as increased NMDAR subunits levels in frontal cortex.