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To evaluate the contribution of individual synaptic constituents, all available  in vivo  imaging studies on schizophrenic patients were subjected to a retrospective analysis. For the pool of drug-naïve, drug-free, and acutely medicated patients, major findings were increases in neostriatal dopamine (DA) synthesis and release and decreases in neostriatal DA transporters and D 1  receptors, neostriatal, thalamic, frontal, and parietal D 2  receptors, mesencephalic/pontine and temporal 5-HT 1A  receptors, frontal and temporal HT 2A  and μ-amino butyric acid (GABA) A  receptors. Based on the findings on drug-naïve and drug-free patients, it may be hypothesized that schizophrenia initially is characterized by an impaired mechanism of D 2  autoreceptor and heteroreceptor sensitization leading to sensitization instead of desensitization in response to increased levels of neostriatal DA. Neuroleptic medication blocks neostriatal D 2  autoreceptor and heteroreceptors, reducing neostriatal DA and disinhibiting DA action mediated by D 2  heteroreceptor binding sites. Ultimately, this may result in a restitution of GABA function, leading to a recovery of inhibitory input to the target regions of the descending corticothalamostriatal efferents. Furthermore, a blockade of inhibitory and excitatory neocortical 5-HT function may be inferred, which is likely to reduce (excitatory) DAergic input to the mesolimbic target regions of corticothalamostriatal projections.

Neurochemical dysfunction in treated and nontreated schizophrenia – a retrospective analysis of in vivo imaging studies