The Nature of Dopamine Dysfunction in Schizophrenia and What This Means for Treatment

摘要: Context Current drug treatments for schizophrenia are inadequate many patients, and despite 5 decades of discovery, all the rely on same mechanism: dopamine D 2 receptor blockade. Understanding pathophysiology disorder is thus likely to be critical rational development new schizophrenia. Objective To investigate nature dopaminergic dysfunction in using meta-analysis vivo studies. Data Sources The MEDLINE, EMBASE, PsycINFO databases were searched studies from January 1, 1960, July 2011. Study Selection A total 44 identified that compared 618 patients with 606 controls, positron emission tomography or single-photon computed measure striatal function. Extraction Demographic, clinical, imaging variables extracted each study, effect sizes determined measures Studies grouped into those presynaptic function transporter availability. Sensitivity analyses conducted explore consistency effects clinical variables. Synthesis There was a highly significant elevation (P  2/3 availability (Cohen d = 0.26), but this not evident drug-naive influenced by approach used. Conclusions locus largest abnormality presynaptic, which affects synthesis capacity, baseline synaptic levels, release. treatments, primarily act at receptors, fail target these abnormalities. Future should focus control release capacity.