title: Schizophrenia as a disorder of too little dopamine: implications for symptoms and treatment.
abstract: Antipsychotics represent the first effective therapy for schizophrenia, with their benefits linked to dopamine D2 blockade. Schizophrenia was soon identified as a hyperdopaminergic disorder, and antipsychotics proved to be reasonably effective in controlling positive symptoms. However, over the years, schizophrenia has been reconceptualized more broadly, now defined as a heterogeneous disorder with multiple symptom domains. Negative and cognitive features, not particularly responsive to antipsychotic therapy, have taken on increased importance--current thinking suggests that these domains predate the onset of positive symptoms and are more closely tied to functional outcome. That they are better understood in the context of decreased dopamine activity suggests that schizophrenia may fundamentally represent a hypodopaminergic disorder. This shift in thinking has important theoretical implications from the standpoint of etiology and pathophysiology, but also clinically in terms of treatment and drug development.
authors.affiliation: University of Toronto, Toronto, Ontario, Canada. gary_remington@camh.net
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.forename: Ofer
authors.initials: O
authors.lastname: Agid
authors.forename: George
authors.initials: G
authors.lastname: Foussias
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D014150:Antipsychotic Agents; D004298:Dopamine