title: Antipsychotic medications: linking receptor antagonism to neuropsychological functioning in first episode psychosis.
abstract: Antipsychotic medications can contribute to neurocognitive and motor impairments, but specific links to individualized pharmacological treatment regimens are unclear. In 68 participants with stabilized first-episode psychosis (FEP), we investigated the links between neuropsychological functions and an established anticholinergic potency index and a new D(2) antagonist potency index developed in our lab. Each participant's psychiatric medication regimen was converted into estimated receptor antagonist loads based upon specific medication dosage(s) and reported in vitro brain muscarinic cholinergic and D(2) receptor antagonism. In addition to the global neuropsychological impairments of FEP participants, the findings supported the hypothesized links between receptor antagonist loads and specific deficits. Higher anticholinergic load was associated with poorer delayed verbal memory but was not related to motor functioning. In contrast, higher D(2) load was associated with poorer motor functioning but not verbal memory. These selective antagonist load associations explained 19% of the variance in motor functioning and 17% of the variance in delayed verbal memory. Evidently, some of the neuropsychological impairments found in persons with FEP are selectively related to the specific pharmacodynamics and the dosing of their medication regimens. Moreover, these effects can be readily estimated from practical and inexpensive indices.
authors.affiliation: Department of Psychology, Simon Fraser University, Burnaby, British Columbia.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Baitz
authors.forename: Allen E
authors.initials: AE
authors.lastname: Thornton
authors.forename: Ric M
authors.initials: RM
authors.lastname: Procyshyn
authors.forename: Geoffrey N
authors.initials: GN
authors.lastname: Smith
authors.forename: G William
authors.initials: GW
authors.lastname: MacEwan
authors.forename: Lili C
authors.initials: LC
authors.lastname: Kopala
authors.forename: Alasdair M
authors.initials: AM
authors.lastname: Barr
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Lang
authors.forename: William G
authors.initials: WG
authors.lastname: Honer
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001288:Attention / Q000502:physiology; D003071:Cognition / Q000502:physiology; D003627:Data Interpretation, Statistical; D039721:Diagnostic and Statistical Manual of Mental Disorders; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000523:psychology; D008570:Memory, Short-Term / Q000502:physiology; D001523:Mental Disorders / Q000188:drug therapy / Q000523:psychology; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000502:physiology; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000523:psychology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2