Genetic factors in the response to neuroleptics in schizophrenia: a psychopharmacogenetic study

Abstract

SynopsisA psychopharmacogenetic strategy was used to investigate a genetic heterogeneity model of schizophrenia. This model consisted of various genetic subtypes represented by patients classified hypothetically according to the types and genealogical (Mendelian) patterns of illnesses in first-degree relatives. The effect of neuroleptics on these subtypes (drug x genetic subtype interactions) were tested for evidence of post-treatment responses which discriminated between them. The findings revealed that schizophrenics who had depressed relatives tended to exhibit (1) depression and more severe pseudoparkinsonism irrespective of types of neuroleptics, and (2) greater remission of paranoid-hostility symptoms when treated with neuroleptics of the aliphatic-piperadine type. Schizophrenics who had schizophrenic relatives failed to show these responses.Interpretation of these findings emphasized the recognition of these responses as arising from neuroleptic-induced alterations of defective neurologic-neurochemical systems underlying this subtype and as ‘pharmacogenetic criteria’ by which it can be discriminated.

Antidepressive therapy in depressed clinical suicides

“…On the one hand, some neuroleptics, e.g. thioridazine, may have antidepressive effects (32); on the other, neuroleptics have been accused of causing depression (33). There is no doubt that the issue of pharmacogenic neuroleptic-induced depression currently remains controversial (34).…”

Depression in Schizophrenia: Perspective in the Era of “Atypical” Antipsychotic Agents

“…Therefore, dopamine blockade by a neuroleptic drug could theoretically lead to anhedonia and, perhaps, depression. Indeed, a state of dysphoria is commonly described by neuroleptic-treated patients (34), a number of older anecdotal reports have suggested a link between neuroleptic use and depression (35)(36)(37)(38)(39), and one study found more anhedonia and depression in maintenance-phase schizophrenic patients who were taking neuroleptics than in others who were not (33). Another study found a positive relationship between haloperidol plasma levels and depressive symptoms in the context of a positive association between extrapyramidal symptoms and depressive symptoms (40), and impairments of quality of life related to neuroleptic-induced dysphoria have been reported (41).…”

Depressive Signs and Symptoms in Schizophrenia

“…Although DSS are described in neuroleptic-naive schizophrenic patients having a first episode, 9 patients receiving conventional antipsychotic drugs may have higher rates. 39,40 Several lines of evidence suggest that neurolepticinduced dysphoria may not encompass full criteria for a depressive disorder, 41 but nonetheless may adversely affect functional well-being. 42,43 In our investigation, the absence of a placebo arm prevented the determination of the disease-associated base rate of treatmentemergent DSS.…”