Patterns of Variation Influencing Antipsychotic Treatment Outcomes in South African First-Episode Schizophrenia Patients

Drögemöller, Britt I.; Niehaus, Dana J.H.; Chiliza, Bonginkosi; Merwe, Lize van der; Asmal, Laila; Malhotra, Anil K.; Wright, Galen E.B.; Emsley, Robin; Warnich, Louise

doi:10.2217/pgs.13.218

Cited by 16 publications

(12 citation statements)

References 33 publications

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“…In initial applications of exome analysis of patients with schizophrenia, Girard et al . sequenced the exomes of 14 trios of schizophrenia and found significantly more nonsense de novo mutations (four of 15 families) than expected (Table ) . On the other hand, Xu et al .…”

Section: Schizophreniamentioning

confidence: 90%

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Whole genome/exome sequencing in mood and psychotic disorders

Kato

2014

Psychiatry Clin Neurosci

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Recent developments in DNA sequencing technologies have allowed for genetic studies using whole genome or exome analysis, and these have been applied in the study of mood and psychotic disorders, including bipolar disorder, depression, schizophrenia, and schizoaffective disorder. In this review, the current situation, recent findings, methodological problems, and future directions of whole genome/ exome analysis studies of these disorders are summarized. Whole genome/exome studies of bipolar disorder have included pedigree analysis and casecontrol studies, demonstrating the role of previously implicated pathways, such as calcium signaling, cyclic adenosine monophosphate response element binding protein (CREB) signaling, and potassium channels. Extensive analysis of trio families and casecontrol studies showed that de novo mutations play a role in the genetic architecture of schizophrenia and indicated that mutations in several molecular pathways, including chromatin regulation, activityregulated cytoskeleton, post-synaptic density, N-methyl-D-aspartate receptor, and targets of fragile X mental retardation protein, are associated with this disorder. Depression is a heterogeneous group of diseases and studies using exome analysis have been conducted to identify rare mutations causing Mendelian diseases that accompany depression. In the near future, clarification of the genetic architecture of bipolar disorder and schizophrenia is expected. Identification of causative mutations using these new technologies will facilitate neurobiological studies of these disorders.

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Section: Schizophreniamentioning

confidence: 90%

“…To identify genetic traits related to responsiveness to antipsychotics, Drogemoller et al . sequenced exomes of 11 patients with first‐episode schizophrenia that was responsive or nonresponsive to antipsychotics.…”

Section: Schizophreniamentioning

confidence: 99%

Whole genome/exome sequencing in mood and psychotic disorders

Kato

2014

Psychiatry Clin Neurosci

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“…These patients formed part of a larger clinical study examining treatment response outcomes, which has been described in further detail previously [21][22][23][24]. In brief, all patients were experiencing their first episode of schizophrenia and received flexible doses of the typical long-acting injectable antipsychotic, flupenthixol decanoate (Fluanxol, Lundbeck, Copenhagen, Denmark), after a washout period of up to 7 days.…”

Section: Discovery Cohortmentioning

confidence: 99%

“…Data from the first 3 months of treatment were utilized for the current study. Extensive demographic and clinical information [including family history of psychiatric illness, history of substance abuse, Social and Occupational Functioning Assessment Scale scores, World Health Organization Quality of Life scores, Premorbid Adjustment Scale scores, Birchwood Insight Scale scores, and Extrapyramidal Symptom Rating Scale scores (described in detail [21][22][23][24] elsewhere)] was also collected for each patient.…”

Section: Discovery Cohortmentioning

confidence: 99%

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The identification of novel genetic variants associated with antipsychotic treatment response outcomes in first-episode schizophrenia patients

Drögemöller

Emsley

Chiliza

et al. 2016

Pharmacogenetics and Genomics

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The use of whole-exome sequencing in a subset of patients from a well-characterized cohort of first-episode schizophrenia patients, for whom longitudinal depot treatment response data were available, allowed for (i) the removal of confounding factors related to treatment progression and compliance and (ii) the identification of two genetic variants that have not been associated previously with antipsychotic treatment response outcomes and whose results were applicable across different classes of antipsychotics. Although the genes that are affected by these variants are involved in pathways that have been related previously to antipsychotic treatment outcomes, the identification of these novel genes will play an important role in improving our understanding of the specific variants involved in antipsychotic treatment response outcomes.

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Ethnic Differences in Antipsychotic Response: What Genetic Variation Does and Does Not Tell Us

Moster

2023

Curr Behav Neurosci Rep

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Patterns of Variation Influencing Antipsychotic Treatment Outcomes in South African First-Episode Schizophrenia Patients

Abstract: This pilot study has highlighted the importance of exome sequencing for antipsychotic pharmacogenomics studies, particularly in African individuals. Furthermore, the results emphasize once again the complexity of antipsychotic pharmacogenomics and the need for future research.

Cited by 16 publications

References 33 publications

Whole genome/exome sequencing in mood and psychotic disorders

Whole genome/exome sequencing in mood and psychotic disorders

The identification of novel genetic variants associated with antipsychotic treatment response outcomes in first-episode schizophrenia patients

Ethnic Differences in Antipsychotic Response: What Genetic Variation Does and Does Not Tell Us

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