The schizophrenia risk gene ZNF804A influences the antipsychotic response of positive schizophrenia symptoms

Mößner, Rainald; Schuhmacher, Anna; Wagner, Michael; Lennertz, Leonhard; Steinbrecher, Anja; Quednow, Boris B.; Rujescu, Dan; Rietschel, Marcella; Maier, Wolfgang

doi:10.1007/s00406-011-0235-1

Cited by 35 publications

(17 citation statements)

References 17 publications

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“…Zhang et al reported that Chinese T allele carriers showed significantly less symptom improvement, using the PANSS scale, while being treated with various SGAs (82). In contrast, Mö ssner et al reported that those individuals of European descent who were homozygous for the A allele showed significantly less symptom improvement in positive symptoms, based on the PANSS scale (81).…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Changasi

Shams

Pouget

et al. 2014

Translational Developmental Psychiatry

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Background and purpose: Antipsychotics (APs) are the primary method of treatment for schizophrenia and other psychotic disorders. Unfortunately, lengthy trial-and-error approaches are typically required to find the optimal medication and dosage due to a large interindividual variability with outcome to AP treatment. The literature has shown abundant evidence for a genetic component in individuals' responses to APs. Pharmacogenetic studies analyze specific genetic markers and their association with symptom improvement and occurrence of side effects with APs. This research aims to optimize AP drug treatment by usage of predictive testing and to personalize medicine. Recent findings: This review will highlight the most consistent findings in pharmacogenetics of APs and will update the reader on the clinical implications. This will include how genetic variants modulate AP drug levels, side effects, and therapeutic symptom improvement (i.e. response) to AP treatment. Summary: Several promising findings were obtained implicating gene variants of the dopamine receptor genes in addition to gene variants of serotonin receptors for response and common side effects. Notably, effect sizes appear to be particularly high in the genetics of side effects compared to response. One example is antipsychotic-induced weight gain where the leptin, HTR2C and in particular the melanocortin-4-receptor (MC4R) genes have been implicated in weight gain in children and adolescents. Consistent findings were also obtained for genes implicated in tardive dyskinesia and agranulocytosis. However, the most clinically relevant findings pertain to genes involved in drug metabolism such as the CYP2D6 and CYP2C19 genes which have been included in the first genetic test kits such as the Amplichip †

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Section: Pharmacodynamicsmentioning

confidence: 99%

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Changasi

Shams

Pouget

et al. 2014

Translational Developmental Psychiatry

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“…However, several clues have emerged through cognitive studies by which this variant is associated with functional connectivity of the dorsolateral prefrontal cortex, both across hemispheres and with the hippocampus, can increase functional connectivity of the amygdala with the regulatory limbic and prefrontal areas and neuropsychological performance, such as visual memory, episodic and working memory, and attention. Consequently, these functions are impaired in patients with schizophrenia as well as bipolar disorders (Esslinger et al, 2009(Esslinger et al, , 2011Donohoe et al, 2010;Hashimoto et al, 2010;Walters et al, 2010;Balog et al, 2011;Steinberg et al, 2011;Walter et al, 2011;Kuswanto et al, 2012;Mö ssner et al, 2012). It has been recently shown that the ZNF804A gene alters expression of genes involved in cell adhesion (Hill et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

ZNF804A rs1344706 Variant and Schizophrenia in a Romanian Population from Cluj Napoca

Zaharie

Ergül

Ozel

et al. 2012

Genetic Testing and Molecular Biomarkers

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The ZNF804A rs1344706 variant was the first risk factor to be identified through genome-wide association studies and follow-up studies with meta-analysis for schizophrenia as well as bipolar disorders; we investigated 231 schizophrenia and 222 controls to see whether this particular variant was associated with schizophrenia in a Romanian population from Cluj Napoca. Clearly, there was no association between the ZNF804A rs1344706 variant and schizophrenia. Our study provides evidence for those that found no association with schizophrenia. A surprising result of our study was that the T allele frequency is the highest, thus far among the ethnic groups studied. We used a PCR-RFLP method that had been recently developed in our laboratory to the genotype ZNF804A rs1344706 variant. In conclusion, the ZNF804A rs1344706 variant was not associated with schizophrenia in the Romanian population from Cluj Napoca (χ(2)=0.734, p=0.693).

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“…Though these viewpoints are supported elsewhere [Walters et al, ; Chen et al, ], most other evidence has implicated rs1344706(A) in neurobiological deficits or severity of mental illness [Hashimoto et al, ; Balog et al, ; Voineskos et al, ; Walter et al, ; Kuswanto et al, ; Wassink et al, ; Paulus et al, ]. From a pharmacotherapeutic standpoint, SZ patients homozygous for the risk allele at rs1344706 exhibited reduced improvement of positive symptoms during antipsychotic treatment compared to patients heterozygous for rs1344706(A) [Mössner et al, ]. These findings suggest a risk‐conferring effect of rs1344706(A) and/or a role in clinical severity of SZ.…”

Section: Literature Reviewmentioning

confidence: 90%

Bioinformatic analyses and conceptual synthesis of evidence linking ZNF804A to risk for schizophrenia and bipolar disorder

Hess

Quinn

Akbarian

et al. 2014

American J of Med Genetics Pt B

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Advances in molecular genetics, fueled by the results of large-scale genome-wide association studies, meta-analyses, and mega-analyses, have provided the means of identifying genetic risk factors for human disease, thereby enriching our understanding of the functionality of the genome in the post-genomic era. In the past half-decade, research on neuropsychiatric disorders has reached an important milestone: the identification of susceptibility genes reliably associated with complex psychiatric disorders at genome-wide levels of significance. This age of discovery provides the groundwork for follow-up studies designed to elucidate the mechanism(s) by which genetic variants confer susceptibility to these disorders. The gene encoding zinc-finger protein 804 A (ZNF804A) is among these candidate genes, recently being found to be strongly associated with schizophrenia and bipolar disorder via one of its non-coding mutations, rs1344706. Neurobiological, molecular, and bioinformatic analyses have improved our understanding of ZNF804A in general and this variant in particular; however, more work is needed to establish the mechanism(s) by which ZNF804A variants impinge on the biological substrates of the two disorders. Here, we review literature recently published on ZNF804A, and analyze critical concepts related to the biology of ZNF804A and the role of rs1344706 in schizophrenia and bipolar disorder. We synthesize the results of new bioinformatic analyses of ZNF804A with key elements of the existing literature and knowledge base. Furthermore, we suggest some potentially fruitful short- and long-term research goals in the assessment of ZNF804A.

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The schizophrenia risk gene ZNF804A influences the antipsychotic response of positive schizophrenia symptoms

Cited by 35 publications

References 17 publications

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

ZNF804A rs1344706 Variant and Schizophrenia in a Romanian Population from Cluj Napoca

Bioinformatic analyses and conceptual synthesis of evidence linking ZNF804A to risk for schizophrenia and bipolar disorder

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