Psychosis susceptibility gene ZNF804A and cognitive performance in schizophrenia.
ABSTRACT The Zinc Finger Protein 804A gene (ZNF804A) has been implicated in schizophrenia susceptibility by several genome-wide association studies. ZNF804A is brain expressed but of unknown function.
To investigate whether the identified risk allele at the disease-associated single nucleotide polymorphism rs1344706 is associated with variation in neuropsychological performance in patients and controls.
Comparison of cases and controls grouped according to ZNF804A genotype (AA vs AC vs CC) on selected measures of cognition in 2 independent samples.
Unrelated patients from general adult psychiatric inpatient and outpatient services and unrelated healthy participants from the general population were ascertained.
Patients with DSM-IV-diagnosed schizophrenia and healthy participants from independent samples of Irish (297 cases and 165 controls) and German (251 cases and 1472 controls) nationality.
In this 2-stage study, we tested for an association between ZNF804A rs1344706 and cognitive functions known to be impaired in schizophrenia (IQ, episodic memory, working memory, and attention) in an Irish discovery sample. We then tested significant results in a German replication sample.
In the Irish samples, the ZNF804A genotype was associated with differences in episodic and working memory in patients but not in controls. These findings replicated in the same direction in the German samples. Furthermore, in both samples, when patients with a lower IQ were excluded, the association between ZNF804A and schizophrenia strengthened.
In a disorder characterized by heterogeneity, a risk variant at ZNF804A seems to delineate a patient subgroup characterized by relatively spared cognitive ability. Further work is required to establish whether this represents a discrete molecular pathogenesis that differs from that of other patient groups and whether this also has consequences for nosologic classification, illness course, or treatment.
SourceAvailable from: PubMed CentralSchizophrenia Bulletin 11/2014; DOI:10.1093/schbul/sbu162 · 8.61 Impact Factor
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ABSTRACT: A substantial proportion of patients suffering from schizophrenia-spectrum disorders (SSDs) exhibit a general intellectual impairment at illness onset, but the subsequent intellectual course remains unclear. Relationships between accumulated time in psychosis and long-term intellectual functioning are largely uninvestigated, but may identify subgroups with different intellectual trajectories. Eighty-nine first-episode psychosis patients were investigated on IQ at baseline and at 10-years follow-up. Total time in psychosis was defined as two separate variables; Duration of psychosis before start of treatment (i.e. duration of untreated psychosis: DUP), and duration of psychosis after start of treatment (DAT). The sample was divided in three equal groups based on DUP and DAT, respectively. To investigate if diagnosis could separate IQ-trajectories beyond that of psychotic duration, two diagnostic categories were defined: core versus non-core SSDs. No significant change in IQ was found for the total sample. Intellectual course was not related to DUP or stringency of diagnostic category. However, a subgroup with long DAT demonstrated a significant intellectual decline, mainly associated with a weaker performance on test of immediate verbal recall/working memory (WAIS-R Digit Span). This indicates a relationship between accumulated duration of psychosis and long-term intellectual course, irrespective of diagnostic category, in a significant subgroup of patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.Psychiatry Research 12/2014; DOI:10.1016/j.psychres.2014.11.054 · 2.68 Impact Factor
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ABSTRACT: There are studies showing that gene polymorphisms within the transforming growth factor-β (TGF-β) signaling constitute schizophrenia risk variants. However, the association between TGFB1 gene polymorphisms (+869T/C and +915G/C), TGF-β level with schizophrenia course, and its symptomatology together with cognitive functioning has not been investigated so far. We included 151 patients with schizophrenia and 279 healthy controls. Cognitive functioning was assessed using Rey Auditory Verbal Learning Test, Trail Making Test (TMT)-A and TMT-B, Verbal Fluency task, Stroop test, as well as selected subtests from the Wechsler Adults Intelligence Scale – Revised, Polish adaptation (WAIS-R-Pl): Digit Symbol Coding, Digit Span Forward and Backward, and Similarities. Additionally, serum TGF-β levels were measured in 88 schizophrenia patients and 88 healthy controls. Serum TGF-β level was significantly higher among patients with schizophrenia in comparison with healthy controls; however, the studied polymorphisms were not associated with TGF-β level in schizophrenia patients. Subjects carrying the +869T allele performed significantly worse in comparison with +869CC homozygotes on Stroop task, Verbal Fluency task and Digit Symbol Coding task. There was a significant difference in age of psychosis onset in female schizophrenia patients with respect to the TGFB1 +869T/C polymorphism. Additionally, adjustment for possible confounders revealed that there was a significant difference in cognitive performance on Digit Symbol Coding task with respect to the TGFB1 +869T/C polymorphism among female schizophrenia patients. Our results suggest that TGF-β signaling might be a valid link contributing to observed differences in age of onset and the level of cognitive decline between male and female schizophrenia patients.Neuropsychiatric Disease and Treatment 03/2015; 2015:11-575. DOI:10.2147/NDT.S74672 · 2.00 Impact Factor