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A genome-wide linkage scan for distinct subsets of schizophrenia characterized by age at onset and neurocognitive deficits.

ABSTRACT: As schizophrenia is genetically and phenotypically heterogeneous, targeting genetically informative phenotypes may help identify greater linkage signals. The aim of the study is to evaluate the genetic linkage evidence for schizophrenia in subsets of families with earlier age at onset or greater neurocognitive deficits.Patients with schizophrenia (n ?=? 1,207) and their first-degree relatives (n ?=? 1,035) from 557 families with schizophrenia were recruited from six data collection field research centers throughout Taiwan. Subjects completed a face-to-face semi-structured interview, the Continuous Performance Test (CPT), the Wisconsin Card Sorting Test, and were genotyped with 386 microsatellite markers across the genome.A maximum nonparametric logarithm of odds (LOD) score of 4.17 at 2q22.1 was found in 295 families ranked by increasing age at onset, which had significant increases in the maximum LOD score compared with those obtained in initial linkage analyses using all available families. Based on this subset, a further subsetting by false alarm rate on the undegraded and degraded CPT obtained further increase in the nested subset-based LOD on 2q22.1, with a score of 7.36 in 228 families and 7.71 in 243 families, respectively.We found possible evidence of linkage on chromosome 2q22.1 in families of schizophrenia patients with more CPT false alarm rates nested within the families with younger age at onset. These results highlight the importance of incorporating genetically informative phenotypes in unraveling the complex genetics of schizophrenia.

SUBMITTER: Lien YJ

PROVIDER: S-EPMC3163684 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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A genome-wide linkage scan for distinct subsets of schizophrenia characterized by age at onset and neurocognitive deficits.

Lien Yin-Ju YJ Hsiao Po-Chang PC Liu Chih-Min CM Faraone Stephen V SV Tsuang Ming T MT Hwu Hai-Gwo HG Chen Wei J WJ

PloS one 20110829 8

<h4>Background</h4>As schizophrenia is genetically and phenotypically heterogeneous, targeting genetically informative phenotypes may help identify greater linkage signals. The aim of the study is to evaluate the genetic linkage evidence for schizophrenia in subsets of families with earlier age at onset or greater neurocognitive deficits.<h4>Methods</h4>Patients with schizophrenia (n = 1,207) and their first-degree relatives (n = 1,035) from 557 families with schizophrenia were recruited fro ...[more]

PMID: 21897869

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Project description:Trichotillomania (TTM), or compulsive hair pulling, is a common psychiatric disorder characterized by psychosocial impairment and reduced quality of life. The aim of this retrospective study was to characterize the impact of age at TTM onset on clinical variables and neuropsychological function using a variety of clinical and neurocognitive measures. The study sample included 98 adult treatment-seeking individuals with a DSM-IV diagnosis of TTM. Correlates were explored by grouping participants into childhood-onset (onset at ≤ 11 years old, n = 42) or later-onset (≥ 12 years old, n = 56) TTM and via linear regression. All subjects underwent a semistructured clinical interview with a psychiatrist and completed a variety of paper-pencil tests regarding TTM severity and quality of life. A subset (n = 44) of subjects underwent neurocognitive testing assessing motor inhibition and set-shifting compared to a sample (n = 27) of age- and gender-matched healthy controls. Data were collected from September 2006 through July 2011. Postpubertal age at onset was significantly associated with greater TTM symptom severity. Clinically, the later-onset group pulled their hair for a significantly greater amount of time daily (P = .008), had higher clinician-rated TTM severity on the Clinical Global Impressions-Severity of Illness scale (P = .042), and had higher patient-rated severity on the Massachusetts General Hospital Hairpulling Scale (P = .022) compared to healthy controls. On the neurocognitive tasks, later-onset TTM was characterized by stop-signal impairments (P = .020) and relatively spared set-shifting, consistent with previous studies in the literature. In contrast, the childhood-onset manifestation was associated with set-shifting deficits in stages of the task completed and total errors adjusted (both P < .001) but relatively spared stop-signal performance compared to healthy controls. Results indicate that childhood-onset of TTM is common, as confirmed by the fact that 42.9% of our sample met childhood-onset criteria, and may differ neurobiologically from the prototypical later-onset form. Future neurobiological and treatment studies should measure age at onset and explore further these putative differences.Trial Registration ClinicalTrials.gov identifiers: NCT00354770 and NCT00775229.

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A genome-wide linkage scan for distinct subsets of schizophrenia characterized by age at onset and neurocognitive deficits.

Publications

A genome-wide linkage scan for distinct subsets of schizophrenia characterized by age at onset and neurocognitive deficits.

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