Why does age of onset predict clinical severity in schizophrenia? A multiplex extended pedigree study
| Autor: | David R. Roalf, Ruben C. Gur, Joel Wood, Christie Musket, Raquel E. Gur, Petra Rupert, Susan S. Kuo, Michael F. Pogue-Geile, Laura Almasy, Konasale M. Prasad, Vishwajit L. Nimgaonkar |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Neuropsychological Tests Genetic correlation Severity of Illness Index Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine mental disorders medicine Humans Clinical severity Family Age of Onset Genetics (clinical) Psychiatric Status Rating Scales business.industry Course of illness Symptom severity Age Factors Cognition Heritability Middle Aged medicine.disease 030227 psychiatry Pedigree Psychiatry and Mental health Schizophrenia Female Schizophrenic Psychology Age of onset business 030217 neurology & neurosurgery Clinical psychology |
| Zdroj: | Am J Med Genet B Neuropsychiatr Genet |
| Popis: | Schizophrenia has substantial variation in symptom severity, course of illness, and overall functioning. Earlier age of onset (AOO) is consistently associated with negative outcomes and yet the causes of this association are still unknown. We used a multiplex, extended pedigree design (total N = 771; 636 relatives from 43 multigenerational families with at least 2 relatives diagnosed with schizophrenia and 135 matched controls) to examine among the schizophrenia relatives (N = 103) the relationship between AOO and negative and positive symptom severity, cognition, and community functioning. Most importantly, we assessed whether there are shared genetic effects between AOO and negative symptoms, positive symptoms, cognition, and community functioning. As expected, earlier AOO was significantly correlated with increased severity of negative and positive symptoms and poorer cognition and community functioning among schizophrenia patients. Notably, the genetic correlation between AOO of schizophrenia and negative symptoms was significant (R(g) = −1.00, p = .007). Although the genetic correlations between AOO and positive symptoms, cognition, and community functioning were estimated at maximum and in the predicted direction, they were not statistically significant. AOO of schizophrenia itself was modestly heritable, although not significant and negative symptoms, positive symptoms, and cognition were all strongly and significantly heritable. In sum, we replicated prior findings indicating that earlier AOO is associated with increased symptom severity and extended the literature by detecting shared genetic effects between AOO and negative symptoms, suggestive of pleiotropy. |
| Databáze: | OpenAIRE |
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