Abstract
Leukocyte telomere length (LTL) is longer in association with advanced paternal age, but this association has not been examined along with family history (FH) in schizophrenia. LTL was measured by PCR and compared across cases and controls as part of a study to examine the characteristics of paternal age related schizophrenia. The 53 schizophrenia cases had similar mean LTL as 20 controls, although cases were significantly older than controls and overwhelmingly smoked cigarettes. Multivariate analyses showed that a FH of schizophrenia was associated with longer LTL in both male and female cases. Later paternal age was also related to longer LTL in male cases, but with shorter LTL in female cases. Male cases with older fathers and a FH had the longest LTL. The genetic architecture associated with a familial risk for schizophrenia may include pathways that lengthen LTL. Paternal aging conferred an additional increase in LTL lengthening in male cases, but reduced LTL in female cases. The gender difference in LTL for paternal aging is consistent with the severe illness features reported for female cases with older fathers and could implicate epigenetic alterations in the paternal X chromosomal region with advanced paternal age in association with the risk for schizophrenia.
Highlights
Schizophrenia is a heterogeneous syndrome typically beginning in late adolescence or early adulthood, characterized by declining function, avolition, deficient emotional expression, and psychotic symptoms
ANCOVA comparing mean relative Leukocyte telomere length (LTL) between case and control groups by gender and covarying for age showed LTL was nonsignificantly longer for cases than controls and for males compared to females
The analyses suggested that a positive family history is associated with longer LTL in males and females
Summary
Schizophrenia is a heterogeneous syndrome typically beginning in late adolescence or early adulthood, characterized by declining function, avolition, deficient emotional expression, and psychotic symptoms. Illness risk is increased for relatives of probands, likely through rare genetic variants of large effect and common variants with small effects, which may interact with life course exposures to determine illness risk, most cases have no family history (FH) of the disease (Svrakic et al 2013). Another risk factor for schizophrenia is advanced paternal age (APA), demonstrated over a decade ago (Malaspina et al 2001) and well replicated (Hubert et al 2011). We have demonstrated that subgroups of schizophrenia cases with older fathers have decreased variability in many measures and that they differ consistently from familial cases, including having greater hypofrontality in regional cerebral metabolism (Malaspina et al 2004), opposite gender differences with more severe symptoms in female than male cases (Rosenfield et al 2010), and specific patterns of cognitive deficits that differ from other cases
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