title: Is there an association between advanced paternal age and endophenotype deficit levels in schizophrenia?
abstract: The children of older fathers have increased risks of developing schizophrenia spectrum disorders, and among those who develop these disorders, those with older fathers present with more severe clinical symptoms. However, the influence of advanced paternal age on other important domains related to schizophrenia, such as quantitative endophenotype deficit levels, remains unknown. This study investigated the associations between paternal age and level of endophenotypic impairment in a well-characterized family-based sample from the Consortium on the Genetics of Schizophrenia (COGS). All families included at least one affected subject and one unaffected sibling. Subjects met criteria for schizophrenia (probands; n = 293) or were unaffected first-degree siblings of those probands (n = 382). Paternal age at the time of subjects' birth was documented. Subjects completed a comprehensive clinical assessment and a battery of tests that measured 16 endophenotypes. After controlling for covariates, potential paternal age-endophenotype associations were analyzed using one model that included probands alone and a second model that included both probands and unaffected siblings. Endophenotype deficits in the Identical Pairs version of the 4-digit Continuous Performance Test and in the Penn Computerized Neurocognitive Battery verbal memory test showed significant associations with paternal age. However, after correcting for multiple comparisons, no endophenotype was significantly associated with paternal age. These findings suggest that factors other than advanced paternal age at birth may account for endophenotypic deficit levels in schizophrenia.
authors: VISN-20 Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington, United States of America ; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, United States of America.
authors: Debby
authors: D
authors: Tsuang
authors: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, United States of America.
authors: Michelle
authors: M
authors: Esterberg
authors: VISN-22 Mental Illness Research, Education, and Clinical Center, VA San Diego Healthcare System, San Diego, California, United States of America ; Department of Psychiatry, University of California San Diego, San Diego, California, United States of America.
authors: David
authors: D
authors: Braff
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Monica
authors: M
authors: Calkins
authors: Department of Psychiatry, University of California San Diego, San Diego, California, United States of America.
authors: Kristin
authors: K
authors: Cadenhead
authors: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, United States of America ; VISN-20 Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington, United States of America.
authors: Dorcas
authors: D
authors: Dobie
authors: Department of Psychiatry, University of Colorado Health Sciences Center, Denver, Colorado, United States of America.
authors: Robert
authors: R
authors: Freedman
authors: Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America ; VA Greater Los Angeles Health Care System, Los Angeles, California, United States of America.
authors: Michael F
authors: MF
authors: Green
authors: Department of Psychiatry, University of California San Diego, San Diego, California, United States of America.
authors: Tiffany
authors: T
authors: Greenwood
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Raquel
authors: R
authors: Gur
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Ruben
authors: R
authors: Gur
authors: Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America ; VA Greater Los Angeles Health Care System, Los Angeles, California, United States of America.
authors: William
authors: W
authors: Horan
authors: Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California, United States of America.
authors: Laura C
authors: LC
authors: Lazzeroni
authors: VISN-22 Mental Illness Research, Education, and Clinical Center, VA San Diego Healthcare System, San Diego, California, United States of America ; Department of Psychiatry, University of California San Diego, San Diego, California, United States of America.
authors: Gregory A
authors: GA
authors: Light
authors: VISN-20 Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington, United States of America.
authors: Steven P
authors: SP
authors: Millard
authors: Department of Psychiatry, University of Colorado Health Sciences Center, Denver, Colorado, United States of America.
authors: Ann
authors: A
authors: Olincy
authors: Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors: Keith
authors: K
authors: Nuechterlein
authors: Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School Department of Psychiatry, Boston, Massachusetts, United States of America.
authors: Larry
authors: L
authors: Seidman
authors: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, United States of America; VISN-3 Mental Illness Research, Education, and Clinical Center, James J. Peters VA Medical Center, New York, New York, United States of America.
authors: Larry
authors: L
authors: Siever
authors: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, United States of America; VISN-3 Mental Illness Research, Education, and Clinical Center, James J. Peters VA Medical Center, New York, New York, United States of America.
authors: Jeremy
authors: J
authors: Silverman
authors: Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School Department of Psychiatry, Boston, Massachusetts, United States of America.
authors: William
authors: W
authors: Stone
authors: Department of Psychiatry, University of California San Diego, San Diego, California, United States of America.
authors: Joyce
authors: J
authors: Sprock
authors: Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America ; VA Greater Los Angeles Health Care System, Los Angeles, California, United States of America.
authors: Catherine
authors: C
authors: Sugar
authors: Department of Psychiatry, University of California San Diego, San Diego, California, United States of America.
authors: Neal
authors: N
authors: Swerdlow
authors: Department of Psychiatry, University of California San Diego, San Diego, California, United States of America.
authors: Ming
authors: M
authors: Tsuang
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Bruce
authors: B
authors: Turetsky
authors: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, United States of America.
authors: Allen
authors: A
authors: Radant
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D058068:Endophenotypes; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010331:Paternal Age; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000235:genetics*; D035781:Siblings; D055815:Young Adult