Mark A Riddle1, Brion S Maher2, Ying Wang1, Marco Grados1, O Joseph Bienvenu1, Fernando S Goes1, Bernadette Cullen1, Dennis L Murphy3, Scott L Rauch4, Benjamin D Greenberg5, James A Knowles6, James T McCracken7, Anthony Pinto8, John Piacentini7, David L Pauls9, Steven A Rasmussen5, Yin Yao Shugart10, Gerald Nestadt1, Jack Samuels1. 1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. 2. Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland. 3. Laboratory of Clinical Science, National Institute of Mental Health, National Institute of Health, Bethesda, Maryland. 4. Department of Psychiatry, McLean Hospital, Harvard Medical School, Boston, Massachusetts. 5. Department of Psychiatry and Human Behavior, Brown Medical School, Butler Hospital, Providence, Rhode Island. 6. Department of Psychiatry, University of Southern California School of Medicine, Los Angeles, California. 7. Department of Psychiatry and Biobehavioral Sciences, School of Medicine, University of California Los Angeles, Los Angeles, California. 8. Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York City, New York. 9. Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 10. Unit of Statistical Genomics, Division of Intramural Research, National Institute of Mental Health, National Institute of Health, Bethesda, Maryland.
Abstract
BACKGROUND: To determine possible dimensions that underlie obsessive-compulsive personality disorder (OCPD) and to investigate their clinical correlates, familiality, and genetic linkage. METHODS: Participants were selected from 844 adults assessed with the Structured Instrument for the Diagnosis of DSM-IV Personality Disorders (SIDP) in the OCD Collaborative Genetics Study (OCGS) that targeted families with obsessive-compulsive disorder (OCD) affected sibling pairs. We conducted an exploratory factor analysis, which included the eight SIDP-derived DSM-IV OCPD traits and the indecision trait from the DSM-III, assessed clinical correlates, and estimated sib-sib correlations to evaluate familiality of the factors. Using MERLIN and MINX, we performed genome-wide quantitative trait locus (QTL) linkage analysis to test for allele sharing among individuals. RESULTS: Two factors were identified: Factor 1: order/control (perfectionism, excessive devotion to work, overconscientiousness, reluctance to delegate, and rigidity); and Factor 2: hoarding/indecision (inability to discard and indecisiveness). Factor 1 score was associated with poor insight, whereas Factor 2 score was associated with task incompletion. A significant sib-sib correlation was found for Factor 2 (rICC = .354, P < .0001) but not Factor 1 (rICC = .129, P = .084). The linkage findings were different for the two factors. When Factor 2 was analyzed as a quantitative trait, a strong signal was detected on chromosome 10 at marker d10s1221: KAC LOD = 2.83, P = .0002; and marker d10s1225: KAC LOD = 1.35, P = .006. CONCLUSIONS: The results indicate two factors of OCPD, order/control and hoarding/indecision. The hoarding/indecision factor is familial and shows modest linkage to a region on chromosome 10.
BACKGROUND: To determine possible dimensions that underlie obsessive-compulsive personality disorder (OCPD) and to investigate their clinical correlates, familiality, and genetic linkage. METHODS:Participants were selected from 844 adults assessed with the Structured Instrument for the Diagnosis of DSM-IV Personality Disorders (SIDP) in the OCD Collaborative Genetics Study (OCGS) that targeted families with obsessive-compulsive disorder (OCD) affected sibling pairs. We conducted an exploratory factor analysis, which included the eight SIDP-derived DSM-IV OCPD traits and the indecision trait from the DSM-III, assessed clinical correlates, and estimated sib-sib correlations to evaluate familiality of the factors. Using MERLIN and MINX, we performed genome-wide quantitative trait locus (QTL) linkage analysis to test for allele sharing among individuals. RESULTS: Two factors were identified: Factor 1: order/control (perfectionism, excessive devotion to work, overconscientiousness, reluctance to delegate, and rigidity); and Factor 2: hoarding/indecision (inability to discard and indecisiveness). Factor 1 score was associated with poor insight, whereas Factor 2 score was associated with task incompletion. A significant sib-sib correlation was found for Factor 2 (rICC = .354, P < .0001) but not Factor 1 (rICC = .129, P = .084). The linkage findings were different for the two factors. When Factor 2 was analyzed as a quantitative trait, a strong signal was detected on chromosome 10 at marker d10s1221: KAC LOD = 2.83, P = .0002; and marker d10s1225: KAC LOD = 1.35, P = .006. CONCLUSIONS: The results indicate two factors of OCPD, order/control and hoarding/indecision. The hoarding/indecision factor is familial and shows modest linkage to a region on chromosome 10.
Authors: Jack Samuels; O Joseph Bienvenu; Janice Krasnow; Ying Wang; Marco A Grados; Bernadette Cullen; Fernando S Goes; Brion Maher; Benjamin D Greenberg; Nicole C Mclaughlin; Steven A Rasmussen; Abby J Fyer; James A Knowles; James T Mccracken; John Piacentini; Dan Geller; S Evelyn Stewart; Dennis L Murphy; Yin-Yao Shugart; Mark A Riddle; Gerald Nestadt Journal: Personal Ment Health Date: 2019-12-20