Evaluation of psychological symptoms among presymptomatic HD gene carriers as measured by selected MMPI scales Sandra Close Kirkwood a,b , Eric Siemers b , Richard J. Viken c , M.E. Hodes a,1 , P. Michael Conneally a , Joe C. Christian a , Tatiana Foroud a, * a Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 West Walnut Street IB 130, Indianapolis, IN 46202, USA b Eli Lilly and Company, Indianapolis, IN, USA c Department of Psychology, Indiana University, Bloomington, IN, USA Received 23 June 2001; received in revised form 22 March 2002; accepted 15 July 2002 Abstract Individuals at-risk for Huntington disease (HD), both HD gene carriers and nongene carriers, were recruited to determine whe- ther psychological changes are detectable among clinically presymptomatic individuals who carry the HD allele. Each participant underwent genotyping to determine HD gene carrier status and a clinical assessment that included a quantified neurological examination and an abbreviated Minnesota Multiphasic Personality Inventory (MMPI): the Hypochondriasis, Depression, Psy- chasthenia, Neuroticism, Cynical Hostility, and Irritability Scales and the Harris Subscales of Depression. The results of the MMPI were evaluated for differences between nongene carriers (NGC) (n=363), presymptomatic gene carriers (PSGC) (n=149), and those with manifest HD (MHD) (n=26). The overall multiple analysis of variance was not significant, indicating that there was no overall difference among the three groups. However, when subscales of the MMPI were examined individually, participants with manifest HD scored higher on the Psychasthenia scale (MHD vs. PSGC, P=0.005; MHD vs. NGC, P=0.03) and the Harris Depression subscale, Brooding (MHD vs. PSGC, P=0.0005; MHD vs. NGC, P=0.003). No significant correlation was found between the number of trinucleotide repeats on the disease-producing allele and any of the MMPI scales for the gene carriers, MHD or PSGC. These results verify the presence of psychological symptoms in the early phases of MHD but not in PSGC. Thus, further study of the behavioral and mood symptoms thought to accompany HD using measures designed specifically to detect depressive symptoms and changes in behavior specific to HD is warranted to delineate the timing of onset of the psychological symptoms. # 2002 Elsevier Science Ltd. All rights reserved. Keywords: Huntington disease; Presymptomatic symptom progression 1. Introduction Huntington disease (HD) is an autosomal dominant, neurodegenerative disorder characterized clinically by a triad of progressive motor, cognitive and emotional symptoms. Although the diagnosis of HD is typically made following the onset of motor abnormalities, psy- chiatric symptoms are generally an accepted cardinal feature of the disease, with the early stages of disease progression characterized by depression, anxiety, irrit- ability, and apathy (Vecsei and Beal, 1996; Harper, 1991; Folstein, 1989). Behavioral symptoms are repor- ted as the presenting symptom in as many as half the individuals with Huntington disease (Harper, 1991). Affective disorder is the most common symptom with depression reported to precede motor signs by an aver- age of five years (Folstein, 1989). Baxter (Baxter et al., 1992) concluded that anger and hostility were sig- nificantly higher among individuals who were not gene tested but determined more likely to develop HD due to linkage results. In a sample of individuals who partici- pated in a presymptomatic testing program, Campodo- nico (Campodonico et al., 1996) found increased hostility among presymptomatic gene carriers as com- pared with nongene carriers. When individuals with recently diagnosed HD were evaluated by the Minne- sota Multiphasic Personality Inventory (MMPI), they 0022-3956/02/$ - see front matter # 2002 Elsevier Science Ltd. All rights reserved. PII: S0022-3956(02)00054-7 Journal of Psychiatric Research 36 (2002) 377–382 www.elsevier.com/locate/jpsychires * Corresponding author. Tel.: +1-317-278-1291; fax: +1-317-274- 2387. E-mail address: tforoud@iupui.edu (T. Foroud). 1 Deceased.