title: Depressive symptoms in prodromal Huntington's Disease correlate with Stroop-interference related functional connectivity in the ventromedial prefrontal cortex.
abstract: Huntington's Disease (HD) is a neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) triplet repeat-expansion in the Huntingtin (HTT) gene. Diagnosis of HD is classically defined by the presence of motor symptoms; however, cognitive and depressive symptoms frequently precede motor manifestations, and may occur early in the prodromal phase. There are sparse data so far on functional brain correlates of depressive symptoms in prodromal HD. A Stroop color-naming test was administered to 32 subjects in the prodromal phase of HD and 52 expansion-negative controls while performing functional magnetic resonance imaging at 3Tesla. Networks of functional connectivity were identified using group independent component analysis, followed by an analysis of functional network interactions. A contrast of temporal regression-based beta-weights was calculated as a reflection of Stroop-interference related activity and correlated with Center for Epidemiologic Studies Depression (CES-D) scores. For secondary analysis, patients were stratified into two subgroups by median split of CAG repeat-length. Stroop performance was independent of HTT mutation-carrier status and CES-D score. Stroop-interference-related activity of the ventromedial prefrontal cortex-node of the default-mode network, calculated by temporal-regression beta-weights, was more highly correlated with depressive symptoms in subjects in the prodromal phase of HD than in controls, differing significantly. The strength of this correlation and its difference from controls increased when a subgroup of patients with longer CAG repeat lengths was analyzed. These findings suggest that depressive symptoms in prodromal HD subjects may reflect altered functional brain network activity in the context of early HD-related brain alterations.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. unschuld@jhmi.edu
authors.forename: Paul G
authors.initials: PG
authors.lastname: Unschuld
authors.forename: Suresh E
authors.initials: SE
authors.lastname: Joel
authors.forename: James J
authors.initials: JJ
authors.lastname: Pekar
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Reading
authors.forename: Kenichi
authors.initials: K
authors.lastname: Oishi
authors.forename: Julie
authors.initials: J
authors.lastname: McEntee
authors.forename: Megan
authors.initials: M
authors.lastname: Shanahan
authors.forename: Arnold
authors.initials: A
authors.lastname: Bakker
authors.forename: Russell L
authors.initials: RL
authors.lastname: Margolis
authors.forename: Susan S
authors.initials: SS
authors.lastname: Bassett
authors.forename: Adam
authors.initials: A
authors.lastname: Rosenblatt
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.forename: Peter C
authors.initials: PC
authors.lastname: van Zijl
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.forename: Graham W
authors.initials: GW
authors.lastname: Redgrave
mesh_terms: D000225:Adenine; D000328:Adult; D003596:Cytosine; D004252:DNA Mutational Analysis; D003866:Depressive Disorder / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D040741:Genetic Load; D006147:Guanine; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D017397:Prefrontal Cortex / Q000503:physiopathology*; D062706:Prodromal Symptoms; D013223:Statistics as Topic; D057190:Stroop Test; D019680:Trinucleotide Repeat Expansion
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D006147:Guanine; D003596:Cytosine; D000225:Adenine