title: Childhood maltreatment is associated with a sex-dependent functional reorganization of a brain inhibitory control network.
abstract: Childhood adversity represents a major risk factor for drug addiction and other mental disorders. However, the specific mechanisms by which childhood adversity impacts human brain organization to confer greater vulnerability for negative outcomes in adulthood is largely unknown. As an impaired process in drug addiction, inhibitory control of behavior was investigated as a target of childhood maltreatment (abuse and neglect). Forty adults without Axis-I psychiatric disorders (21 females) completed a Childhood Trauma Questionnaire (CTQ) and underwent functional MRI (fMRI) while performing a stop-signal task. A group independent component analysis identified a putative brain inhibitory control network. Graph theoretical analyses and structural equation modeling investigated the impact of childhood maltreatment on the functional organization of this neural processing network. Graph theory outcomes revealed sex differences in the relationship between network functional connectivity and inhibitory control which were dependent on the severity of childhood maltreatment exposure. A network effective connectivity analysis indicated that a maltreatment dose-related negative modulation of dorsal anterior cingulate (dACC) activity by the left inferior frontal cortex (IFC) predicted better response inhibition and lesser attention deficit hyperactivity disorder (ADHD) symptoms in females, but poorer response inhibition and greater ADHD symptoms in males. Less inhibition of the right IFC by dACC in males with higher CTQ scores improved inhibitory control ability. The childhood maltreatment-related reorganization of a brain inhibitory control network provides sex-dependent mechanisms by which childhood adversity may confer greater risk for drug use and related disorders and by which adaptive brain responses protect individuals from this risk factor.
authors.affiliation: Brain Imaging Research Center, Psychiatric Research Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Amanda
authors.initials: A
authors.lastname: Elton
authors.forename: Shanti P
authors.initials: SP
authors.lastname: Tripathi
authors.forename: Tanja
authors.initials: T
authors.lastname: Mletzko
authors.forename: Jonathan
authors.initials: J
authors.lastname: Young
authors.forename: Josh M
authors.initials: JM
authors.lastname: Cisler
authors.forename: G Andrew
authors.initials: GA
authors.lastname: James
authors.forename: Clinton D
authors.initials: CD
authors.lastname: Kilts
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000523:psychology; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods; D002648:Child; D002649:Child Abuse; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D007175:Impulsive Behavior; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000502:physiology; D012737:Sex Factors; D012815:Signal Processing, Computer-Assisted; D011795:Surveys and Questionnaires; D013647:Task Performance and Analysis
keywords: adult survivors; child abuse; child neglect; drug addiction; functional brain imaging; inhibition; psychological adaptation; sex differences