title: Abnormal fear circuitry in Attention Deficit Hyperactivity Disorder: A controlled magnetic resonance imaging study.
abstract: We examined whether non-traumatized subjects with Attention Deficit Hyperactivity Disorder (ADHD) have dysfunctional activation in brain structures mediating fear extinction, possibly explaining the statistical association between ADHD and other disorders characterized by aberrant fear processing such as PTSD. Medication naïve, non-traumatized young adult subjects with (N=27) and without (N=20) ADHD underwent a 2-day fear conditioning and extinction protocol in a 3T functional magnetic resonance imaging (fMRI) scanner. Skin conductance response (SCR) was recorded as a measure of conditioned response. Compared to healthy controls, ADHD subjects had significantly greater insular cortex activation during early extinction, lesser dorsal anterior cingulate cortex (dACC) activation during late extinction, lesser ventromedial prefrontal cortex (vmPFC) activation during late extinction learning and extinction recall, and greater hippocampal activation during extinction recall. Hippocampal and vmPFC deficits were similar to those documented in PTSD subjects compared to traumatized controls without PTSD. Non-traumatized, medication naive adults with ADHD had abnormalities in fear circuits during extinction learning and extinction recall, and some findings were consistent with those previously documented in subjects with PTSD compared to traumatized controls without PTSD. These findings could explain the significant association between ADHD and PTSD as well as impaired emotion regulation in ADHD.
authors.affiliation: Pediatric Psychopharmacology and Adult ADHD Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Electronic address: andrea.spencer@bmc.org.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Spencer
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Marin
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Milad
authors.affiliation: Pediatric Psychopharmacology and Adult ADHD Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Spencer
authors.affiliation: Pediatric Psychopharmacology and Adult ADHD Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Olivia E
authors.initials: OE
authors.lastname: Bogucki
authors.affiliation: Pediatric Psychopharmacology and Adult ADHD Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Pope
authors.affiliation: Pediatric Psychopharmacology and Adult ADHD Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Plasencia
authors.affiliation: Pediatric Psychopharmacology and Adult ADHD Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Brittany
authors.initials: B
authors.lastname: Hughes
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: Edward F
authors.initials: EF
authors.lastname: Pace-Schott
authors.affiliation: Pediatric Psychopharmacology and Adult ADHD Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Maura
authors.initials: M
authors.lastname: Fitzgerald
authors.affiliation: Pediatric Psychopharmacology and Adult ADHD Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Mai
authors.initials: M
authors.lastname: Uchida
authors.affiliation: Pediatric Psychopharmacology and Adult ADHD Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Biederman
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003214:Conditioning, Classical / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology* / Q000523:psychology; D005260:Female; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D055815:Young Adult
keywords: ADHD; Extinction Recall; Fear extinction; PTSD; fMRI