4.0 Article

Neural Abnormalities in Early-Onset and Adolescence-Onset Conduct Disorder

Journal

ARCHIVES OF GENERAL PSYCHIATRY
Volume 67, Issue 7, Pages 729-738

Publisher

AMER MEDICAL ASSOC
DOI: 10.1001/archgenpsychiatry.2010.75

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Funding

  1. Wellcome Trust [077029, 083140]
  2. Medical Research Council [U.1055.02.001.00001.01]
  3. Clare Hall in Cambridge University
  4. Medical Research Council [MC_U105579214] Funding Source: researchfish
  5. MRC [MC_U105579214, MC_U105597119] Funding Source: UKRI

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Context: Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. Objective: To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. Design: Case-control study. Setting: Government research institute, university department. Participants: Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure: Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. Results: Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for by attention-deficit/hyperactivity disorder symptoms. Conclusions: Neurophysiological abnormalities are observed in both CD subtypes, contrary to the developmental taxonomic theory of CD. Additional amygdala hypofunction in relation to sad expressions might indicate why EO-CD is more severe and persistent than AO-CD.

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