Resting state default mode network connectivity in children and adolescents with ADHD after acute tryptophan depletion

Acta Psychiatr Scand. 2016 Aug;134(2):161-71. doi: 10.1111/acps.12573. Epub 2016 May 4.


Objective: Alterations of the default mode network (DMN) have been described in patients with neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), and the neurotransmitter serotonin (5-HT) is known to modulate DMN activity. This study aimed to explore the role of 5-HT on the DMN and its functional connectivity (FC) in young patients with ADHD.

Methods: Young male patients with ADHD (n = 12) and healthy controls (n = 10) (both aged 12-17 years) were subjected to acute tryptophan depletion (ATD) and subsequently diminished brain 5-HT synthesis. Three hours after challenge intake (ATD or a balanced control condition, BAL), resting state fMRI scans were obtained.

Results: In patients, ATD led to attenuated FC of the right superior premotor cortex (BA 6) with the DMN, comparable to the extent found in controls after BAL administration. ATD lowered FC of the left somatosensory cortex (BA 3) with the DMN, independently of the factor group, but with stronger effects in controls.

Conclusions: Data reveal a serotonergic modulation of FC between BA 6 and 3, known to be relevant for motor planning and sensory perception, and the DMN, thereby possibly pointing toward ATD acting beneficially on neural planning of motor activity in patients with ADHD.

Keywords: Serotonin; adolescence; attention deficit hyperactivity disorder; fMRI; premotor cortex; somatosensory cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / diagnostic imaging
  • Attention Deficit Disorder with Hyperactivity / metabolism
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain / physiopathology*
  • Brain Mapping / methods
  • Child
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology*
  • Rest
  • Serotonin / metabolism
  • Tryptophan / deficiency*


  • Serotonin
  • Tryptophan