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

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 .