Single-dose methylphenidate induces shift in functional connectivity associated with positive longer term clinical response in adult attention-deficit/hyperactivity disorder

TY - JOUR

T1 - Single-dose methylphenidate induces shift in functional connectivity associated with positive longer term clinical response in adult attention-deficit/hyperactivity disorder

AU - Pretzsch, Charlotte M

AU - Parlatini, Valeria

AU - Murphy, Declan

N1 - Publisher Copyright: © The Author(s) 2025.

PY - 2025/2/17

Y1 - 2025/2/17

N2 - Stimulants, such as methylphenidate (MPH), are beneficial for attention-deficit/hyperactivity disorder (ADHD), but individual response varies. A deeper understanding of the mechanisms underpinning response is needed. Previous studies suggest that a single MPH dose modulates resting-state functional connectivity (rs-fc). We investigated whether single-dose induced rs-fc changes were associated with post-dose optimization clinical response. Fifty-six adults with ADHD underwent rs-functional magnetic resonance imaging (rs-fMRI) under placebo and a single MPH dose, before starting MPH treatment. Clinical response was measured at two months. We tested if a single MPH dose (vs. placebo) shifted rs-fc; how these shifts were associated with treatment response (categorical approach); and whether these associations were driven by improvement on either ADHD symptom domain. A single MPH dose (vs. placebo) increased rs-fc in three subcortical-cortical and cerebellar-cortical clusters. Enhanced rs-fc between the cerebellar vermis (lobule 6) and the left precentral gyrus was associated with a greater probability of responding to treatment (χ2(7) = 22.740, p = .002) and with an improvement on both inattentive and hyperactive/impulsive symptoms (both p ≤ .001). We provide proof-of-concept that the brain functional response to a single MPH dose, administered before starting routine treatment, is indicative of two-month clinical response in adult ADHD. This may encourage future replication using clinically applicable measures.

AB - Stimulants, such as methylphenidate (MPH), are beneficial for attention-deficit/hyperactivity disorder (ADHD), but individual response varies. A deeper understanding of the mechanisms underpinning response is needed. Previous studies suggest that a single MPH dose modulates resting-state functional connectivity (rs-fc). We investigated whether single-dose induced rs-fc changes were associated with post-dose optimization clinical response. Fifty-six adults with ADHD underwent rs-functional magnetic resonance imaging (rs-fMRI) under placebo and a single MPH dose, before starting MPH treatment. Clinical response was measured at two months. We tested if a single MPH dose (vs. placebo) shifted rs-fc; how these shifts were associated with treatment response (categorical approach); and whether these associations were driven by improvement on either ADHD symptom domain. A single MPH dose (vs. placebo) increased rs-fc in three subcortical-cortical and cerebellar-cortical clusters. Enhanced rs-fc between the cerebellar vermis (lobule 6) and the left precentral gyrus was associated with a greater probability of responding to treatment (χ2(7) = 22.740, p = .002) and with an improvement on both inattentive and hyperactive/impulsive symptoms (both p ≤ .001). We provide proof-of-concept that the brain functional response to a single MPH dose, administered before starting routine treatment, is indicative of two-month clinical response in adult ADHD. This may encourage future replication using clinically applicable measures.

KW - Humans

KW - Methylphenidate/administration & dosage

KW - Attention Deficit Disorder with Hyperactivity/drug therapy

KW - Adult

KW - Male

KW - Female

KW - Magnetic Resonance Imaging

KW - Central Nervous System Stimulants/administration & dosage

KW - Brain/drug effects

KW - Treatment Outcome

KW - Middle Aged

KW - Young Adult

UR - https://www.scopus.com/pages/publications/85218949965

U2 - 10.1038/s41598-025-87204-3

DO - 10.1038/s41598-025-87204-3

M3 - Article

C2 - 39962109

SN - 2045-2322

VL - 15

SP - 5794

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 5794

ER -