Effects of Methylphenidate on Somatic Symptoms and Brain Functional Connectivity in Adolescents with Attention Deficit Hyperactivity Disorder: A Pilot Study

Abstract

Objective: This study aimed to evaluate whether somatic symptoms in adolescents with attention deficit hyperactivity disorder (ADHD) are associated with a dissociative pattern of functional connectivity (FC) within the default mode network (DMN) and whether methylphenidate administration can improve clinical and somatic symptoms. We also evaluated whether the improvement of somatic symptoms is associated with increased FC within the DMN in response to methylphenidate treatment.

Methods: Fifteen male adolescents with somatic symptoms of ADHD and 15 male adolescents with ADHD without somatic symptoms were included. At baseline and after 6 months of methylphenidate treatment, all adolescents were asked to complete questionnaires for the Korean version of the Dupaul's ADHD rating scale, the symptom checklist-90- revised-somatization subscales, the Beck Depression Inventory, and the Beck Anxiety Inventory. Additionally, a resting- state functional magnetic resonance imaging scan was conducted.

Results: Methylphenidate treatment improved clinical and somatic symptoms in adolescents with ADHD. In addition, it increased brain FC within the DMN from the posterior cingulate cortex (posterior DMN) to the middle prefrontal cortex (anterior DMN). The improvement of somatic symptoms was associated with FC within the DMN from the posterior cingulate cortex to the middle prefrontal cortex in ADHD adolescents with somatic symptoms.

Conclusion: Methylphenidate increased brain FC between the anterior and posterior DMN. The improvement of somatic symptoms in adolescents with ADHD was associated with FC within the DMN. The DMN in adolescents with ADHD seems to be associated with the severity of the clinical and somatic symptoms of ADHD.

Keywords: Attention deficit hyperactivity disorder; Default mode network; Methylphenidate; Somatic symptoms.

Fig. 1

Comparison of the functional connectivity from the posterior cingulate cortex seed to other brain regions between study groups at baseline. (A) ADHD+SOM group showed FC from the posterior cingulate cortex PCC seed to both inferior parietal lobules (x, y, z: −51, −57, 24/x, y, z: 51, −57, 24, ke = 204, T = 22.77, FDRp < 0.01) and both superior frontal gyri (x, y, z: −7, 48, 12/x, y, z: 7, 48, 12, ke = 551, T = 16.62, FDRp < 0.01); the ADHD-SOM group showed FC from the PCC seed to the right inferior parietal lobule (x, y, z: 54, −60, 39, ke = 322, T = 14.12, FDRp < 0.01) and both superior frontal gyri (x, y, z: −6, 57, 15/x, y, z: 6, 57, 15, ke = 517, T = 15.51, FDRp < 0.01). (B) Compared to the ADHD-SOM group, the ADHD+SOM group showed decreased FC from the PCC seed to the left middle frontal gyrus (x, y, z: −36, 15, 51, ke = 47, T = 4.52, FDRp = 0.02) and increased FC from the PCC seed to the left inferior parietal lobule (x, y, z: −36, −72, 42, ke = 90, T = 3.53, FDRp = 0.03). ADHD+SOM, adolescents with attention deficit hyperactivity disorder (ADHD) with somatic symptoms; ADHD-SOM, adolescents with ADHD without somatic symptoms; FC, functional connectivity; PCC, posterior cingulate cortex.

Fig. 2

Changes in functional connectivity from the posterior cingulate cortex seed to other brain regions in study groups during the treatment period. (A) During the treatment period, the ADHD+SOM group showed increased FC from the PCC seed to the right superior frontal gyrus (x, y, z: 3, 54, −3, ke = 60, T = 4.32, FDRp = 0.04). (B) During the treatment period, the ADHD-SOM group showed decreased FC from the PCC seed to the right superior temporal gyrus (x, y, z: 54, 18, −12, ke = 122, T = 3.99, FDRp = 0.03). (C) Compared to the ADHD-SOM group, the ADHD+SOM group showed greater changes in FC from the PCC seed to the right superior frontal gyrus (x, y, z: 27, 18, 42, ke = 60, F = 3.13, FDRp = 0.04). ADHD+SOM, adolescents with attention deficit hyperactivity disorder (ADHD) with somatic symptoms; ADHD-SOM, adolescents with ADHD without somatic symptoms; FC, functional connectivity; PCC, posterior cingulate cortex.

Fig. 3

Correlations between clinical scale scores and brain functional connectivity. (A) At baseline, the correlation between the K-ARS scores and FC from the PCC seed to the right middle frontal gyrus in the ADHD+SOM group (r = −0.58, p = 0.03). (B) At baseline, the correlation between the K-ARS scores and FC from the PCC seed to the right middle frontal gyrus in the ADHD-SOM group (r = −0.61, p = 0.02). (C) At baseline, the correlation between the SCL-90R-SOM scores with FC from the PCC seed to the right middle frontal gyrus in the ADHD+SOM group (r = −0.56, p = 0.03). (D) At baseline, the correlation between the SCL-90R-SOM scores with FC from the PCC seed to the right middle frontal gyrus in the ADHD+SOM group (r = −0.11, p = 0.69). ADHD+SOM, adolescents with attention deficit hyperactivity disorder (ADHD) with somatic symptoms; ADHD-SOM, adolescents with ADHD without somatic symptoms; B K-ARS, baseline Korean version of Dupaul’s ADHD rating scale; B SCL-90R-SOM, baseline symptom checklist-90- revised-somatization subscale; FC Rt. MFC, functional connectivity (FC) from the posterior cingulate cortex (PCC) seed to the right middle frontal gyrus.

Fig. 4

Correlations between changes in clinical scale scores and brain functional connectivity. (A) During the treatment period, there was a correlation between the change in the K-ARS scores and FC from the PCC seed to the right superior frontal gyrus in the ADHD+SOM group (r = −0.67, p < 0.01). (B) During the treatment period, there was a correlation between the change in the K-ARS and FC from the PCC seed to the right superior frontal gyrus in the ADHD-SOM group (r = −0.60, p = 0.02). (C) During the treatment period, there was a correlation between the change in the SCL-90R-SOM and FC from the PCC seed to the right superior frontal gyrus in the ADHD+SOM group (r = −0.61, p = 0.02). (D) During the treatment period, there was a correlation between the change in the scores of the SCL-90R-SOM and FC from the PCC seed to the right superior frontal gyrus in the ADHD-SOM group (r = −0.09, p = 0.74). ADHD+SOM, adolescents with attention deficit hyperactivity disorder (ADHD) with somatic symptoms; ADHD-SOM, adolescents with ADHD without somatic symptoms; K-ARS, Korean version of Dupaul’s ADHD rating scale; SCL-90R-SOM, symptom checklist-90-revised-somatization subscales; FC Rt. SFG, functional connectivity (FC) from the posterior cingulate cortex (PCC) seed to the right superior frontal gyrus.