Usable fMRI data were acquired from subjects with bipolar disorder (N=43), ADHD (N=18), and severe mood dysregulation (N=29) as well as healthy comparison subjects (N=37). Participants, ages 8 to 17 years, were enrolled in an Institutional Review Board-approved study at the National Institute of Mental Health. Parents and youths gave written informed consent/assent. Patients were recruited through advertisements to mental health support groups and mental healthcare professionals. Healthy comparison subjects were recruited by advertisement and had no lifetime psychiatric diagnoses and no first-degree relatives with a mood disorder.
Subjects were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime Version (K-SADS-PL) (35 (link)). Interviewers were master's- and doctoral-level clinicians, with excellent interrater reliability (κ>0.9 for all diagnoses, including differentiating bipolar disorder from severe mood dysregulation). Diagnoses were based on best-estimate procedures generated in a consensus conference led by two psychiatrists. Youths with bipolar disorder met “narrow phenotype” criteria, with at least one DSM-IV full-duration hypomanic/manic episode characterized by abnormally elevated mood and at least three B mania symptoms (1 (link)). Youths with severe mood dysregulation had nonepisodic irritability, overreactivity to negative emotional stimuli ≥3 times per week, and hyperarousal (i.e., at least three of the following symptoms: insomnia, distractibility, psychomotor agitation, racing thoughts/flight of ideas, pressured speech, intrusiveness). Symptoms began before age 12; were present for at least 1 year, with no symptom-free periods exceeding 2 months; and caused severe impairment in at least one setting (i.e., home, school, peer) and mild impairment in another. Euphoric mood or distinct episodes lasting more than 1 day were exclusionary (1 (link)). Youths with ADHD met DSM-IV criteria for ADHD but not for severe mood dysregulation or any mood disorder. In the ADHD group, anxiety disorders were exclusionary, except for separation anxiety and social phobia.
The Wechsler Abbreviated Scale of Intelligence was administered to determine IQ. To evaluate mood in patients with bipolar disorder or severe mood dysregulation, clinicians with interrater reliability (κ>0.9) administered the Children's Depression Rating Scale and the Young Mania Rating Scale to the parent and child within 48 hours of scanning. Elevated Young Mania Rating Scale scores in patients with severe mood dysregulation reflect hyperarousal symptoms because, by definition (1 (link)), patients with this type of mood dysregulation cannot meet criteria for hypomania, mania, or a mixed episode.
Exclusion criteria for all subjects were an IQ <70, a history of head trauma, a neurological disorder, a pervasive developmental disorder, an unstable medical illness, or substance abuse/dependence. Patients with ADHD taking short-acting stimulants were included but were medication-free for ≥48 hours before scanning. Thus, both healthy comparison subjects and ADHD patients were medication-free at testing. Patients receiving medication for bipolar disorder or severe mood dysregulation were included. For ethical reasons, only those patients who were not responding to current psychotropic medication were withdrawn from treatment.
One hundred eighty-six subjects were scanned, yielding 127 (68.3%) usable scans. Groups differed in the proportion of excluded scans (p=0.02) but not in reasons for exclusion. Relative to patients with bipolar disorder, more severe mood dysregulation patients (p<0.01) and healthy comparison subjects (p=0.02) had unusable scans. Of the 59 excluded scans, 25 were excluded for poor behavioral data (no response ≥7 times), 22 for a >3.5-mm movement in any plane, and 12 for technical malfunction. Data from 20 bipolar disorder patients and 12 healthy comparison subjects have been published previously (11 (link)). Thus, among the 127 participants studied, data from 95 have not been presented previously.
Subjects were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime Version (K-SADS-PL) (35 (link)). Interviewers were master's- and doctoral-level clinicians, with excellent interrater reliability (κ>0.9 for all diagnoses, including differentiating bipolar disorder from severe mood dysregulation). Diagnoses were based on best-estimate procedures generated in a consensus conference led by two psychiatrists. Youths with bipolar disorder met “narrow phenotype” criteria, with at least one DSM-IV full-duration hypomanic/manic episode characterized by abnormally elevated mood and at least three B mania symptoms (1 (link)). Youths with severe mood dysregulation had nonepisodic irritability, overreactivity to negative emotional stimuli ≥3 times per week, and hyperarousal (i.e., at least three of the following symptoms: insomnia, distractibility, psychomotor agitation, racing thoughts/flight of ideas, pressured speech, intrusiveness). Symptoms began before age 12; were present for at least 1 year, with no symptom-free periods exceeding 2 months; and caused severe impairment in at least one setting (i.e., home, school, peer) and mild impairment in another. Euphoric mood or distinct episodes lasting more than 1 day were exclusionary (1 (link)). Youths with ADHD met DSM-IV criteria for ADHD but not for severe mood dysregulation or any mood disorder. In the ADHD group, anxiety disorders were exclusionary, except for separation anxiety and social phobia.
The Wechsler Abbreviated Scale of Intelligence was administered to determine IQ. To evaluate mood in patients with bipolar disorder or severe mood dysregulation, clinicians with interrater reliability (κ>0.9) administered the Children's Depression Rating Scale and the Young Mania Rating Scale to the parent and child within 48 hours of scanning. Elevated Young Mania Rating Scale scores in patients with severe mood dysregulation reflect hyperarousal symptoms because, by definition (1 (link)), patients with this type of mood dysregulation cannot meet criteria for hypomania, mania, or a mixed episode.
Exclusion criteria for all subjects were an IQ <70, a history of head trauma, a neurological disorder, a pervasive developmental disorder, an unstable medical illness, or substance abuse/dependence. Patients with ADHD taking short-acting stimulants were included but were medication-free for ≥48 hours before scanning. Thus, both healthy comparison subjects and ADHD patients were medication-free at testing. Patients receiving medication for bipolar disorder or severe mood dysregulation were included. For ethical reasons, only those patients who were not responding to current psychotropic medication were withdrawn from treatment.
One hundred eighty-six subjects were scanned, yielding 127 (68.3%) usable scans. Groups differed in the proportion of excluded scans (p=0.02) but not in reasons for exclusion. Relative to patients with bipolar disorder, more severe mood dysregulation patients (p<0.01) and healthy comparison subjects (p=0.02) had unusable scans. Of the 59 excluded scans, 25 were excluded for poor behavioral data (no response ≥7 times), 22 for a >3.5-mm movement in any plane, and 12 for technical malfunction. Data from 20 bipolar disorder patients and 12 healthy comparison subjects have been published previously (11 (link)). Thus, among the 127 participants studied, data from 95 have not been presented previously.
