Ron Steingard

OBJECTIVE: To test by MRI-based morphometry the a priori hypotheses that developmental anomalies exist in attention-deficit hyperactivity disorder (ADHD) in left caudate and right prefrontal/frontal/ and/or posterior parietal hemispheric regions, in accord with neurochemical, neuronal circuitry and attentional network hypotheses, and prior imaging studies. DESIGN: Case-control study. SETTING: Academic medical center. PARTICIPANTS: Fifteen male subjects with ADHD without comorbid diagnoses (aged 12.4 +/- 3.4 years) and 15 male normal controls (aged 14.4 +/- 3.4), group-matched for age, IQ, and handedness. MAIN OUTCOME MEASURES: Global and hemispheric regional volumes (in cm3) of cerebral hemispheres, cortex, white matter, ventricles, caudate, lenticulate, central gray nuclei, insula, amygdala, and hippocampus. RESULTS: Despite similar hemispheric volumes, ADHD subjects had smaller volumes of (1) left total caudate and caudate head (p < 0.04), with reversed asymmetry (p < 0.03); (2) right anterior-superior (frontal) region en bloc (p < 0.03) and white matter (p < 0.01); (3) bilateral anterior-inferior region en bloc (p < 0.04); and (4) bilateral retrocallosal (parietal-occipital) region white matter (p < 0.03). Possible structural correlates of ADHD response to stimulants were noted in an exploratory analysis, with the smallest and symmetric caudate, and smallest left anterior-superior cortex volumes found in the responders, but reversed caudate asymmetry and the smallest retrocallosal white matter volumes noted in the nonresponders. CONCLUSIONS: This study is the first to report localized hemispheric structural anomalies in ADHD, which are concordant with theoretical models of abnormal frontal-striatal and parietal function, and with possible differing morphologic substrates of response to stimulant medication.

OBJECTIVE: Anger attacks are sudden, intense spells of anger associated with a surge of autonomic arousal including such symptoms as tachycardia, sweating, flushing, and a feeling of being out of control. The purpose of this study was to determine whether depressed patients with and without anger attacks exhibit distinct psychological characteristics and whether these attacks respond to treatment with fluoxetine. METHOD: The Anger Attacks Questionnaire, the Hamilton Rating Scale for Depression, the Symptom Questionnaire, and the Cook-Medley Hostility Scale were among the scales administered at the Depression Research Program of the Clinical Psychopharmacology Unit at the Massachusetts General Hospital to 127 medication-free outpatients with major depression and to 85 of these patients after 8 weeks of open treatment with a fixed dose (20 mg/day) of fluoxetine. RESULTS: At baseline, 44% of the depressed outpatients reported having anger attacks; these patients had significantly higher scores on measures of anxiety, somatization, and state and trait hostility than did the subjects who did not exhibit such attacks. After treatment, there were significant reductions in these measures, and the anger attacks disappeared in the majority (71%) of the patients who had previously reported them. There was a trend toward greater overall clinical improvement for patients with anger attacks than for patients without them. CONCLUSIONS: This study identified a subgroup of highly irritable and hostile depressed patients who report the presence of anger attacks and have a psychological profile distinct from that of depressed patients without anger attacks. Furthermore, fluoxetine treatment appears to be beneficial in reducing anger and hostility in these patients.

BACKGROUND AND METHOD: This study tested hypotheses about patterns of familial association between attention deficit disorder (ADD) and anxiety disorders among 356 first-degree relatives of 73 clinically referred children with ADD and 26 normal comparison children. Through structured diagnostic interviews with trained raters, relatives were assessed for adult and childhood psychopathology. After stratifying the sample of ADD probands into those with anxiety disorders and those without, the authors examined patterns of aggregation of ADD and anxiety disorders in the relatives of these probands as well as in the relatives of the normal comparison subjects. RESULTS: Familial risk analyses revealed that 1) familial risk for anxiety disorders was higher among all ADD probands than among the normal subjects; 2) familial risk for ADD was similar in the relatives of the ADD probands and of the probands with ADD and anxiety disorder; 3) the relatives of the ADD probands with and without anxiety disorders were at greater risk for ADD than the relatives of the normal subjects; 4) the risk for anxiety disorders was two times higher in the relatives of the probands who had ADD with anxiety disorder than in those of the ADD probands without anxiety disorders; and 5) there was a tendency for ADD probands' relatives who themselves had ADD to have a higher risk for anxiety disorders than ADD probands' relatives who did not have ADD (cosegregation). CONCLUSIONS: The results were most consistent with the hypotheses indicating that ADD and anxiety disorders segregate independently in families.

We report 7 children who received gabapentin (GBP) as adjunctive medic ation and subsequently developed behavioral side effects. These behavioral changes consisted of intensification of baseline behaviors as well as new behavioral problems. Behaviors that parents considered most troublesome were tantrums, aggression directed toward others, hyperactivity, and defiance. All behavioral changes were reversible and were managed by dose reduction or discontinuation of GBP. All children had baseline attention deficit hyperactivity disorder and developmental delays.

"Anger attacks" are spells of anger that are inappropriate to the situation and have physical features resembling panic attacks. The Anger Attacks Questionnaire, designed to assess these attacks, was administered to 79 consecutive patients (25 men and 54 women, mean age 38.8 +/- 10.3 years) diagnosed as having major depression with the Structured Clinical Interview for DSM-III-R. Of these 79 depressed patients, 34 (13 men and 21 women) reported having anger attacks according to our criteria. The prevalence of anger attacks in a group of 31 younger depressed patients (48%) was significantly higher (p = .048) than that of 29 normal controls (21%) of similar age. Of the 79 depressed patients, 19 (7 men, 12 women) were treated openly with fluoxetine at 20 mg/day for at least 8 weeks. At pretreatment, 9 patients (47%) had reported anger attacks, only 3 (16%) continued to report them after treatment, and the difference was statistically significant (p less than .05).