Faculty Bibliography

Introduction and method. Tic disorders can be severe enough to be incapacitating, but in most cases the observation of tics should alert the clinician to the possible presence of other conditions that may be more impairing even if less directly observable. The comorbid diagnoses that are best documented are obsessive compulsive disorder and attention deficit/hyperactivity disorder (ADHD). Conclusions. Treatment of Tourette syndrome combined with ADHD is often challenging. Alpha 2 agonists, such as guanfacine, or non stimulant options such as atomoxetine, where available, are worth considering, although many individuals with Tourette syndrome and ADHD can be successfully treated with judicious doses of stimulant medications

Neuroleptics are generally highly effective in suppressing tics, but their many adverse effects limit their usefulness. Animal studies have shown that, compared with both typical and atypical neuroleptics, metoclopramide has effects that are regionally circumscribed to rat motor striatum. Based on this observation and two prior case reports, metoclopramide was openly prescribed and individually titrated to diminish tics in 10 patients with Tourette syndrome. All patients improved on the Yale Global Tic Severity Scale by an average of 55%. Although we did not observe frank extrapyramidal symptoms, including tardive dyskinesia, these data are not sufficient to support clinical recommendations because of many limitations, including the absence of systematic ratings of nontic abnormal movements. However, controlled clinical studies and additional basic investigations of metoclopramide are warranted

An emerging literature on the neuroanatomical correlates of social cognition in pervasive developmental disorders is reviewed. Studies conducted with high-functioning adults with autism or Asperger's syndrome highlight patterns of decreased activation in ventromedial prefrontal cortex, temporo-parietal junction, amygdala, and periamygdaloid cortex, along with aberrantly increased activation in primary sensory cortices. Future studies should extend these important initial results to younger and more severely affected subjects

OBJECTIVE: To examine brain-behavior relationships in attention deficit hyperactivity disorder (ADHD), the authors obtained magnetic resonance imaging (MRI) scans of monozygotic twins discordant for ADHD. METHOD: National recruitment was followed by in-person assessment. MRI scans were measured algorithmically for nine pairs of monozygotic twins discordant for ADHD. RESULTS: The affected twins had significantly smaller caudate volumes (mean difference=-0.56 ml, CI=-0.92 to -0.21) than their unaffected co-twins. CONCLUSIONS: These results provide further support for striatal models of ADHD pathophysiology

Findings from the Watamura, Donzella, Alwin, and Gunnar (this issue) study support the growing recognition of the importance of context on physiology and affective and behavioral regulation early in human development. This discussion focuses on the role of context and development on hypothalamic-pituitary-adrenal (HPA) axis regulation in young children. Discussed in this article are the Watamura et al. findings with regard to relevant animal studies, extension of these observations to samples of children at elevated risk for psychopathology, and experimental prevention studies with young children. It is contended that environmental factors operating at key points in development may shape affective and behavioral regulation as well as HPA axis function in children, much as environmental factors have been shown to shape HPA axis regulation in animals

OBJECTIVE: Childhood-onset schizophrenia is a severe and unremitting form of the disorder. Prospective brain magnetic resonance imaging (MRI) studies have found progressive loss of total cerebral volume during adolescence, primarily attributable to accelerated loss of cortical gray matter. Because there is evidence of cerebellar involvement in schizophrenia, the authors examined cerebellar volume and its relation to cortical gray matter development during adolescence in patients with childhood-onset schizophrenia and healthy comparison subjects. METHOD: Total cerebellar volume was algorithmically calculated for 108 anatomical brain MRI scans from 50 patients (20 of whom were female) and 101 scans from 50 age- and gender-matched healthy volunteers (20 of whom were female). The age range of the patients and comparison subjects was 8 to 24. Midsagittal vermal area and posterior-inferior vermal lobe volume were measured by hand. Prospective rescans were obtained at approximately 2-year intervals. Cross-sectional and longitudinal data were combined in mixed model regressions to compare developmental changes for the groups. RESULTS: In contrast to healthy volunteers, patients with schizophrenia showed a progressive loss of cerebellar volume during adolescence. Cerebellar and cerebral volume decreases were significantly correlated in childhood-onset schizophrenia. CONCLUSIONS: Childhood-onset schizophrenia is associated with significant progressive loss of cerebellar volume during adolescence, consistent with previously reported decreases in total cerebral and cortical gray matter. At least in these patients with severe early-onset schizophrenia, the loss appears secondary to a generalized process

OBJECTIVE: Nongenetic factors and phenomenology of attention-deficit/hyperactivity disorder (ADHD) were examined in monozygotic (MZ) twin pairs discordant for ADHD. METHOD: Recruitment included telephone screening (n = 297 pairs), behavioral ratings obtained from parents and teachers (n = 59 pairs), and, finally, in-person assessment (n = 25 pairs; structured classroom observation, diagnostic interview, psychoeducational evaluation, birth record review, establishment of monozygosity, and anatomic brain imaging). Affected twins were further contrasted with previously studied affected singletons. RESULTS: Of the 25 MZ twin pairs qualifying for in-person evaluation, only 10 proved discordant for ADHD. Affected twins were mostly comparable with affected singletons on clinical measures, although fathers' self-ratings of childhood ADHD status were significantly lower in twins than in singletons. CONCLUSIONS: Discordance for ADHD in MZ twins appears to be ascribable to greater environmental discordance and decreased familiality. Despite these differences, affected twins were phenotypically comparable with affected singletons. Thus MZ twins discordant for ADHD, while rare, can inform research on the etiology and pathophysiology of this disorder

Neuroimaging techniques are increasingly being applied to the study of attention-deficit/hyperactivity disorder (ADHD). This review focuses on magnetic resonance imaging studies of the brain anatomy of ADHD. Such studies were first conducted over a decade ago, and most focus on frontal-striatal regions and tend to find smaller volumes in ADHD children than in controls. Recently published analyses with the largest sample so far of patients and controls found that ADHD is associated with a statistically significant 3% to 4% global reduction in brain volume in both boys and girls, with abnormally small caudate nuclei only being found in younger patients. After adjusting for global brain differences, only cerebellar hemispheric volumes remained significantly smaller in ADHD, and these differences continued throughout childhood and adolescence. Pathophysiological models of ADHD need take into account cerebellar dysfunction, as well as prefrontal-striatal dysregulation