Faculty Bibliography

Several natural lipids have emerged as candidate modulators of central nervous system (CNS) functions. Fatty acid amides and their coupled signaling pathways are known to regulate several physiological and behavioral processes. Recent studies from our laboratory and others also have implicated endogenous marijuana-like brain constituents, endocannabinoids (ECs), and cannabinoid-1 (CB1) receptors in the neural circuitry that mediate drug addiction and neuropsychiatric disorders. Neuroadaptation to chronic ethanol (EtOH) has been shown to involve changes in the EC system. These changes include alterations in the synthesis of EC, their precursors, as well as density and coupling efficacy of CB1 receptors. The evidence for the participation of the EC system in the pathophysiology of various neuropsychiatric disorders is just beginning to evolve. It is of great interest to explore the components of EC system in different areas of the CNS for further understanding of its role in health and disease. This article presents a comprehensive overview of the currently available literature pertaining to the role of the EC system in alcoholism, schizophrenia, depression and/or suicide

STUDY OBJECTIVE: To review evidence on the association between restless legs syndrome (RLS) and attention-deficit/hyperactivity disorder (ADHD), to discuss the hypothetical mechanisms underlying this association, and to consider the potential interest for common pharmacologic treatments of RLS and ADHD when co-occurring. METHOD: A PubMed search. RESULTS: In clinical samples, up to 44% of subjects with ADHD have been found to have RLS or RLS symptoms, and up to 26% of subjects with RLS have been found to have ADHD or ADHD symptoms. Several mechanisms may explain this association. Sleep disruption associated with RLS might lead to inattentiveness, moodiness, and paradoxical overactivity. Diurnal manifestations of RLS, such as restlessness and inattention, might mimic ADHD symptoms. Alternatively, RLS might be comorbid with idiopathic ADHD. Subjects with RLS and a subset of subjects with ADHD might share a common dopamine dysfunction. Limited evidence suggests that some dopaminergic agents, such as levodopa/carbidopa, pergolide, and ropinirole, may be effective in children with RLS associated with ADHD symptoms. CONCLUSIONS: Although still limited, evidence from clinical studies demonstrates an association between RLS and ADHD or ADHD symptoms. Further clinical studies using standard criteria and procedures are needed to better estimate the degree of association. Epidemiologic studies are required to assess the relationship between ADHD and RLS symptoms in nonclinical samples. Further investigations should address the mechanisms underlying the relationship between RLS and ADHD. Several dopaminergic agents seem to be promising treatment for RLS associated with ADHD symptoms. To date, however, the absence of randomized and blinded controlled studies does not allow evidence-based recommendations.

Functional magnetic resonance imaging in association with an instructed fear/anticipatory anxiety paradigm was used to explore sex differences in the human fear response. During anticipation of mild electrodermal stimulation, women, as compared with men, demonstrated increased activity in the subgenual anterior cingulate cortex and functionally related regions of the insula and brainstem. The subgenual anterior cingulate cortex is a region critical for emotional control implicated in the pathogenesis of psychiatric disease. Present findings suggest a contributory neural substrate for the greater susceptibility of women to anxiety and affective disorders, and emphasize the importance of considering participant sex when designing and interpreting functional neuroimaging studies

OBJECTIVE: The aim of this study was to assess the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, for executive functioning in adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: Two identical studies using a double-blind, placebo-controlled, parallel design were conducted. Patients were adults (Study 1, n = 280; Study 2, n = 256) with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)-defined ADHD recruited by referral and advertising. They were randomized to 10 weeks of treatment with atomoxetine or placebo. Executive functions were measured by the Stroop task. RESULTS: There was no evidence of cognitive deterioration associated with atomoxetine treatment. Atomoxetine treatment was associated with an improvement of the Stroop colorword score. CONCLUSIONS: Our results provide further support for Spencer et al.'s (1998) report that atomoxetine improves inhibitory capacity, as measured by the Stroop task. The absence of cognitive deterioration from atomoxetine, along with improved performance in a subgroup of patients in this large study, supports the safety of atomoxetine in this regard and its potential for improving a significant source of impairment for adults with ADHD

INTRODUCTION: Anxiety disorders in adults involve aberrant processing of emotional information that is hypothesized to reflect perturbations in the amygdala. This study examines the relationship between face-emotion recognition and anxiety in a sample of children and adolescents participating in a brain-imaging study of amygdala structure and function. METHODS: This study recruited 15 children and adolescents with ongoing anxiety disorders and 11 psychiatrically healthy comparisons group-matched on age, gender, and IQ. Face-emotion recognition was assessed using the Diagnostic Analysis of Nonverbal Accuracy Scale (DANVA). RESULTS: Children and adolescents with anxiety disorders exhibited significantly poorer performance on the face-emotion recognition task compared to healthy controls (z = 2.2; p < 0.05). This difference was found only for expressions posed by adults but not children. Discussion: Reduced accuracy on a face-emotion recognition test is consistent with perturbed amygdala function in pediatric anxiety disorders. CONCLUSION: As this study was conducted in a sample undergoing a neuroimaging investigation of amygdala integrity, future analyses will examine associations among amygdala function, clinical anxiety, and face-recognition abilities.

OBJECTIVE: Characterize maturation of transcallosal inhibition (ipsilateral silent period [iSP]) in attention deficit/hyperactivity disorder (ADHD) using transcranial magnetic stimulation (TMS). BACKGROUND: Maturation of the iSP is related to acquisition of fine motor skills in typically developing children suggesting that dexterous fine motor skills depend upon mature interhemispheric interactions. Since neuromotor maturation is abnormal in boys with ADHD we hypothesized that iSP maturation in these children would be abnormal. We studied iSP maturation in 12 boys with ADHD and 12 age-matched, typically developing boys, 7-13 years of age. METHODS: Surface electromyographic activity was recorded from right first dorsal interosseus (FDI). During background activation, focal TMS was delivered at maximal stimulator output over the ipsilateral motor cortex. RESULTS: Maturation of finger speed in boys with ADHD was significantly slower than that in the control group. The iSP latency decreased with age in the control group but not in the ADHD group. CONCLUSIONS: These findings suggest the presence of a complex relationship between abnormalities of certain interhemispheric interactions (as represented by iSP latency) and delayed maturation of neuromotor skills in boys with ADHD. SIGNIFICANCE: These data provide preliminary physiologic evidence supporting delayed or abnormal development of interhemispheric interactions in boys with ADHD

Three dimensions of temperament -- difficult temperament, unadaptablility and unsociability -- were assessed in the first year of life by maternal interview in twins born in Puerto Rico during 2001 and 2002. Eight hundred and sixty-five eligible mothers (80%) were traced and interviewed. Model-fitting results showed that additive genetic factors and the individual specific environment contributed to variation in all three dimensions. In addition, the pattern of variances and correlations suggested that sibling contrast effects influence ratings of difficult temperament. Moderate effects of the shared environment contributed to ratings of adaptability and sociability. There was a significant genetic correlation between difficult temperament and unadaptability. Genetic and environmental effects do not differ significantly between boys and girls. The study is the first population-based study of Puerto Rican twins and one of few to attempt the assessment of behavior in the first year. Preliminary results for difficult temperament and sociability were consistent with those in other populations and ages. In contrast, a significant effect of the shared environment on the temperamental trait of unadaptability has not been reported previously.

This study reports a one-year prospective investigation of the relations between overt and relational victimization and social anxiety and phobia in a sample of adolescents. The Social Experience Questionnaire-Self Report Form (SEQ-S), Social Anxiety Scale for Adolescents (SAS-A), and Social Phobia and Anxiety Inventory for Children (SPAI-C) were administered to 144 ninth grade adolescents. A follow-up assessment with the SEQ-S, SAS-A, and SPAI-C was conducted one year later. Results indicated that relational victimization predicted symptoms of social phobia but not general social anxiety and avoidance one year later. Overt victimization was not a significant predictor of social anxiety and phobia one year later. Social anxiety and phobia did not predict peer victimization one year later. However, increases in social anxiety and social phobia symptoms (for boys) over time were positively associated with increases in relational victimization over time. Implications of these findings for peer victimization and social anxiety in the development of social phobia and negative peer experiences are discussed

OBJECTIVE: There has been limited research on anxiety in pediatric bipolar disorder (BPD). Adult BPD studies suggest comorbid anxiety disorders are common and impact treatment outcome. We explored the association of comorbid anxiety with two phenotypes of pediatric BPD. METHODS: We studied two groups of children. The first group (BPD; N = 31) represents the "narrow phenotype" of pediatric BPD, meeting stringent DSM-IV criteria for mania, including duration and elevated/expansive mood. The second group (ED; N = 32) exhibited chronic, non-episodic irritability without elation or grandiosity ("broad phenotype"). RESULTS: Both samples demonstrate high prevalence of anxiety (BPD 77.4%; ED 46.9%). In the BPD sample, anxiety predates BPD onset, and those with comorbid anxiety have earlier age of onset of BPD than those without. Children with BPD plus anxiety have more hospitalizations than those without anxiety. ED subjects with and without comorbid anxiety did not differ with respect to onset of ED symptoms or number of hospitalizations. CONCLUSIONS: Narrow and broad phenotype BPD children have high rates of comorbid anxiety, although only in the narrow phenotype group is comorbid anxiety associated with greater functional impairment BPD plus comorbid anxiety may represent a particularly severe phenotype of pediatric BPD.