Faculty Bibliography

OBJECTIVE: Increasing evidence suggests a significant comorbidity between attention-deficit/hyperactivity disorder (ADHD) and restless legs syndrome (RLS). Iron deficiency may underlie common pathophysiological mechanisms in subjects with ADHD plus RLS (ADHD+RLS). To date, the impact of iron deficiency, RLS and familial history of RLS on ADHD severity has been scarcely examined in children. These issues are addressed in the present study. METHODS: Serum ferritin levels, familial history of RLS (diagnosed using National Institutes of Health (NIH) criteria) and previous iron supplementation in infancy were assessed in 12 ADHD+RLS children, 10 ADHD children and 10 controls. RLS was diagnosed using NIH-specific pediatric criteria, and ADHD severity was assessed using the Conners' Parent Rating scale. RESULTS: ADHD symptom severity was higher, although not significantly, in children with ADHD+RLS compared to ADHD. The mean serum ferritin levels were significantly lower in children with ADHD than in the control group (p<0.0005). There was a trend for lower ferritin levels in ADHD+RLS subjects versus ADHD. Both a positive family history of RLS and previous iron supplementation in infancy were associated with more severe ADHD scores. CONCLUSIONS: Children with ADHD and a positive family history of RLS appear to represent a subgroup particularly at risk for severe ADHD symptoms. Iron deficiency may contribute to the severity of symptoms. We suggest that clinicians consider assessing children with ADHD for RLS, a family history of RLS, and iron deficiency.

BACKGROUND: A panel of academic psychiatrists and pharmacists, clinicians from the Texas public mental health system, advocates, and consumers met in June 2006 in Dallas, Tex., to review recent evidence in the pharmacologic treatment of schizophrenia. The goal of the consensus conference was to update and revise the Texas Medication Algorithm Project (TMAP) algorithm for schizophrenia used in the Texas Implementation of Medication Algorithms, a statewide quality assurance program for treatment of major psychiatric illness. METHOD: Four questions were identified via premeeting teleconferences. (1) Should antipsychotic treatment of first-episode schizophrenia be different from that of multiepisode schizophrenia? (2) In which algorithm stages should first-generation antipsychotics (FGAs) be an option? (3) How many antipsychotic trials should precede a clozapine trial? (4) What is the status of augmentation strategies for clozapine? Subgroups reviewed the evidence in each area and presented their findings at the conference. RESULTS: The algorithm was updated to incorporate the following recommendations. (1) Persons with first-episode schizophrenia typically require lower antipsychotic doses and are more sensitive to side effects such as weight gain and extrapyramidal symptoms (group consensus). Second-generation antipsychotics (SGAs) are preferred for treatment of first-episode schizophrenia (majority opinion). (2) FGAs should be included in algorithm stages after first episode that include SGAs other than clozapine as options (group consensus). (3) The recommended number of trials of other antipsychotics that should precede a clozapine trial is 2, but earlier use of clozapine should be considered in the presence of persistent problems such as suicidality, comorbid violence, and substance abuse (group consensus). (4) Augmentation is reasonable for persons with inadequate response to clozapine, but published results on augmenting agents have not identified replicable positive results (group consensus). CONCLUSIONS: These recommendations are meant to provide a framework for clinical decision making, not to replace clinical judgment. As with any algorithm, treatment practices will evolve beyond the recommendations of this consensus conference as new evidence and additional medications become available.

AIM: The trajectory in psychotic disorders which leads from a relatively normal premorbid state in young people to a first episode of psychosis is only partly understood. Qualitative research methods can be used to begin to elucidate the temporal unfolding of symptoms leading to a first episode of psychosis, and its impact on families. METHODS: We conducted open-ended interviews with family members of 13 patients with recent onset non-affective psychotic disorders, which focused on changes observed, effects on the family, explanatory models, help-seeking patterns and future expectations. Standard data analytic methods employed for qualitative research were used. RESULTS: Narratives by family members were remarkably similar. First, social withdrawal and mood symptoms developed in previously normal children; these changes were typically ascribed to drugs or stress, or to the 'storminess' of adolescence. Coping strategies by family members included prayer and reasoning/persuasion with the young person, and family initially sought help from friends and religious leaders. Entry into the mental health system was then catalysed by the emergence of overt symptoms, such as 'hearing voices', or violent or bizarre behaviour. Family members perceived inpatient hospitalization as traumatic or difficult, and had diminished expectations for the future. CONCLUSIONS: Understanding families' explanatory models for symptoms and behavioural changes, and their related patterns of help-seeking, may be useful for understanding evolution of psychosis and for the design of early intervention programmes. Dissatisfaction with hospitalization supports the mandate to improve systems of care for recent-onset psychosis patients, including destigmatization and a focus on recovery

In adult female rats, robust hippocampal changes occur when estradiol rises on the morning of proestrus. Whether estradiol mediates these changes, however, remains unknown. To address this issue, we used sequential injections of estradiol to simulate two key components of the preovulatory surge: the rapid rise in estradiol on proestrous morning, and the slower rise during the preceding day, diestrus 2. Animals were examined mid-morning of simulated proestrus, and compared to vehicle-treated or intact rats. In both simulated and intact rats, CA1-evoked responses were potentiated in hippocampal slices, and presynaptic mechanisms appeared to contribute. In CA3, multiple population spikes were evoked in response to mossy fiber stimuli, and expression of brain-derived neurotrophic factor was increased. Simulation of proestrous morning also improved performance on object and place recognition tests, in comparison to vehicle treatment. Surprisingly, effects on CA1-evoked responses showed a dependence on estradiol during simulated diestrus 2, as well as a dependence on proestrous morning. Increasing estradiol above the physiological range on proestrous morning paradoxically decreased evoked responses in CA1. However, CA3 pyramidal cell activity increased further, and became synchronized. Together, the results confirm that physiological estradiol levels are sufficient to profoundly affect hippocampal function. In addition: (i) changes on proestrous morning appear to depend on slow increases in estradiol during the preceding day; (ii) effects are extremely sensitive to the peak serum level on proestrous morning; and (iii) there are striking subfield differences within the hippocampus

OBJECTIVE: To determine whether a past diagnosis of anorexia nervosa (AN) predicts longitudinal course and outcome among women with bulimia nervosa (BN). METHOD: A subset (n = 176) of participants in the Longitudinal Study of Anorexia and Bulimia Nervosa who met DSM-IV criteria for BN either at study intake (n = 144) or during follow-up (n = 32; 4 had restricting AN at intake, 28 had binge/purge AN at intake) were included in this report. Over a median of 9 years, weekly eating disorder symptom data were collected from participants using the Longitudinal Interview Follow-up Examination, Eating Disorders Version. RESULTS: While there were no between-group differences in likelihood of partial recovery, women with BN who had a history of AN were more likely to have a protracted illness, relapsing into AN during follow-up, compared to those with no AN history who were more likely to move from partial to full recovery. CONCLUSION: Lifetime AN is an important prognostic indicator among women with BN and these longitudinal data would support the subtyping of BN on the basis of AN history.

This study examines the relationship between contextual factors and attendance in a family-based HIV prevention program for low-income, urban, African-American women and their children. Participants' motivations to become involved, their concerns about discussing sex-related issues with their children, recruiters' perceptions of respondents' understanding of the program, and environmental stressors were examined. Participants' level of motivation and recruiters' success in improving respondents' understanding of the program were significant correlates of attendance. Stressors experienced by the family and concerns around talking with children about sex were not significantly associated with participation. Recommendations to enhance involvement in family-based HIV prevention programs are made.

OBJECTIVE: Many studies have linked the structure and function of frontostriatal circuitry to cognitive control deficits in attention deficit hyperactivity disorder (ADHD). Few studies have examined the role of white matter tracts between these structures or the extent to which white matter tract myelination and regularity correlate in family members with the disorder. METHOD: Functional imaging maps from a go/nogo task were used to identify portions of the ventral prefrontal cortex and striatum involved in suppressing an inappropriate action (i.e., cognitive control) in 30 parent-child dyads (N=60), including 20 dyads (N=40) with ADHD and 10 dyads (N=20) without ADHD. An automated fiber-tracking algorithm was used to delineate white matter fibers adjacent to these functionally defined regions based on diffusion tensor images. Fractional anisotropy, an index of white matter tract myelination and regularity derived from diffusion tensor images, was calculated to characterize the associations between white matter tracts and function. RESULTS: Fractional anisotropy in right prefrontal fiber tracts correlated with both functional activity in the inferior frontal gyrus and caudate nucleus and performance of a go/nogo task in parent-child dyads with ADHD, even after controlling for age. Prefrontal fiber tract measures were tightly associated between ADHD parents and their children. CONCLUSIONS: Collectively, these findings support previous studies suggesting heritability of frontostriatal structures among individuals with ADHD and suggest disruption in frontostriatal white matter tracts as one possible pathway to the disorder

Mothers of 110 children with autism spectrum disorders (ASD) were interviewed with the Child and Adolescent Impact Assessment when their children were approximately 9 years old. Regression analyses revealed that African American mothers reported lower levels of perceived negative impact of having a child with ASD than did Caucasian mothers. Higher repetitive behavior scores on the Autism Diagnostic Interview-Revised, lower adaptive behavior scores on the Vineland Adaptive Behavior Scales, and less perceived social support were also significant predictors of higher perceived negative impact. Identifying predictors of perceived negative impact is an important first step in designing interventions to support families and target parents who may be at risk for experiencing higher levels of stress

BACKGROUND: Autism spectrum disorder (ASD) and fetal alcohol spectrum disorder (FASD) are both characterized by social difficulties, but overall clinical descriptions of the two disorders are different. METHOD: Twenty-nine children with autism and 33 children with pervasive developmental disorder-not otherwise specified (PDD-NOS) were compared to 29 children with FASD of equivalent age and full-scale IQ. To isolate social deficits that are most unique to ASD, all participants were administered the Autism Diagnostic Observation Schedule (ADOS). Parents of the children completed the Autism Diagnostic Interview-Revised (ADI-R). RESULTS: Difficulties in initiating social interaction, sharing affect, and using nonverbal communication were common in children with ASD but rare in children with FASD. Socially inappropriate behaviors and difficulty with peers were common in both groups. CONCLUSIONS: These findings suggest that whereas propensity for social interaction appears to be a differentiating factor between children with ASD and those with non-spectrum disorders, impaired quality of social interaction may be less diagnostically discriminative

BACKGROUND: Inconsistent findings obscure understanding the relationship between socioeconomic status (SES) and schizophrenia. The aim of the current study was to test the association between individual and community SES at birth and risk of schizophrenia. METHOD: Population-based longitudinal follow forward study of a 13-year birth cohort (n = 71 165). Effects of individual and community socioeconomic variables were examined using multilevel regression in MLwiN. RESULTS: Years of education of fathers and mothers, respectively, (0-8 vs 13+ odds ratio [OR] = 1.17, P < .0001; OR = 1.14, P < .001) lower occupational status of fathers (OR = 1.29, P = .036), and poorer residential area SES (OR = 1.26, P = .012) were risk factors for schizophrenia. CONCLUSIONS: Individual- and community-level SES at the time of birth are associated with an increased risk of schizophrenia