Faculty Bibliography

This paper examines factors associated with adherence to antiretroviral medications (ARVs) in an HIV-infected population at high risk for non-adherence: individuals living with psychiatric and substance abuse disorders. Data were examined from baseline interviews of a multisite cohort intervention study of 1138 HIV-infected adults with both a psychiatric and substance abuse disorder (based on a structured psychiatric research interview using DSM-IV criteria). The baseline interview documented mental illness and substance use in the past year, mental illness and substance abuse severity, demographics, service utilization in the past three months, general health and HIV-related conditions, self-reported spirituality and self-reported ARV medication use. Among the participants, 62% were prescribed ARVs at baseline (n = 542) and 45% of those on ARVs reported skipping medications in the past three days. Reports of non-adherence were significantly associated with having a detectable viral load (p<.01). The factors associated with non-adherence were current drug and alcohol abuse, increased psychological distress, less attendance at medical appointments, non-adherence to psychiatric medications and lower self-reported spirituality. Increased psychological distress was significantly associated with non-adherence, independent of substance abuse (p<.05). The data suggest that both mental illness and substance use must be addressed in HIV-infected adults living with these co-morbid illnesses to improve adherence to ARVs

Classical fear-conditioning is central to many etiologic accounts of panic disorder (PD), but few lab-based conditioning studies in PD have been conducted. One conditioning perspective proposes associative-learning deficits characterized by deficient safety learning among PD patients. The current study of PD assesses acquisition and retention of discriminative aversive conditioning using a fear-potentiated startle paradigm. This paradigm was chosen for its specific capacity to independently assess safety- and danger learning in the service of characterizing putative anomalies in each type of learning among those with PD. Though no group difference in fear-potentiated startle was found at retention, acquisition results demonstrate impaired discriminative learning among PD patients as indexed by measures of conditioned startle-potentiation to learned safety and danger cues. Importantly, this discrimination deficit was driven by enhanced startle-potentiation to the learned safety cue rather than aberrant reactivity to the danger cue. Consistent with this finding, PD patients relative to healthy individuals reported higher expectancies of dangerous outcomes in the presence of the safety cue, but equal danger expectancies during exposure to the danger cue. Such results link PD to impaired discrimination learning, reflecting elevated fear responding to learned safety cues.

We examined the differences in conflict interaction between depressed mothers and their toddler and non-depressed dyads and whether these differences mediated the association of maternal depression with compromised child socioemotional development. Mother/ child interaction was videotaped during a teaching task and during a free play task as part of a home visit when the target child was between 16 and 18 months old. Each turn of every conflict was coded for behavior and affect of each member of the dyad. Interaction data were summarized to calculate the number of conflict turns, the rate of conflict, and the proportion of mother-initiated versus child-initiated conflicts per dyad. Sequential analysis was used to estimate the probability of specific maternal responses to specific child behaviors. Bivariate comparisons indicated that depressed dyads experienced higher rates of conflict, especially during the teaching task, and that depressed mothers were more likely to respond destructively to child oppositional behavior. Results of multivariate linear regression indicated that the higher probability of destructive response mediated the association of maternal depression with lower quality of mother-child attachment. These findings have implications for the development of interventions to support mothers in dealing with the conflicts that are so common during the second year of a child's life.

Child maltreatment has been associated with different psychiatric disorders. Studies on both animals and humans have suggested that some brain areas would be directly affected by severe psychological trauma. The pathophysiology of post-traumatic stress disorder (PTSD) appears to be related to a complex interaction involving genetic and environmental factors. Advanced neuroimaging techniques have been used to investigate neurofunctional and neurostructural abnormalities in children, adolescents, and adults with PTSD. This review examined structural brain imaging studies that were performed in abused and traumatized children, and discusses the possible biological mechanisms involved in the pathophysiology of PTSD, the implications and future directions for magnetic resonance imaging (MRI) studies. Published reports in refereed journals were reviewed by searching Medline and examining references of the articles related to structural neuroimaging of PTSD. Structural MRI studies have been performed in adults and children to evaluate the volumetric brain alterations in the PTSD population. In contrast with studies involving adults, in which hippocampus volumetric reduction was the most consistent finding, studies involving children and adolescents with PTSD have demonstrated smaller medial and posterior portions of the corpus callosum

The way in which sex hormones influence cognitive and affective brain development is poorly understood. Despite increasing knowledge in the area of pediatric mood disorders, little is known about the influence of sex hormones on the regulation of emotion. Animal studies and preliminary human studies suggest a strong impact of testosterone on limbic structures such as the hippocampus and amygdala. We used functional magnetic resonance imaging (fMRI) to examine emotional processing in familial male-precocious puberty (FMPP), an extremely rare gonadotropin-independent form of precocious puberty characterized by early excess testosterone secretion. We compared this group (n = 7, mean age = 13 +/- 3.3 years) to healthy age and sex-matched controls (n = 14, mean age = 13 +/- 2.3 years). Participants were presented with emotional and neutral face stimuli and were required either to judge the hostility of the presented face, their subjective level of anxiety, or the width of the nose of the presented faces (nonemotional condition). In a fourth, passive viewing condition, no responses were required. Boys with FMPP responded faster to fearful faces during perception of threat compared to unaffected controls. Concurrently, fMRI data revealed significant differences in hippocampus activation in response to fearful faces relative to baseline whereas controls showed no differences. In contrast, no significant activation of the amygdala was found. These data are consistent with previous studies of the effects of sex hormones on brain function and support the role of testosterone on emotional development.

BACKGROUND: The Early Intervention (EI) Program of the New York City (NYC) Department of Health and Mental Hygiene provides therapeutic services to children under 3 years of age with developmental delays or disabilities. Although the EI Program targets delivery of services within 21 days of the meeting at which the Individualized Family Service Plan (IFSP) is developed, the designation of a service provider alone often takes longer than that. OBJECTIVE: This study examined associations between individual and neighborhood characteristics and timeliness of provider designation in NYC. METHODS: Multivariable logistic regression analyses were performed for 14,623 children who had their initial IFSPs developed in Fiscal Year 2004. RESULTS: Provider designation was delayed 13.4% of the time for speech therapy, 10.0% of the time for special instruction, 8.2% of the time for occupational therapy, and 4.2% of the time for physical therapy. Individual characteristics independently associated with provider designation delay were: being older than 24 months, having the IFSP meeting between July and December, having an adaptive delay, and having speech therapy or special instruction in the IFSP. Neighborhood characteristics independently associated with provider designation delay included living in a low-income neighborhood and living in a heavily Spanish-speaking neighborhood. CONCLUSION: Delayed provider designation occurs because of both individual and neighborhood factors. Interventions are needed to address shortages of providers in certain neighborhoods or with specific skills, and to address surges in administrative program functions at certain times of the year.

This study explores relationships among childhood sexual abuse (CSA), age of substance use initiation, additional traumatic events, and posttraumatic stress disorder (PTSD) in a sample of adolescents. A history of CSA that preceded substance use was not related to an earlier age of substance use initiation. Early initiation of substance use predicted exposure to additional traumatic experiences. This relationship was partially mediated by engagement in risky behavior while under the influence of substances. Posttraumatic stress disorder was related to CSA, additional traumatic experiences and engagement in risky behavior while under the influence of substances

It is hypothesised that autism symptoms are present in Attention-Deficit/Hyperactivity Disorder (ADHD), are familial and index subtypes of ADHD. Autism symptoms were compared in 821 ADHD probands, 1050 siblings and 149 controls. Shared familiality of autism symptoms and ADHD was calculated using DeFries-Fulker analysis. Autism symptoms were higher in probands than siblings or controls, and higher in male siblings than male controls. Autism symptoms were familial, partly shared with familiality of ADHD in males. Latent class analysis using SCQ-score yielded five classes; Class 1(31%) had few autism symptoms and low comorbidity; Classes 2-4 were intermediate; Class 5(7%) had high autism symptoms and comorbidity. Thus autism symptoms in ADHD represent a familial trait associated with increased neurodevelopmental and oppositional/conduct disorders

OBJECTIVE: The diagnosis and treatment of youth with severe nonepisodic irritability and hyperarousal, a syndrome defined as severe mood dysregulation (SMD) by Leibenluft, has been the focus of increasing concern. We conducted the first randomized double-blind, placebo-controlled trial in SMD youth, choosing lithium on the basis of its potential in treating irritability and aggression and neuro-metabolic effects. METHODS: SMD youths 7-17 years were tapered off their medications. Those who continued to meet SMD criteria after a 2-week, single-blind, placebo run-in were randomized to a 6-week double-blind trial of either lithium (n = 14) or placebo (n = 11). Clinical outcome measures were: (1) Clinical Global Impressions-Improvement (CGI-I) score less than 4 at trial's end and (2) the Positive and Negative Syndrome Scale (PANSS) factor 4 score. Magnetic resonance spectroscopy (MRS) outcome measures were myoinositol (mI), N-acetyl-aspartate (NAA), and combined glutamate/glutamine (GLX), all referenced to creatine (Cr). RESULTS: In all, 45% (n = 20/45) of SMD youths were not randomized due to significant clinical improvement during the placebo run-in. Among randomized patients, there were no significant between-group differences in either clinical or MRS outcome measures. CONCLUSION: Our study suggests that although lithium may not result in significant clinical or neurometabolic alterations in SMD youths, further SMD treatment trials are warranted given its prevalence.

Fear extinction, which involves learning to suppress the expression of previously learned fear, requires N-methyl-D-aspartate receptors (NMDARs) and is mediated by the amygdala and ventromedial prefrontal cortex (vmPFC). Like other types of learning, extinction involves acquisition and consolidation phases. We recently demonstrated that NR2B-containing NMDARs (NR2Bs) in the lateral amygdala (LA) are required for extinction acquisition, but whether they are involved in consolidation is not known. Further, although it has been shown that NMDARs in the vmPFC are required for extinction consolidation, whether NR2Bs in vmPFC are involved in consolidation is not known. In this report, we investigated the possible role of LA and vmPFC NR2Bs in the consolidation of fear extinction using the NR2B-selective antagonist ifenprodil. We show that systemic treatment with ifenprodil immediately after extinction training disrupts extinction consolidation. Ifenprodil infusion into vmPFC, but not the LA, immediately after extinction training also disrupts extinction consolidation. In contrast, we also show pre-extinction training infusions into vmPFC has no effect. These results, together with our previous findings showing that LA NR2Bs are required during the acquisition phase in extinction, indicate a double dissociation for the phase-dependent role of NR2Bs in the LA (acquisition, not consolidation) and vmPFC (consolidation, not acquisition)