Faculty Bibliography

Substance use disorders are highly prevalent in the United States and cause considerable damage to our society. They are underrecognized and undertreated despite a vast body of literature demonstrating the efficacy of treatment using both psychosocial and psychopharmacological modalities. For the last decade, research and progress into the biological basis of the addictive process has led to a rapidly growing number of pharmacological agents used to interrupt the addictive process at its various stages such as the initiation of substance abuse, the transition from abuse to dependence, and the prevention of drug reinstatement or relapse. Food and Drug Administration-approved medications exist for nicotine, alcohol, and opioid use disorders, and progress is being made to develop agents for stimulant use disorders. Regarding nicotine use disorders, nicotine replacement therapies,bupropion and varenicline, have Food and Drug Administration approval, and future options exist with endocannabinoid antagonists and immune therapy. Aversive agents, opiate antagonists, and glutamate based interventions are currently approved to treat alcohol use disorders with future promise with GABAergic, serotonergic, and endocannabinoid system agents. Opiate addiction is treated by approved agonist and antagonist mu-opioid medications with the future potential for agents that can modulate the stress systems and the iboga alkaloids. Although no pharmacotherapies are currently approved for cocaine addiction, promising lines of research include agents that affect dopaminergic, GABAergic, serotonergic,and glutamatergic systems as well as the promise for immune therapies

The present study examines the mechanisms by which students' perceptions of family and school experiences moderate the association between their emotionality and their habitual involvement in bullying and victimization. The authors hypothesize that students with internalizing and/or externalizing difficulties are less likely to be categorized as bullies and/or victims if they report coming from more cohesive and adaptable families and attending schools characterized by higher adult monitoring, lower levels of aggression and disorder, and higher levels of school bonding. Home and school environments in which these characteristics are less evident to students were expected to exacerbate the likelihood of being bullies and/or victims. Middle school youth (N = 2,506) and their teachers completed surveys assessing emotionality, peer relationships, academic performance, and home and school contexts. Using multinomial logistic regression, the authors found that perceived climates low in student misconduct increase the likelihood that internalizing difficulties predicted classification as victims. Increased student-reported adult monitoring decreased the likelihood for students with externalizing problems to be characterized as bullies, particularly for girls. These findings have implications for the development of school-based intervention programming

Addiction is increasingly understood as a neurobiological illness where repetitive substance abuse corrupts the normal circuitry of rewarding and adaptive behaviors causing drug-induced neuroplastic changes. The addictive process can be examined by looking at the biological basis of substance initiation to the progression of substance abuse to dependence to the enduring risk of relapse. Critical neurotransmitters and neurocircuits underlie the pathological changes at each of these stages. Enhanced dopamine transmission in the nucleus accumbens is part of the common pathway for the positively rewarding aspects of drugs of abuse and for initiation of the addictive process. F-Aminobutyric acid,opioid peptides, serotonin, acetylcholine, the endocannabinoids, and glutamate systems also play a role in the initial addictive process. Dopamine also plays a key role in conditioned responses to drugs of abuse, and addiction is now recognized as a disease of pathological learning and memory. In the path from substance abuse to addiction, the neurochemistry shifts from a dopamine-based behavioral system to a predominantly glutamate-based one marked by dysregulated glutamate transmission from the prefrontal cortex to the nucleus accumbens in relation to drug versus biologically oriented stimuli. This is a core part of the executive dysfunction now understood as one of the hallmark features of addiction that also includes impaired decision making and impulse dysregulation.Understanding the neurobiology of the addictive process allows for a theoretical psychopharmacological approach to treating addictive disorders,one that takes into account biological interventions aimed at particular stages of the illness

The adoption into the UK of children who have been reared in severely deprived conditions provides an opportunity to study possible association between very early negative experiences and subsequent brain development. This cross-sectional study was a pilot for a planned larger study quantifying the effects of early deprivation on later brain structure. We used magnetic resonance imaging (MRI) to measure the sizes of three key brain regions hypothesized to be sensitive to early adverse experiences. Our sample was a group of adoptee adolescents (N = 14) who had experienced severe early institutional deprivation in Romania and a group of non-institutionalised controls (N = 11). The total grey and white matter volumes were significantly smaller in the institutionalised group compared with a group of non-deprived, non-adopted UK controls. After correcting for difference in brain volume, the institutionalised group had greater amygdala volumes, especially on the right, but no differences were observed in hippocampal volume or corpus callosum mid-sagittal area. The left amygdala volume was also related to the time spent in institutions, with those experiencing longer periods of deprivation having a smaller left amygdala volume. These pilot findings highlight the need for future studies to confirm the sensitivity of the amygdala to early deprivation

OBJECTIVE: The sociocommunicative abnormalities of young children with Williams syndrome (WS) with limited language were compared with those of children with clinical diagnoses of autism, Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), or nonspectrum developmental disability. METHOD: Participants were 30 children with WS and individually matched groups of participants with autism (n = 28), PDD-NOS (n = 17), and mixed etiology nonspectrum developmental disabilities (n = 16). The autism, PDD-NOS, and mixed etiology groups were matched individually to the children with WS for age, sex, and developmental level. All participants were administered the Autism Diagnostic Observation Schedule Module 1 and the Mullen Scales of Early Learning. RESULTS: As a group, children with WS with limited language showed fewer sociocommunicative abnormalities than children with autism, about the same level as children with PDD-NOS, and more abnormalities in reciprocity social interaction than participants in the mixed etiology group. Examination of the subgroup of participants with WS matched and compared with children with PDD-NOS indicated that half of the children showed fewer abnormalities than their individual matches with PDD-NOS, whereas half of the children with WS showed more abnormalities than their matches with PDD-NOS. CONCLUSION: Sociocommunicative difficulties are present for many children with WS and overlap with the autism spectrum. The results of this investigation suggest that these abnormalities are not accounted for by developmental delay alone, and care should be taken to avoid diagnostic overshadowing in young children with WS

BACKGROUND: Increased systemic cytokine levels, modulators of the immune system, have been repeatedly documented in adult and adolescent major depressive disorder (MDD). This preliminary study extends this work to test the role of cytokines in suicidal symptomatology in adolescent MDD. Hypotheses were that acutely suicidal depressed adolescents would have: (1) increased plasma levels of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1beta, and (2) a proinflammatory/antiinflammatory cytokine imbalance (indexed by plasma IFN-gamma/IL-4), compared to nonsuicidal depressed adolescents and healthy controls. METHODS: Twelve suicidal adolescents with MDD (7 females [58%]; 5 medication-free/naive), 18 nonsuicidal adolescents with MDD (12 females [67%]; 8 medication-free/naive), and 15 controls (8 females [53%]) were enrolled. MDD had to be of at least 6 weeks duration, with a minimum severity score of 40 on the Children's Depression Rating Scale-Revised. Plasma cytokines were examined using enzyme-linked immunosorbent assays. Nonparametric tests were used to compare subject groups. RESULTS: Unexpectedly, suicidal adolescents with MDD had significantly decreased plasma TNF-alpha concentrations compared to nonsuicidal adolescents with MDD (1.33 +/- 2.95 pg/mL versus 30.9 +/- 110.9 pg/mL; p = 0.03). IFN-gamma was increased in both suicidal and nonsuicidal adolescents with MDD compared to controls (2.14 +/- 6.22 and 4.20 +/- 14.48 versus 0.37 +/- 0.64; p < 0.02, p = 0.005). Findings remained evident when controlled for age and gender. CONCLUSIONS: Our preliminary findings suggest that immune system dysregulation may be associated with suicidal symptomatology in adolescent MDD. These findings should be replicated in larger samples with medication-free adolescents

The 31st Annual Association for Chemoreception Sciences (AChemS) met in Sarasota, Florida April 22-26, 2009, attracting approximately 600 registrants and nearly 400 abstracts. In addition to poster and platform presentations, the program offered symposia, special lectures, and various National Institutes of Health (NIH)-sponsored workshops, including one on computational approaches to olfaction