Faculty Bibliography

Depression is associated with alterations in hormone and catecholamine circadian rhythms. Analysis of these alterations has the potential to distinguish between three neurobiological models of depression, the catecholamine model, the phase advance model and the dysregulation model. Although a number of studies of 24-h rhythms have been reported, inconsistencies among the findings have complicated efforts to model the chronobiology of depression. The present study takes advantage of frequent plasma sampling over the 24-h period and a multioscillator cosinor model to fit the 24-h rhythms. METHOD: Plasma levels of norepinephrine, cortisol, prolacatin and growth hormone were sampled at 30-min intervals, and MHPG at 60-min intervals, over a 24-h period in 22 patients with major depressive disorder and 20 healthy control volunteers. RESULTS: The depressed patients had phase advanced circadian rhythms for cortisol, norepinephrine and MHPG, phase advanced hemicircadian rhythms for cortisol and prolactin, and a phase advanced ultradian rhythm for prolactin compared to healthy control subjects. In addition, the rhythm-corrected 24-h mean value (mesor) of norepinephrine was lower in the depressed patients compared to the healthy controls. There also was a poorer goodness-of-fit for norepinephrine to the circadian oscillator in the depressed patients relative to the healthy controls. CONCLUSIONS: These findings provide partial support for the dysregulation model of depression and are consistent with those studies that have found phase advances in cortisol, norepinephrine and MHPG rhythms in depression

INTRODUCTION: An expanding database supports the notion that the deficit syndrome (DS) is a discrete condition within schizophrenia and recent data argues that Smell Identification Deficits (SID) may have a primary relationship with its pathophysiology. If so, then the relationship of University of Pennsylvania Smell Identification Test (UPSIT) scores with other neurocognitive measures in DS patients may point to the neural substrate of the deficit syndrome. METHOD: We examined the relationship of UPSIT scores and Wechsler Adult Intelligence Scale-Revised (WAIS-R) performance in 46 DSM-IV schizophrenia patients. The Schedule for the Deficit Syndrome (SDS) interview was used to subgroup the sample into 13 DS and 33 nondeficit syndrome (NDS) patients. RESULTS: DS and NDS groups had similar mean ages, age of onset, and GAF scores, but DS patients had fewer years of education. DS and NDS patients also did not differ in full scale, verbal or performance IQ or in any WAIS-R subtest. However, UPSIT scores were significantly worse in the DS patients, most of whom met criteria for a clinically meaningful olfactory impairment. In DS patients, UPSIT scores were significantly correlated with Performance IQ, Block Design, and Object Assembly, all of which are associated with complex visual-motor organizational function thought to be mediated by parietal circuitry. UPSIT scores in NDS patients were significantly related with Vocabulary, Similarities, and Digit Symbol subtests, which are indicative of verbal functioning. CONCLUSION: These preliminary data support previous findings suggesting that in addition to frontal neuropsychological abnormalities, DS patients may have greater performance impairments on tasks associated with parietal functioning. Our findings furthermore suggest that the parietal circuitry may be a conspicuous substrate for impaired odor identification ability in these patients. The lesser abnormalities in UPSIT ability in NDS patients may be attributed to verbal ability. These data are preliminary and further investigations with larger samples are needed to support our findings

OBJECTIVE: To test the hypothesis that multimodal psychosocial intervention, which includes parent training, combined with methylphenidate significantly enhances the behavior of parents of children with attention-deficit/hyperactivity disorder (ADHD), compared with methylphenidate alone and compared with methylphenidate and nonspecific psychosocial treatment (attention control). METHOD: One hundred three children with ADHD (ages 7-9), free of conduct and learning disorders, who responded to short-term methylphenidate therapy were randomized for 2 years to receive either (1) methylphenidate treatment alone; (2) methylphenidate plus psychosocial treatment that included parent training and counseling, social skills training, academic assistance, and psychotherapy; or (3) methylphenidate plus attention control treatment. Parents rated their knowledge of parenting principles and negative and positive parenting behavior. Children rated their parents' behavior. RESULTS: Psychosocial treatment led to significantly better knowledge of parenting principles but did not enhance parenting practices, as rated by parents and children. Significant improvement in mothers' negative parenting occurred across all treatments and was maintained. CONCLUSIONS: In nonconduct-disordered, stimulant-treated children with ADHD, parent training does not improve self-rated parental behavior. The benefits of brief stimulant treatment for negative parental behavior are sustained with extended treatment

OBJECTIVE: To test the hypotheses that in children with attention-deficit/hyperactivity disorder (ADHD) (1) symptoms of ADHD, oppositional defiant disorder, and overall functioning are significantly improved by methylphenidate combined with intensive multimodal psychosocial treatment compared with methylphenidate alone and with methylphenidate plus attention control and (2) more children receiving combined treatment can be taken off methylphenidate. METHOD: One hundred three children with ADHD (ages 7-9), free of conduct and learning disorders, who responded to short-term methylphenidate were randomized for 2 years to (1) methylphenidate alone; (2) methylphenidate plus psychosocial treatment that included parent training and counseling, social skills training, psychotherapy, and academic assistance, or (3) methylphenidate plus attention psychosocial control treatment. Assessments included parent, teacher, and psychiatrist ratings, and observations in academic and gym classes. RESULTS: Combination treatment did not lead to superior functioning and did not facilitate methylphenidate discontinuation. Significant improvement occurred across all treatments and continued over 2 years. CONCLUSIONS: In stimulant-responsive children with ADHD, there is no support for adding ambitious long-term psychosocial intervention to improve ADHD and oppositional defiant disorder symptoms. Significant benefits from methylphenidate were stable over 2 years

OBJECTIVE: To describe the rationale, methodology, and sample characteristics of a dual-site treatment study (New York and Montreal) of children with attention-deficit/hyperactivity disorder (ADHD) conducted between 1990 and 1995. The hypotheses were that (1) methylphenidate combined with comprehensive multimodal psychosocial treatment was superior to methylphenidate alone in improving multiple functions and (2) the efficacy of the psychosocial intervention resulted from its specific components and not from nonspecific treatment effects. METHOD: One hundred three children with ADHD (ages 7-9), free of conduct and learning disorders, who responded to methylphenidate, were randomized for 2 years to (1) methylphenidate treatment alone; (2) methylphenidate combined with multimodal psychosocial treatment that included parent training and counseling, academic assistance, psychotherapy, and social skills training; or (3) methylphenidate plus attention control treatment that excluded specific aspects of the psychosocial intervention. Children were switched to single-blind placebo after 12 months; methylphenidate was reinstituted when clinically indicated. Assessments included ratings by parents, teachers, children, and psychiatrists; school observations in academic and gym classes; and academic performance tests. Almost 80% of families completed the 2-year study. Companion papers present treatment effects. CONCLUSIONS: A comprehensive 2-year psychosocial treatment was delivered successfully to children with ADHD and their families

In many altricial species, fear responses such as freezing do not emerge until sometime later in development. In infant rats, fear to natural predator odors emerges around postnatal day (PN) 10 when infant rats begin walking. The behavioral emergence of fear is correlated with two physiological events: functional emergence of the amygdala and increasing corticosterone (CORT) levels. Here, we hypothesize that increasing corticosterone levels influence amygdala activity to permit the emergence of fear expression. We assessed the relationship between fear expression (immobility similar to freezing), amygdala function (c-fos) and the level of corticosterone in pups in response to presentation of novel male odor (predator), littermate odor and no odor. CORT levels were increased in PN8 pups (no fear, normally low CORT) by exogenous CORT (3 mg/kg) and decreased in PN12 pups (express fear, CORT levels higher) through adrenalectomy and CORT replacement. Results showed that PN8 expression of fear to a predator odor and basolateral/lateral amygdala activity could be prematurely evoked with exogenous CORT, while adrenalectomy in PN12 pups prevented both fear expression and amygdala activation. These results suggest that low neonatal CORT level serves to protect pups from responding to fear inducing stimuli and attenuate amygdala activation. This suggests that alteration of the neonatal CORT system by environmental insults such as alcohol, stress and illegal drugs, may also alter the neonatal fear system and its underlying neural control

This study investigated demographic and cognitive correlates of cued odor identification in a population-based sample from the Betula project: 1906 healthy adults varying in age from 45 to 90 years were assessed in a number of tasks tapping various cognitive domains, including cognitive speed, semantic memory and executive functioning. The results revealed a gradual and linear deterioration in cued odor identification across the adult life span. Overall, females identified more odors than men, although men and women performed at the same level in the oldest age cohort (85-90 years). Hierarchical regression analyses revealed that age, sex, education, cognitive speed and vocabulary were reliable correlates of performance in the odor identification task. In addition, age-related deficits in the included demographic and cognitive variables could not fully account for the observed age-related impairment in identification, suggesting that additional factors are underlying the observed deterioration. Likely candidates here are sensory abilities such as olfactory detection and discrimination.

It is currently believed that the acquisition of classically conditioned fear involves potentiation of conditioned thalamic inputs in the lateral amygdala (LA). In turn, LA cells would excite more neurons in the central nucleus (CE) that, via their projections to the brain stem and hypothalamus, evoke fear responses. However, LA neurons do not directly contact brain stem-projecting CE neurons. This is problematic because CE projections to the periaqueductal gray and pontine reticular formation are believed to generate conditioned freezing and fear-potentiated startle, respectively. Moreover, like LA, CE may receive direct thalamic inputs communicating information about the conditioned and unconditioned stimuli. Finally, recent evidence suggests that the CE itself may be a critical site of plasticity. This review attempts to reconcile the current model with these observations. We suggest that potentiated LA outputs disinhibit CE projection neurons via GABAergic intercalated neurons, thereby permitting associative plasticity in CE. Thus plasticity in both LA and CE would be necessary for acquisition of conditioned fear. This revised model also accounts for inhibition of conditioned fear after extinction

Children who experience homelessness are at increased risk for a range of health and mental health problems. In spite of this increased risk, they are often less likely to receive appropriate services. School-based programs offer considerable potential to reduce the gap between needs and appropriate services for these youth; however, there are few examples of such programs in the published literature. This article provides information from a mental and physical health prevention program and needs assessment for at-risk children, who were experiencing homelessness or were from very low-income families, which was piloted during a summer camp program in an urban school. Results of the needs assessment indicated that children residing in homeless shelters reported less consistent access to medical and dental care than children residing with their families. It is interesting that children experiencing homelessness were more likely to report that they had participated in counseling than did children from low-income families. Satisfaction ratings of prevention activities conducted in the program were positive for students and teachers.