Faculty Bibliography

This study assessed the efficacy, durability, and tolerability of fluoxetine for hypochondriasis, a disorder for which controlled pharmacological trials are scarce. Fifty-seven patients with hypochondriasis were enrolled: 12 discontinued during the placebo run-in, and 45 were randomized to either fluoxetine or placebo for 12 weeks (acute treatment). Responder status was defined as a Clinical Global Impression rating for hypochondriasis of much or very much improved. Secondary outcome measures included severity of hypochondriasis, somatization, anxiety, and depression. Responders to acute treatment entered a 12-week maintenance phase to week 24. Sustained responders at week 24 entered a 12-week double-masked discontinuation phase. Primary analysis used the intent-to-treat sample. More patients responded with improvement in hypochondriasis when given fluoxetine compared with placebo, starting at week 8 (50.0% vs 19.0%, P = 0.03) and continuing to week 12 (62.5% vs 33.3%, P = 0.05). Mean dose at week 12 dose was 51.4 mg (SD, +/-23 mg). The acute treatment response was maintained to week 24 with more responders in the fluoxetine compared with the placebo group (54.2% vs 23.8%, P = 0.04). Significant improvement was not noted on the continuous secondary outcomes measures of hypochondriasis, with the exception of the Clinical Global Impression hypochondriasis severity scale at week 24. Likelihood of response was not associated with severity of psychiatric comorbidity. Durability of response after controlled drug discontinuation could not be reasonably assessed, given the small sample size of patients who entered the discontinuation phase (n = 10). Fluoxetine was well tolerated, with no significant differences in discontinuation due to side effects between treatment groups. Fluoxetine is a moderately effective and well-tolerated treatment for hypochondriasis

Brain development in the first 2 years after birth is extremely dynamic and likely plays an important role in neurodevelopmental disorders, including autism and schizophrenia. Knowledge regarding this period is currently quite limited. We studied structural brain development in healthy subjects from birth to 2. Ninety-eight children received structural MRI scans on a Siemens head-only 3T scanner with magnetization prepared rapid gradient echo T1-weighted, and turbo spin echo, dual-echo (proton density and T2 weighted) sequences: 84 children at 2-4 weeks, 35 at 1 year and 26 at 2 years of age. Tissue segmentation was accomplished using a novel automated approach. Lateral ventricle, caudate, and hippocampal volumes were also determined. Total brain volume increased 101% in the first year, with a 15% increase in the second. The majority of hemispheric growth was accounted for by gray matter, which increased 149% in the first year; hemispheric white matter volume increased by only 11%. Cerebellum volume increased 240% in the first year. Lateral ventricle volume increased 280% in the first year, with a small decrease in the second. The caudate increased 19% and the hippocampus 13% from age 1 to age 2. There was robust growth of the human brain in the first two years of life, driven mainly by gray matter growth. In contrast, white matter growth was much slower. Cerebellum volume also increased substantially in the first year of life. These results suggest the structural underpinnings of cognitive and motor development in early childhood, as well as the potential pathogenesis of neurodevelopmental disorders.

Many adults with attention-deficit/hyperactivity disorder (ADHD) were never diagnosed as children. The impairment caused by untreated ADHD can complicate, or even lead to, other psychiatric conditions. Accurate diagnosis and efficacious treatment of ADHD in adults, which may include pharmacologic and nonpharmacologic interventions, is vital to improve their functioning. When a patient has ADHD and a co-occurring condition, the clinician should usually treat the most impairing condition first

With the widespread availability of functional magnetic resonance imaging (fMRI), there has been rapid progress in identifying neural correlates of cognition and emotion in the human brain. In conjunction with basic research studies, fMRI has been increasingly applied in clinical disorders, making it a central research tool in human psychopathology, psychopharmacology, and genetics. In the present article, we discuss a number of conceptual and methodological challenges that confront the implementation of fMRI in clinical and translational research, and we offer a set of recommendations intended to enhance the interpretability and reproducibility of results in clinical fMRI.

Filtering of redundant or stable inputs is a critical function of all sensory pathways. Normal sensory gating can allow processing resources to be differentially devoted to changing or otherwise biologically significant stimuli. In olfaction, short-term odor habituation is mediated by a metabotropic glutamate receptor (mGluR)-mediated depression of afferent synapses in the piriform cortex. Given the role of early experience in shaping cortical function and anatomy, the present experiments examined the effects of chronic habituation disruption during development on behavior and local circuit anatomy. Rats were chronically intra-cerebrally infused with the mGluR group III antagonist (RS)-a-cyclopropyl-4-phosphonophenylglycine (CPPG) during early development. The results demonstrated that early onset mGluRIII blockade resulted in a long-lasting decrement in odor habituation compared to controls, evident for at least 2 weeks post-infusion offset. Odor investigation time in the youngest animals was correlated with cortical laminar thickness, though the long-lasting behavioral effect showed no such correlation. No changes in apical dendritic spine density in the piriform cortex were detected. Combined with previous work, these results suggest that sensory gating disruption during development can have both immediate and long-lasting effects on sensory-guided behavior

Fear learning is a rapid and persistent process that promotes defense against threats and reduces the need to relearn about danger. However, it is also important to flexibly readjust fear behavior when circumstances change. Indeed, a failure to adjust to changing conditions may contribute to anxiety disorders. A central, yet neglected aspect of fear modulation is the ability to flexibly shift fear responses from one stimulus to another if a once-threatening stimulus becomes safe or a once-safe stimulus becomes threatening. In these situations, the inhibition of fear and the development of fear reactions co-occur but are directed at different targets, requiring accurate responding under continuous stress. To date, research on fear modulation has focused mainly on the shift from fear to safety by using paradigms such as extinction, resulting in a reduction of fear. The aim of the present study was to track the dynamic shifts from fear to safety and from safety to fear when these transitions occur simultaneously. We used functional neuroimaging in conjunction with a fear-conditioning reversal paradigm. Our results reveal a unique dissociation within the ventromedial prefrontal cortex between a safe stimulus that previously predicted danger and a 'naive' safe stimulus. We show that amygdala and striatal responses tracked the fear-predictive stimuli, flexibly flipping their responses from one predictive stimulus to another. Moreover, prediction errors associated with reversal learning correlated with striatal activation. These results elucidate how fear is readjusted to appropriately track environmental changes, and the brain mechanisms underlying the flexible control of fear

OBJECTIVE: The Strategies to Enhance Positive Parenting (STEPP) program was developed to address putative factors related to poor engagement in and outcomes following traditional behavioral parent training (BPT) for single mothers of children diagnosed with ADHD. METHOD: Twelve single mothers of children with ADHD were enrolled in an initial investigation of the feasibility and preliminary efficacy of the 9-week STEPP program. RESULTS: Results indicated that the STEPP program was effective in reducing problematic child behavior and improving parental stress and psychopathology at posttreatment. The STEPP program resulted in high rates of treatment attendance and completion and consumer satisfaction with the program. However, results also indicated that the STEPP program did not improve childrens' overall psychosocial impairment and resulted in small effect size findings across measures. CONCLUSION: The results of the pilot study are encouraging but indicate a need to improve the potency and delivery of certain aspects of the STEPP program.

Mothers of children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for an ADHD diagnosis themselves, which is likely associated with impairments in parenting. The present study utilized a multi-method assessment of maternal ADHD and parenting to examine the extent to which maternal ADHD symptoms are associated with maladaptive parenting. Participants included 70 6-10 year old children with DSM-IV ADHD and their biological mothers. Results suggested that mothers with higher levels of ADHD symptoms reported lower levels of involvement and positive parenting and higher levels of inconsistent discipline. During observed parent-child interactions, maternal ADHD symptoms were negatively associated with positive parenting, and positively associated with negative parenting and repeated commands before giving the child an opportunity to comply. Given prior research suggesting that maladaptive parenting behaviors are risk factors for the later development of conduct problems among children with ADHD, these findings have important clinical implications for family-based assessment and treatment of ADHD

OBJECTIVE: This study investigated pediatrician-reported practices in identifying, assessing, and treating traumatic exposure and posttraumatic stress disorder (PTSD) in children. METHOD: Focus groups guided the development of a survey that was mailed to primary care pediatricians in Massachusetts in 2005. Descriptive statistics and multivariate analyses were used to describe clinical practices and perceived barriers to care. RESULTS: A 60% (N=597) survey response-rate was obtained. On average, pediatricians reported that less than 8% of patients had psychological problems that may be related to traumatic exposure. Only 18% of pediatricians agreed that they had adequate knowledge of childhood PTSD. About 15% of pediatricians reported frequently learning about traumatic event(s) from direct inquiry in the past year. Only 10% of pediatricians reported frequent assessment and treatment of posttraumatic stress symptoms. Most pediatricians (72%) agreed that greater collaborations with mental health providers would improve pediatric assessment of PTSD. Finally, having received PTSD-specific training and believing that pediatricians should identify and manage PTSD were each significantly associated with learning about a traumatic event from direct inquiry. CONCLUSION(S): Providing PTSD-specific training and changing pediatricians' attitudes about childhood PTSD may be useful first steps in improving care for children