Faculty Bibliography

Reviews the book, Child and Adolescent Psychiatric Clinics of North America: Neuropsychiatric genetic syndromes, edited by Doron Gothelf. The overall goal of the volume appears to be to provide the reader with a small and succinct book to reach for when looking for a description of these, thankfully, infrequently diagnosed disorders. This particular volume is well organized; the division of the volume into a series of articles concerning the general aspects of neuropsychiatry syndromes, covering approaches to diagnosis, (including the new field of imaging genetics), is interesting and informative. There is a comprehensive index, and each chapter has its own bibliography. The graphics, brain imaging, and pictures are of excellent quality (many are in full color) and are clearly explained. On a slightly less positive note, each chapter has different authors, so the writing style varies; as a result, some articles are easier to read than others. This volume of the Child and Adolescent Psychiatry Clinics of North America is a much appreciated reference and review for any clinician desiring to refresh their memory about these disorders.

OBJECTIVE: To investigate whether incidence of twin deliveries is related to father's age, independently of mother's age, and whether it differs for same-sex or opposite-sex twin sets. STUDY DESIGN: In a program of research on effects of paternal age, this study used data from a prospective cohort of 92,408 offspring born in Jerusalem from 1964 to 1976. Of the 91,253 deliveries in the Jerusalem Perinatal Study, 1115 were twin deliveries. The data were analyzed with General Estimate Equations to inform unconditional logistic regression. RESULTS: After controlling for maternal age, odds ratios (ORs) and 95% confidence intervals (95% CI) associated with father's ages 25-34 and 35+ were 1.3 (1.1, 1.7) and 1.5 (1.2, 2.1) respectively, compared with fathers <25 years old. The effect of maternal age was partly explained by paternal age. The ORs for opposite-sex twin sets and male-male twin sets increased slightly with paternal age, while the OR for same-sex and female-female twin decreased. CONCLUSION: Studies of twins are used to estimate effects of genes and environment in a variety of diseases. Our findings highlight the need to consider paternal as well as maternal age when analyzing data on twins to explore etiology of diseases

The objective of this study was to determine the effects and mechanisms of serum amyloid A (SAA) on coronary endothelial function. Porcine coronary arteries and human coronary arterial endothelial cells (HCAECs) were treated with SAA (0, 1, 10, or 25 microg/ml). Vasomotor reactivity was studied using a myograph tension system. SAA significantly reduced endothelium-dependent vasorelaxation of porcine coronary arteries in response to bradykinin in a concentration-dependent manner. SAA significantly decreased endothelial nitric oxide (NO) synthase (eNOS) mRNA and protein levels as well as NO bioavailability, whereas it increased ROS in both artery rings and HCAECs. In addition, the activities of internal antioxidant enzymes catalase and SOD were decreased in SAA-treated HCAECs. Bio-plex immunoassay analysis showed the activation of JNK, ERK2, and IkappaB-alpha after SAA treatment. Consequently, the antioxidants seleno-l-methionine and Mn(III) tetrakis-(4-benzoic acid)porphyrin and specific inhibitors for JNK and ERK1/2 effectively blocked the SAA-induced eNOS mRNA decrease and SAA-induced decrease in endothelium-dependent vasorelaxation in porcine coronary arteries. Thus, SAA at clinically relevant concentrations causes endothelial dysfunction in both porcine coronary arteries and HCAECs through molecular mechanisms involving eNOS downregulation, oxidative stress, and activation of JNK and ERK1/2 as well as NF-kappaB. These findings suggest that SAA may contribute to the progress of coronary artery disease.

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