Faculty Bibliography

Measures of human mental development suggest that behavioral skills displayed during early life can predict an individual's subsequent cognitive performance. Support for this draws from longitudinal studies that reveal compelling within-subject correlations during childhood. If this idea applies across the life span, then correlations in performance should persist into adulthood. Here, we address this prediction in juvenile and adult gerbils by evaluating within-subject measures of auditory learning and perception. Animals were trained and tested as juveniles on either an amplitude modulation (AM) or a frequency modulation (FM) detection task. Measures of learning and perception obtained from juveniles were then compared to similar measures obtained when each subject was tested in adulthood on either the same task or the untrained task. For animals trained and tested on the AM detection task as juveniles and adults, there was no correlation between juvenile and adult learning metrics, or perceptual sensitivity. For animals trained and tested on FM detection as juveniles, we observed a significant relationship to their adult performance. Juveniles that performed the best on FM detection were the poorest at AM detection, and the best at FM detection, when tested as adults. Thus, across-age correlations for sensory and cognitive measures, obtained during development and in adulthood, depend heavily on the specific type of developmental experience and the outcome measure. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Psychogenic seizures (PSs) convincingly mimic seizure phenomena but with no underlying epileptic activity. However, not much is known about their neurophysiological basis. We had the rare opportunity to analyze intracranial brain recordings of PSs occurring besides epileptic seizures (ESs), which identified distinct frequency changes over the parietal cortex. For further validation, we applied topographic frequency analysis to two other patients who presented PSs and ESs during long-term monitoring. The analysis revealed a power decrease in the theta band at the posterior parietal cortex in all three patients during PSs but not during ESs. These changes may reflect disturbed self-referential processing associated with some PSs.

OBJECTIVE: Psychotic symptoms are common in the population and index risk for a range of severe psychopathological outcomes. We wished to investigate functional connectivity in a community sample of adolescents who reported psychotic symptoms (the extended psychosis phenotype). METHOD: This study investigated intrinsic functional connectivity (iFC) during resting-state functional magnetic resonance imaging (fMRI; rs-fMRI). Following screening in schools, 11 non-treatment seeking, youth with psychotic symptoms (aged 11-13) and 14 community controls participated in the study. Seed regions of interest comprised brain regions previously shown to exhibit aberrant activation during inhibitory control in adolescents with psychotic symptoms. RESULTS: Relative to controls, adolescents with psychotic symptoms exhibited reduced iFC between regions supporting inhibitory control. Specifically, they showed weaker iFC between the right inferior frontal gyrus (IFG) and the cingulate, IFG and the striatum, anterior cingulate and claustrum, and precuneus and supramarginal gyrus. Conversely, the psychotic symptoms group exhibited stronger iFC between the superior frontal gyrus and claustrum and IFG and lingual gyrus. CONCLUSION: The present findings are the first to reveal aberrant functional connectivity in resting-state networks in a community sample of adolescents with psychotic symptoms and suggest that disruption in integration between distributed neural networks (particularly between prefrontal, cingulate and striatal brain regions) may be a key neurobiological feature of the extended psychosis phenotype.

We examined whether conversion to dementia can be predicted by self-reported olfactory impairment and/or by an inability to identify odors. Common forms of dementia involve an impaired sense of smell, and poor olfactory performance predicts cognitive decline among the elderly. We followed a sample of 1529 participants, who were within a normal range of overall cognitive function at baseline, over a 10-year period during which 159 were classified as having a dementia disorder. Dementia conversion was predicted from demographic variables, Mini-Mental State Examination score, and olfactory assessments. Self-reported olfactory impairment emerged as an independent predictor of dementia. After adjusting for effects of other predictors, individuals who rated their olfactory sensitivity as "worse than normal" were more likely to convert to dementia than those who reported normal olfactory sensitivity (odds ratio [OR] = 2.17; 95% confidence interval [CI] [1.40, 3.37]). Additionally, low scores on an odor identification test also predicted conversion to dementia (OR per 1 point increase = 0.89; 95% CI [0.81, 0.98]), but these two effects were additive. We suggest that assessing subjective olfactory complaints might supplement other assessments when evaluating the risk of conversion to dementia. Future studies should investigate which combination of olfactory assessments is most useful in predicting dementia conversion.

Psychiatric disorders have been hypothesized to originate during development, with genetic and environmental factors interacting in the etiology of disease. Therefore, developmentally regulated genes have received attention as risk modulators in psychiatric diseases. Reelin is an extracellular protein essential for neuronal migration and maturation during development, and its expression levels are reduced in psychiatric disorders. Interestingly, several perinatal insults that increase the risk of behavioral deficits alter Reelin signaling. However, it is not known whether a dysfunction in Reelin signaling during perinatal stages increases the risk of psychiatric disorders. Here we used a floxed dab1 allele to study whether a transient decrease in Dab1, a key component of the Reelin pathway, is sufficient to induce behavioral deficits related to psychiatric disorders. We found that transient Dab1 downregulation during perinatal stages leads to permanent abnormalities of structural layering in the neocortex and hippocampus. In contrast, conditional inactivation of the dab1 gene in the adult brain does not result in additional layering abnormalities. Furthermore, perinatal Dab1 downregulation causes behavior impairments in adult mice, such as deficits in memory, maternal care, pre-pulse inhibition, and response to cocaine. Some of these deficits were also found to be present in adolescence. We also show that D-cycloserine rescues the cognitive deficits observed in floxed dab1 mice with layering alterations in the hippocampus and neocortex. Our results indicate a causal relation between the downregulation of Dab1 protein levels during development and the structural and behavioral deficits associated with psychiatric diseases in the adult.

The Child PTSD Symptom Scale (Foa, Johnson, Feeny, & Treadwell, ) is a self-report measure of posttraumatic stress disorder symptoms (PTSD) in children and adolescents. Despite widespread use of this measure, no study to our knowledge has examined its psychometric properties in Latino children. This study examined the factor structure, internal consistency, and convergent validity of the measure utilizing a sample of 161 Latino students (M = 11.42 years, SD = 0.70) at high risk of exposure to community violence. Confirmatory factor analyses suggested that a 3-factor model consistent with the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR; American Psychiatric Association, ) provided the best fit to the data. Internal consistency of the total scale and subscales was high when completed in English or Spanish. All Child PTSD Symptom Scale scores were positively correlated with violence exposure. As additional evidence of convergent validity, scores evidenced stronger correlations with internalizing symptoms than with externalizing symptoms. Results supported the use of the Child PTSD Symptom Scale as a measure of PTSD severity in Latino children, but additional research is needed to determine appropriate clinical cutoffs for Latino youths exposed to chronic levels of violence. Implications for clinical practice and future research are discussed.

Anxiety-related disorders are among the most common psychiatric illnesses, thought to have both genetic and environmental causes. Early-life trauma, such as abuse from a caregiver, can be predictable or unpredictable, each resulting in increased prevalence and severity of a unique set of disorders. In this study, we examined the influence of early unpredictable trauma on both the behavioral expression of adult anxiety and gene expression within the amygdala. Neonatal rats were exposed to unpaired odor-shock conditioning for 5days, which produces deficits in adult behavior and amygdala dysfunction. In adulthood, we used the Light/Dark box test to measure anxiety-related behaviors, measuring the latency to enter the lit area and quantified urination and defecation. The amygdala was then dissected and a microarray analysis was performed to examine changes in gene expression. Animals that had received early unpredictable trauma displayed significantly longer latencies to enter the lit area and more defecation and urination. The microarray analysis revealed over-represented genes related to learning and memory, synaptic transmission and trans-membrane transport. Gene ontology and pathway analysis identified highly represented disease states related to anxiety phenotypes, including social anxiety, obsessive-compulsive disorders, post-traumatic stress disorder and bipolar disorder. Addiction-related genes were also overrepresented in this analysis. Unpredictable shock during early development increased anxiety-like behaviors in adulthood with concomitant changes in genes related to neurotransmission, resulting in gene expression patterns similar to anxiety-related psychiatric disorders.

We propose a fused lasso logistic regression to analyze callosal thickness profiles. The fused lasso regression imposes penalties on both the l1-norm of the model coefficients and their successive differences, and finds only a small number of non-zero coefficients which are locally constant. An iterative method of solving logistic regression with fused lasso regularization is proposed to make this a practical procedure. In this study we analyzed callosal thickness profiles sampled at 100 equal intervals between the rostrum and the splenium. The method was applied to corpora callosa of elderly normal controls (NCs) and patients with very mild or mild Alzheimer's disease (AD) from the Open Access Series of Imaging Studies (OASIS) database. We found specific locations in the genu and splenium of AD patients that are proportionally thinner than those of NCs. Callosal thickness in these regions combined with the Mini Mental State Examination scores differentiated AD from NC with 84% accuracy.