Faculty Bibliography

Aquaporin-4 (AQP4) is the major water channel expressed in the central nervous system (CNS) and is primarily expressed in glial cells. Many studies have shown that AQP4 regulates the response of the CNS to insults or injury, but far less is known about the potential for AQP4 to influence synaptic plasticity or behavior. Recent studies have examined long-term potentiation (LTP), long-term depression (LTD), and behavior in AQP4 knockout (KO) and wild-type mice to gain more insight into its potential role. The results showed a selective effect of AQP4 deletion on LTP of the Schaffer collateral pathway in hippocampus using an LTP induction protocol that simulates pyramidal cell firing during theta oscillations (theta-burst stimulation; TBS). However, LTP produced by a different induction protocol was unaffected. There was also a defect in LTD after low frequency stimulation (LFS) in AQP4 KO mice. Interestingly, some slices from AQP4 KO mice exhibited LTD after TBS instead of LTP, or LTP following LFS instead of LTD. These data suggest that AQP4 and astrocytes influence the polarity of long-term synaptic plasticity (potentiation or depression). These potentially powerful roles expand the influence of AQP4 and astrocytes beyond the original suggestions related to regulation of extracellular potassium and water balance. Remarkably, AQP4 KO mice did not show deficits in basal transmission, suggesting specificity for long-term synaptic plasticity. The mechanism appears to be related to neurotrophins and specifically brain-derived neurotrophic factor (BDNF) because pharmacological blockade of neurotrophin trk receptors or scavenging ligands such as BDNF restored plasticity. The in vitro studies predicted effects in vivo of AQP4 deletion because AQP4 KO mice performed worse using a task that requires memory for the location of objects (object placement). However, performance on other hippocampal-dependent tasks was spared. The results suggest an unanticipated and selective role of AQP4 in synaptic plasticity and spatial memory, and underscore the growing appreciation of the role of glial cells in functions typically attributed to neurons. Implications for epilepsy are discussed because of the previous evidence that AQP4 influences seizures, and the role of synaptic plasticity in epileptogenesis.

BACKGROUND: Advanced paternal age (APA) is associated with increased risk for schizophrenia, but its effect on treatment response has not been longitudinally studied. METHODS: Association of parental ages at the time of the child's birth with age of onset, initial symptom severity and treatment response (to placebo and three different weight-based doses of paliperidone ER) in adolescents with schizophrenia was assessed in a post-hoc analysis using data from a 6-week double-blind study, the primary results of which are published (NCT00518323). RESULTS: The mean (SD) paternal age was 29.2 (6.2) years, range (16-50) and maternal age was 26.8 (5.7) years, range (17-42) at childbirth for the 201 adolescents (ages 12-17years) included in the analysis. While parental ages were uncorrelated with age of onset or initial symptom severity, both maternal and paternal ages showed significant effects on treatment response (p<0.03) of all paliperidone ER arms versus placebo. Paternal age was significantly correlated to improvement in positive symptoms and maternal age significantly related to negative symptoms, although only paternal age remained significantly associated with the treatment response in analyses that included both parents' ages. CONCLUSIONS: APA was associated with greater treatment response to both paliperidone ER and placebo, but not to age of onset or initial symptom severity in adolescents with schizophrenia. The results support the contention that APA-related schizophrenia has distinct underpinnings from other cases. Further studies are required to explore the role of genetic and environmental factors, and their interactions, in treatment response in this complex disorder.

Progress disseminating and implementing evidence-based psychological treatments (EBPTs) for the anxiety disorders has been gradual. To date, the dominant approach for promoting the uptake of EBPTs in clinical settings has been to target the education and training of mental health providers, with many consumers remaining unaware of the potential benefits of EBPTs for anxiety disorders. Direct-to-consumer (DTC) marketing may be a promising vehicle for increasing EBPT utilization rates in the treatment of anxiety disorders. This paper provides an overview of the rationale and important considerations for applying DTC efforts to promote evidence-based care in the treatment of anxiety disorders, and reviews current DTC efforts in this area, including resources on the Internet and other media and in-person events. We conclude with recommendations for future efforts in the DTC marketing of EBPTs for the anxiety disorders, including the need for increased funding and grassroots efforts to inform consumers about anxiety disorders and their most effective treatments.

We examined whether error monitoring, operationalized as the degree to which individuals slow down after committing an error (i.e., posterror slowing), is differentially important in the learning of rule-based versus information-integration category structures. Rule-based categories are most efficiently solved through the application of an explicit verbal strategy (e.g., "sort by color"). In contrast, information-integration categories are believed to be learned in a trial-by-trial, associative manner. Our results indicated that posterror slowing predicts enhanced rule-based but not information-integration category learning. Implications for multiple category-learning systems are discussed.

Over the past decade there has been increasing interest in the idea that marriage and perhaps other forms of interpersonal support can buffer the negative effects of poverty. The current study tests the hypothesis that marital status, perceived social support and neighborhood collective efficacy can moderate the effects of economic adversity on depressive symptoms among parents. Hierarchical Linear Modeling was used to analyze data from the Project on Human Development in Chicago Neighborhoods. Participants were 1,957 mothers of minor children. Analysis of main effects revealed associations between neighborhood SES (beta = -0.69, SE (0.15), p < .001), family income (beta = -0.11, SE (0.05), p = .02) financial strain (beta = 0.51, SE (0.18), p = .004), being single (beta = 0.63, SE (0.24), p = .009) and perceived social support (beta = -0.22, SE (0.03), p < .001) on depressive symptoms. The hypothesis that interpersonal resources can buffer the effects of economic adversity was not supported. There were no significant interactions between marital status and economic adversity. There was a significant interaction between perceived social support and neighborhood level socioeconomic status (beta = -0.07, SE (0.03), p = .04) but the effects of social support were weakest in neighborhoods characterized by low socioeconomic status.

Greater knowledge of cortical brain regions in reward processing may set the stage for using transcranial magnetic stimulation (TMS) as a treatment in patients with avolition, apathy or other drive-related symptoms. This study examined the effects of single pulse (sp) TMS to two reward circuit targets on drive in healthy subjects. Fifteen healthy subjects performed the monetary incentive delay task (MID) while receiving fMRI-guided spTMS to either inferior parietal lobe (IPL) or supplemental motor area (SMA). The study demonstrated decreasing reaction times (RT) for increasing reward. It also showed significant differences in RT modulation for TMS pulses to the IPL versus the SMA. TMS pulses during the delay period produced significantly more RT slowing when targeting the IPL than those to the SMA. This RT slowing carried over into subsequent trials without TMS stimulation, with significantly slower RTs in sessions that had targeted the IPL compared to those targeting SMA. The results of this study suggest that both SMA and IPL are involved in reward processing, with opposite effects on RT in response to TMS stimulation. TMS to these target cortical regions may be useful in modulating reward circuit deficits in psychiatric populations.

Relations between parental socialization and infants' prosocial behavior were investigated in sixty three 18- and 30-month old children. Parents' socialization techniques (e.g., directives, negotiation, reasoning) differed for the two age groups, as did relations between socialization and different forms of emerging prosocial behavior (helping; sharing).

Effective navigation of the social world relies on the correct interpretation of facial emotions. This may be particularly important in formative years. Critically, literature examining the emergence of face processing in youth (children and adolescents) has focused on the neural and behavioral correlates of processing adult faces, which are relationally different from youth participants, and whose facial expressions may convey different meaning than faces of their peers. During a functional magnetic resonance imaging (fMRI) scan, we compared concurrent neural and behavioral responses as youth (N=25) viewed validated, emotionally varied (i.e., anger, fear, happy, and neutral) adult and child face stimuli. We observed that participants made fewer errors when matching adult, compared to child, face stimuli, and that while similar brain regions were involved in processing both adult and child faces, activation in the face processing neural network was greater for adult than child faces. This was true across emotions, and also when comparing neutral adult versus neutral child faces. Additionally, a valence by stimuli-type effect was observed within the amygdala. That is, within adult face stimuli, negative and neutral face stimuli elicited the largest effects, whereas within child face stimuli, happy face stimuli elicited the largest amygdala effects. Thus, heightened engagement of the amygdala was observed for happy child and angry adult faces, which may reflect age-specific salience of select emotions in early life. This study provides evidence that the relational age of the perceived face influences neural processing in youth.

In reconsolidation studies, memories are typically retrieved by an exposure to a single conditioned stimulus (CS). We have previously demonstrated that reconsolidation processes are CS-selective, suggesting that memories retrieved by the CS exposure are discrete and reconsolidate separately. Here, using a compound stimulus in which two distinct CSs are concomitantly paired with the same aversive unconditioned stimulus (US), we show in rats that reexposure to one of the components of the compound CS triggers extinction or reconsolidation of the other component. This suggests that the original training conditions play a critical role in memory retrieval and reconsolidation.