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.

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.

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.

This study provides preliminary evidence of the feasibility and efficacy of the Stanford cue-centered treatment for reducing posttraumatic stress, depression, and anxiety in children chronically exposed to violence. Sixty-five youth aged 8-17 years were recruited from 13 schools. Participants were randomly assigned to cue-centered treatment or a waitlist control group. Assessments were conducted at 4 discrete time points. Self-report measures assessed youth symptoms of posttraumatic stress disorder (PTSD), anxiety, and depression.Self-report ratings of caregiver anxiety and depression as well as caregiver report of child PTSD were also obtained. Therapists evaluated participants' overall symptom improvement across treatment sessions. Hierarchal linear modeling analyses showed that compared to the waitlist group, the cue-centered treatment group had greater reductions in PTSD symptoms both by caregiver and child report, as well as caregiver anxiety. Cue-centered treatment, a hybrid trauma intervention merging diverse theoretical approaches, demonstrated feasibility,adherence, and efficacy in treating youth with a history of interpersonal violence.

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.

OBJECTIVE: Pediatric bipolar disorder involves poor social functioning, but the neural mechanisms underlying these deficits are not well understood. Previous neuroimaging studies have found deficits in emotional face processing localized to emotional brain regions. However, few studies have examined dysfunction in other regions of the face processing circuit. This study assessed hypoactivation in key face processing regions of the brain in pediatric bipolar disorder. METHOD: Youth with a bipolar spectrum diagnosis (n = 20) were matched to a nonbipolar clinical group (n = 20), with similar demographics and comorbid diagnoses, and a healthy control group (n = 20). Youth participated in a functional magnetic resonance imaging (fMRI) scanning which employed a task-irrelevant emotion processing design in which processing of facial emotions was not germane to task performance. RESULTS: Hypoactivation, isolated to the fusiform gyrus, was found when viewing animated, emerging facial expressions of happiness, sadness, fearfulness, and especially anger in pediatric bipolar participants relative to matched clinical and healthy control groups. CONCLUSIONS: The results of the study imply that differences exist in visual regions of the brain's face processing system and are not solely isolated to emotional brain regions such as the amygdala. Findings are discussed in relation to facial emotion recognition and fusiform gyrus deficits previously reported in the autism literature. Behavioral interventions targeting attention to facial stimuli might be explored as possible treatments for bipolar disorder in youth.