Faculty Bibliography

Noradrenergic signaling in the amygdala is important for processing threats and other emotionally salient stimuli, and β-adrenergic receptor activation is known to enhance neuronal spiking in the lateral amygdala (LA) of juvenile animals. Nevertheless, intracellular recordings have not yet been conducted to determine the effect of β-adrenergic receptor activation on spike properties in the adult LA, despite the potential significance of developmental changes between adolescence and adulthood. Here we demonstrate that the β-adrenergic agonist isoproterenol (15 μM) enhances spike frequency in dorsal LA principal neurons of juvenile male C57BL/6 mice and fails to do so in strain- and sex-matched adults. Furthermore, we find that the age-dependent effect of isoproterenol on spike frequency is occluded by the GABA_A receptor blocker picrotoxin (75 μM), suggesting that β-adrenergic receptors downregulate tonic inhibition specifically in juvenile animals. These findings indicate a significant shift during adolescence in the cellular mechanisms of β-adrenergic modulation in the amygdala. NEW & NOTEWORTHY β-Adrenergic receptors (β-ARs) in amygdala are important in processing emotionally salient stimuli. Most cellular recordings have examined juvenile animals, while behavioral data are often obtained from adults. We replicate findings showing that β-ARs enhance spiking of principal cells in the lateral amygdala of juveniles, but we fail to find this in adults. These findings have notable scientific and clinical implications regarding the noradrenergic modulation of threat processing, alterations of which underlie fear and anxiety disorders.

OBJECTIVE:Impulsive choices can lead to suboptimal decision making, a tendency which is especially marked in individuals with ADHD. We compared two different paradigms assessing impulsive choice: the simple choice paradigm (SCP) and the temporal discounting paradigm (TDP). METHOD/METHODS:Random effects meta-analyses on 37 group comparisons (22 SCP; 15 TDP) consisting of 3.763 participants (53% ADHD). RESULTS:Small-to-medium effect sizes emerged for both paradigms, confirming that participants with ADHD choose small immediate over large delayed rewards more frequently than controls. Moderation analyses show that offering real rewards in the SCP almost doubled the odds ratio for participants with ADHD. CONCLUSION/CONCLUSIONS:We suggest that a stronger than normal aversion toward delay interacts with a demotivating effect of hypothetical rewards, both factors promoting impulsive choice in participants with ADHD. Furthermore, we suggest the SCP as the paradigm of choice due to its larger ecological validity, contextual sensitivity, and reliability.

BACKGROUND:Accurate assessment of pediatric bipolar disorder (BD) is important for allocating appropriate treatment, but it is complicated by significant heterogeneity in symptom presentation and high rates of comorbidity. Investigating clinical subtypes of the disorder may help to clarify diagnostic boundaries and inform targeted treatment. This study used a full diagnostic instrument to examine symptom patterns among youth with BD. METHOD:Trained interviewers completed the Washington University Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) with 71 children (7 to 13 y of age) and families as part of the baseline assessment for a randomized clinical trial of Child- and Family-focused Cognitive-Behavioral Therapy (CFF-CBT) compared with treatment as usual (TAU) for pediatric BD. All participants met DSM-IV-TR criteria for a bipolar spectrum disorder. Hierarchical and K-means cluster analyses were performed. Resultant clusters were compared on symptom severity and psychosocial functioning at baseline and across treatment. RESULTS:Two distinct symptom profiles emerged: "dysregulated/defiant" and "classic presentation." The dysregulated/defiant cluster was characterized by more externalizing and disruptive behaviors, whereas the classic cluster presented with more severe depression, hallmark manic symptoms, anxiety, and inattention. CFF-CBT consistently promoted psychosocial coping skills, such as problem solving and self-control, for the dysregulated/defiant cluster. TAU also promoted these skills among the individuals in the classic presentation group but not those with symptoms in the dysregulated/defiant cluster. DISCUSSION:Pediatric BD may be characterized by distinct phenotypes with unique etiologies and pathways to impairment. The use of a parametric approach to classify the diverse symptom presentations helped yield valuable insights into how to promote the best prognosis for improved functional outcomes in CFF-CBT versus TAU for youth with pediatric BD.

Mounting evidence supports a genetic-vascular-inflammatory etiology of schizophrenia. The retina provides an indirect assessment of inflammation and degeneration in the brain. In particular, the use of spectral domain optical coherence tomography (SD-OCT) has emerged as a powerful tool for examining single retinal nerve cell layers and the choroid, the vascular layer supplying the outer retina. In this study, choroidal and macular thicknesses were measured in six patients with psychosis with either schizophrenia or bipolar disorder, and in 18 age- and sex-matched healthy controls. Mean choroidal thickness was reduced in psychosis, though not significantly so. There was a statistically significant decrease in macular thickness in psychosis patients predominantly affecting the inner layers of the macula. Significant macular thinning may signal vascular, inflammatory, or degenerative processes that may also be occurring in the brain. This is one of the first studies to examine choroidal thickness in psychosis. Further studies are needed to determine whether the retinal changes in psychosis are correlated with microvascular dysfunction, neuroinflammation, and neurodegeneration.

OBJECTIVE:Integrating primary care services into specialty mental health clinics has been proposed as a method for improving health care utilization for medical conditions by adults with serious mental illness. This paper examines the impact of a mental health based primary care program on emergency department (ED) visits and hospitalizations. METHOD/METHODS:The program was implemented in seven New York City outpatient mental health clinics in two waves. Medicaid claims were used to identify patients treated in intervention clinics and a control group of patients treated in otherwise similar clinics in New York City. Impacts of the program were estimated using propensity score adjusted difference-in-differences models on a longitudinally followed cohort. RESULTS:Hospital stays for medical conditions increased significantly in intervention clinics relative to control clinics in both waves (ORs = 1.21 (Wave 1) and 1.33 (Wave 2)). ED visits for behavioral health conditions decreased significantly relative to controls in Wave 1 (OR = 0.89), but not in Wave 2. No other significant differences in utilization trends between the intervention and control clinics were found. CONCLUSION/CONCLUSIONS:Introducing primary care services into mental health clinics may increase utilization of inpatient services, perhaps due to newly identified unmet medical need in this population.

Purpose To investigate the temporal and causal relationships of structural changes in the brain in patients with schizophrenia. Materials and Methods T1-weighted magnetic resonance (MR) images of 97 patients with schizophrenia (29 women; mean ± standard deviation age, 41 years ± 11.5; range, 16-66 years; illness duration, 16.3 years ± 10.9; range, 0-50 years) and 126 age- and sex-matched (38 years ± 14.9; range, 18-68 years; 42 women) healthy control subjects were evaluated. The causal network of structural covariance was used to assess the causal relationships of structural changes in patients with schizophrenia. This was accomplished by applying Granger causality analysis to the morphometric T1-weighted images ranked according to duration of disease. Results With greater disease duration, reduction in gray matter volume began in the thalamus and progressed to the frontal lobe, and then to the temporal and occipital cortices as well and the cerebellum (P < .00001, false discovery rate corrected). The thalamus was shown to be the primary hub of the directional network and exhibited positive causal effects on the frontal, temporal, and occipital regions as well as on the cerebellum (P < .05, false discovery rate corrected). The frontal regions, which were identified to be transitional points, projected causal effects to the occipital lobe, temporal regions, and the cerebellum and received causal effects from the thalamus (P < .05, false discovery rate corrected). Conclusion Schizophrenia shows progression of gray matter abnormalities over time, with the thalamus as the primary hub and the frontal regions as prominent nodes.^©RSNA, 2018 Online supplemental material is available for this article.

Severe temper outbursts (STO) in children are associated with impaired school and family functioning and may contribute to negative outcomes. These outbursts can be conceptualized as excessive frustration responses reflecting reduced emotion regulation capacity. The anterior cingulate cortex (ACC) has been implicated in negative affect as well as emotional control, and exhibits disrupted function in children with elevated irritability and outbursts. This study examined the intrinsic functional connectivity (iFC) of a region of the ACC, the anterior midcingulate cortex (aMCC), in 5- to 9-year-old children with STO (n = 20), comparing them to children with attention-deficit/hyperactivity disorder (ADHD) without outbursts (ADHD; n = 18). Additional analyses compared results to a sample of healthy children (HC; n = 18) and examined specific associations with behavioral and emotional dysregulation. Compared to the ADHD group, STO children exhibited reduced iFC between the aMCC and surrounding regions of the ACC, and increased iFC between the aMCC and precuneus. These differences were also seen between the STO and HC groups; ADHD and HC groups did not differ. Specificity analyses found associations between aMCC-ACC connectivity and hyperactivity, and between aMCC-precuneus iFC and emotion dysregulation. Disruption in aMCC networks may underlie the behavioral and emotional dysregulation characteristic of children with STO.