Faculty Bibliography

Abstract Background: Poor sleep, common during pregnancy, is associated with negative health risks. The study aimed to identify predictors of clinically significant insomnia among pregnant Latinas. Methods: A total of 1289 pregnant Latinas recruited from obstetric clinics completed the Insomnia Severity Index (ISI) and questions about demographics and sleep. Results: Clinically significant insomnia (ISI>/=10) was present among 17% of participants. Significant correlates of clinically significant insomnia were higher scores on the Edinburgh Postnatal Depression Scale (EPDS) after removing the sleep item (47% of women with EPDS>/=9 and 9% with EPDS<9), completing measures in English (rather than Spanish: 26% versus 13%), and income but not pregnancy week, age, highest education level, or marital status. The highest percentage of clinically significant insomnia (59%) was experienced by women with EPDS>/=9 who completed measures in English. The lowest percentage of clinically significant insomnia (6.2%) was experienced by women with EPDS<9 who completed measures in Spanish. Conclusions: In this sample of low-income, mostly Spanish-speaking pregnant Latinas, rates of clinically significant insomnia appear to be higher than rates among nonpregnant Latinas. Rates of clinically significant insomnia are particularly high among Latinas with elevated depressive symptom severity, a known risk for insomnia. Acculturation, as indicated by completing measures in English, may be another risk specific to Latinas, possibly owing to loss of some ethnicity-specific protective factors (e.g., social support, strong family ties, and group identity). It will be important to directly test this explanation in future research.

A recent meta-regression of antidepressant efficacy on baseline depression severity has caused considerable controversy in the popular media. A central source of the controversy is a lack of clarity about the relation of meta-regression parameters to corresponding parameters in models for subject-level data. This paper focuses on a linear regression with continuous outcome and predictor, a case that is often considered less problematic. We frame meta-regression in a general mixture setting that encompasses both finite and infinite mixture models. In many applications of meta-analysis, the goal is to evaluate the efficacy of a treatment from several studies, and authors use meta-regression on grouped data to explain variations in the treatment efficacy by study features. When the study feature is a characteristic that has been averaged over subjects, it is difficult not to interpret the meta-regression results on a subject level, a practice that is still widespread in medical research. Although much of the attention in the literature is on methods of estimating meta-regression model parameters, our results illustrate that estimation methods cannot protect against erroneous interpretations of meta-regression on grouped data. We derive relations between meta-regression parameters and within-study model parameters and show that the conditions under which slopes from these models are equal cannot be verified on the basis of group-level information only. The effects of these model violations cannot be known without subject-level data. We conclude that interpretations of meta-regression results are highly problematic when the predictor is a subject-level characteristic that has been averaged over study subjects.

BACKGROUND: The negative consequences of olfactory dysfunction for the quality of life are not widely appreciated and the condition is therefore often ignored or trivialized. METHODS: 1,000 patients with olfactory dysfunction participated in an online study by submitting accounts of their subjective experiences of how they have been affected by their condition. In addition, they were given the chance to answer 43 specific questions about the consequences of their olfactory dysfunction. RESULTS: Although there are less practical problems associated with impaired or distorted odor perception than with impairments in visual or auditory perception, many affected individuals report experiencing olfactory dysfunction as a debilitating condition. Smell loss-induced social isolation and smell loss-induced anhedonia can severely affect quality of life. CONCLUSIONS: Olfactory dysfunction is a serious condition for those affected by it and it deserves more attention from doctors who treat affected patients as well as from scientist who research treatment options.

Active avoidance (AA) is an important paradigm for studying mechanisms of aversive instrumental learning, pathological anxiety, and active coping. Unfortunately, AA neurocircuits are poorly understood, partly because behavior is highly variable and reflects a competition between Pavlovian reactions and instrumental actions. Here we exploited the behavioral differences between good and poor avoiders to elucidate the AA neurocircuit. Rats received Sidman AA training and expression of the activity-dependent immediate-early gene c-fos was measured after a shock-free AA test. Six brain regions with known or putative roles in AA were evaluated: amygdala, periaqueductal gray, nucleus accumbens, dorsal striatum, prefrontal cortex (PFC), and hippocampus. Good avoiders showed little Pavlovian freezing and high AA rates at test, the opposite of poor avoiders. Although c-Fos activation was observed throughout the brain, differential activation was found only in subregions of amygdala and PFC. Interestingly, c-Fos correlated with avoidance and freezing in only five of 20 distinct areas evaluated: lateral amygdala, central amygdala, medial amygdala, basal amygdala, and infralimbic PFC. Thus, activity in specific amygdala-PFC circuits likely mediates the competition between instrumental actions and Pavlovian reactions after AA training. Individual differences in AA behavior, long considered a nuisance by researchers, may be the key to elucidating the AA neurocircuit and understanding pathological response profiles.

BACKGROUND: In rodents, drugs of abuse induce locomotor hyperactivity, and repeating injections enhance this response. This effect, called behavioral sensitization, persists months after the last administration. It has been shown that behavioral sensitization to amphetamine develops parallel to an increased release of norepinephrine (NE) in the prefrontal cortex (PFC). METHODS: Rats and mice were repeatedly treated with amphetamine (1 or 2 mg/kg intraperitoneally, respectively) to obtain sensitized animals. The NE release in the PFC was measured by microdialysis in freely moving mice (n = 55). Activity of locus coeruleus (LC) noradrenergic neurons was determined in anaesthetized rats (n = 15) by in vivo extracellular electrophysiology. The alpha2A-adrenergic autoreceptor (alpha2A-AR) expression was assessed by autoradiography on brain slices, and Galphai proteins expression was measured by western blot analysis of LC punches. RESULTS: In sensitized rats LC neurons had a higher spontaneous firing rate, and clonidine-an alpha2A-adrenergic agonist-inhibited LC neuronal firing less efficiently than in control animals. Clonidine also induced lower levels of NE release in the PFC of sensitized mice. This desensitization was maintained by a lower density of Galphai1 and Galphai2 proteins in the LC of sensitized mice rather than weaker alpha2A-AR expression. Behavioral sensitization was facilitated by alpha2A-AR antagonist, efaroxan, during amphetamine injections and abolished by clonidine treatment. CONCLUSIONS: Our data indicate that noradrenergic inhibitory feedback is impaired for at least 1 month in rats and mice repeatedly treated with amphetamine. This work highlights the key role of noradrenergic autoreceptor signaling in the persistent modifications induced by repeated amphetamine administration.

While right ventricular (RV) dysfunction has long been known to affect the performance of left ventricle (LV), the mechanisms remain poorly defined. Recently, speckle-tracking echocardiography has demonstrated that preservation of strain and rotational dynamics is crucial to both LV systolic and diastolic function. We hypothesized that alteration in septal strain and rotational dynamics of the LV occurs during acute RV pressure overload (RVPO) and leads to decreased cardiac performance. Seven anesthetized pigs underwent median sternotomy and placement of intraventricular pressure-volume conductance catheters. Two-dimensional echocardiographic images and LV pressure-volume loops were acquired for offline analysis at baseline and after banding of the pulmonary artery to achieve RVPO (>50 mmHg) induced RV dysfunction. RVPO resulted in a significant decrease (P < 0.05) in LV end-systolic elastance (50%), systolic change in pressure over change in time (19%), end-diastolic volume (22%), and cardiac output (37%) that correlated with decrease in LV global circumferential strain (58%), LV apical rotation (28%), peak untwisting (reverse rotation) rate (27%), and prolonged time to peak rotation (17%), while basal rotation was not significantly altered. RVPO reduced septal radial and circumferential strain, while no other segment of the LV midpapillary wall was affected. RVPO decreased septal radial strain on LV side by 27% and induced a negative radial strain from 28 ± 5 to -16 ± 2% on the RV side of the septum. The septal circumferential strain on both LV and RV side decreased by 46 and 50%, respectively, following RVPO (P < 0.05). Our results suggest that acute RVPO impairs LV performance by primarily altering septal strain and apical rotation.

OBJECTIVE The chronic workforce shortage in child and adolescent psychiatry (CAP) remains a germane issue that has been difficult to deal with effectively. Collaboration between medical schools without sufficient CAP resources and those with enough to share may help improve interest in the field. METHOD This lecture series piloted a collaborative effort between CAP residents from a Midwest academic center and student-led interest groups from two osteopathic medical schools. CAP residents led nine interactive lectures with medical students on relevant topics, using video-teleconferencing. Baseline and follow-up surveys were used to assess attitudes and responses to the lecture series. RESULTS A group of 175 students completed the baseline survey; 43 students completed the follow-up survey; 21 of 43 (48%) reported that the lectures would positively influence their career choice toward CAP. CONCLUSION Interactive lectures via video teleconferencing demonstrated potential to improve medical students' exposure to CAP, and they were well received in this initial pilot study.

BACKGROUND:Functional brain imaging of young people at increased genetic risk for bipolar disorder provides a means of identifying potential endophenotypes for this condition. Dysfunctional neural mechanisms for the cognitive control of emotion are implicated in the genetic predisposition to bipolar disorder, with aberrant activity in frontocortical, striatal, and limbic brain regions previously reported in subjects with established bipolar disorder during inhibitory and emotion processing tasks. METHODS:Functional brain activity during inhibition of emotional material in young people at increased genetic risk for bipolar disorder was investigated using a facial-emotion go/no-go task during functional magnetic resonance imaging. Data from 47 genetically high-risk individuals aged 18 to 30 years with at least one first-degree relative with bipolar disorder were compared with 49 control subjects (within the same age range but without a family history of bipolar disorder or other severe mental illness). RESULTS:Whole-brain corrected analyses revealed a highly specific and significant lack of recruitment of the inferior frontal gyrus when inhibiting responses to fearful faces in the high-risk participants compared with control subjects (p = .011, family-wise error, peak voxel). CONCLUSIONS:Impaired inhibitory function of the inferior frontal cortex may represent a trait marker of vulnerability to bipolar disorder. That this finding was revealed during inhibition of emotional material further implicates dysregulated frontolimbic brain networks as a potential neurocognitive endophenotype for bipolar disorder and provides evidence for pre-existing functional disturbances in those at high genetic risk for bipolar disorder.