Depressive and anxiety symptom trajectories from school age through young adulthood in samples with autism spectrum disorder and developmental delay.

OBJECTIVE: The objectives of this study were to model growth in anxiety and depressive symptoms from late school age through young adulthood in individuals with autism spectrum disorder (ASD) and controls with developmental delay (DD), and to assess relationships among internalizing growth patterns, participant characteristics, baseline predictors, and distal outcomes. METHOD: Data were collected between ages 6 and 24 years in 165 participants (n = 109 with ASD; n = 56 with nonspectrum DD), most of whom received diagnostic evaluations in both childhood and early adulthood. Questionnaires were collected approximately every 3 to 6 months between ages 9 and 24 years. Parent-rated Child Behavior Checklist (CBCL), Adult Behavior Checklist (ABCL), and Developmental Behaviour Checklist anxiety- and depression-related subscale distributions were modeled with mixed-effects Poisson models, covarying diagnosis, age, verbal IQ (VIQ), gender, and significant 2- and 3-way interactions. RESULTS: Anxiety was positively associated with VIQ, and controlling for VIQ, both anxiety and depressive symptoms were greater in ASD than nonspectrum participants. Female gender predicted greater increases over time in anxiety and depressive symptoms for both diagnostic groups. Lower maternal education was associated with increasing internalizing symptoms in a subset of less verbal individuals with ASD. In exploratory post hoc analyses, internalizing symptoms were associated with poorer emotional regulation in school age, and with lower life satisfaction and greater social difficulties in early adulthood. CONCLUSION: Findings support previous claims that individuals with ASD are at particular risk for affect- and anxiety-specific problems. Although symptom levels in females increase at a faster rate throughout adolescence, males with ASD appear to have elevated levels of depressive symptoms in school age that are maintained into young adulthood

Positive allosteric modulation as a potential therapeutic strategy in anti-NMDA receptor encephalitis

N-methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors important for synaptic plasticity, memory, and neuropsychiatric health. NMDAR hypofunction contributes to multiple disorders, including anti-NMDAR encephalitis (NMDARE), an autoimmune disease of the CNS associated with GluN1 antibody-mediated NMDAR internalization. Here we characterize the functional/pharmacological consequences of exposure to CSF from female human NMDARE patients on NMDAR function, and we characterize the effects of intervention with recently described positive allosteric modulators (PAMs) of NMDARs. Incubation (48 h) of rat hippocampal neurons of both sexes in confirmed NMDARE patient CSF, but not control CSF, attenuated NMDA-induced current. Residual NMDAR function was characterized by lack of change in channel open probability, indiscriminate loss of synaptic and extrasynaptic NMDARs, and indiscriminate loss of GluN2B-containing and GluN2B-lacking NMDARs. NMDARs tagged with N-terminal pHluorin fluorescence demonstrated loss of surface receptors. Thus, function of residual NMDARs following CSF exposure was indistinguishable from baseline, and deficits appear wholly accounted for by receptor loss. Coapplication of CSF and PAMs of NMDARs (SGE-301 or SGE-550, oxysterol-mimetic) for 24 h restored NMDAR function following 24 h incubation in patient CSF. Curiously, restoration of NMDAR function was observed despite washout of PAMs before electrophysiological recordings. Subsequent experiments suggested that residual allosteric potentiation of NMDAR function explained the persistent rescue. Further studies of the pathogenesis of NMDARE and intervention with PAMs may inform new treatments for NMDARE and other disorders associated with NMDAR hypofunction.SIGNIFICANCE STATEMENTAnti-N-methyl-d-aspartate receptor encephalitis (NMDARE) is increasingly recognized as an important cause of sudden-onset psychosis and other neuropsychiatric symptoms. Current treatment leaves unmet medical need. Here we demonstrate cellular evidence that newly identified positive allosteric modulators of NMDAR function may be a viable therapeutic strategy.</jats:p

The Effects of the COVID-19 Stay-at-Home Orders on Pain and Mental Health in OMM Patients

New Jersey was placed in a state of emergency and a statewide stay-at-home order during the COVID-19 pandemic Very little has been published examining the effects of chronic pain after stopping osteopathic manipulative medicine (OMM), although it seems unethical to stop a treatment shown to work so well that is both minimally invasive and cost effective We hypothesized OMM patients experienced an increase in pain since the onset of COVID-19 pandemic and closure of OMM/Family Medicine office

Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma?:Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalization in infants and children globally. Many observational studies have found an association between RSV LRTI in early life and subsequent respiratory morbidity, including recurrent wheeze of early childhood (RWEC) and asthma. Conversely, two randomized placebo-controlled trials of efficacious anti-RSV monoclonal antibodies (mAbs) in heterogenous infant populations found no difference in physician-diagnosed RWEC or asthma by treatment group. If a causal association exists and RSV vaccines and mAbs can prevent a substantial fraction of RWEC/asthma, the full public health value of these interventions would markedly increase. The primary alternative interpretation of the observational data is that RSV LRTI in early life is a marker of an underlying predisposition for the development of RWEC and asthma. If this is the case, RSV vaccines and mAbs would not necessarily be expected to impact these outcomes. To evaluate whether the available evidence supports a causal association between RSV LRTI and RWEC/asthma and to provide guidance for future studies, the World Health Organization convened a meeting of subject matter experts on February 12-13, 2019 in Geneva, Switzerland. After discussing relevant background information and reviewing the current epidemiologic evidence, the group determined that: (i) the evidence is inconclusive in establishing a causal association between RSV LRTI and RWEC/asthma, (ii) the evidence does not establish that RSV mAbs (and, by extension, future vaccines) will have a substantial effect on these outcomes and (iii) regardless of the association with long-term childhood respiratory morbidity, severe acute RSV disease in young children poses a substantial public health burden and should continue to be the primary consideration for policy-setting bodies deliberating on RSV vaccine and mAb recommendations. Nonetheless, the group recognized the public health importance of resolving this question and suggested good practice guidelines for future studies

Depressive Symptoms during the Transition to College: Evaluating Trajectories and Predictors among Freshmen & Transfer Students.

In recent years, there has been increasing concern about the emotional welfare of students on college campuses. Mental health problems, like depression, are common in the college student population and are associated with significant impairments in academic and psychosocial functioning. The transition to a postsecondary institution may be a time of increased risk for mental health problems as students must adjust to new academic, social, and living environments. The overarching goal of this dissertation was to improve our understanding of the processes that confer risk for depression during this transition. We approached this task using a cognitive-behavioral framework which posits that pessimistic cognitive style and frequent avoidant behaviors interfere with the development of social connectedness within the campus community. This, in turn, increases risk for depressive symptoms. This dissertation is comprised of three separate studies evaluating mental health outcomes of undergraduate students. The purpose of Study 1 was to evaluate the course of depressive symptoms among first-semester freshmen and transfer students (N = 351) and evaluate the impact of these symptoms on functioning. Additionally, we evaluated the hypothesis that social connectedness buffers against the negative impact of stress. In Study 2, we developed a multidimensional measure of avoidant behavior using a large cross-sectional data set (N =703). We then used this questionnaire to evaluate the role of avoidant behaviors in the development of depressive symptoms during the college transition in a smaller longitudinal data set (N = 82). In Study 3, we evaluated whether there are significant differences between freshmen and first-semester transfer students in the development of depressive symptoms during the college transition using two separate data sets. Findings are discussed in terms of their implications for early identification and prevention efforts.PHDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/93919/1/stevemb_1.pd

The prospective associations between self-efficacy and depressive symptoms from early to middle adolescence: A cross-lagged model.

Over the course of adolescence, an increasing number of adolescents experience depression. In order to effectively target depression, identifying risk factors for depressive symptoms is pivotal. Since low levels of self-efficacy were associated with higher levels of depressive symptoms in previous studies, the current study investigated the bidirectional and prospective associations between depressive symptoms and academic, social and emotional self-efficacy from early to mid adolescence in a cross-lagged path model. The sample consisted of 1,341 adolescents (47 % girls) with a mean age of 14 years, SD = 0.56. Depressive symptoms and self-efficacy levels were assessed every 6 months over a period of 2.5 years. Depressive symptoms predicted subsequent levels of academic and emotional self-efficacy on all time points, and social self-efficacy on one time point. Self-efficacy did not predict subsequent levels of depressive symptoms. There was no evidence of sex differences in the cross-lagged associations between depressive symptoms and self-efficacy levels. Implications of the findings are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved

A new model of wheezing severity in young children using the validated ISAAC wheezing module: A latent variable approach with validation in independent cohorts

Background: The International Study of Asthma and Allergies in Children (ISAAC) Wheezing Module is commonly used to characterize pediatric asthma in epidemiological studies, including nearly all airway cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) consortium. However, there is no consensus model for operationalizing wheezing severity with this instrument in explanatory research studies. Severity is typically measured using coarsely-defined categorical variables, reducing power and potentially underestimating etiological associations. More precise measurement approaches could improve testing of etiological theories of wheezing illness. Methods: We evaluated a continuous latent variable model of pediatric wheezing severity based on four ISAAC Wheezing Module items. Analyses included subgroups of children from three independent cohorts whose parents reported past wheezing: infants ages 0–2 in the INSPIRE birth cohort study (Cohort 1; n = 657), 6-7-year-old North American children from Phase One of the ISAAC study (Cohort 2; n = 2,765), and 5-6-year-old children in the EHAAS birth cohort study (Cohort 3; n = 102). Models were estimated using structural equation modeling. Results: In all cohorts, covariance patterns implied by the latent variable model were consistent with the observed data, as indicated by non-significant χ2 goodness of fit tests (no evidence of model misspecification). Cohort 1 analyses showed that the latent factor structure was stable across time points and child sexes. In both cohorts 1 and 3, the latent wheezing severity variable was prospectively associated with wheeze-related clinical outcomes, including physician asthma diagnosis, acute corticosteroid use, and wheeze-related outpatient medical visits when adjusting for confounders Conclusion: We developed an easily applicable continuous latent variable model of pediatric wheezing severity based on items from the well-validated ISAAC Wheezing Module. This model prospectively associates with asthma morbidity, as demonstrated in two ECHO birth cohort studies, and provides a more statistically powerful method of testing etiologic hypotheses of childhood wheezing illness and asthma

Effect of a Cognitive-Behavioral Prevention Program on Depression 6 Years After Implementation Among At-Risk Adolescents: A Randomized Clinical Trial.

IMPORTANCE: Adolescents whose parents have a history of depression are at risk for developing depression and functional impairment. The long-term effects of prevention programs on adolescent depression and functioning are not known. OBJECTIVE: To determine whether a cognitive-behavioral prevention (CBP) program reduced the incidence of depressive episodes, increased depression-free days, and improved developmental competence 6 years after implementation. DESIGN, SETTING, AND PARTICIPANTS: A 4-site randomized clinical trial compared the effect of CBP plus usual care vs usual care, through follow-up 75 months after the intervention (88% retention), with recruitment from August 2003 through February 2006 at a health maintenance organization, university medical centers, and a community mental health center. A total of 316 participants were 13 to 17 years of age at enrollment and had at least 1 parent with current or prior depressive episodes. Participants could not be in a current depressive episode but had to have subsyndromal depressive symptoms or a prior depressive episode currently in remission. Analysis was conducted between August 2014 and June 2015. INTERVENTIONS: The CBP program consisted of 8 weekly 90-minute group sessions followed by 6 monthly continuation sessions. Usual care consisted of any family-initiated mental health treatment. MAIN OUTCOMES AND MEASURES: The Depression Symptoms Rating scale was used to assess the primary outcome, new onsets of depressive episodes, and to calculate depression-free days. A modified Status Questionnaire assessed developmental competence (eg, academic or interpersonal) in young adulthood. RESULTS: Over the 75-month follow-up, youths assigned to CBP had a lower incidence of depression, adjusting for current parental depression at enrollment, site, and all interactions (hazard ratio, 0.71 [95% CI, 0.53-0.96]). The CBP program\u27s overall significant effect was driven by a lower incidence of depressive episodes during the first 9 months after enrollment. The CBP program\u27s benefit was seen in youths whose index parent was not depressed at enrollment, on depression incidence (hazard ratio, 0.54 [95% CI, 0.36-0.81]), depression-free days (d = 0.34, P = .01), and developmental competence (d = 0.36, P = .04); these effects on developmental competence were mediated via the CBP program\u27s effect on depression-free days. CONCLUSIONS AND RELEVANCE: The effect of CBP on new onsets of depression was strongest early and was maintained throughout the follow-up period; developmental competence was positively affected 6 years later. The effectiveness of CBP may be enhanced by additional booster sessions and concomitant treatment of parental depression. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00073671