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Department/Unit:Child and Adolescent Psychiatry

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Brain alterations in children/adolescents with ADHD revisited: a neuroimaging meta-analysis of 96 structural and functional studies

Samea, Fateme; Soluki, Solmaz; Nejati, Vahid; Zarei, Mojtaba; Cortese, Samuele; Eickhoff, Simon B; Tahmasian, Masoud; Eickhoff, Claudia R
The findings of neuroimaging studies in children/adolescents with ADHD, and even those of previous meta-analyses, are divergent. Here, Activation Likelihood Estimation meta-analysis, following the current best-practice guidelines, was conducted. We searched multiple databases and traced the references up to June 2018. Then, we extracted the reported coordinates reflecting group comparison between ADHD and healthy subjects from 96 eligible studies, containing 1914 unique participants. The analysis of pooled structural and functional, sub-analyses restricted to modality, and in-/decreased contrast did not yield any significant findings. However, further sub-analyses in the task-fMRI experiments (neutral stimuli only) led to aberrant activity in the left pallidum/putamen and decreased activity (male subjects only) in the left inferior frontal gyrus. The overall findings indicate a lack of regional convergence in children/adolescents with ADHD, which might be due to heterogeneous clinical populations, various experimental design, preprocessing, statistical procedures in individual publications. Our results highlight the need for further high-powered investigations, but may also indicate ADHD pathophysiology might rest in network interactions rather than just regional abnormality.
PMID: 30790635
ISSN: 1873-7528
CID: 3686622

Application of a transdiagnostic treatment for emotional disorders to body dysmorphic disorder: A randomized controlled trial

Mohajerin, Banafsheh; Bakhtiyar, Maryam; Olesnycky, Olenka S; Dolatshahi, Behrouz; Motabi, Fereshteh
BACKGROUND:Body dysmorphic disorder (BDD) is a common disorder which is associated with a high rate of comorbidity and functional impairment. Although research shows that cognitive-behavioral therapy can be an efficacious treatment for BDD, there is growing evidence that dysregulated emotion is a core deficit. The Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders (UP) is a transdiagnostic, emotion focused cognitive-behavioral therapy protocol that has been developed to target emotion regulation processes that play an important role in the development and maintenance of many emotional disorders METHODS: : In the present study, 128 patients meeting criteria for BDD were randomized to either the UP (n = 64) or waitlist/treatment-as-usual (WL/TAU) condition. Diagnoses were determined using semi-structural interviews and patients also completed the Brown Assessment of Beliefs Scale (BABS), the Appearance Anxiety Inventory (AAI), the Difficulties in Emotion Regulation Scale (DERS), the Beck Depression Inventory (BDI) and the Clinical Global Impression (CGI). RESULTS:Repeated measure ANOVA indicated that the UP significantly decreased depression, BDD symptoms and body-related anxiety, as well as significantly improving emotional regulation all with large effect sizes compared to the TAU/WL condition. Treatment gains as well as remission of comorbid conditions were maintained at the three-month follow-up. LIMITATIONS:Our study limitations include restricted follow-up periods and excluding participants who were actively suicidal. CONCLUSIONS:To our knowledge, this is the first examination of the UP for BDD, and results suggest that this disorder shares common mechanisms with other disorders of emotion, and that the UP may be an additional efficacious treatment for this condition.
PMID: 30445389
ISSN: 1573-2517
CID: 5807152

Sustainability of an Evidence-Based Practice in Community Mental Health Agencies Serving Children

Horwitz, Sarah McCue; Lewis, Kristen; Gleacher, Alissa; Wang, Nicole; Bradbury, Donna M; Ray-LaBatt, Meredith; Hoagwood, Kimberly Eaton
OBJECTIVE:/UNASSIGNED:The authors documented rates of sustained use of an evidence-based practice following training sponsored by New York State (NYS), and they identified clinician characteristics related to sustained use. METHODS:/UNASSIGNED:Clinicians (N=89) who were employed in licensed NYS Office of Mental Health agencies serving children and adolescents and who were trained to proficiency in Managing and Adapting Practice (MAP) in 2016 were contacted between 9 and 18 months later and asked whether they were still using (users) or had stopped using (nonusers) MAP and their reason for doing so. RESULTS:/UNASSIGNED:Responses were received from 57% of trainees and of those, 80% reported continued use of MAP. Score on the appeal subscale of the Evidence-Based Practices Attitude Scale (EBPAS) was the only significant difference between users and nonusers. CONCLUSIONS:/UNASSIGNED:Most clinicians reported sustained use of MAP. The EBPAS appeal subscale can be used to identify clinicians who are likely to discontinue use.
PMID: 30755132
ISSN: 1557-9700
CID: 3656222

Persistent mental and physical health impact of exposure to the September 11, 2001 World Trade Center terrorist attacks

Jordan, Hannah T; Osahan, Sukhminder; Li, Jiehui; Stein, Cheryl R; Friedman, Stephen M; Brackbill, Robert M; Cone, James E; Gwynn, Charon; Mok, Ho Ki; Farfel, Mark R
BACKGROUND:Asthma, gastroesophageal reflux disease (GERD), posttraumatic stress disorder (PTSD) and depression have each been linked to exposure to the September 11, 2001 World Trade Center (WTC) terrorist attacks (9/11). We described the prevalence and patterns of these conditions and associated health-related quality of life (HRQOL) fifteen years after the attacks. METHODS:We studied 36,897 participants in the WTC Health Registry, a cohort of exposed rescue/recovery workers and community members, who completed baseline (2003-2004) and follow-up (2015-16) questionnaires. Lower respiratory symptoms (LRS; cough, dyspnea, or wheeze), gastroesophageal reflux symptoms (GERS) and self-reported clinician-diagnosed asthma and GERD history were obtained from surveys. PTSD was defined as a score > 44 on the PTSD checklist, and depression as a score > 10 on the Patient Health Questionnaire (PHQ). Poor HRQOL was defined as reporting limited usual daily activities for > 14 days during the month preceding the survey. RESULTS:In 2015-16, 47.8% of participants had ≥1 of the conditions studied. Among participants without pre-existing asthma, 15.4% reported asthma diagnosed after 9/11; of these, 76.5% had LRS at follow up. Among those without pre-9/11 GERD, 22.3% reported being diagnosed with GERD after 9/11; 72.2% had GERS at follow-up. The prevalence of PTSD was 14.2%, and of depression was 15.3%. HRQOL declined as the number of comorbidities increased, and was particularly low among participants with mental health conditions. Over one quarter of participants with PTSD or depression reported unmet need for mental health care in the preceding year. CONCLUSIONS:Nearly half of participants reported having developed at least one of the physical or mental health conditions studied by 2015-2016; comorbidity among conditions was common. Poor HRQOL and unmet need for health were frequently reported, particularly among those with post-9/11 PTSD or depression. Comprehensive physical and mental health care are essential for survivors of complex environmental disasters, and continued efforts to connect 9/11-exposed persons to needed resources are critical.
PMID: 30755198
ISSN: 1476-069x
CID: 3656232

Prenatal lead exposure impacts cross-hemispheric and long-range connectivity in the human fetal brain

Thomason, Moriah E; Hect, Jasmine L; Rauh, Virginia A; Trentacosta, Christopher; Wheelock, Muriah D; Eggebrecht, Adam T; Espinoza-Heredia, Claudia; Burt, S Alexandra
Lead represents a highly prevalent metal toxicant with potential to alter human biology in lasting ways. A population segment that is particularly vulnerable to the negative consequences of lead exposure is the human fetus, as exposure events occurring before birth are linked to varied and long-ranging negative health and behavioral outcomes. An area that has yet to be addressed is the potential that lead exposure during pregnancy alters brain development even before an individual is born. Here, we combine prenatal lead exposure information extracted from newborn bloodspots with the human fetal brain functional MRI data to assess whether neural network connectivity differs between lead-exposed and lead-naïve fetuses. We found that neural connectivity patterns differed in lead-exposed and comparison groups such that fetuses that were not exposed demonstrated stronger age-related increases in cross-hemispheric connectivity, while the lead-exposed group demonstrated stronger age-related increases in posterior cingulate cortex (PCC) to lateral prefrontal cortex (PFC) connectivity. These are the first results to demonstrate metal toxicant-related alterations in human fetal neural connectivity. Remarkably, the findings point to alterations in systems that support higher-order cognitive and regulatory functions. Objectives for future work are to replicate these results in larger samples and to test the possibility that these alterations may account for significant variation in future child cognitive and behavioral outcomes.
PMID: 30739062
ISSN: 1095-9572
CID: 3655952

Salivary melatonin onset in youth at familial risk for bipolar disorder

Ghaziuddin, Neera; Shamseddeen, Wael; Bertram, Holli; McInnis, Melvin; Wilcox, Holly C; Mitchell, Philip B; Fullerton, Janice M; Roberts, Gloria M P; Glowinski, Anne L; Kamali, Masoud; Stapp, Emma; Hulvershorn, Leslie A; Nurnberger, John; Armitage, Roseanne
Melatonin secretion and polysomnography (PSG) were compared among a group of healthy adolescents who were at high familial risk for bipolar disorder (HR) and a second group at low familial risk (LR). Adolescent participants (n = 12) were a mean age 14 ± 2.3 years and included 8 females and 4 males. Saliva samples were collected under standardized condition light (red light) and following a 200 lux light exposure over two consecutive nights in a sleep laboratory. Red Light Melatonin onset (RLMO) was defined as saliva melatonin level exceeding the mean of the first 3 readings plus 2 standard deviations. Polysomnography was also completed during each night. HR youth, relative to LR, experienced a significantly earlier melatonin onset following 200 lux light exposure. Polysomnography revealed that LR youth, relative to HR, spent significantly more time in combined stages 3 and 4 (deep sleep) following red light exposure. Additionally, regardless of the group status (HR or LR), there was no significant difference in Red Light Melatonin Onset recorded at home or in the laboratory, implying its feasibility and reliability.
PMID: 30780062
ISSN: 1872-7123
CID: 3686042

Behavioral correlates of activity of optogenetically identified locus coeruleus noradrenergic neurons in rats performing T-maze tasks

Xiang, Liyang; Harel, Antoine; Gao, HongYing; Pickering, Anthony E; Sara, Susan J; Wiener, Sidney I
The nucleusLocus Coeruleus (LC) is the major source of forebrain norepinephrine. LC is implicated in arousal, response to novelty, and cognitive functions, including decision-making and behavioral flexibility. One hypothesis is that LC activation promotes rapid shifts in cortical attentional networks following changes in environmental contingencies. Recent recordings further suggest LC is critical for mobilizing resources to deal with challenging situations. In the present study optogenetically identified LC neuronal activity was recorded in rats in a self-paced T-maze. Rats were trained on visual discrimination; then place-reward contingencies were instated. In the session where the animal shifted tasks the first time, the LC firing rate after visual cue onset increased significantly, even as the animal adhered to the previous rule. Firing rate also increased prior to crossing photodetectors that controlled stimulus onset and offset, and this was positively correlated with accelerations, consistent with a role in mobilizing effort. The results contribute to the growing evidence that the noradrenergic LC is essential for behavioral adaptation by promoting cognitive flexibility and mobilizing effort in face of changing environmental contingencies.
PMCID:6362200
PMID: 30718532
ISSN: 2045-2322
CID: 3632032

Reduction in gray matter of cerebellum in schizophrenia and its influence on static and dynamic connectivity

He, Hui; Luo, Cheng; Luo, Yuling; Duan, Mingjun; Yi, Qizhong; Biswal, Bharat B; Yao, Dezhong
Pathophysiological and atrophic changes in the cerebellum have been well-documented in schizophrenia. Reduction of gray matter (GM) in the cerebellum was confirmed across cognitive and motor cerebellar modules in schizophrenia. Such abnormalities in the cerebellum could potentially have widespread effects on both sensorimotor and cognitive symptoms. In this study, we investigated how reduction change in the cerebellum affects the static and the dynamic functional connectivity (FC) between the cerebellum and cortical/subcortical networks in schizophrenia. Reduction of GM in the cerebellum was confirmed across the cognitive and motor cerebellar modules in schizophrenic subjects. Results from this study demonstrates that the extent of reduction of GM within cerebellum correlated with increased static FCs between the cerebellum and the cortical/subcortical networks, including frontoparietal network (FPN), and thalamus in patients with schizophrenia. Decreased GM in the cerebellum was also associated with a declined dynamic FC between the cerebellum and the FPN in schizophrenic subjects. The severity of patients' positive symptom was related to these structural-functional coupling score of cerebellum. These findings identified potential cerebellar driven functional changes associated with positive symptom deficits. A post hoc analysis exploring the effect of changed FC within cerebellum, confirmed that a significant positive relationship, between dynamic FCs of cerebellum-thalamus and intracerebellum existed in patients, but not in controls. The reduction of GM within the cerebellum might be associated with modulation of cerebellum-thalamus, and contributes to the dysfunctional cerebellar-cortical communication in schizophrenia. Our results provide a new insight into the role of cerebellum in understanding the pathophysiological of schizophrenia.
PMID: 30240503
ISSN: 1097-0193
CID: 3300962

Vitamin D Deficiency is Associated with Poor Ovarian Stimulation Outcome in PCOS but not Unexplained Infertility

Butts, Samantha F; Seifer, David B; Koelper, Nathanael; Senapati, Suneeta; Sammel, Mary D; Hoofnagle, Andrew N; Kelly, Andrea; Krawetz, Steven A; Santoro, Nanette; Zhang, Heping; Diamond, Michael P; Legro, Richard S
Context/UNASSIGNED:The impact of vitamin D deficiency on the success of ovarian stimulation according to underlying infertility diagnosis has not been investigated. Objective/UNASSIGNED:To evaluate the relationship between vitamin D deficiency and reproductive outcomes after ovarian stimulation in women with either polycystic ovary syndrome (PCOS) or unexplained infertility. Design/UNASSIGNED:Retrospective cohort study. Setting/UNASSIGNED:Analysis of randomized controlled trial (RCT) data. Participants/UNASSIGNED:Participants from the Pregnancy in PCOS II RCT (n=607); participants from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) RCT of unexplained infertility (n=647). Interventions/UNASSIGNED:Serum 25(OH)D levels measured in banked sera. Main Outcome Measures/UNASSIGNED:Primary: live birth; secondary: ovulation (PPCOS II), pregnancy, and early pregnancy loss. Results/UNASSIGNED:In PPCOS II, subjects with vitamin D deficiency (25(OH)D <20 ng/mL or 50 nmol/L) were less likely to ovulate (AOR 0.82, 95% CI 0.68-0.99, p=0.04) and experienced a 40% lower chance of live birth (AOR 0.63, 95% CI 0.41-0.98, p=0.04) than those not deficient. In AMIGOS, no significant association between vitamin D deficiency and live birth was noted. In pregnant subjects from both studies, vitamin D deficiency was associated with elevated risk of early pregnancy loss (OR 1.6, 95% CI 1.0-2.6, p=0.05). Conclusions/UNASSIGNED:In this investigation of women pursuing ovarian stimulation, the association between vitamin D deficiency and diminished live birth relied on carrying the diagnosis of PCOS and was not observed in unexplained infertility. Given the generally modest success of ovarian stimulation, addressing vitamin D deficiency may prove an important treatment adjunct for many infertile women.
PMID: 30085176
ISSN: 1945-7197
CID: 3236222

Model selection for spatiotemporal modeling of early childhood sub-cortical development

Fishbaugh, James; Paniagua, Beatriz; Mostapha, Mahmoud; Styner, Martin; Murphy, Veronica; Gilmore, John; Gerig, Guido
Spatiotemporal shape models capture the dynamics of shape change over time and are an essential tool for monitoring and measuring anatomical growth or degeneration. In this paper we evaluate non-parametric shape regression on the challenging problem of modeling early childhood sub-cortical development starting from birth. Due to the flexibility of the model, it can be challenging to choose parameters which lead to a good model fit yet does not over fit. We systematically test a variety of parameter settings to evaluate model fit as well as the sensitivity of the method to specific parameters, and we explore the impact of missing data on model estimation.
PMCID:6503845
PMID: 31073259
ISSN: 0277-786x
CID: 3903192