Faculty Bibliography

Statistical learning-extracting regularities in the environment-may underlie complex social behavior. 124 children, 56 with autism and 68 typically developing, ages 2-8 years, completed a novel visual statistical learning task on an iPad. Averaged together, children with autism demonstrated less learning on the task compared to typically developing children. However, multivariate classification analyses characterized individual behavior patterns, and demonstrated a subset of children with autism had similar learning patterns to typically developing children and that subset of children had less severe autism symptoms. Therefore, statistically averaging data resulted in missing critical heterogeneity. Variability in statistical learning may help to understand differences in autism symptoms across individuals and could be used to tailor and inform treatment decisions.

Chronic pain (CP) and opioid use disorder (OUD) remain challenging complex public health concerns. This is an updated review on the relationship between CP and OUD and the use of stepped care models for assessment and management of this vulnerable population. A literature search was conducted from 2008 to the present in PubMed, Embase, and PsycInfo using the terms pain or chronic pain and opioid-related disorders, opiate, methadone, buprenorphine, naltrexone, opioid abuse, opioid misuse, opioid dependen*, heroin addict, heroin abuse, heroin misuse, heroin dependen*, or analgesic opioids, and stepped care, integrated services, multidisciplinary treatment, or reinforcement-based treatment. Evidenced-based data exists on the feasibility, implementation, and efficacy of stepped care models in primary care settings for the management of CP and opioid use. Although these studies did not enroll participants with OUD, they included a sub-set of patients at risk for the development of OUD. There remains a dearth of treatment options for those with comorbid CP and OUD. Future research is needed to explore the aetiology and impact of CP and OUD, and greater emphasis is needed to improve access to comprehensive pain and substance use programmes for high-risk individuals.

New York City (NYC) public hospitals recently mandated that all pregnant women be screened for depression, but no funds were allocated for screening or care coordination/treatment, and research suggests that unfunded mandates are not likely to be successful. To address this, we implemented an on-site depression prevention intervention (NYC ROSE) for positive depression screens among pregnant, mostly Black and Hispanic, lower-income women in one public hospital. In this paper, we used Aarons' implementation model to describe the successes and challenges of screening and intervention. Patient tracking sheets and electronic medical records were abstracted. Key informant interviews and an informal focus group were conducted, and staff observations were reviewed; common implementation themes were identified and fit into Aarons' model. We found that a lack of funding and staff training, which led to minimal psychoeducation for patients, were outer context factors that may have made depression screening difficult, screening results unreliable, and NYC ROSE enrollment challenging. Although leadership agreed to implement NYC ROSE, early involvement of all levels of staff and patients would have better informed important inner context factors, like workflow and logistical/practical challenges. There was also a mismatch between the treatment model and the population being served; patients often lived too far away to receive additional services on site, and economic issues were often a higher priority than mental health services. Screening and interventions for perinatal depression are essential for optimal family health, and a detailed, thoughtful and funded approach can help ensure effectiveness of such efforts.

Through unbiased transcriptomics and multiple molecular tools, transient downregulation of the Orthodenticle homeobox 2 (OTX2) gene was recently causatively associated with the development of depressive-like behaviors in a mouse model of early life stress. The analyses presented in this manuscript test the translational applicability of these findings by examining peripheral markers of methylation of OTX2 and OTX2-regulated genes in relation to measures of depression and resting-state functional connectivity data collected as part of a larger study examining risk and resilience in maltreated children. The sample included 157 children between the ages of 8 and 15 years (χ = 11.4, SD = 1.9). DNA specimens were derived from saliva samples and processed using the Illumina 450 K beadchip. A subset of children (N = 47) with DNA specimens also had resting-state functional MRI data. After controlling for demographic factors, cell heterogeneity, and three principal components, maltreatment history and methylation in OTX2 significantly predicted depression in the children. In terms of the imaging data, increased OTX2 methylation was found to be associated with increased functional connectivity between the right vmPFC and bilateral regions of the medial frontal cortex and the cingulate, including the subcallosal gyrus, frontal pole, and paracingulate gyrus-key structures implicated in depression. Mouse models of early stress hold significant promise in helping to unravel the mechanisms by which child adversity confers risk for psychopathology, with data presented in this manuscript supporting a potential role for OTX2 and OTX2-related (e.g., WNT1, PAX6) genes in the pathophysiology of stress-related depressive disorders in children.

Adolescents with conduct disorder (CD) and elevated callous-unemotional (CU) traits have been reported to present with a more severe and persistent pattern of antisocial behaviour than those with low levels of CU traits. However, relatively few studies have investigated whether there are differences in brain structure between these subgroups.We acquired diffusion tensor imaging data and used tract-based spatial statistics (TBSS) to compare adolescents with CD and high levels of CU traits (CD/CU+; n = 18, CD and low levels of CU traits (CD/CU-; n = 17) and healthy controls (HC; n = 32) on measures of fractional anisotropy (FA), axial (AD), radial (RD) and mean (MD) diffusivity. Compared to CD/CU- adolescents, those with CD/CU+ presented increased FA and reduced RD and MD (lower diffusivity) in several tracts including: body and splenium of the corpus callosum, right inferior longitudinal fasciculus, ILF; right inferior fronto-occipital fasciculus, IFOF; left superior longitudinal fasciculus, SLF; left cerebral peduncle, bilateral internal capsule, left superior and posterior corona radiata, bilateral thalamic radiation and left external capsule. In addition, relative to CD/CU- individuals, adolescents with CD/CU+ showed lower diffusivity (indexed by reduced RD and MD) in left uncinate fasciculus and bilateral fornix. Finally, relative to healthy controls, CD/CU+ individuals showed lower diffusivity (reduced RD) in the genu and body of the corpus callosum and left anterior corona radiata. These results suggest that CD/CU+ individuals present with white-matter microstructural abnormalities compared to both CD/CU- individuals and age-matched healthy controls. This finding is consistent with emerging evidence suggesting that CD/CU+ represents a distinct subtype of CD, and illustrates the importance of accounting for heterogeneity within CD populations.

PIM (postictal mania) or PIP (postictal psychosis) usually comes on after a single episode or a seizure cluster of generalized tonic-clonic or complex partial secondarily generalized seizures. Patients maintain a lucid interval of clear consciousness which precedes a psychotic episode. The symptoms may include insomnia, hallucinations, delusions, elated expansive mood, euphoria, and distractibility. We present a case of a 62-year-old male with PIP or mania preceding an episode of seizure. In the light of this case report, we illustrate the importance of being vigilant about the psychotic symptoms in a patient with epilepsy in order to minimize the morbidity.

We report on a search for weakly interacting massive particles (WIMPs) using 278.8 days of data collected with the XENON1T experiment at LNGS. XENON1T utilizes a liquid xenon time projection chamber with a fiducial mass of (1.30±0.01)  ton, resulting in a 1.0 ton yr exposure. The energy region of interest, [1.4,10.6]  keV_{ee} ([4.9,40.9] keV_{nr}), exhibits an ultralow electron recoil background rate of [82_{-3}^{+5}(syst)±3(stat)]  events/(ton yr keV_{ee}). No significant excess over background is found, and a profile likelihood analysis parametrized in spatial and energy dimensions excludes new parameter space for the WIMP-nucleon spin-independent elastic scatter cross section for WIMP masses above 6  GeV/c^{2}, with a minimum of 4.1×10^{-47}  cm^{2} at 30  GeV/c^{2} and a 90% confidence level.

Valproic acid, first manufactured as an anticonvulsant, is commonly used to treat both neurological and psychiatric conditions. A rare and deadly side effect of this medication is hyperammonemia, presenting as lethargy, confusion, seizure, and, ultimately, coma. In rare circumstances, hyperammonemia can be recurrent and devastating, especially in patients with an underlying N-acetyl glutamate synthase (NAGS) deficiency, as the valproic acid can enhance this enzyme deficiency and inhibit the conversion of ammonia into urea in the liver. For these subtypes of patients, the United States Food and Drug Administration (US FDA) has recently approved carglumic acid, a medication that can act as a scavenger by effectively increasing the levels of NAGS, ultimately enhancing the conversion of ammonia to urea. In our case report, we have mentioned a patient with treatment-resistant bipolar disorder, who presented with elevated ammonia levels secondary to valproic acid treatment. Valproic acid was the only drug that was effective in his case, so we initiated therapy to reduce his elevated ammonia levels. After a thorough evaluation, we found the patient had a genetic NAGS deficiency. Carglumic acid was initiated and proved efficacious in our patient.

Background Post-traumatic stress disorder (PTSD) is prevalent in children, adolescents and adults. It can occur alone or in comorbidity with other disorders. A broad range of psychotherapies such as cognitive behavioral therapy (CBT) and eye movement desensitization and reprocessing (EMDR) have been developed for the treatment of PTSD. Aim Through quantitative meta-analysis, we aimed to compare the efficacy of CBT and EMDR: (i) relieving the post-traumatic symptoms, and (ii) alleviating anxiety and depression, in patients with PTSD. Methods We systematically searched EMBASE, Medline and Cochrane central register of controlled trials (CENTRAL) for articles published between 1999 and December 2017. Randomized clinical trials (RCTs) that compare CBT and EMDR in PTSD patients were included for quantitative meta-analysis using RevMan Version 5. Results Fourteen studies out of 714 were finally eligible. Meta-analysis of 11 studies (n = 547) showed that EMDR is better than CBT in reducing post-traumatic symptoms [SDM (95% CI) = -0.43 (-0.73 - -0.12), p = 0.006]. However, meta-analysis of four studies (n = 186) at three-month follow-up revealed no statistically significant difference [SDM (95% CI) = -0.21 (-0.50 - 0.08), p = 0.15]. The EMDR was also better than CBT in reducing anxiety [SDM (95% CI) = -0.71 (-1.21 - -0.21), p = 0.005]. Unfortunately, there was no difference between CBT and EMDR in reducing depression [SDM (95% CI) = -0.21 (-0.44 - 0.02), p = 0.08]. Conclusion The results of this meta-analysis suggested that EMDR is better than CBT in reducing post-traumatic symptoms and anxiety. However, there was no difference reported in reducing depression. Large population randomized trials with longer follow-up are recommended to build conclusive evidence.