Faculty Bibliography

OBJECTIVE:To perform a systematic review of studies of lurasidone in children and/or adolescents and to present a case report aimed to add further insights into its use in clinical practice with youth. METHODS:We searched the following databases for empirical studies, of any design, focusing on the pharmacokinetics, efficacy, or safety of lurasidone in children and/or adolescents: Pubmed (Medline), OVID (PsycInfo, EMBASE+EMBASE classic, OVID Medline), Web of Knowledge, and ClinicalTrials.gov (last search January 23, 2018). RESULTS:From a pool of 301 potentially relevant references, we retained 12 pertinent studies (reported in 28 references), including 1 pharmacokinetics study, 1 double blind randomized controlled trial (RCT) for bipolar depression (BD) with 1 related interim analysis study of its extension phase and 1 related external posterior predictive check study, 1 double blind RCT for schizophrenia with 3 related interim analyses of its extension phase, 1 RCT and 1 case report for autism spectrum disorder, and 2 open-label studies focusing on a variety of disorders. Overall, these studies show that lurasidone is significantly more efficacious than placebo, with moderate effect sizes, and is well tolerated for BD and schizophrenia in youth. Published studies in youth have in general used doses up to 80 mg/day. Our case report suggests that high doses of lurasidone (148 mg/day) were well tolerated and might have contributed to substantial functional improvement in a 14-year old girl with psychosis and a previous history of anorexia nervosa, who had not responded to previous antipsychotics (olanzapine, risperidone, aripiprazole). CONCLUSIONS:There is increasing evidence that lurasidone may be moderately effective and well tolerated for the treatment of BD and psychosis in youth and may have procognitive effects. Our case report suggests that future RCTs should assess the efficacy and tolerability of high doses (>80 mg/day) of lurasidone in youth.

Background/Purpose: Hyperuricemia is common, and along with other comorbidities (CM), is increasing in prevalence. Though often asymptomatic, it is associated with subclinical urate deposition detectable by ultrasound (US) imaging. This study aims to evaluate the association of CM with urate deposition in individuals with asymptomatic hyperuricemia (ASU) via US.
Method(s): ASU was defined as serum urate (sUA) >6mg/dl; sUA <6mg/dl served as controls. Demographic factors,

OBJECTIVES/OBJECTIVE:Emotional lability (EL) is an important trans-diagnostic concept that is associated with significant functional impairment in childhood and adolescence. EL is typically measured with questionnaires, although little is known about the ecological validity of these ratings. In this paper, we undertook 2 studies addressing this issue by examining the relationship between rating-based measures of EL and directly measured emotional expressions and experiences. Furthermore, the associations between directly measured emotional expressions and experiences and attention-deficit/hyperactivity disorder (ADHD) symptomatology were also examined, given the clear association of EL with ADHD in former research. METHODS:In Study 1, we examined the relationship between parental report of children's EL and ADHD, and children's emotional expressions in an experimental context (N = 67). In Study 2, we examined the relationship between parental ratings and real-time measures of emotional experiences in daily life in adolescents (N = 65). RESULTS:EL ratings were associated with different elements of real-time emotional experiences and expressions. Elements of emotional expressions but not emotional experiences were also associated with ADHD symptom reports. CONCLUSIONS:These studies provide evidence for the ecological validity of EL ratings. Furthermore, they add evidence for the associations between EL and ADHD.

Neurofilament (NFL) proteins have recently been found to play unique roles in synapses. NFL is known to interact with the GluN1 subunit of N-methyl-D-aspartic acid (NMDAR) and be reduced in schizophrenia though functional consequences are unknown. Here we investigated whether the interaction of NFL with GluN1 modulates synaptic transmission and schizophrenia-associated behaviors. The interaction of NFL with GluN1 was assessed by means of molecular, pharmacological, electrophysiological, magnetic resonance spectroscopy (MRS), and schizophrenia-associated behavior analyses. NFL deficits cause an NMDAR hypofunction phenotype including abnormal hippocampal function, as seen in schizophrenia. NFL-/- deletion in mice reduces dendritic spines and GluN1 protein levels, elevates ubiquitin-dependent turnover of GluN1 and hippocampal glutamate measured by MRS, and depresses hippocampal long-term potentiation. NMDAR-related behaviors are also impaired, including pup retrieval, spatial and social memory, prepulse inhibition, night-time activity, and response to NMDAR antagonist, whereas motor deficits are minimal. Importantly, partially lowering NFL in NFL+/- mice to levels seen regionally in schizophrenia, induced similar but milder NMDAR-related synaptic and behavioral deficits. Our findings support an emerging view that central nervous system neurofilament subunits including NFL in the present report, serve distinctive, critical roles in synapses relevant to neuropsychiatric diseases.

High-density electroencephalography (EEG) was used to examine the utility of the P1 event-related potential (ERP) as a marker of visual motion sensitivity to luminance defined low-spatial frequency drifting gratings in 16 children with autism and 16 neurotypical children. Children with autism displayed enhanced sensitivity to large, high-contrast low-spatial frequency stimuli as indexed by significantly shorter P1 response latencies to large vs. small gratings. The current study also found that children with autism had larger amplitude responses to large gratings irrespective of contrast. A linear regression established that P1 adaptive mean amplitude for large, high-contrast sinusoidal gratings significantly predicted hyperresponsiveness item mean scores on the Sensory Experiences Questionnaire for children with autism, but not for neurotypical children. We conclude that children with autism have differences in the mechanisms that underlie low-level visual processing potentially related to altered visual spatial suppression or contrast gain control.

Herein we present the unique case of a 21-year-old African American woman who presented with psychotic features and the incidental finding of basal ganglia calcifications on computed tomography (CT) scan of the head. She was initially presumed to have Fahr's syndrome in the context of idiopathic bilateral basal ganglia calcifications and psychotic features. Genetic testing performed revealed the deletion of 22q11.2, thus establishing the diagnosis of DiGeorge syndrome. This case highlights the importance of noticing subtle physical exam findings along with laboratory findings as this led to the diagnosis of DiGeorge syndrome for this patient. This case is unique in two aspects; first, the finding of basal ganglia calcification via CT of the brain in patients with DiGeorge syndrome has rarely been reported in the literature. Second, this case highlights the strong genetic predisposition for schizophrenia in patients with DiGeorge syndrome.

Cancer is highly prevalent and one of the leading causes of global morbidity and mortality. Psychological and existential suffering is common in cancer patients, associated with poor psychiatric and medical outcomes. Promising early-phase clinical research (1960s to early 1970s) suggested a therapeutic signal for serotoninergic psychedelics (e.g. psilocybin, LSD) in treating cancer-related psychiatric distress. After several decades of quiescence, research on psychedelic-assisted therapy to treat psychiatric disorders in cancer patients has resumed within the last 2 decades in the US and Europe. This review article is based on a systematic search of clinical trials from 1960-2018 researching the therapeutic use of psychedelic treatment in patients with serious or terminal illnesses and related psychiatric illness. The search found 10 eligible clinical trials, with a total of 445 participants, with the vast majority of the patients having advanced or terminal cancer diagnoses. Six open label trials, published between 1964 and 1980 (n = 341), suggested that psychedelic therapy (mostly with LSD) may improve cancer-related depression, anxiety, and fear of death. Four RCTs trials were published between 2011 and 2016 (n = 104), mostly with psilocybin treatment (n = 92), and demonstrated that psychedelic-assisted treatment can produce rapid, robust, and sustained improvements in cancer-related psychological and existential distress.

A brain-computer-interface (BCI)-based attention training game system has shown promise for treating attention deficit/hyperactivity disorder (ADHD) children with inattentive symptoms. However, little is known about brain network organizational changes underlying behavior improvement following BCI-based training. To cover this gap, we aimed to examine the topological alterations of large-scale brain functional networks induced by the 8-week BCI-based attention intervention in ADHD boys using resting-state functional magnetic resonance imaging method. Compared to the non-intervention (ADHD-NI) group, the intervention group (ADHD-I) showed greater reduction of inattention symptoms accompanied with differential brain network reorganizations after training. Specifically, the ADHD-NI group had increased functional connectivity (FC) within the salience/ventral attention network (SVN) and increased FC between task-positive networks (including the SVN, dorsal attention (DAN), somatomotor, and executive control network) and subcortical regions; in contrast ADHD-I group did not have this pattern. In parallel, ADHD-I group had reduced degree centrality and clustering coefficient as well as increased closeness in task-positive and the default mode networks (prefrontal regions) after the training. More importantly, these reduced local functional processing mainly in the SVN were associated with less inattentive/internalizing problems after 8-week BCI-based intervention across ADHD patients. Our findings suggest that the BCI-based attention training facilitates behavioral improvement in ADHD children by reorganizing brain functional network from more regular to more random configurations, particularly renormalizing salience network processing. Future long-term longitudinal neuroimaging studies are needed to develop the BCI-based intervention approach to promote brain maturation in ADHD.

Background It remains unclear if naltrexone combined with psychotherapy is superior to naltrexone alone in treating alcohol use disorders (AUD). The current meta-analysis examined the hypothesis that psychotherapy is a significant moderator that influences AUD-related outcomes and that naltrexone combined with psychotherapy is associated with significantly better AUD-related outcomes than naltrexone alone. Methods A total of 30 studies (N_naltrexone = 2317; N_placebo = 2056) were included. Random effects model meta-analyses were carried out for each of the studied outcomes. Subsequently, the random effects model pooled estimates from studies with and without psychotherapy were compared using a Wald test. A mixed-effect model, incorporating psychotherapy as a moderator, was used to examine the impact of psychotherapy on treatment outcomes. Results Naltrexone had a significant treatment effect on abstinence relapse and Gamma-Glutamyl Transferase levels, but not cravings. The pooled estimates for studies with and without psychotherapy were not significantly different for any of the studied outcomes. Psychotherapy was not a significant moderator in the mixed effects models for any of the studied outcomes. Conclusions Naltrexone treatment is efficacious in reducing alcohol consumption, but not reducing cravings. Adding psychotherapy on top naltrexone did not result in any significant additional benefit for AUD patients.