Faculty Bibliography

BACKGROUND:While an established clinical outcome of high importance, social functioning has been emerging as possibly having a broader significance to the evolution of psychosis and long term disability. In the current study we explored the association between social decline, conversion to psychosis, and functional outcome in individuals at clinical high risk (CHR) for psychosis. METHODS:585 subjects collected in the North American Prodrome Longitudinal Study (NAPLS2) were divided into 236 Healthy Controls (HCs), and CHR subjects that developed psychosis (CHR + C, N = 79), or those that did not (Non-Converters, CHR-NC, N = 270). CHR + C subjects were further divided into those that experienced an atypical decline in social functioning prior to baseline (beyond typical impairment levels) when in min-to-late adolescence (CHR + C-SD, N = 39) or those that did not undergoing a decline (CHR + C-NSD, N = 40). RESULTS:Patterns of poor functional outcomes varied across the CHR subgroups: CHR-NC (Poor Social 36.3%, Role 42.2%) through CHR + C-NSD (Poor Social 50%, Poor Role 67.5%) to CHR + C-SD (Poor Social 76.9%, Poor Role 89.7%) functioning. The two Converter subgroups had comparable positive symptoms at baseline. At 12 months, the CHR + C-SD group stabilized, but social functioning levels remained significantly lower than the other two subgroups. CONCLUSIONS:The current study demonstrates that pre-baseline social decline in mid-to-late adolescence predicts psychosis. In addition, we found that this social decline in converters is strongly associated with especially poor functional outcome and overall poorer prognosis. Role functioning, in contrast, has not shown similar predictor potential, and rather appears to be an illness indicator that worsens over time.

Individuals with delayed sleep phase disorder (DSPD) are unable to naturally fall asleep and awake at conventional times; for this reason, DSPD is often mistaken for insomnia. However, unlike many patients with insomnia, those with DSPD struggle to get up at appropriate times. DSPD is associated with school refusal, academic difficulties, and lower employment rate. DSPD in youth has prevalence as high as 16%, and is often comorbid with other psychiatric disorders. Treatments include appropriate light exposure during the day, melatonin use, developing an evening routine that minimizes arousal-increasing activities, and gradually shifting sleep-wake times toward more functional ones.

Sleep disturbances have been linked to suicidal ideation and behaviors in adolescents. Specifically, insomnia and nightmares are associated with current suicide risk and predict future ideation. Associations between hypersomnia, sleep apnea, and suicide remain inconclusive. Potential biological mechanisms underlying these relationships include executive functioning deficits and hyperarousal. Related psychological factors may include thwarted belongingness, perceived burdensomeness, and negative appraisals. Assessing suicide risk in patients with sleep disturbances, and vice versa, is needed. Therapeutic interventions such as cognitive behavior therapy for insomnia and imagery rehearsal treatment, as well as pharmacologic treatments, show promise in treating sleep disorders and suicidal behavior.

Children with psychiatric comorbidities frequently are referred for evaluation of sleep complaints. Common sleep symptoms can include difficulty falling asleep, frequent nocturnal awakening, restless sleep, and symptoms of restless legs syndrome (RLS). The understanding of the sleep condition in relation to the psychiatric comorbidity often is a challenge to the physician and often sleep disorders remain undiagnosed, untreated, or undertreated. Restless legs syndrome has been associated with psychiatric comorbidities and with certain medications, such as antidepressants, antihistamines, and antipsychotics. This article reviews the presentation of RLS and restless sleep, the association with psychiatric comorbidities, and treatment options.

There is, in the content of the Journal, an embarrassment of riches, and picking a "best" seems to demand a certain qualification: is the "best" the most interesting, most surprising, most educational, most important, most provocative, most enjoyable? How to choose? We are hardly unbiased and can admit to a special affection for the ones that we and the authors worked hardest on, hammering version after version into shape. Acknowledging these biases, here are the 2020 articles that we think deserve your attention, or at least a second read.

BACKGROUND:Consistent research findings indicate that parents and teachers observe genuinely different Attention Deficit/Hyperactivity Disorder (ADHD) behaviours in their respective settings. OBJECTIVE:To evaluate the utility of information provided by teacher informant assessments (INFAs) of ADHD symptoms, and the implications of aggregation algorithms in combing parents' information, i.e. using 'or-rule' (endorsement by either one informant) versus 'and-rule' (endorsement by both informants). METHOD/METHODS:Teacher ratings on Conners scales and clinical data from parental accounts on 1383 probands and their siblings from the IMAGE study were analysed. The psychometric properties of teacher and combined ratings using the item response theory model (IRT) are presented. Kappa coefficients, intraclass correlations and linear regression were employed. RESULTS:First, teacher endorsement of symptoms is located in a narrow part of the trait continuum close to the average levels. Symptoms exhibit comparable perception in the measurement of the trait(s) with similar discrimination ability and information (reliability). Second, the IRT properties of the 'or-rule' ratings are predominantly influenced by parent-INFAs; and the 'and-rule' ratings predominantly by teacher-INFAs ratings. Third, parent-teacher INFAs agreement was low, both for individual items (κ = 0.01-0.15) and for dimensional scores (r = 0.12-0.16). The 'or-rule' captured milder expressions of ADHD symptoms, whereas the 'and-rule' indexed greater severity of ADHD. CONCLUSIONS:Parent and teacher-INFAs provide different kinds of information, while both are useful. Teacher-INFA and the 'and-rule' provide a more accurate index of severity than an additive symptom count. Parent-INFA and the 'or-rule' are more sensitive for detecting cases with milder ADHD.

Angelman syndrome (AS), a genetic disorder that primarily affects the nervous system, is characterized by delayed development, intellectual disability, severe speech impairment, and problems with movement and balance (ataxia). Most affected children also have recurrent seizures (epilepsy). No existing therapies are capable of comprehensively treating the deficits in AS; hence, there is an urgent need to identify new treatments. Here we show that insulin-like growth factor 2 (IGF-2) and mannose-6-phosphate (M6P), ligands of two independent binding sites of the cation-independent M6P/IGF-2 receptor (CIM6P/IGF-2R), reverse most major deficits of AS modeled in mice. Subcutaneous injection of IGF-2 or M6P in mice modeling AS restored cognitive impairments as assessed by measurements of contextual and recognition memories, motor deficits assessed by rotarod and hindlimb clasping, and working memory/flexibility measured by Y-maze. IGF-2 also corrected deficits in marble burying and significantly attenuated acoustically induced seizures. An observational battery of tests confirmed that neither ligand changed basic functions including physical characteristics, general behavioral responses, and sensory reflexes, indicating that they are relatively safe. Our data provide strong preclinical evidence that targeting CIM6P/IGF-2R is a promising approach for developing novel therapeutics for AS. LAY SUMMARY: There is no effective treatment for the neurodevelopmental disorder Angelman syndrome (AS). Using a validated AS mouse model, the Ube3a^m-/p+ , in this study we show that systemic administration of ligands of the cation independent mannose-6-phosphate receptor, also known as insulin-like growth factor 2 receptor (CIM6P/IGF-2R) reverses cognitive impairment, motor deficits, as well as seizures associated with AS. Thus, ligands that activate the CIM6P/IGF-2R may represent novel, potential therapeutic targets for AS.

While youth with autism spectrum disorder (ASD) are psychiatrically hospitalized at high rates, general psychiatric settings are not designed to meet their unique needs. Previous evaluations of an ASD-Care Pathway (ASD-CP) on a general psychiatric unit revealed sustained reductions in crisis interventions (intramuscular medication use, holds/restraints; Cervantes et al. in J Autism Dev Disord 49(8):3173-3180, https://doi.org/10.1007/s10803-019-04029-6, 2019; Kuriakose et al. in J Autism Dev Disord 48(12):4082-4089, https://doi.org/10.1007/s10803-018-3666-y, 2018). The current study investigated staff perceptions of the ASD-CP (N = 30), and examined rates of ASD-CP implementation fidelity in relation to patient outcomes (N = 28). Staff identified visual communication aids and reward strategies as most helpful. The number of days of reward identification early in the inpatient stay was associated with fewer crisis interventions later in a patient's stay.

Despite the extensive literature on the deleterious effects of perceived neighborhood disadvantage on academic achievement, there is a dearth of information on racial/ethnic differences in the underlying roles of future orientation and parental support that may mediate or moderate this association. Using data from 3618 students in grades 6-9 (50% female, Mean_age = 12.9 [1.3], 6.99% Black, 10.39% Hispanic/Latino, 82.61% White) in two communities in North Carolina during 2009-2014 who completed the School Success Profile, a self-report social environmental assessment, this study conducted multiple group analyses across three racial/ethnic groups (Black, Hispanic/Latino, White), revealing that perceived neighborhood disadvantage was associated with lower future orientation, which in turn was related to poorer academic achievement. The mediating effects were stronger among Black youth compared to White and Hispanic/Latino adolescents. Adolescents with high parental support were minimally affected by perceived neighborhood disadvantage. The findings identify nuanced racial/ethnic disparities in perceived neighborhood influences on academic achievement and raise important intervention targets to promote academic achievement among disadvantaged subgroups.