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The purpose of this study was to investigate possible rapid effects of light therapy on depressed mood in patients with seasonal affective disorder. Participants received 1 hour of bright light therapy and 1 hour of placebo dim red light in a randomized order crossover design. Depressed mood was measured at baseline and after each hour of light treatment using two self-report depression scales (Profile of Mood States-Depression-Dejection [POMS-D] subscale and the Beck Depression Inventory II [BDI-II]). When light effects were grouped for the two sessions, there was significantly greater reduction in self-report depression scores by -1.3 (p = 0.02) on the BDI-II and -1.2 (p = 0.02) on the POMS-D. A significant but modest improvement was detected after a single active light session. This is the first study, to our knowledge, to document an immediate improvement with light treatment using a placebo-controlled design with a clinical sample of depressed individuals. [ABSTRACT FROM AUTHOR]

Simon P Kelly, Graham MB ReevesThe Royal Bolton Hospital, Bolton, UKPurpose: To consider the potential for ocular injury from writing implements by presenting four such cases, and to consider the incidence of such eye injuries from analysis of a national trauma database.Methods: The Home and Leisure Accident Surveillance System was searched for records of eye injuries from writing instruments to provide UK estimates of such injuries. Four patients with ocular penetrating injury from pens or pencils (especially when caused by children), and examined by the authors, are described which illustrate mechanisms of injury.Results: It is estimated that around 748 ocular pen injuries and 892 ocular pencil injuries of undetermined severity occurred annually in the UK during the database surveillance period 2000–2002. No eye injuries from swords, including toy swords and fencing foils, were reported.Conclusion: Ocular perforation sometimes occur from writing instruments that are thrown in the community, especially by children. Implications for policy and prevention are discussed. Non-specialists should have a low threshold for referring patients with eye injuries if suspicious of ocular penetration, even where caused by everyday objects, such as writing instruments.Keywords: eye injury, eye, children, mechanism, writing instruments, prevention

Competing Interests: The authors report no financial relationships with commercial interests.

Introduction: Despite considerable investment in suicide prevention since 2001, there is limited evidence for the effect of suicide prevention interventions among children and adolescents. This study aimed to estimate the potential population impact of different interventions in preventing suicide-related behaviors in children and adolescents., Methods: A microsimulation model study used data from national surveys and clinical trials to emulate the dynamic processes of developing depression and care-seeking behaviors among a US sample of children and adolescents. The simulation model examined the effect of four hypothetical suicide prevention interventions on preventing suicide and suicide attempt in children and adolescents as follows: (1) reduce untreated depression by 20, 50, and 80% through depression screening; (2) increase the proportion of acute-phase treatment completion to 90% (i.e., reduce treatment attrition); (3) suicide screening and treatment among the depressed individuals; and (4) suicide screening and treatment to 20, 50, and 80% of individuals in medical care settings. The model without any intervention simulated was the baseline. We estimated the difference in the suicide rate and risk of suicide attempts in children and adolescents between baseline and different interventions., Results: No significant reduction in the suicide rate was observed for any of the interventions. A significant decrease in the risk of suicide attempt was observed for reducing untreated depression by 80%, and for suicide screening to individuals in medical settings as follows: 20% screened: -0.68% (95% credible interval (CI): -1.05%, -0.56%), 50% screened: -1.47% (95% CI: -2.00%, -1.34%), and 80% screened: -2.14% (95% CI: -2.48%, -2.08%). Combined with 90% completion of acute-phase treatment, the risk of suicide attempt changed by -0.33% (95% CI: -0.92%, 0.04%), -0.56% (95% CI: -1.06%, -0.17%), and -0.78% (95% CI: -1.29%, -0.40%) for reducing untreated depression by 20, 50, and 80%, respectively. Combined with suicide screening and treatment among the depressed, the risk of suicide attempt changed by -0.27% (95% CI: -0.dd%, -0.16%), -0.66% (95% CI: -0.90%, -0.46%), and -0.90% (95% CI: -1.10%, -0.69%) for reducing untreated depression by 20, 50, and 80%, respectively., Conclusion: Reducing undertreatment (the untreated and dropout) of depression and suicide screening and treatment in medical care settings may be effective in preventing suicide-related behaviors in children and adolescents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Zafari, Slejko, Camelo Castillo, Reeves and dosReis.)

Undertreatment of depression is common among children and adolescents, but evidence of the impact of undertreatment of depression on risk of suicide is limited due to the low base rate of suicide in the population and lack of sufficient data sources. We developed a microsimulation model that uses evidence from multiple sources to study the impact of different durations of antidepressant treatment on suicide risk in a synthesized sample that is nationally representative of children and adolescents with major depressive disorder. Compared with receiving no treatment, suicide rate and risk of suicide attempt both decreased with increasing duration of antidepressant treatment (for 12 weeks, suicide rate ratios = 0.78 (95% credible interval (CrI): 0.58, 1.15), 36 weeks, 0.65 (95% CrI: 0.44, 0.90), and 52 weeks, 0.63 (95% CrI: 0.45, 0.72); for suicide attempt: 12 weeks, suicide risk ratios = 0.68 (95% CrI: 0.62, 0.69), 36 weeks, 0.56 (95% CrI: 0.52, 0.57), and 52 weeks, 0.55 (95% CrI: 0.51, 0.56). The suicide rate and risk of suicide attempt were lower in children than in adolescents. Males had a lower risk of suicide attempt but higher suicide rate than females. The findings from the microsimulation model show that completion of 12-36 weeks of antidepressant treatment may reduce suicide attempt and suicide among children and adolescents with major depressive disorder., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Suicide is a leading cause of death among youth on the psychosis spectrum. Internalized mental health stigma is one risk factor for suicide that may be particularly salient for youth with psychosis-risk syndromes and early psychosis. Among this population, Black youth may face exposure to racism-related stressors that may exacerbate the negative effects of internalized stigma. This study examined whether internalized stigma and race interact to predict suicidal thoughts and behaviors (STB) in a help-seeking sample of Black and White adolescents with psychosis-risk syndromes and early psychosis. Findings suggest that Black youth with early psychosis spectrum disorders may be particularly vulnerable to the negative effects of internalized stigma as they pertain to STB. Internalized stigma may therefore represent an important treatment target in suicide prevention efforts among this population., Competing Interests: Conflict of Interest All authors declare that they have no conflicts of interest.

Subjective quality of life can be compromised in individuals with psychosis-risk symptoms, with poorer quality of life being associated with worse functioning and later transition to psychosis. Individuals who experience psychosis-related symptoms also tend to endorse more internalized (or self-) mental health stigma when compared to controls, potentially contributing to delays in seeking treatment and increased duration of untreated psychosis, as well as interfering with treatment engagement and retention in those already receiving care. Despite these findings, and the growing recognition for prevention in earlier phases of psychotic illness, few studies have examined the relation between psychosis-risk symptoms, internalized stigma, and subjective quality of life in a younger, help-seeking sample. The present study examined whether internalized stigma mediates the relation between psychosis-risk symptoms and subjective quality of life in a transdiagnostic sample of youth (M age = 17.93, SD = 2.90) at clinical high-risk for psychosis (CHR), with early psychosis, or with non-psychotic disorders (N = 72). Psychosis-risk symptom severity was assessed using the Structured Interview for Psychosis-Risk Syndromes (SIPS). Internalized stigma was assessed using the Internalized Stigma of Mental Illness Inventory (ISMI), and subjective quality of life was assessed using the Youth Quality of Life Instrument - Short Form (YQOL-SF). Internalized stigma fully mediated the relation between psychosis-risk symptoms and subjective quality of life across the full sample (p < .05, f 2  = 0.06). Findings suggest that internalized stigma may be an important target in efforts to improve quality of life for individuals in early stages of psychosis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Evidence supports the use of brief psychosis-spectrum screening tools for identifying individuals at an increased risk of developing a psychotic disorder. Screening has not been well studied in general mental health settings that serve young adults in the age range associated with highest risk for psychosis. This study explored the feasibility of psychosis-risk screening and assessment among help-seeking students at a university counseling center. The PRIME Screen-Revised was administered to students at clinic intake. Participants who screened positively were offered a follow-up assessment using the Structured Interview for Psychosis-risk Syndromes (SIPS). At intake, 510 students completed the PRIME Screen-Revised, with 132 (25.9%) screening positive. Comprehensive psychosis-spectrum evaluations were completed with 38 participants, and 22 met criteria for a psychosis-spectrum disorder, representing 57.9% of this subsample. Findings suggest that psychosis-risk screening in a college clinic is a promising approach to identifying those at high risk for or in the early stages of psychosis.

Dysfunction in the neural circuits underlying salience signaling is implicated in symptoms of psychosis and may predict conversion to a psychotic disorder in youth at clinical high risk (CHR) for psychosis. Additionally, negative symptom severity, including consummatory and anticipatory aspects of anhedonia, may predict functional outcome in individuals with schizophrenia-spectrum disorders. However, it is unclear whether anhedonia is related to the ability to attribute incentive salience to stimuli (through reinforcement learning [RL]) and whether measures of anhedonia and RL predict functional outcome in a younger, help-seeking population. We administered the Salience Attribution Test (SAT) to 33 participants who met criteria for either CHR or a recent-onset psychotic disorder and 29 help-seeking youth with nonpsychotic disorders. In the SAT, participants must identify relevant and irrelevant stimulus dimensions and be sensitive to different reinforcement probabilities for the 2 levels of the relevant dimension ("adaptive salience"). Adaptive salience attribution was positively related to both consummatory pleasure and functioning in the full sample. Analyses also revealed an indirect effect of adaptive salience on the relation between consummatory pleasure and both role (αβ = .22, 95% CI = 0.02, 0.48) and social functioning (αβ = .14, 95% CI = 0.02, 0.30). These findings suggest a distinct pathway to poor global functioning in help-seeking youth, via impaired reward sensitivity and RL., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Experiencing psychosis-spectrum symptoms is challenging to youth. Among many difficulties, internalized mental health stigma-the internalization of negative stereotypes-can lead to shame and withdrawal. The objective of this study was to better understand the correlates of internalized stigma among a clinical sample of youth with psychosis-spectrum symptoms. Participants (n = 66; 12-25 years old) were referred by community providers in Maryland, United States. Psychosis-spectrum symptoms were measured via the Structured Interview for Psychosis-Risk Syndromes (SIPS); family-functioning was measured via the Family Assessment Device . Interviewers rated participants' social/role functioning via the Global Functioning: Social and Role Scales . Internalized stigma was measured using the Internalized Stigma of Mental Illness (ISMI) total scale and subscales. The sample included 34 individuals at clinical high risk for psychosis, 16 experiencing early psychosis, and 16 help-seeking controls. Regression analyses indicated that unusual beliefs, avolition, role functioning, and lower family-functioning (caregiver-reported) were significantly associated with higher aspects of internalized stigma, controlling for other symptoms and sociodemographics. These models explained 27% of the variance (adjusted R2) in the total ISMI scale and between 15% to 49% of the variance in ISMI-subscales. Among this help-seeking sample, unusual beliefs, avolition, higher role functioning, and lower family-functioning (caregiver-reported) were associated with more internalized stigma. Pending future research with larger samples, therapeutic interventions focused on these factors and their correlates may benefit youth. Future research is needed to determine temporal precedence of these associations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Abnormal reward processing is thought to play an important role in the development of psychosis, but relatively few studies have examined reward prediction errors, reinforcement learning (RL), and the reward circuitry that subserves these interconnected processes among individuals at clinical high-risk (CHR) for the disorder. Here, we present behavioral and functional neuroimaging results of two experimental tasks designed to measure overlapping aspects of reward processing among individuals at CHR (n = 22) and healthy controls (n = 19). We found no group differences in response times to positive, negative, or neutral outcome-signaling cues, and no significant differences in brain activation during reward anticipation or receipt. Youth at CHR, however, displayed clear RL impairments, as well as attenuated responses to rewards and blunted prediction error signals in the ventral striatum, dorsal anterior cingulate cortex (dACC), and ventromedial prefrontal cortex (vmPFC). Greater contrasts for cue valence (gain-loss) and outcome magnitude (large-small) in the vmPFC were associated with more severe negative symptoms, and deficits in dACC signaling during RL were associated with more depressive symptoms. Our results provide evidence for RL deficits and abnormal prediction error signaling in the brain's reward circuitry among individuals at CHR, while also suggesting that reward motivation may be relatively preserved at this stage in development. Longitudinal studies, medication-free participants, and comparison of neurobehavioral measures against both healthy and clinical controls are needed to better understand the role of reward system abnormalities in the development of psychosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Early detection and prevention of psychosis has become an international priority. Much of this work has focused on youth presenting with attenuated symptoms of psychosis-those at Clinical High Risk for psychosis (CHR)-given their elevated probability of developing the full disorder in subsequent years. Individuals at CHR may be prone to exacerbated psychological distress during the COVID-19 pandemic and its subsequent physical isolation measures, due to heightened stress sensitivity and comorbid mental health problems. Telepsychotherapy holds promise for reaching this population, especially during the current COVID-19 outbreak. However, there are limited evidence-based guidelines or interventions for use of telepsychotherapy with this population. In this paper, we review common clinical issues for individuals at CHR and how they might be exacerbated by the COVID-19 pandemic; best practices for treatment and adaptations for telepsychotherapy for individuals at CHR; and highlight real clinical issues that we are currently experiencing in a United States-based specialized CHR clinic as we conduct telepsychotherapy via videoconferencing. We conclude with questions for those in the field to contemplate, as well as potential challenges and benefits in using telepsychotherapy with individuals at CHR and their families.

Objective: Self-report screening instruments for emerging psychosis have the potential to improve early detection efforts by increasing the number of true positives among persons deemed to be at "clinical high risk" of the disorder, but their practical utility depends on their validity across race. This study sought to examine whether a commonly used self-report screening tool for psychosis risk performed equally among black and white youths in its ability to predict clinical high-risk status., Methods: Black (N=58) and white (N=50) help-seeking individuals ages 12-25 (61% female) were assessed with the Prime Screen and the Structured Interview for Psychosis-Risk Syndromes (SIPS). A logistic regression model estimated race differences in the strength of the relation between Prime Screen scores and SIPS-defined risk status., Results: Higher Prime Screen scores significantly predicted clinical high-risk status among white (p<.01) but not black participants. Among black youths without clinical high risk, self-reported Prime Screen scores more closely resembled scores for youths (black or white) with clinical high risk than scores of white peers who were also without clinical high risk., Conclusions: Results suggest that consideration of race or ethnicity and associated cultural factors is important when screening for clinical high-risk status. Findings support the need to develop culturally valid early psychosis screening tools to promote appropriately tailored early intervention efforts.

Self-report screening instruments offer promise in furthering early identification of at-risk youth, yet current efforts are limited by false positive rates. Identifying moderators of accuracy is a potential step towards improving identification and prevention efforts. We investigated the moderating effect of age on self-reported attenuated positive symptoms from the Prime Screen and clinician diagnosed clinical high-risk/early psychosis (CHR/EP) status. Participants (N = 134) were racially diverse, lower-income, help-seeking adolescents and young adults from a primarily urban community. The overall model predicting CHR/EP status was significant, with results suggesting the presence of a trending interaction between age and Prime Screen symptoms. Analyses indicated that number of items endorsed to predict CHR/EP decreased with age (youngest group [M = 12.99] cut off = 6 items; middle age group [M = 14.97] cut off = 3; oldest age group [M = 18.40] cut off = 1). Although younger participants endorsed more risk items on average, follow up analyses suggested that the Prime Screen was a more accurate predictor of clinician-diagnosed-risk among older participants relative to their younger peers. The current study builds on the literature identifying moderators of psychosis-risk screening measure accuracy, highlighting potential limitations of CHR/EP screening tools in younger populations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Youth at clinical high-risk (CHR) for psychosis often experience difficulties in social and role functioning. Given evidence that family stress and support can impact psychosis-risk symptoms, as well as an individual's ability to fulfill social and role functions, family dynamics are hypothesized to moderate the effect of psychosis-risk symptoms on functioning., Methods: Participants at CHR (N = 52) completed the clinician-administered Structured Interview for Psychosis-risk Syndromes (SIPS) and the Family Assessment Device (FAD) General Functioning Scale, a self-report measure of family functioning including cohesion and support. Interviewers rated participants' current social and role functioning using the Global Functioning: Social and Role Scales., Results: Regression results indicated that positive symptoms, but not ratings of family functioning, statistically predicted social and role functioning. Perceived family functioning, however, moderated the effect of symptoms on social/role functioning. For individuals who perceived lower levels of family functioning, symptoms were moderately associated with social and role functioning (f 2  = 0.17 and f 2  = 0.23, respectively). In contrast, psychosis-risk symptoms were not significantly associated with social/role functioning for individuals with higher levels of perceived family functioning. Notably, positive symptoms and perceived family functioning were not associated with one another, suggesting that perceived family functioning did not directly impact symptom severity, or vice versa., Conclusions: Findings support the notion that family functioning may be a clinically meaningful factor for individuals at CHR. Although this cross-sectional data limits our discussion of potential mechanisms underlying the pattern of findings, results suggest that familial support may be beneficial for individuals at risk for psychosis., (Copyright © 2018. Published by Elsevier B.V.)

Objective: Care management entity models have a positive impact on functioning and symptom control among youths with serious emotional and behavioral disorders. However, little is known about whether treatment benefits are sustained after discharge. The study objective was to examine the association between enrollment in a care management entity and mental health outcomes during the year after discharge., Methods: Data from care management entity administrative claims were linked with Medicaid claims for youths enrolled in a care management entity anytime from December 2009 through December 2013. Inverse probability treatment weighting was used to balance baseline characteristics between the youths enrolled in the care management entity and a comparison group. Study outcomes were psychiatry-related hospitalizations and emergency department (ED) visits during the year after discharge. Two models were used to compare the two groups, one modeling the probability of using any psychiatric service and one modeling the number of visits for each outcome among users of either service., Results: After adjustment with inverse probability treatment weighting, 2,381 youths (care management, N=488; comparison, N=1,893) were identified. Care management was associated with a significantly lower likelihood of any psychiatry-related ED visit (odds ratio [OR]=.65, p=.017) and any psychiatric hospitalization (OR=.60, p=.011). No significant differences in outcomes were observed when the comparison was limited to users of services., Conclusions: Reduced use of psychiatric inpatient and ED services among youths enrolled in a care management entity was sustainable after discharge. Multiagency collaboration is needed to enrich the ability to assess outcomes across broader domains.

Research suggests that social stress exposure influences illness presentation and course among youth at clinical high-risk (CHR) for psychosis, though less is known about the extent to which self-reported perceptions of social stress relate to the severity of positive symptoms. Importantly, despite the notion that youth at CHR are especially susceptible to elevations in positive symptoms under conditions of stress, no study has examined this presumption relative to other psychiatric groups. Extending previous work demonstrating that perceived social stress was higher in a CHR group than in a clinical group of non-CHR, help-seeking controls, the current study aimed to: (1) examine whether perceived social stress is related to the severity of attenuated positive symptoms in the full sample (N=110); and (2) determine whether CHR status moderates the stress-symptom relation. Exploratory analyses examined relations of perceived social stress to negative, disorganized, and general symptoms. Greater perceptions of social stress were associated with more severe positive symptoms in the entire sample; however, although positive symptoms and perceived social stress were higher in the CHR group, the strength of this relation was statistically indistinguishable across groups. No differential effect of perceived social stress was observed for any symptom domain. Results provide some support for the diathesis-stress model of psychosis, while also suggesting that social stress and symptomatology are related independent of clinical vulnerability to psychosis. Future research would benefit from longitudinal studies of stress-symptom relations across CHR and help-seeking control groups., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A state Care Management Entity (CME) using the wraparound practice model provided intensive care coordination for youth with severe mental illness, those most likely to receive antipsychotics. The model has led to improved clinical/functional outcomes, but little is known about the impact on antipsychotic prescribing and safety monitoring. A pre-post study was conducted to evaluate antipsychotic dosing, concomitant antipsychotic use, and metabolic monitoring among CME-enrolled and non-CME-enrolled comparison groups. CME-enrolled youth had greater decrease in concomitant antipsychotic use than non-CME-enrolled youth, but no difference in dosing or metabolic monitoring. More education of prescribing antipsychotics and team-based engagement in care coordination are needed.

Background: We tested the hypothesis that the early improvement in mood after the first hour of bright light treatment compared to control dim-red light would predict the outcome at six weeks of bright light treatment for depressed mood in patients with Seasonal Affective Disorder (SAD). We also analyzed the value of Body Mass Index (BMI) and atypical symptoms of depression at baseline in predicting treatment outcome., Methods: Seventy-eight adult participants were enrolled. The first treatment was controlled crossover, with randomized order, and included one hour of active bright light treatment and one hour of control dim-red light, with one-hour washout. Depression was measured on the Structured Interview Guide for the Hamilton Rating Scale for Depression-SAD version (SIGH-SAD). The predictive association of depression scores changes after the first session. BMI and atypical score balance with treatment outcomes at endpoint were assessed using multivariable linear and logistic regressions., Results: No significant prediction by changes in depression scores after the first session was found. However, higher atypical balance scores and BMI positively predicted treatment outcome., Limitations: Absence of a control intervention for the six-weeks of treatment (only the first session in the laboratory was controlled). Exclusion of patients with comorbid substance abuse, suicidality and bipolar I disorder, and patients on antidepressant medications, reducing the generalizability of the study., Conclusion: Prediction of outcome by early response to light treatment was not replicated, and the previously reported prediction of baseline atypical balance was confirmed. BMI, a parameter routinely calculated in primary care, was identified as a novel predictor, and calls for replication and then exploration of possible mediating mechanisms., (Published by Elsevier B.V.)

Research suggests that perceived social stress influences illness presentation and course among youth in the clinical high-risk (CHR) phase of psychosis. Little is known, however, about the social cognitive factors associated with social stress perception in this population, particularly relative to youth with non-CHR psychopathology. Individuals with psychosis tend to endorse an external locus of control (LOC), which is associated with the stress response in healthy individuals. LOC may therefore be related to perceived social stress in youth at CHR. We examined the differential relations of self-reported LOC and perceived social stress, as measured by the Behavior Assessment System for Children, Second Edition, across 45 CHR and 65 help-seeking control (HSC) participants. Youth at CHR reported more social stress (F[1, 107]=6.28, p=0.01) and a more external LOC (F[1, 107]=4.98, p=0.03) than HSCs. Further, external LOC was more strongly associated with feelings of social stress in the CHR group relative to the HSC group (interaction: b=0.35, t[105]=2.32, p<0.05, f 2 =0.05). Group differences in social stress, however, were nonsignificant at internal levels of LOC (b=-2.0, t[105]=-0.72, p=0.48; f 2 =0.00). Results suggest that perceptions of uncontrollability over one's social environment may more often induce or exacerbate feelings of stress and tension in CHR youth relative to HSCs. A better understanding of the social cognition-stress relation may improve understanding of CHR phenomenology, etiology, and treatment., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Sleep problems are prominent and pervasive clinical issues experienced by many people with psychotic disorders, often causing distress and functional impairment. Sleep problems are also related to psychosis-like experiences (PLE; non-diagnosable phenomenon such as transient perceptual disturbances, unusual thoughts, periodic suspiciousness) in epidemiological studies. Prior studies in this field have used brief measures that precluded the ability to test (1) whether risk for psychosis-like experiences are related to specific sub-types of sleep disturbance, and (2) whether sleep disturbance is specifically related to clinically significant (i.e., distressing) psychosis-like experiences. The current project examined the relation between specific sleep issues, and PLEs and distress associated with PLEs, in a college sample. Participants (N=420) completed the Prodromal Questionnaire-Brief (PQ-B), which assesses PLEs and associated distress, and the Iowa Sleep Disturbances Inventory - extended version (ISDI-E), which assesses thirteen separate disturbed sleep domains. Symptoms of fragmented sleep, sleep hallucinations, and night anxiety significantly correlated with PLEs, and several sleep domains were significantly associated with PLE-related distress., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Smoking is highly prevalent in patients with schizophrenia and exerts a negative impact on cardiovascular mortality in these patients. Smoking has complex interactions with monoamine metabolism through the ability of cigarette smoke to suppress Type 1 T helper cell (Th1) type immunity, the immunophenotype that is implicated in phenylalanine hydroxylase (PAH) dysfunction and tryptophan (Trp) breakdown to kynurenine (Kyn) via indoleamine 2,3-dioxygenase. Nicotine also induces tyrosine hydroxylase (TH) gene expression, leading to increased synthesis of catecholamines. Furthermore, there is evidence for PAH dysfunction in schizophrenia. This study aimed to compare the plasma levels of selected monoamine precursors and their metabolites in smokers vs. non-smokers in a large sample of patients with schizophrenia. We measured plasma phenylalanine (Phe), tyrosine (Tyr), Trp, and Kyn levels using high-performance liquid chromatography and calculated Phe:Tyr and Kyn:Trp ratios in 920 patients with schizophrenia. Analysis of variance and linear regression analyses were used to compare these endpoints between three groups of patients with schizophrenia: (1) current smokers, (2) past smokers, and (3) non-smokers. There were significant differences among the three groups with regards to Tyr levels [F (2,789) = 3.77, p = 0.02], with current smokers having lower Tyr levels when compared with non-smokers (p = 0.02). Kyn levels and Kyn:Trp ratio were different among the three groups [F (2,738) = 3.17, p = 0.04, F (2,738) = 3.61, p = 0.03] with current smokers having lower Kyn levels (p = 0.04) and higher Kyn:Trp ratio (p = 0.02) when compared with past smokers. These findings need to be replicated with protocols that include healthy controls to further elucidate the neurobiological underpinnings of altered Tyr and Kyn levels in smokers. Results do suggest potential molecular links between schizophrenia and smoking that may represent biomarkers and treatment targets for reducing an important modifiable cause of general morbidity and mortality in patients with schizophrenia.

Schizophrenia (SCZ) and type 2 diabetes (T2D) are clinically associated, and common knowledge attributes this association to side effects of antipsychotic treatment. However, even drug-naive patients with SCZ are at increased risk for T2D. Dopamine dysfunction has a central role in SCZ. It is well-known that dopamine constitutively inhibits prolactin (PRL) secretion via the dopamine receptor 2 (DR2D). If dopamine is increased or if dopamine receptors hyperfunction, PRL may be reduced. During the first SCZ episode, low PRL levels are associated with worse symptoms. PRL is essential in human and social bonding, as well as it is implicated in glucose homeostasis. Dopamine dysfunction, beyond contributing to SCZ symptoms, may lead to altered appetite and T2D. To our knowledge, there are no studies of the genetics of the SCZ-T2D comorbidity focusing jointly on the dopamine and PRL pathway in the attempt to capture molecular heterogeneity correlated to possible disease manifestation heterogeneity. In this dopamine-PRL pathway-focused-hypothesis-driven review on the association of SCZ with T2D, we report a specific revision of what it is known about PRL and dopamine in relation to what we theorize is one of the missing links between the two disorders. We suggest that new studies are necessary to establish the genetic role of PRL and dopamine pathway in SCZ-T2D comorbidity.

Aim: A growing body of research documents a relation between psychosis risk and functional impairment. Although a general picture of psychosis risk and impaired functioning is emerging, less is known about how different functional measures relate to specific psychosis-risk symptoms., Methods: The current study examines the relative contribution of psychosis-risk symptoms across multiple measures of functioning in a sample of treatment-seeking adolescents and young adults., Results: Results indicate that different domains of psychosis-risk symptoms (negative and positive psychotic symptoms, related affective symptoms) contribute differentially to measures of different types of functioning., Conclusion: Study of the relation between psychosis-risk symptoms and different measures of functional impairment can potentially contribute towards a more efficient use of measures of functioning and help inform individualized treatment considerations., (© 2014 Wiley Publishing Asia Pty Ltd.)

The Patient Protection and Affordable Care Act focuses on improving consumer engagement and patient-centered care. This article describes the design and rationale of a study targeting family engagement in pediatric mental health services. The study is a 90-day randomized trial of a telephone-delivered Family Navigator services versus usual care for parents of Medicaid-insured youth younger than 13 years with serious mental illness. Youth are identified through a pediatric antipsychotic medication preauthorization program. Family Navigators offer peer support to empower and engage parents in their child's recovery. Outcomes include parent report of empowerment, social support, satisfaction with child mental health services, and child functioning as well as claims-based measures of psychotherapy service utilization and antipsychotic medication dosage. The focus on "family-centered" care in this study is strongly supported by the active role of consumers in study design and implementation.

Purpose: The aim of this study was to estimate the prevalence of first-generation antipsychotics (FGA) prescribed for treatment of psychiatric and neurological conditions and use of benztropine to reduce extrapyramidal side effects (EPS) by patient race/ethnicity in a nationally representative sample of adult outpatient visits., Methods: The study sample included all outpatient visits (N = 8154) among patients aged 18-69 years where a prescription for one or more antipsychotics was recorded across 6 years of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (2005-2010). Use of FGA was compared by race/ethnicity using multiple logistic regression models accounting for patient and clinical characteristics stratified by neighborhood poverty rate. Frequency of EPS was determined by use of benztropine to reduce or prevent EPS., Results: Black patients were significantly more likely than White patients to use FGA (odds ratio = 1.48, p = 0.040) accounting for psychiatric and neurological diagnoses, treatment setting, metabolic factors, neighborhood poverty, and payer source. Black patients were more than twice as likely as White patients to receive higher-potency FGA (haloperidol or fluphenazine), particularly in higher-poverty areas (odds ratio = 2.50, p < 0.001). Use of FGA, higher among Black than White patients, was positively associated with use of benztropine to reduce EPS., Conclusions: Racial disparities in the pharmacological treatment of severe mental disorders persist 30 years after the introduction of second-generation antipsychotics. The relatively high frequency of FGA of use among Black patients compared with White patients despite more Food and Drug Administration-approved indications and lower EPS risk for second-generation antipsychotics requires additional research., (Copyright © 2015 John Wiley & Sons, Ltd.)

Youth and young adults at clinical high risk (CHR) for psychosis experience a broad range of difficulties, including attenuated psychotic symptoms, comorbid concerns, functional impairments, and family and interpersonal stress. Given emerging evidence that early interventions may improve functioning and reduce symptomatology while also lowering risk of transition to full-threshold psychosis, several randomized controlled trials have systematically evaluated the efficacy of CHR treatment approaches. This article describes and summarizes psychosocial intervention approaches that have demonstrated efficacy in treating people at CHR, with a focus on distilling individual components of these treatments. On the basis of the existing literature, we propose an empirically based, flexible, and comprehensive modularized approach to early intervention that meets the varying needs of individuals experiencing CHR-related distress and dysfunction, many of whom may be on a trajectory toward psychosis.

Aim: To compare adherence, response, and remission with light treatment in African-American and Caucasian patients with Seasonal Affective Disorder., Methods: Seventy-eight study participants, age range 18-64 (51 African-Americans and 27 Caucasians) recruited from the Greater Baltimore Metropolitan area, with diagnoses of recurrent mood disorder with seasonal pattern, and confirmed by a Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV, were enrolled in an open label study of daily bright light treatment. The trial lasted 6 wk with flexible dosing of light starting with 10000 lux bright light for 60 min daily in the morning. At the end of six weeks there were 65 completers. Three patients had Bipolar II disorder and the remainder had Major depressive disorder. Outcome measures were remission (score ≤ 8) and response (50% reduction) in symptoms on the Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-SAD) as well as symptomatic improvement on SIGH-SAD and Beck Depression Inventory-II. Adherence was measured using participant daily log. Participant groups were compared using t-tests, chi square, linear and logistic regressions., Results: The study did not find any significant group difference between African-Americans and their Caucasian counterparts in adherence with light treatment as well as in symptomatic improvement. While symptomatic improvement and rate of treatment response were not different between the two groups, African-Americans, after adjustment for age, gender and adherence, achieved a significantly lower remission rate (African-Americans 46.3%; Caucasians 75%; P = 0.02)., Conclusion: This is the first study of light treatment in African-Americans, continuing our previous work reporting a similar frequency but a lower awareness of SAD and its treatment in African-Americans. Similar rates of adherence, symptomatic improvement and treatment response suggest that light treatment is a feasible, acceptable, and beneficial treatment for SAD in African-American patients. These results should lead to intensifying education initiatives to increase awareness of SAD and its treatment in African-American communities to increased SAD treatment engagement. In African-American vs Caucasian SAD patients a remission gap was identified, as reported before with antidepressant medications for non-seasonal depression, demanding sustained efforts to investigate and then address its causes.

Background: Several studies documented that lower scores on the Morningness-Eveningness Questionnaire (MEQ) are associated with a higher global seasonality of mood (GSS). As for the Modern Man artificial lighting predominantly extends evening activity and exposure to light, and as evening bright light phase is known to delay circadian rhythms, this chronic exposure could potentially lead to both lower Morningness as well as higher GSS. The aim of the study was to investigate if the MEQ-GSS relationship holds in the Old Order Amish of Lancaster County, PA, a population that does not use network electrical light., Methods: 489 Old Order Amish adults (47.6% women), with average (SD) age of 49.7 (14.2) years, completed both the Seasonal Pattern Assessment Questionnaire (SPAQ) for the assessment of GSS, and MEQ. Associations between GSS scores and MEQ scores were analyzed using linear models, accounting for age, gender and relatedness by including the relationship matrix in the model as a random effect., Results: GSS was inversely associated with MEQ scores (p=0.006, adjusted)., Limitations: include a potential recall bias associated with self-report questionnaires and no actual light exposure measurements., Conclusion: We confirmed the previously reported inverse association between MEQ scores and lower seasonality of mood, for the first time in a population that does not use home network electrical lighting. This result suggests that the association is not a byproduct of exposure to network electric light, and calls for additional research to investigate mechanisms by which Morningness is negatively associated with seasonality., (Published by Elsevier B.V.)

Subthreshold psychosis-like experiences are typically the focus of psychosis-risk screening as they are associated with a greater propensity for future illness. Potentially prodromal individuals identified as being at clinical high-risk (CHR), however, report a variety of distressing and impairing mental health symptoms in addition to subthreshold psychosis symptoms, indicating that this population is of clinical interest regardless of whether or not they develop psychosis. In the current study, 90 young people (12-21) seeking mental health services completed the Behavior Assessment System for Children, Second Edition (BASC-2), a broad-range checklist of emotional and behavioral concerns and adaptive skills, followed by the Structured Interview for Psychosis-risk Syndromes to assess psychosis risk. Those who met criteria for CHR (n=35) reported elevated scores across several BASC-2 scales including depression, attention problems, locus of control, and sense of inadequacy compared to help-seeking youth without CHR (n=55). Most of these scales were also elevated compared to general population norms. Further, the CHR group had significantly lower scores on two adaptive scales, self-reliance and relations with parents, indicating more impairment in these domains. Results indicate that young people at CHR experience more pervasive and/or more severe symptomatology across several domains of clinical significance compared to a similar group of help-seeking youth not at CHR. Results from this study aid in the understanding of symptom correlates of CHR status beyond attenuated symptoms that can provide clinical information relevant for treatment., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Family members of consumers with mental illness often play important roles in initiating and supporting treatment. Self-help programs such as the National Alliance on Mental Illness (NAMI) Family-to-Family Education Program (FTF) have been shown to provide a variety of benefits for family members. Despite recognizing the benefits of FTF, little is known about who may benefit most, and in what ways they might benefit. One group of interest is family members of younger consumers, a group shown to report more negative caregiving experiences and more depression and anxiety than caregivers of older consumers. The current study assesses whether relatives of youth (ages 8-18) differ in their response to FTF as opposed to relatives of adults (19 years and older). Results suggest that all members benefit from FTF. Family members of youth in FTF, however, reported gains more pronounced on their depressive symptoms, and negative perceptions and experiences, relative to family members of adults. The importance of peer support programs is discussed, as well as the specific usefulness of these programs to effectively address concerns of relatives of youth with serious mental health concerns.

There is a dearth of information on the association of atopy with schizophrenia. The few available studies used population-based registers to classify the atopy status of the patients but this strategy is not reliable. This study measured seropositivity with a multiallergen screen of allergen specific IgE antibodies in schizophrenia patients versus healthy controls. A subset of 66 schizophrenia patients and 34 healthy controls were randomly selected from a large comparative study of schizophrenia patients and controls. The Phadiatop multi-allergen screen was performed on sera from all the participants to assess their atopic status. Logistic regression was used to calculate the odds ratio for the association of schizophrenia with Phadiatop seropositivity as a measure of atopy. The prevalence of Phadiatop seropositivity was significantly lower (χ 2 4.59, p = 0.032) and there was a reduced odds ratio for atopy in schizophrenia patients relative to controls (OR 0.40; 95% CI 0.17 to 0.94, p = 0.036). Though limited by a relatively small sample size and potentially confounded by anti-psychotic medications, this study suggests that the prevalence of atopy is lower in patients with schizophrenia. Replicating these results in larger samples could add to our growing understanding of immunological implications in mental illness.

Obesity is a global public health problem that is linked with morbidity, mortality, and functional limitations and has limited options for sustained interventions. Novel targets for prevention and intervention require further research into the pathogenesis of obesity. Consistently, elevated markers of inflammation have been reported in association with obesity, but their causes and consequences are not well understood. An emerging field of research has investigated the association of infections and environmental pathogens with obesity, potential causes of low grade inflammation that may mediate obesity risk. In this study, we estimate the possible association between Toxoplasma gondii (T. gondii) infection and obesity in a sample of 999 psychiatrically healthy adults. Individuals with psychiatric conditions, including personality disorders, were excluded because of the association between positive serology to T. gondii and various forms of serious mental illness that have a strong association with obesity. In our sample, individuals with positive T. gondii serology had twice the odds of being obese compared to seronegative individuals (p = 0.01). Further, individuals who were obese had significant higher T. gondii IgG titers compared to individuals who were non-obese. Latent T. gondii infection is very common worldwide, so potential public health interventions related to this parasite can have a high impact on associated health concerns.

Background: Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) study, a federally funded, randomized trial comparing two pharmacologic strategies against a control condition to manage SGA-related weight gain., Methods: The design and methodology considerations of the IMPACT trial are described and embedded in a description of health risks associated with antipsychotic-related weight gain and the limitations of currently available research., Results: The IMPACT study is a 4-site, six month, randomized, open-label, clinical trial of overweight/obese youth ages 8-19 years with pediatric schizophrenia-spectrum and bipolar-spectrum disorders, psychotic or non-psychotic major depressive disorder, or irritability associated with autistic disorder. Youth who have experienced clinically significant weight gain during antipsychotic treatment in the past 3 years are randomized to either (1) switch antipsychotic plus healthy lifestyle education (HLE); (2) add metformin plus HLE; or (3) HLE with no medication change. The primary aim is to compare weight change (body mass index z-scores) for each pharmacologic intervention with the control condition. Key secondary assessments include percentage body fat, insulin resistance, lipid profile, psychiatric symptom stability (monitored independently by the pharmacotherapist and a blinded evaluator), and all-cause and specific cause discontinuation. This study is ongoing, and the targeted sample size is 132 youth., Conclusion: Antipsychotic-related weight gain is an important public health issue for youth requiring ongoing antipsychotic treatment to maintain psychiatric stability. The IMPACT study provides a model for pediatric research on adverse event management using state-of-the art methods. The results of this study will provide needed data on risks and benefits of two pharmacologic interventions that are already being used in pediatric clinical settings but that have not yet been compared directly in randomized trials., Trial Registration: Clinical Trials.gov NCT00806234.

In a 2009 policy statement focused on children's mental health, the American Academy of Pediatrics recommended that pediatric primary care physicians achieve competence in initiating care for children with attention-deficit/hyperactivity disorder (ADHD), anxiety, depression, and substance use/abuse. Because treatment for 3 of these conditions--ADHD, anxiety, and depression--may, under certain conditions, include medication, the primary purpose of this article is to offer guidance to assist primary care physicians in decision-making about their use of psychotropic medications for these conditions. A few medications with proven efficacy and safety are emphasized. Secondarily, other medications that may be useful for other disorders are noted.

Background/objective: We examined seasonality and winter seasonal affective disorder (SAD) in the Old Order Amish of Lancaster County, Pennsylvania, a unique population that prohibits use of network electric light in their homes., Methods: We estimated SAD using the seasonal pattern assessment questionnaire (SPAQ) in 1306 Amish adults and compared the frequencies of SAD and total SAD (i.e., presence of either SAD or subsyndromal-SAD) between men and women, young and old, and awareness of (ever vs. never heard about) SAD. Heritability of global seasonality score (GSS) was estimated using the maximum likelihood method, including a household effect to capture shared environmental effects., Results: The mean (±SD) GSS was 4.36 (±3.38). Prevalence was 0.84% (95% CI: 0.36-1.58) for SAD and 2.59% (95% CI: 1.69-3.73) for total SAD. Heritability of GSS was 0.14±0.06 (SE) (p=0.002) after adjusting for age, gender, and household effects., Limitations: Limitations include likely overestimation of the rates of SAD by SPAQ, possible selection bias and recall bias, and limited generalizability of the study., Conclusions: In the Amish, GSS and SAD prevalence were lower than observed in earlier SPAQ-based studies in other predominantly Caucasian populations. Low heritability of SAD suggests dominant environmental effects. The effects of awareness, age and gender on SAD risk were similar as in previous studies. Identifying factors of resilience to SAD in the face of seasonal changes in the Amish could suggest novel preventative and therapeutic approaches to reduce the impact of SAD in the general population., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Purpose: Retinal vasculitis is an important component of posterior uveitis. It may be difficult to detect either clinically or with conventional angiography. We assessed the role of Staurenghi lens angiography (SLA) in the diagnosis and management of patients with posterior uveitis., Methods: A total of 26 patients attending the St Paul's Eye Unit uveitis clinic with posterior uveitis underwent wide-angle (150 degree) retinal angiography with the Heidelberg Retina Angiograph 2 Scanning Laser Ophthalmoscope using the Staurenghi SLO 230 contact lens. We determined the percentage of patients in whom this imaging modality assisted in diagnosing and quantifying the extent of vasculitis, planning treatment or monitoring disease activity., Results: Staurenghi lens angiography assisted in diagnosing and quantifying the extent of vasculitis in 62% of patients, and in planning laser photocoagulation or immunosuppression titration in 62% of patients and enhanced disease monitoring in 35% of patients. In 31% of cases, SLA revealed vasculitis that was not evident clinically., Conclusion: Staurenghi lens angiography is a valuable tool in the management of patients with posterior uveitis and can be used for the diagnosis, treatment and follow-up of these patients., (© 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.)

Background: To investigate the effect of adding indocyanine green to mitomycin C in augmented trabeculectomy., Design: A prospective, non-comparative interventional case series., Participants: A total of 37 eyes of 37 patients followed up for 1 year., Methods: A solution containing 12.5 mg/mL of indocyanine green was added to mitomycin C, resulting in an mitomycin C concentration of 0.2-0.4 mg/mL, which was applied to bare sclera and Tenon's capsule for 3 min during trabeculectomy., Main Outcome Measures: Visual acuity, intraocular pressure, bleb morphology, Moorfields Bleb Grading System scores and complications., Results: Indocyanine green could be visualized on clinical examination for all eyes on the first postoperative day. Mean intraocular pressure decreased from 22.9 ± 6.2 mmHg to 12.1 ± 4.4 mmHg postoperatively (P < 0.001) at 1 year. Thirty-four eyes (91.9%) achieved an intraocular pressure of less than 21 mmHg at final visit without additional topical intraocular pressure-lowering medications. Three eyes (8.1%) developed bleb failure and required Baerveldt device implantation. There were no cases of blebitis or late bleb leak. No adverse effects attributable to indocyanine green could be identified postoperatively., Conclusion: The addition of indocyanine green during trabeculectomy improves the visibility of antimetabolites intraoperatively and allows for the estimation of antimetabolite treatment area intraoperatively and postoperatively. It appears to have no adverse effect on surgical outcomes and complication rates, while improving safety of antimetabolite use., (© 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.)

Background: The purpose of this study is to define treatment response and remission cut-point scores for the Beck Depression Inventory-Second Edition (BDI-II) when used to monitor seasonal affective disorder (SAD) treatment., Methods: Data from two published randomized clinical trials for SAD were utilized to complete a ROC analysis to define response and remission thresholds for the BDI-II. The Structured Interview Guide for the Hamilton Rating Scale for Depression-Seasonal Affective Disorder Version (SIGH-SAD) was used as a reference standard. Data from the two trials included BDI-II and SIGH-SAD scores for patients at baseline, 6 weeks (post-treatment), and 1 year (next winter)., Results: BDI-II score of ≤ 9 was the derived criterion for remission of SAD, and BDI-II score decrease of 50% from baseline was the criterion for treatment response., Limitations: Study participants were primarily female (94%) and Caucasian (80%) so demographic diversity of the sample was limited., Conclusion: This study validated BDI-II scores compared to the SIGH-SAD reference standard. The BDI-II has greater potential for widespread use by clinicians than the SIGH-SAD to monitor SAD patients because it is a brief self-report instrument that can be conveniently administered in the waiting room., Competing Interests: The authors have no conflict of interest to report., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: A variety of methods have been described for grading ocular mucous membrane pemphigoid (MMP), each with their own limitations. In contrast, there are no reported grading systems for involvement of the oral mucosa. We wished to evaluate two ocular (one established and one proposed) and an oral mucosal grading system for MMP., Methods: Patients with MMP were assessed by three ophthalmologists and two oral medicine physicians. Ocular disease was graded using the system described by Rowsey and a proposed system based on measurement of vertical depth and horizontal width measured from the bulbar conjunctival aspect. Oral assessment used a 'mucosal disease severity score' originally described for lichen planus, in which 17 areas of the mouth are scored for involvement, together with a pain score. Levels of agreement were evaluated using Fleiss' Kappa Statistic (k)., Results: Forty-four patients with MMP encompassing mild to severe disease were included. Good levels of agreement were observed between observers for both vertical (k:0.86) (upper 95% CI: 1.03 mm) and horizontal (k:0.80) (upper 95% CI: 3.01 mm) involvement for the proposed ocular system and the Rowsey system (k: 0.83) (upper 95% confidence interval: 3.19 mm). There was a high coefficient of determination (R(2)) between the ocular grading systems (0.81, p < 0.01). Oral grading showed excellent levels of agreement (k: 0.71) between observers. There was no significant association between the severity of oral and ocular disease using described grading systems., Conclusions: The proposed grading systems for both oral and ocular involvement in MMP are easy to use, and show good agreement between observers. The proposed ocular system correlates well with a currently used system, and overcomes some of the difficulties encountered with existing systems. For the individual patient, changes greater than 1.5 mm (vertical) and 3 mm (horizontal) are significant. This may increase our ability to detect change or disease progression. Although the risk of ocular involvement in patients with only oral involvement has been demonstrated, the severity of oral and ocular disease are not well-correlated, due in part to an absence of an ocular disease activity score.

Working memory impairments are frequent in Attention Deficit/Hyperactivity Disorder (ADHD) and create problems along numerous functional dimensions. The present study utilized the Visual Serial Addition Task (VSAT) and functional magnetic resonance imaging (fMRI) to explore working memory processes in thirteen typically developing (TD) control and thirteen children with ADHD, Combined type. Analysis of Variance (ANOVA) was used to examine both main effects and interactions. Working memory-specific activity was found in TD children in the bilateral prefrontal cortex. In contrast the within-group map in ADHD did not reveal any working-memory specific regions. Main effects of condition suggested that the right middle frontal gyrus (BA6) and the right precuneus were engaged by both groups during working memory processing. Group differences were driven by significantly greater, non-working memory-specific, activation in the ADHD relative to TD group in the bilateral insula extending into basal ganglia and the medial prefrontal cortex. A region of interest analysis revealed a region in left middle frontal gyrus that was more active during working memory in TD controls. Thus, only the TD group appeared to display working memory-modulated brain activation. In conclusion, children with ADHD demonstrated reduced working memory task specific brain activation in comparison to their peers. These data suggest inefficiency in functional recruitment by individuals with ADHD represented by a poor match between task demands and appropriate levels of brain activity.

Purpose: We report ocular findings in a patient with Darier disease. In particular, we discuss the in vivo confocal images., Method: A retrospective noninterventional case report., Results: Confocal microscopy revealed collections of intercellular material, separating the cells of the patient's basal corneal epithelium. Discrete foci of this material were scattered throughout the central corneal basal epithelium in both eyes. These deposits had a similar reflectance as corneal nerves, were 3-5-microm thick, and of note in places conformed to the cell borders., Conclusions: The findings of abnormal intercellular collections at the basal epithelial layer of the cornea correlate with the previously reported histological findings. They are consistent with the abnormal keratocyte-to-keratocyte adhesions that are described both in the skin and cornea of Darier disease. The abnormalities we describe occurred in the absence of other ocular signs of Darier disease. These findings on confocal microscopy may help with the diagnosis and monitoring of disease progression.