Abstract
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.
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.
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.
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.
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.
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.
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.
To investigate the risk of cardiovascular events associated with concomitant use of stimulants and atypical antipsychotics (AAPs) among youth and evaluate whether AAP dose and duration of concomitant ...use modifies the risk.
We used IQVIA PharMetrics® Plus data from 2006 to 2015 to construct a retrospective cohort of commercially-insured youth aged 5-17 years old who initiated a stimulant medication. Time-varying concomitant stimulant/AAP use was defined as current, past and no concomitant use based on person months. The primary time-varying Cox proportional hazard regression analysis evaluated the risk of cardiovascular events comparing current concomitant use with past and no concomitant use, adjusted for baseline cardiovascular risk. A secondary analysis assessed the risk of cardiovascular events comparing AAP daily doses (<1, 1-2, >2 mg) and duration (<3, 3-6, >6 months) of current concomitant use to no concomitant use. Cardiovascular outcomes included severe (i.e., stroke, acute myocardial infarction, ischemic heart disease) and less severe (i.e., angina pectoris, cardiac dysrhythmias, transient cerebral ischemia, hypertensive disease, tachycardia, palpitations, syncope).
For this cohort of 61,438 youths, the incidence rate of severe cardiovascular events was 0.18 per 10,000 person-months, and all events occurred in no concomitant use months. The risk of less severe cardiovascular events was significantly higher in current concomitant users compared with no HR: 2.59 (95%CI: 1.72, 3.90) and past HR: 1.89 (95%CI: 1.10, 3.24) concomitant users. Compared to no concomitant use, the risk of less severe cardiovascular events was significantly higher at all AAP daily doses HR: <1 mg: 2.82 (95%CI: 1.72, 4.61); 1-2 mg: 2.22 (95%CI: 1.16, 4.25); >2 mg: 2.65 (95%CI: 1.50, 4.71). The risk of less severe cardiovascular events significantly elevated for all duration of use and was higher for <3 months of concomitant use HR: <3 months: 3.45 (95%CI: 2.17, 5.47) relative to 3-6 months: 2.60 (95%CI: 1.29, 5.25) or >6 months: 2.61 (95%CI: 1.59, 4.30).
Severe cardiovascular events are rare. Concomitant stimulant/AAP use elevates the risk of less severe cardiovascular events. Periodic heart rate or blood pressure monitoring for youth on stimulant/AAP treatment may be warranted.
Abstract 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.
Abstract Brief self-report questionnaires that assess attenuated psychosis symptoms have the potential to quickly and effectively screen many people who may benefit from clinical monitoring or early ...intervention. The current study sought to examine and compare the criterion validities of attenuated symptoms screening tools with diagnoses obtained from the clinician-administered Structured Interview for Psychosis Risk Syndromes (SIPS). Three screening questionnaires (Prime Screen, Prodromal Questionnaire-Brief, and Youth Psychosis At-Risk Questionnaire-Brief) were administered just prior to the SIPS interview in a sample of adolescents and young adults seeking mental health services. Using thresholds recommended by instrument authors as well as empirically derived optimal thresholds, the sensitivity, specificity, positive predictive value, and overall accuracy of each self-report measure with regard to SIPS diagnosis were obtained. Screeners correlated highly with the SIPS and demonstrated equivalent overall efficiency in capturing psychosis risk status. All three screeners appear to be useful and valid assessment tools for attenuated symptoms, with each instrument demonstrating relative benefits. The validation of attenuated symptoms screening tools is an important step toward enabling early, wide-reaching identification of individuals on a course toward psychotic illness.
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.
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.
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 (f2 = 0.17 and f2 = 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.
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.
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.
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