Scoping Review: Digital Mental Health Interventions for Children and Adolescents Affected by War.

OBJECTIVE: More than 200 million children and adolescents live in countries affected by violent conflict, are likely to have complex mental health needs, and struggle to access traditional mental health services. Digital mental health interventions have the potential to overcome some of the barriers in accessing mental health support. We performed a scoping review to map existing digital mental health interventions relevant for children and adolescents affected by war, to examine the strength of the evidence base, and to inform the development of future interventions. METHOD: Based on a pre-registered strategy, we systematically searched MEDLINE, Embase, Global Health, APA PsychInfo, and Google Scholar from the creation of each database to September 30, 2022, identifying k = 6,843 studies. Our systematic search was complemented by extensive consultation with experts from the GROW Network. RESULTS: The systematic search identified 6 relevant studies: 1 study evaluating digital mental health interventions for children and adolescents affected by war, and 5 studies for those affected by disasters. Experts identified 35 interventions of possible relevance. The interventions spanned from universal prevention to specialist-guided treatment. Most interventions directly targeted young people and parents or carers/caregivers and were self-guided. A quarter of the interventions were tested through randomized controlled trials. Because most interventions were not culturally or linguistically adapted to relevant contexts, their implementation potential was unclear. CONCLUSION: There is very limited evidence for the use of digital mental health interventions for children and adolescents affected by war at present. The review provides a framework to inform the development of new interventions. DIVERSITY & INCLUSION STATEMENT: We actively worked to promote sex and gender balance in our author group. STUDY PREREGISTRATION INFORMATION: Digital mental health interventions for children and young people affected by war: a scoping review; https://osf.io/; hrny9.

The association between daily life changes and anxiety among Ukrainians following the Russian invasion.

This study sought to explore the association between changes in daily life and war-related anxiety. In this study, we analyzed self-reported data from 2,004 Ukrainian adults, obtained through an opportunistic survey in the Ukraine. Our assessment focused on changes in everyday routines and generalized anxiety symptoms since the Russian invasion of Ukraine on the 24 February 2022. The data were collected between July-September 2022. Results show a significant dose-response connection between everyday routine changes and increased war-related anxiety. Not surprisingly, the ongoing Ukraine-Russia conflict is impacting the lives of Ukrainians. These changes are linked to heightened anxiety levels. Effective population-based crisis management should consider both war-related stressors and changes in daily life routines.

Parent-reported posttraumatic stress reactions in children and adolescents: Findings from the mental health of parents and children in Ukraine study.

BACKGROUND: Despite the long-standing ongoing war in Ukraine, information regarding war-related negative mental health outcomes in children is limited. A nationwide sample of parents in Ukraine was surveyed to assess posttraumatic stress disorder (PTSD) symptoms in their children and to identify risk factors associated with child PTSD status. METHOD: A nationwide opportunistic sample of 1,238 parents reported on a single randomly chosen child within their household as part of The Mental Health of Parents and Children in Ukraine Study. Data were collected approximately 6 months after the war escalation in February 2022. The prevalence of PTSD was estimated using the parent-reported Child and Adolescent Trauma Screen (CATS). RESULTS: Based on parental reports, 17.5% of preschoolers and 12.6% of school-age children met Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria for PTSD. Delay in milestone development (AOR = 2.38, 95% confidence interval [CI] [1.38-4.08]), having a parent affiliated with the emergency services or army (AOR = 2.13, [1.28-3.53]), parental PTSD/complex PTSD status (AOR = 1.88, [1.22-2.89]), and mean changes in parental anxiety (AOR = 1.98, [1.44-2.72]) were among the strongest predictors of increased risk of pediatric PTSD. CONCLUSION: Russia's war escalation in Ukraine resulted in an increased estimated prevalence of war-related PTSD in children of various ages. Urgent efforts to increase the capacity of national pediatric mental health services are critically needed to mitigate these challenges in an environment of limited financial and human resources. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Change in child mental health during the Ukraine war: evidence from a large sample of parents.

The ongoing war in Ukraine is expected to negatively impact the mental health of the country's population. This study aims to provide a preliminary estimate of the degree of change in the mental health problems of Ukrainian children following Russia's invasion in February 2022, and to identify the sociodemographic and war-related risk factors associated with these changes. A nationwide, opportunistic sample of 1238 parents reported on a single randomly chosen child within their household as part of The Mental Health of Parents and Children in Ukraine Study. Data were collected between July 15th and September 5th, 2022. Participants completed modified versions of the Pediatric Symptom Checklist (PSC-17) which was adapted to capture change in the frequency of symptoms since the beginning of the war. Parents reported increases across all 17 indicators of internalizing, externalizing, and attention problems of the PSC-17. Increased problems were most pronounced within the internalizing domain, with 35% of parents reporting that their child worried more since the beginning of the war. A number of individual, parental, and war-related factors were associated with increases across the three domains. Exposure to war trauma, pre-existing mental health problems, and child age were among the strongest predictors of change. This survey provides preliminary evidence that the Russian war on Ukraine has led to an increase in common mental health problems among children in the general population. Further research is required to determine the extent and sequela of this increase, and to develop intervention strategies for those most in need.

Investigating the latent structure of the International Trauma Questionnaire to assess ICD-11 posttraumatic stress disorder (PTSD) and complex PTSD in an adult civilian sample during the Ukraine war.

The symptom structure of ICD-11 posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) and the validity of the International Trauma Questionnaire (ITQ) are yet to be tested among civilians in an active war zone. The present investigation examined the factor structure of the ITQ, the internal consistency of observed scores, and their associations with demographic characteristics and war-related experiences using a nationwide sample of 2,004 adults from the general population of Ukraine approximately 6 months after the full-scale Russian invasion in 2022. Overall, rates of endorsement across all symptom clusters were high. The mean total number of war-related stressors reported was 9.07 (SD = 4.35, range: 1-26). Internal reliability was good for all six ITQ subscales, Cronbach's αs = .73-.88, and the correlated six-factor model was found to provide the best representation of the latent structure of the ITQ in the present sample based on fit indices. There was evidence of a dose-response relationship, with increasing scores on all symptom clusters associated with higher total reported war-related stressors.

War exposure, posttraumatic stress disorder, and complex posttraumatic stress disorder among parents living in Ukraine during the Russian war.

BACKGROUND: High rates of posttraumatic stress disorder (PTSD) have been documented in war-affected populations. The prevalence of Complex PTSD (CPTSD) has never been assessed in an active war zone. Here, we provide initial data on war-related experiences, and prevalence rates of ICD-11 PTSD and CPTSD in a large sample of adults in Ukraine during the Russian war. We also examined how war-related stressors, PTSD, and CPTSD were associated with age, sex, and living location in Ukraine. METHOD: Self-report data were gathered from a nationwide sample of 2004 adult parents of children under 18 from the general population of Ukraine approximately 6 months after Russia's invasion. RESULTS: All participants were exposed to at least one war-related stressor, and the mean number of exposures was 9.07 (range = 1-26). Additionally, 25.9% (95% CI = 23.9%, 27.8%) met diagnostic requirements for PTSD and 14.6% (95% CI = 12.9%, 16.0%) met requirements for CPTSD. There was evidence of a strong dose-response relationship between war-related stressors and meeting criteria for PTSD and CPTSD. Participants who had the highest exposure to war-related stressors were significantly more likely to meet the requirements for PTSD (OR = 4.20; 95% CI = 2.96-5.95) and CPTSD (OR = 8.12; 95% CI = 5.11-12.91) compared to the least exposed. CONCLUSIONS: Humanitarian responses to the mental health needs of the Ukrainian population will need to take account of posttraumatic stress reactions. Education in diagnosing and treating PTSD/CPTSD, especially in the situation of a significant lack of human resources and continuing displacement of the population, is necessary.

Psychopharmacological Treatment Algorithms of Manic/Mixed and Depressed Episodes in Pediatric Bipolar Disorder.

Introduction: Pediatric bipolar disorder (PBD) is a severe psychiatric illness diagnosed before the age of 18, which is associated with extreme shifts in mood characterized by manic and depressive episodes. In 2005, AACAP published algorithms to guide pharmacological treatment of manic/mixed episodes associated with PBD. At that time, lithium was the only Food and Drug Administration (FDA)-approved treatment for pediatric bipolar manic/mixed episodes. The goal of this article is to review evidence that has emerged since the AACAP algorithm in 2005. Methods: Literature searches were conducted through PubMed and limited to studies published between 2005 and 2021, using keywords that focused on randomized controlled trials (RCTs) for available psychopharmacological medications. In addition, the authors conducted in-depth searches for articles providing evidence for agents included in the 2005 AACAP algorithm. Results: Since the publication of the AACAP algorithm in 2005, multiple RCTs have been conducted in PBD, leading to FDA approval of five medications (aripiprazole, asenapine, olanzapine, quetiapine, and risperidone) for the treatment of manic/mixed episodes and two medications (lurasidone and olanzapine-fluoxetine combination) for the treatment of depressed episodes. Divalproex sodium and oxcarbazepine were studied in pediatric RCTs and failed to separate from placebo. Conclusions: We offer an update to the 2005 AACAP algorithms for the treatment of pediatric bipolar mixed/manic episodes and added an evidence-based algorithm for the treatment of depression in PBD. In addition to treatment algorithms, we review current evidence for efficacy of agents proposed in the AACAP algorithm and provide tables summarizing medication side effects and efficacy.

Psychiatric Readmission of Children and Adolescents: A Systematic Review and Meta-Analysis.

OBJECTIVE: To investigate predictors of psychiatric hospital readmission of children and adolescents, a systematic review and meta-analysis was conducted. METHODS: Following PRISMA statement guidelines, a systematic literature search of articles published between 1997 and 2018 was conducted in PubMed/MEDLINE, Google Scholar, and PsycINFO for original peer-reviewed articles investigating predictors of psychiatric hospital readmission among youths (<18 years old). Effect sizes were extracted and combined by using random-effects meta-analysis. Covariates were investigated with meta-regression and subgroup analyses. RESULTS: Thirty-three studies met inclusion criteria, containing information on 83,361 children and adolescents, of which raw counts of readmitted vs. non-readmitted youths were available for 76,219. Of these youths, 13.2% (N=10,076) were readmitted. The mean±SD study follow-up was 15.9±15.0 months, and time to readmission was 13.1±12.8 months. Readmission was associated with, but not limited to, suicidal ideation at index hospitalization (pooled odds ratio [ORpooled]=2.35, 95% confidence interval [CI]=1.64-3.37), psychotic disorders (ORpooled=1.87, 95% CI=1.53-2.28), prior hospitalization (ORpooled=2.51, 95% CI=1.76-3.57), and discharge to residential treatment (ORpooled=1.84, 95% CI=1.07-3.16). There was evidence of moderate study bias. Prior investigations were methodologically and substantively heterogeneous, particularly for measurement of family-level factors. CONCLUSIONS: Interventions to reduce child psychiatric readmissions should place priority on youths with indicators of high clinical severity, particularly with a history of suicidality, psychiatric comorbidity, prior hospitalization, and discharge to residential treatment. Standardization of methods to determine prevalence rates of readmissions and their predictors is needed to mitigate potential biases and inform a national strategy to reduce repeated child psychiatric hospital readmissions.

Increased ratio of anti-apoptotic to pro-apoptotic Bcl2 gene-family members in lithium-responders one month after treatment initiation.

BACKGROUND: Lithium is considered by many as the gold standard medication in the management of bipolar disorder (BD). However, the clinical response to lithium is heterogeneous, and the molecular basis for this difference in response is unknown. In the present study, we sought to determine how the peripheral blood gene expression profiles of patients with bipolar disorder (BD) changed over time following intitiation of treatment with lithium, and whether differences in those profiles over time were related to the clinical response. METHODS: Illumina Sentrix Beadchip (Human-6v2) microarrays containing > 48,000 transcript probes were used to measure levels of expression of gene-expression in peripheral blood from 20 depressed subjects with BD prior to and every two weeks during 8 weeks of open-label treatment with lithium.Changes in gene-expression were compared between treatment responders (defined as a decrease in the Hamilton Depression Rating Scale of 50% or more) and non-responders. Pathway analysis was conducted using GeneGO Metacore software. RESULTS: 127 genes showed a differential response in responders vs. non-responders. Pathway analysis showed that regulation of apoptosis was the most significantly affected pathway among these genes. Closer examination of the time-course of changes among BCL2 related genes showed that in lithium-responders, one month after starting treatment with lithium, several anti-apoptotic genes including Bcl2 and insulin receptor substrate 2 (IRS2) were up-regulated, while pro-apoptotic genes, including BCL2-antagonist/killer 1 (BAK1) and BCL2-associated agonist of cell death (BAD), were down-regulated. In contrast, in lithium non-responders, BCL2 and IRS2 were down-regulated, while BAK1 and BAD up-regulated at the one-month time-point. CONCLUSIONS: These results suggest that differential changes in the balance of pro- and anti- apoptotic gene-expression following treatment with lithium may explain some of the heterogeneity in clinical response in BD patients.

Levetiracetam in the management of bipolar depression: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To study the efficacy of adjunctive levetiracetam therapy compared with placebo in the treatment of subjects with depression with bipolar disorder. METHOD: This double-blind, placebo-controlled clinical trial randomly assigned outpatients with bipolar disorder type I and type II who were experiencing a major depressive episode (Structured Clinical Interview for DSM-IV Axis I Disorders-Clinician Version criteria) to treatment with either placebo or adjunctive levetiracetam (up to 2,500 mg/d flexibly dosed) for 6 weeks. The subjects were recruited from October 2005 to June 2008. The primary efficacy measure was mean change from baseline to week 6 in the Hamilton Depression Rating Scale (21-item). Secondary efficacy assessments included the Montgomery-Åsberg Depression Rating Scale, the Beck Depression Inventory, the Clinical Global Impressions-Bipolar Version scale, the Hamilton Anxiety Rating Scale, and the Young Mania Rating Scale. RESULTS: Of 42 subjects randomly assigned to placebo or drug, 32 received at least 1 postbaseline assessment and thus were included in the analysis. The mean (SD) levetiracetam daily dose at endpoint evaluation was 1,132 (425) mg/d. There was no significant difference in the mean change from baseline to week 6 in the Hamilton Depression Rating Scale scores for levetiracetam compared with placebo. There were no significant differences in any of the secondary outcome measures. CONCLUSIONS: Levetiracetam adjunctive therapy was not superior to placebo in the short-term treatment of subjects with depression with bipolar disorder in the population studied. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00566150.

Increased peripheral blood expression of electron transport chain genes in bipolar depression.

OBJECTIVE: To identify specific genetic pathways showing altered expression in peripheral blood of depressed subjects with bipolar disorder (BPD). METHODS: Illumina Sentrix BeadChip (Human-6v2) microarrays containing >48,000 transcript probes were used to measure levels of gene expression in peripheral blood from 20 depressed subjects with BPD and in 15 healthy control subjects. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to confirm a subset of these differences. RESULTS: A total of 1,180 genes were differentially expressed between subjects with BPD and healthy controls (fold-change >1.3, false discovery rate-corrected p < 0.05, covaried for age and sex). Of these, 559 genes were up-regulated in BPD subjects and 621 were down-regulated. Surprisingly, there was no difference between medicated (n = 11) and unmedicated (n = 9) subjects with BPD for any of these genes. Pathway analysis using GeneGo MetaCore software showed that the most significantly affected pathway was the mitochondrial electron transport chain (ETC). Of the 85 objects (genes or proteins) in this pathway, 22 were up-regulated and 2 down-regulated in subjects with BPD. qRT-PCR confirmed up-regulation of nuclear encoded ETC genes in complexes I, III, IV, and V and, in addition, demonstrated up-regulation of mitochondrially encoded genes in each of these complexes. CONCLUSION: These results suggest that increased expression of multiple components of the mitochondrial ETC may be a primary deficit in bipolar depression, rather than an effect of medication.

Reasons for substance use among adolescents with bipolar disorder.

We examined whether children and adolescents with bipolar disorder (BPD) "self-medicate" with cigarettes, alcohol, or other substances of abuse. One hundred and five adolescents with BPD and 98 controls were comprehensively assessed with a structured psychiatric diagnostic interview for psychopathology and the Drug Use Screening Inventory (DUSI) for self-medication. Thirteen control (mean ± standard deviation [SD]= 15.31 ± 1.18 years) and 27 BPD (15.30 ± 2.09 years) subjects endorsed use of one of the listed drugs in the DUSI Section A within the past year and were included in all analyses. BPD adolescents were more likely than nonmood disordered, substance-using controls to report starting to use their preferred drug for mood-altering effects. There were no differences between groups in motivation for use with respect to starting substances to sleep better or get high, or in continuing substances to change mood, sleep better, or get high. These data may contribute to increased prevention of substance use disorders and to the treatment of adolescent BPD. Further studies clarifying the characteristics of self-medication are necessary.

Lamotrigine-associated rash: to rechallenge or not to rechallenge?

The major burden of illness in bipolar disorder (BD) is in the depressive pole. Lamotrigine has been shown to be useful in the long-term prophylaxis of depressive episodes in BD. Current guidelines recommend discontinuing lamotrigine in patients who develop rash. Our objective in this paper is to review literature to identify possible predictors of serious vs. benign rash that might help guide clinical decision-making and recommend titration strategy for re-introduction of lamotrigine, if indicated. We performed a search of the literature between 1966 and July 2008 to investigate the phenomenon of lamotrigine-induced rash and rechallenge procedures. The search identified six reports, and we were able to identify another case series from reviewing the bibliography of all of the above papers. We reviewed all the papers of lamotrigine rash rechallenge that resulted from the literature search. These papers describe 44 cases of lamotrigine rechallenge. Currently, there are 39 reported cases in the literature of successful lamotrigine rechallenge after a rash and five cases with rash recurrence. There are some characteristics of the rash that can help identify serious cases from benign ones. In addition, very slow titration of lamotrigine is crucial to the reduction of rash recurrence rate. Several cases that develop benign rash on lamotrigine can be rechallenged without adverse consequences. We believe that lamotrigine rechallenge in bipolar depression is an under-utilized option in our clinical armamentarium, and further studies are needed to guide us in this area.

ADHD symptoms and associated psychopathology in a community sample of adolescents from the European north of Russia.

OBJECTIVE: To assess the prevalence of ADHD symptoms and their relationship to psychopathology in adolescents from the European North of Russia. METHOD: The prevalence of ADHD symptoms is assessed by teacher reports in 536 adolescents. Internalizing and externalizing problems are assessed by teacher ratings and student self-reports. RESULTS: Prevalence of individual ADHD symptoms ranges between 3.3% and 35%. Only 8.9% of boys and 3.6% of girls have positive ratings on six items in either inattention or hyperactivity subtype. These adolescents fare significantly worse regarding externalizing but not internalizing problems. Compared to girls with ADHD, boys with ADHD report higher levels of violent and nonviolent delinquency and are described by teachers as having more conduct problems. Possible ADHD status is associated with depressive symptoms in boys but not in girls. CONCLUSION: The estimates of ADHD prevalence rates obtained in this study are similar to those of other countries, suggesting the need for identification and treatment of the disorder. Evaluation of associated disruptive behavior disorders and depression, particularly in boys, is warranted.

Treatments for late-life bipolar disorder.

BACKGROUND: Bipolar affective disorder is not uncommon in the elderly; prevalence rates in the United States range from 0.1% to 0.4%. However, it accounts for 10% to 25% of all geriatric patients with mood disorders and 5% of patients admitted to geropsychiatric inpatient units. These patients often present a tremendous treatment challenge to clinicians. They frequently have differing treatment needs compared with their younger counterparts because of substantial medical comorbidity and age-related variations in response to therapy. Unfortunately, the management of geriatric bipolar disorder has been relatively neglected compared with the younger population. There continues to be a scarcity of published, controlled trials in the elderly, and no treatment algorithms specific to bipolar disorder in the elderly have been devised. OBJECTIVE: The goal of this article was to review the current literature on both the pharmacologic and nonpharmacologic management of late-life bipolar disorder. METHODS: English-language articles written on the treatment of bipolar disorder in the elderly were identified. The first step in data collection involved a search for evidence-based clinical practice guidelines in the Cochrane Database of Systematic Reviews (up until the third quarter of 2006). Systematic reviews were then located in the following databases: MEDLINE (1966-September 2006), EMBASE (1980-2006 [week 36]), and PsycINFO (1967-September 2006 [week 1]). Additional use was made of these 3 databases in searching for single randomized controlled trials, meta-analyses, cohort studies, case-control studies, case series, and case reports. "Elderly," used synonymously with "geriatric," was defined as individuals aged > or =60 years. However, to take into account ambiguity in the nomenclature, the key words aged, geriatric, elderly, and older were combined with words indicating pharmacologic treatments such as pharmacotherapy; classes of medications (eg, lithium, antidepressants, antipsychotics, anticonvulsants, benzodiazepines); and names of selected individual medications (eg, lithium, valproic acid, lamotrigine, carbamazepine, oxcarbazepine, topiramate, gabapentin, zonisamide, clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole). These terms were then combined with the diagnostic terms bipolar disorder, mania, hypomania, depression, or bipolar depression. Finally, the terms ECT and psychotherapy were also queried in combination with indicators for age and diagnosis. A few articles on "older adults," usually defined as individuals aged 50 to 55 years, were also included. They may allow for possible extrapolation of data to the geriatric population. Additionally, several mixed-age studies were included for similar considerations. Case reports and case series were described for their potential heuristic value. RESULTS: Unfortunately, there is a considerable dearth of literature involving evidence-based clinical practice guidelines and even randomized controlled trials in elderly individuals with bipolar disorder. Available options for the treatment of bipolar disorder (including those for mania, hypomania, depression, or maintenance) in the elderly include lithium, antiepileptics, antipsychotics, benzodiazepines, antidepressants, electroconvulsive therapy (ECT), and psychotherapy. CONCLUSIONS: The data for the treatment of late-life bipolar disorder are limited, but the available evidence shows efficacy for some commonly used treatments. Lithium, divalproex sodium, carbamazepine, lamotrigine, atypical antipsychotics, and antidepressants have all been found to be beneficial in the treatment of elderly patients with bipolar disorder. Although there are no specific guidelines for the treatment of these patients, monotherapy followed by combination therapy of the various classes of drugs may help with the resolution of symptoms. ECT and psychotherapy may be useful in the treatment of refractory disease. There is a need for more controlled studies in this age group before definitive treatment strategies can be enumerated.