Systematic review: emotion dysregulation and challenging behavior interventions for children and adolescents on the autism spectrum with graded key evidence-based strategy recommendations.

Challenging behavior, such as aggression, is highly prevalent in children and adolescents on the autism spectrum and can have a devastating impact. Previous reviews of challenging behavior interventions did not include interventions targeting emotion dysregulation, a common cause of challenging behavior. We reviewed emotion dysregulation and challenging behavior interventions for preschoolers to adolescents to determine which evidence-based strategies have the most empirical support for reducing/preventing emotion dysregulation/challenging behavior. We reviewed 95 studies, including 29 group and 66 single case designs. We excluded non-behavioral/psychosocial interventions and those targeting internalizing symptoms only. We applied a coding system to identify discrete strategies based on autism practice guidelines with the addition of strategies common in childhood mental health disorders, and an evidence grading system. Strategies with the highest quality evidence (multiple randomized controlled trials with low bias risk) were Parent-Implemented Intervention, Emotion Regulation Training, Reinforcement, Visual Supports, Cognitive Behavioral/Instructional Strategies and Antecedent-Based Interventions. Regarding outcomes, most studies included challenging behavior measures, while few included emotion dysregulation measures. This review highlights the importance of teaching emotion regulation skills explicitly, positively reinforcing replacement/alternative behaviors, using visuals and metacognition, addressing stressors proactively, and involving parents. It also calls for more rigorously designed studies and for including emotion dysregulation as an outcome/mediator in future trials.

Psychometric Properties of the Emotion Dysregulation Inventory in a Nationally Representative Sample of Youth.

Objective: The Emotion Dysregulation Inventory (EDI) is an informant questionnaire developed based on the Patient-Reported Outcomes Measurement Information System (PROMIS®) Scientific Standards and refined through factor analyses and item response theory (IRT) analyses. Although it was developed to improve measurement of emotion dysregulation in youth with autism spectrum disorder, emotion dysregulation has transdiagnostic significance. Therefore, the aim of this study was to evaluate the EDI's psychometric properties and to establish IRT-based scores for a general population of youth.Methods: Data were collected from a sample of 1000 caregivers of 6- to 17-year-old youth matched to the US census on age, gender, race/ethnicity, years of education, and region. Confirmatory factor analyses and IRT analyses using the two-parameter graded response model were performed to evaluate the EDI's structure and psychometric properties.Results: Analyses supported the original two-factor structure of the EDI, reflecting factors for Reactivity and Dysphoria. Simulations of computerized adaptive testing supported use of the same items for a Reactivity short form as those that emerged as most informative in the original autism psychometric analyses. IRT co-calibration with commonly used measures of emotion regulation and irritability in child clinical or community samples indicated the EDI scales provide more information across a wider range of emotion dysregulation. Validity was supported by moderate correlations with measures of related constructs and expected known-group differences.Conclusions: The EDI is an efficient and precise measure of emotion dysregulation for use in general community and clinical samples as well as samples of youth with ASD.

Predictors of Severity and Change in Emotion Dysregulation among Children and Adolescents with ASD.

OBJECTIVE: Emotion dysregulation problems are prevalent and disruptive for many with autism spectrum disorder (ASD). This study compared severity and perceived change in emotion dysregulation in youth with and without ASD and probed correlates of emotion dysregulation (including possible two-way interactions) among youth with ASD. METHOD: Participants were drawn from two large online samples (mean age = 12; range: 6-17) with (N = 1323) and without (N = 921) ASD. The study used the Emotion Dysregulation Inventory (EDI), a parent-report measure designed for youth with ASD. The EDI asks parents about current severity and perceived change (i.e. how current severity compares to lifetime severity) in emotion dysregulation, and includes two factors: Reactivity (rapidly escalating, intense negative affect) and Dysphoria (poorly upregulated positive affect, general unease). RESULTS: Results indicated that youth with ASD had greater Reactivity severity and also greater positive change in Reactivity than non-ASD peers. Furthermore, differences between youth with and without ASD in the relationship between Reactivity and Dysphoria suggest a distinct profile of emotion dysregulation in ASD. Within the ASD sample, age and severity of stereotyped behavior predicted Reactivity and Dysphoria severity and Reactivity change. Female gender, lower parent education, and fluent verbal ability were additional predictors of increased Reactivity severity, while intellectual disability predicted lower Dysphoria severity. CONCLUSIONS: This study provides new insight into predictors of emotion dysregulation in youth with ASD and represents a first step toward identifying which children with ASD may be most vulnerable to severe emotion dysregulation problems.

Evidence Base Update for Questionnaires of Emotion Regulation and Reactivity for Children and Adolescents.

Objective: Emotion regulation (ER) is a multi-faceted and dynamic process relevant to both normative emotional development and transdiagnostic emotional dysfunction for a range of psychological disorders. There has been tremendous growth in ER research over the past decade, including the development of numerous new measures to assess ER. This Evidence Base Update included a systematic review to identify self- and informant-report questionnaire measures of ER for children and adolescents, including measures of ER strategies and effectiveness (or emotion dysregulation).Methods: PubMed, PsycInfo, and Health and Psychosocial Instruments databases were searched using the terms emotion OR affect AND regulation OR control OR reactivity OR response, as well as terms related to questionnaires and psychometrics, restricted to articles on youth (< 18 years old). Each measure's psychometrics was evaluated based on modified criteria by De Los Reyes and Langer (2018).Results: Nine-hundred ninety-seven papers were identified yielding 87 measures that met inclusion for review. Although the majority (60%) of identified ER measures could not be recommended based on these criteria, 8% were Excellent, 14% were Good, and 17% were Adequate. The recommended measures included: 11 general ER measures (5 focused on strategies, 5 focused on dysregulation/ effectiveness), 13 measures of ER as it relates to specific emotions or contexts such as irritability or peer stress (4 focused on strategies, 9 focused on dysregulation/effectiveness), and 11 measures of other constructs that include an ER subscale (all focused on dysregulation). Conclusions: The characteristics, strengths, and weaknesses of the recommended ER measures are described in order to guide measure selection for clinical or research uses. A synthesis of themes identified during this review includes commonly observed areas of weakness and gaps in the literature to provide a foundation for future research and measure development.

Psychosocial Treatments Targeting Anxiety and Depression in Adolescents and Adults on the Autism Spectrum: Review of the Latest Research and Recommended Future Directions.

PURPOSE OF REVIEW: This synthesis of treatment research related to anxiety and depression in adolescents and adults with autism spectrum disorder (ASD) focuses on the scientific support for various forms of psychosocial interventions, useful adaptations to standard interventions, and engagement of candidate therapeutic mechanisms. RECENT FINDINGS: There is considerable evidence for the efficacy of cognitive-behavioral therapy (CBT) to treat co-occurring problems with anxiety, but there has been relatively little research on treatment of co-occurring depression. Multiple mechanisms of treatment effect have been proposed, but there has been little demonstration of target engagement via experimental therapeutics. Comorbidity between ASD and anxiety and/or mood problems is common. Although there is evidence for the use of CBT for anxiety, little work has addressed how to effectively treat depression. There is emerging support for alternative treatment approaches, such as mindfulness-based interventions. We encourage rigorous, collaborative approaches to identify and manipulate putative mechanisms of change.

Co-occurring psychiatric conditions in autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) are at increased risk for experiencing one or more co-occurring psychiatric conditions. When present, these conditions are associated with additional impairment and distress. It is therefore crucial that clinicians and researchers adequately understand and address these challenges. However, due to symptom overlap, diagnostic overshadowing, and ambiguous symptom presentation in ASD, the assessment of co-occurring conditions in ASD is complex and challenging. Likewise, individual difference factors, such as age, intellectual functioning, and gender, may influence the presentation of co-occurring symptoms. Relatedly, a transdiagnostic framework may offer utility in assessing and treating co-occurring conditions. However, with the exception of anxiety disorders, treatment research for co-occurring psychiatric conditions in ASD is relatively limited. Therefore, the present paper aims to summarize and review available research on the most common co-occurring psychiatric disorders in ASD, with a focus on estimated population-based prevalence rates, diagnostic challenges, the influence of individual differences, and assessment guidelines. The utility of a transdiagnostic framework for conceptualizing co-occurring disorders in ASD is discussed, and the state of treatment research for co-occurring disorders is summarized. This study concludes with a summary of the extant literature, as well as recommendations for future research.

Future directions for research in autism spectrum disorders.

This article suggests future directions for research aimed at improving our understanding of the etiology and pathophysiology of autism spectrum disorder (ASD) as well as pharmacologic and psychosocial interventions for ASD across the lifespan. The past few years have witnessed unprecedented transformations in the understanding of ASD neurobiology, genetics, early identification, and early intervention. However, recent increases in ASD prevalence estimates highlight the urgent need for continued efforts to translate novel ASD discoveries into effective interventions for all individuals with ASD. In this article we highlight promising areas for ongoing and new research expected to quicken the pace of scientific discovery and ultimately the translation of research findings into accessible and empirically supported interventions for those with ASD. We highlight emerging research in the following domains as particularly promising and pressing: (a) preclinical models, (b) experimental therapeutics, (c) early identification and intervention, (d) psychiatric comorbidities and the Research Domain Criteria initiative, (e) ecological momentary assessment, (f) neurotechnologies, and (g) the needs of adults with ASD. Increased research emphasis in these areas has the potential to hasten the translation of knowledge on the etiological mechanisms of ASD to psychosocial and biological interventions to reduce the burden of ASD on affected individuals and their families.

Are autistic females at greater risk of suicide? A call for clarity to advance suicide prevention for the whole community.

Understanding suicide risk is critical for supporting prevention. A growing body of evidence shows autistic people are at greater risk for multiple suicide-related outcomes than non-autistic people. This commentary is in response to an observed pattern of miscommunication in scientific and community spaces about autistic females having higher risk of suicide. However, it is not always clear who they are being compared with in these statements. To address this confusion, we summarize the current population-based evidence on autistic suicide risk, highlighting findings related to sex similarities and differences, which actually indicates comparable rates of suicide death among autistic males and females, and mixed findings related to sex differences in risk of other suicidal behaviors. We call for greater clarity in suicide risk communication moving forward focused on outcomes, measurement, sampling methods, and comparison groups to reflect accurate conclusions about existing evidence. Further research is needed about the full range of suicide-related outcomes for autistic people, including a greater understanding of sex differences as well as potential gender differences to include transgender and nonbinary autistic people. However, studies of sex and gender differences should not overshadow the compelling need for efforts to understand and address the elevated risk of suicidal thoughts, behaviors, and death among autistic people across sex and gender boundaries.

Valence and Intensity of Emotional Expression in Autistic and Non-Autistic Toddlers.

PURPOSE: Differences in emotional experience and expression have long been recognized as common in the presentation of autism, yet research examining emotional expression in early childhood is limited, with mixed findings. Understanding emotional reactivity and expression in autism in early life is an essential step towards uncovering the mechanisms of these risks and identifying targets for intervention. METHODS: The present study examined emotional expression in autistic (N = 17) and non-autistic (N = 20) toddlers (mean age = 25.27; SD = 1.88) during emotion elicitation tasks aimed at eliciting joy, frustration, and unease. Video recorded tasks were coded in ten second intervals for emotional valence and intensity, and the following variables were computed: proportion of time in positive, neutral, and negative affect; maximum intensity of positive and negative affect; and range of affect (i.e., most negative to most positive intensity). RESULTS: Autistic toddlers spent more time in neutral facial expressions, less time displaying positive affect, and had somewhat less intense positive emotional expression than non-autistic peers. Small differences were apparent in intensity of negative affect expression, while no differences emerged in duration of time spent in negative affect. CONCLUSION: Findings emphasize that differences may be more apparent in duration, rather than intensity of emotional expression, and that it may be particularly important to examine periods of "neutral" affect in young autistic children. Future research should consider the best ways to understand emotional reactivity in this population considering their unique interests, challenges, and communication styles.

Expression and co-regulation of negative emotion in 18-month-olds at increased likelihood for autism with diverse developmental outcomes.

LAY ABSTRACT: Managing negative emotion can be challenging for autistic individuals and their families from a young age. Parents help young children manage negative emotions by responding in comforting or supportive ways. Not much research has examined how negative emotions and parent responses to negative emotions are different in very young autistic children. This study used videotapes of 18-month-old toddlers and parents at home. We examined how much and how intensely toddlers expressed negative emotion in everyday situations, and how parents responded. Participants were younger siblings of autistic children, and we compared three groups-children that (1) later received an autism diagnosis; (2) had language delays but not autism; and (3) had no delays or autism. We found that autistic toddlers' negative emotion was more likely to be intense and to continue once it started compared with children without delays or autism. Language-delayed toddlers also showed some, but not all these differences. Parents responded similarly to negative emotions in all groups. When parents used strategies to help, it reduced the chances of the negative emotions continuing, although it may have been less helpful for autistic toddlers. This study shows that autistic children may express more intense and long-lasting negative emotions from an early age. It also shows that parents of autistic children are very responsive to their children's negative emotions, but these responses may not be as helpful to autistic children. While more research is needed, this study helps us understand how autistic toddlers may express and experience emotions differently.

The Emotion Dysregulation Inventory-Young Child: Psychometric Properties and Item Response Theory Calibration in 2- to 5-Year-Olds.

OBJECTIVE: The Emotion Dysregulation Inventory (EDI) was designed and validated to quantify emotion dysregulation (ED) in children aged 6+ years. The purpose of this study was to adapt the EDI for use in young children (EDI-YC). METHOD: Caregivers of 2,139 young children (aged 2-5 years) completed 48 candidate EDI-YC items. Factor and item response theory (IRT) analyses were conducted separately for clinical (neurodevelopmental disabilities; N = 1,369) and general population (N = 768) samples. The best-performing items across both samples were selected. Computerized adaptive testing simulations were used to develop a short-form version. Concurrent calibrations and convergent/criterion validity analyses were performed. RESULTS: The final calibrated item banks included 22 items: 15 items for Reactivity, characterized by rapidly escalating, intense, and labile negative affect, and difficulty down-regulating that affect; and 7 items for Dysphoria, characterized primarily by poor up-regulation of positive emotion, as well an item each on sadness and unease. The final items did not show differential item functioning based on age, sex, developmental status, or clinical status. IRT co-calibration of the EDI-YC Reactivity with psychometrically robust measures of anger/irritability and self-regulation demonstrated its superiority in assessing emotion dysregulation in as few as 7 items. EDI-YC validity was supported by expert review and its association with related constructs (eg, anxiety, depression, aggression, temper loss). CONCLUSION: The EDI-YC captures a broad range of emotion dysregulation severity with a high degree of precision in early childhood. It is suitable for use in all children aged 2 to 5 years, regardless of developmental concerns, and would be an ideal broadband screener for emotional/behavioral problems during well-child checks and to support early childhood irritability and emotion regulation research.

Correlates of Impairment and Growth in Families of Young Autistic Children.

The purpose of this project was to investigate potential correlates of family life impairment in families of young autistic children. This project incorporated measures of specific child and parent challenges in addition to a commonly used unidimensional measure of autism characteristics. In this way, we could assess whether such challenges explain variance in family life impairment, and whether their inclusion diminish associations between autism characteristics and family life impairment. Cross-sectional data were collected from 564 parents of autistic children aged 2 to 5 years who participated in a larger online study. Participants completed measures on child characteristics (autism characteristics, emotion dysregulation, speaking ability, flexibility, and sleep problems), parent depression, and family life impairment, using the Family Life Impairment Scale (FLIS). Multiple linear regression models were generated to examine whether any of the independent variables were associated with the four domains of the FLIS. Models controlled for child age and sex, parent education, and single-parent homes. All independent variables were associated with impairment in one or more FLIS domains. None of the primary independent variables were significantly associated with positive growth. More overt characteristics and behaviors (e.g., autism characteristics, reactivity, speaking ability, and flexibility) were associated with impairment in domains that reflected a family's ability to navigate the community. However, sleep challenges and parent and child emotional difficulties were most strongly associated with parent impairment. Findings suggests that families may have different needs across contexts and provide new avenues through which they might be better supported.

Developing a Measure of Key Adult Outcomes in Adults with Developmental Disabilities: Conceptual Model and Item Generation of the REALS (Relationships, Employment, Autonomy, and Life Satisfaction).

Employment, social relationships, and autonomy are priorities to people with intellectual and developmental disabilities (IDDs). However, few validated measures exist to systematically assess these key adult outcomes in this population. This research includes first steps to develop self- and proxy report measures of life outcomes for adults with IDDs-the Relationships, Employment, Autonomy, and Life Satisfaction (REALS). A literature search identified existing adult outcome measures, and comparison of their domains informed initial conceptual model development. External consultants revised the model, and items were generated. Autistic adults (n = 15), adults with other IDDs (n = 7), caregivers of autistic adults (n = 13), and caregivers of adults with other IDDs (n = 10) completed in-depth cognitive interviews to assess comprehension of items and response categories, factors influencing how participants respond to items, and the inclusiveness of the item pool. A final conceptual model was generated with three subdomains (social relationships, employment, and autonomy), including assessment of life satisfaction within each domain. Cognitive interviews revealed that response set restructuring and item-level revisions were needed to capture the complexity of adult life and make the measure more accessible across a range of abilities. This study developed a conceptual model of relationships, work, and autonomy specific to adults with IDDs. Future work will involve collecting data from 800 + self-reporters with IDDs and 800 + caregivers of adults with IDDs to conduct psychometric analyses. Improving measurement in this area is critical to better understanding the needs of adults with IDDs and improving services available to them.

Irritability in Youths: A Critical Integrative Review.

Irritability, defined as proneness to anger that may impair an individual's functioning, is common in youths. There has been a recent upsurge in relevant research. The authors combine systematic and narrative review approaches to integrate the latest clinical and translational findings and provide suggestions for addressing research gaps. Clinicians and researchers should assess irritability routinely, and specific assessment tools are now available. Informant effects are prominent, are stable, and vary by age and gender. The prevalence of irritability is particularly high among individuals with attention deficit hyperactivity disorder, autism spectrum disorder, and mood and anxiety disorders. Irritability is associated with impairment and suicidality risk independent of co-occurring diagnoses. Developmental trajectories of irritability (which may begin early in life) have been identified and are differentially associated with clinical outcomes. Youth irritability is associated with increased risk of anxiety, depression, behavioral problems, and suicidality later in life. Irritability is moderately heritable, and genetic associations differ based on age and comorbid illnesses. Parent management training is effective for treating psychological problems related to irritability, but its efficacy in treating irritability should be tested rigorously, as should novel mechanism-informed interventions (e.g., those targeting exposure to frustration). Associations between irritability and suicidality and the impact of cultural context are important, underresearched topics. Analyses of large, diverse longitudinal samples that extend into adulthood are needed. Data from both animal and human research indicate that aberrant responses to frustration and threat are central to the pathophysiology of irritability, revealing important translational opportunities.

A PROMIS®ing New Measure for Quantifying Emotion Dysregulation in Toddlers and Preschoolers: Development of the Emotion Dysregulation Inventory-Young Child.

The Emotion Dysregulation Inventory (EDI) was designed and validated to quantify emotion dysregulation (ED) in school-age children, with a particular emphasis on capturing ED in youth with ASD. We saw a need to adapt the EDI for use in young children (ages 2-5) given early childhood is a formative time for emotion regulation development. The present study discusses the adaptation process for the EDI-Young Child (EDI-YC), including item refinement/generation and cognitive interviews (N = 10 with ASD), consistent with the Patient-Reported Outcomes Measurement Information System (PROMIS®) methodology. The item bank was piloted in a sample of 2-year-olds with and without ASD (N = 31), which provided initial support for the EDI-YC as a valid and reliable measure.

Obtaining a First Diagnosis of Autism Spectrum Disorder: Descriptions of the Diagnostic Process and Correlates of Parent Satisfaction from a National Sample.

Obtaining an autism spectrum disorder (ASD) diagnosis is often challenging for parents. The purpose of this study was to better understand this process and examine how elements of the process may influence parent satisfaction. A total of 406 parents of autistic children participated. Participants were administered a survey covering the ASD diagnostic process. Parents had developmental concerns early but experienced long wait times and usually attended many appointments. Mean diagnostic age was 3.26 years and overall delay was 1.20 years. Stress and being told there was "no problem" were significantly associated with parental satisfaction with the process. Findings provide insight into challenges experienced by families of autistic children and can help pinpoint areas where the diagnostic process may be improved.

From Alert Child to Sleepy Adolescent: Age Trends in Chronotype, Social Jetlag, and Sleep Problems in Youth with Autism.

PURPOSE: Developmental changes in sleep in youth with autism spectrum disorder (ASD) are understudied. In non-ASD youth, adolescents exhibit a "night owl chronotype" (i.e., later sleep/wake timing) and social jetlag (i.e., shifts in sleep timing across school nights and weekends), with corresponding sleep problems. The purpose of this study is to evaluate age trends in chronotype, social jetlag, and sleep problems in high-risk youth with ASD. METHODS: Youth with ASD (N = 171), ages 5-21 years old, were enrolled at the time of admission to specialized psychiatric units. Caregivers reported children's demographic information, habitual sleep timing, and sleep problems. Multivariate analyses evaluated the effect of age on chronotype, social jetlag, and sleep problems and the effects of chronotype and social jetlag on sleep problems. Covariates and moderators included sex, race, verbal ability, autism symptom severity, supplemental melatonin, and pubertal status. RESULTS: Older age was associated with later chronotype, more social jetlag, fewer sleep anxiety/co-sleeping problems, fewer night waking and parasomnia problems, and more daytime alertness problems. The effect of age on chronotype was stronger for youth with greater social affective symptom severity. Mediation analyses showed that later chronotype statistically mediated the association between age and daytime alertness problems. CONCLUSIONS: Youth with ASD may exhibit night owl chronotype behavior and social jetlag as they enter adolescence. Shifts toward a later chronotype may be exacerbated by autism severity and may contribute to alertness problems and sleepiness during the day. Chronotype is modifiable and may be leveraged to improve daytime functioning in youth with ASD.

Feedback Related Negativity Amplitude is Greatest Following Deceptive Feedback in Autistic Adolescents.

The purpose of this study is to investigate if feedback related negativity (FRN) can capture instantaneous elevated emotional reactivity in autistic adolescents. A measurement of elevated reactivity could allow clinicians to better support autistic individuals without the need for self-reporting or verbal conveyance. The study investigated reactivity in 46 autistic adolescents (ages 12-21 years) completing the Affective Posner Task which utilizes deceptive feedback to elicit distress presented as frustration. The FRN event-related potential (ERP) served as an instantaneous quantitative neural measurement of emotional reactivity. We compared deceptive and distressing feedback to both truthful but distressing feedback and truthful and non-distressing feedback using the FRN, response times in the successive trial, and Emotion Dysregulation Inventory (EDI) reactivity scores. Results revealed that FRN values were most negative to deceptive feedback as compared to truthful non-distressing feedback. Furthermore, distressing feedback led to faster response times in the successive trial on average. Lastly, participants with higher EDI reactivity scores had more negative FRN values for non-distressing truthful feedback compared to participants with lower reactivity scores. The FRN amplitude showed changes based on both frustration and reactivity. The findings of this investigation support using the FRN to better understand emotion regulation processes for autistic adolescents in future work. Furthermore, the change in FRN based on reactivity suggests the possible need to subgroup autistic adolescents based on reactivity and adjust interventions accordingly.

Systematic Review: Emotion Dysregulation and Challenging Behavior Interventions for Children andAdolescents with Autism with Graded Key Evidence-Based Strategy Recommendations.

Challenging behavior, such as aggression, is highly prevalent in children and adolescents with autism and can have a devastating impact. Previous reviews of challenging behavior interventions did not include interventions targeting emotion dysregulation, a common cause of challenging behavior. We reviewed emotion dysregulation and challenging behavior interventions for preschoolers to adolescents to determine which evidence-based strategies have the most empirical support for reducing/preventing emotion dysregulation/challenging behavior. We reviewed 95 studies, including 29 group and 66 single-case designs. We excluded non-behavioral/psychosocial interventions and those targeting internalizing symptoms only. We applied a coding system to identify discrete strategies based on autism practice guidelines with the addition of strategies common in childhood mental health disorders, and an evidence grading system. Strategies with the highest quality evidence (multiple randomized controlled trials with low bias risk) were Parent-Implemented Intervention, Emotion Regulation Training, Reinforcement, Visual Supports, Cognitive Behavioral/Instructional Strategies and Antecedent-Based Interventions. Regarding outcomes, most studies included challenging behaviors measures while few included emotion dysregulation measures. This review highlights the importance of teaching emotion-regulation skills explicitly, positively reinforcing replacement/alternative behaviors, using visuals and metacognition, addressing stressors proactively, and involving parents. It also calls for more rigorously-designed studies and for including emotion dysregulation as an outcome/mediator in future trials.

Systematic Review: White Matter Microstructural Organization in Adolescents With Depression.

Objective: A growing body of literature has focused on the neural mechanisms of depression. Our goal was to conduct a systematic review on the white matter microstructural differences in adolescents with depressive disorders vs adolescents without depressive disorders. Method: We searched PubMed and PsycINFO for publications on August 3, 2022 (original search conducted in July 2021). The review was registered on PROSPERO (registration number: CRD42021268200), and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Eligible studies were original research papers comparing diffusion tensor/spectrum imaging findings in adolescents with vs without depression (originally ages 12-19 years, later expanded to 11-21 years). Studies were excluded if they focused on depression exclusively in the context of another condition, used only dimensional depressive symptom assessment(s), or used the same dataset as another included publication. Results: The search yielded 575 unique records, of which 14 full-text papers were included (824 adolescents with depression and 686 without depression). The following white matter regions showed significant differences in fractional anisotropy in at least 3 studies: uncinate fasciculus, cingulum, anterior corona radiata, inferior fronto-occipital fasciculus, and corpus callosum (genu and body). Most studies reported decreased, rather than increased, fractional anisotropy in adolescents with depression. Limitations include the possibility for selective reporting bias and risk of imprecision, given the small sample sizes in some studies. Conclusion: Our systematic review suggests aberrant white matter microstructure in limbic-cortical-striatal-thalamic circuits, and the corpus callosum, in adolescents with depression. Future research should focus on developmental trajectories in depression, identifying sources of heterogeneity and integrating findings across imaging modalities.