Community-guided, autism-adapted group cognitive behavioral therapy for depression in autistic youth (CBT-DAY): Preliminary feasibility, acceptability, and efficacy.

LAY ABSTRACT: Depression in youth is a significant public health problem worldwide, particularly for autistic youth who are over twice as likely to experience depression than their non-autistic peers. Although pathways to depression are complex, emotional reactivity and negative self-esteem are two risk factors for depression in autistic and non-autistic youth. Although autistic youth are more likely to experience depression than their non-autistic peers, psychotherapy options for autistic youth are very limited; community guidance in the development and testing of psychotherapy programs is a promising approach in autism. Therefore, in this study, we designed an autism-adapted CBT-DAY, in collaboration with autistic community members. Specifically, CBT-DAY combined neurodiversity-affirming and cognitive behavioral approaches to target emotional reactivity and self-esteem in youth to improve depressive symptom severity in a group setting across 12 weeks. We examined the preliminary feasibility, acceptability, and efficacy of CBT-DAY in a pilot non-randomized trial. In addition, we implemented a rigorous protocol for assessing, monitoring, and addressing potential harms in this intervention. Results from 24 autistic youth (11-17 years old) suggest that CBT-DAY may be feasible to use in an outpatient clinical setting and generally acceptable to youth and their caregivers. Participation in CBT-DAY may be associated with significant improvements in youth emotional reactivity and self-esteem, as well as depressive symptom severity per self-report only. Exploratory analyses showed that participation in CBT-DAY may also be associated with significant improvements in internalizing symptoms. Findings demonstrate the potential promise of neurodiversity-affirming and cognitive behavioral approaches to treating depressive symptoms in some autistic youth.

Impairments to executive function in emerging adults with Huntington disease.

BACKGROUND AND OBJECTIVES: The clinical diagnosis of Huntington disease (HD) is typically made once motor symptoms and chorea are evident. Recent reports highlight the onset of cognitive and psychiatric symptoms before motor manifestations. These findings support further investigations of cognitive function across the lifespan of HD sufferers. METHODS: To assess cognitive symptoms in the developing brain, we administered assessments from the National Institutes of Health Toolbox Cognitive Battery, an age-appropriate cognitive assessment with population norms, to a cohort of children, adolescents and young adults with (gene-expanded; GE) and without (gene-not-expanded; GNE) the trinucleotide cytosine, adenine, guanine (CAG) expansion in the Huntingtin gene. These five assessments that focus on executive function are well validated and form a composite score, with population norms. We modelled these scores across age, and CAP score to estimate the slope of progression, comparing these results to motor symptoms. RESULTS: We find significant deficits in the composite measure of executive function in GE compared with GNE participants. GE participant performance on working memory was significantly lower compared with GNE participants. Modelling these results over age suggests that these deficits occur as early as 18 years of age, long before motor manifestations of HD. CONCLUSIONS: This work provides strong evidence that impairments in executive function occur as early as the second decade of life, well before anticipated motor onset. Future investigations should delineate whether these impairments in executive function are due to abnormalities in neurodevelopment or early sequelae of a neurodegenerative process.

Maternal attachment insecurity, maltreatment history, and depressive symptoms are associated with broad DNA methylation signatures in infants.

The early environment, including maternal characteristics, provides many cues to young organisms that shape their long-term physical and mental health. Identifying the earliest molecular events that precede observable developmental outcomes could help identify children in need of support prior to the onset of physical and mental health difficulties. In this study, we examined whether mothers' attachment insecurity, maltreatment history, and depressive symptoms were associated with alterations in DNA methylation patterns in their infants, and whether these correlates in the infant epigenome were associated with socioemotional and behavioral functioning in toddlerhood. We recruited 156 women oversampled for histories of depression, who completed psychiatric interviews and depression screening during pregnancy, then provided follow-up behavioral data on their children at 18 months. Buccal cell DNA was obtained from 32 of their infants for a large-scale analysis of methylation patterns across 5 × 106 individual CpG dinucleotides, using clustering-based significance criteria to control for multiple comparisons. We found that tens of thousands of individual infant CpGs were alternatively methylated in association with maternal attachment insecurity, maltreatment in childhood, and antenatal and postpartum depressive symptoms, including genes implicated in developmental patterning, cell-cell communication, hormonal regulation, immune function/inflammatory response, and neurotransmission. Density of DNA methylation at selected genes from the result set was also significantly associated with toddler socioemotional and behavioral problems. This is the first report to identify novel regions of the human infant genome at which DNA methylation patterns are associated longitudinally both with maternal characteristics and with offspring socioemotional and behavioral problems in toddlerhood.

Inhibitory control, working memory and coping with stress: Associations with symptoms of anxiety and depression in adults with Huntington's disease.

OBJECTIVE: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by neuropsychiatric symptoms (e.g., anxiety and depression), where individuals suffer high levels of stress from the social, physical, and cognitive burden of the disease. The present study examined two factors associated with increased risk for symptoms of anxiety and depression: executive function skills (inhibitory control/attention and working memory) and skills to cope with stress. METHOD: Adults with HD completed the NIH Toolbox measures of inhibitory control/attention and working memory, as well as self-report measures of coping with HD-related stress and symptoms of anxiety and depression. Path analyses were used to test direct and indirect associations among the subtypes of executive functioning, coping, and symptoms. RESULTS: No significant associations were found in the full sample (n = 47), due to a significant portion of the sample with very low executive function abilities. Additional analyses were conducted on a subset of the sample (participants in the top three quartiles on both measures of executive functioning, n = 32). Significant indirect associations emerged among inhibitory control/attention skills, secondary control coping (e.g., acceptance and reappraisal), and symptoms of anxiety and depression in the subsample. Higher inhibitory control/attention skills were associated with greater use of secondary control coping, and greater use of these coping skills was related to lower symptoms of anxiety and depression. No direct or indirect associations were found among working memory skills, coping, and symptoms of anxiety and depression. CONCLUSIONS: Implications for interventions to enhance executive function and coping skills in adults with HD are highlighted. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Posttraumatic stress symptoms and financial toxicity among adolescent and young adult oncology patients and their caregivers at cancer diagnosis.

BACKGROUND: Adolescent and young adult oncology (AYAO) patients and caregivers may experience significant psychosocial dysfunction and financial toxicity. Understanding early risk factors is critical to improving survivorship trajectories. METHODS: The authors conducted a cross-sectional study of baseline survey data from a prospective cohort of AYAO patient-caregiver dyads enrolled within 1 month of medical oncology treatment initiation. Posttraumatic stress symptoms (PTSS) were measured by the Impacts of Events Scale-Revised, and financial toxicity was measured with the Comprehensive Score (COst). The authors fit models of linear association between PTSS, financial toxicity, and other end points and pairwise associations of PTSS and financial toxicity within dyads. RESULTS: The analytic cohort contained 41 patients, 37 caregivers, and 34 complete dyads. Clinically-concerning PTSS were observed among patients (44%) and caregivers (52%). The median COst scores were 20.0 for patients (quartiles, 12.5-29.5) and 22.0 for caregivers (quartiles, 12.8-26.0), which were consistent with high financial toxicity (patients, 46%; caregivers, 44%). PTSS were positively associated with financial toxicity (P = .013 for patients, P = .039 for caregivers), subjective distress (P < .001 for all), depressive (P < .001 for all) and anxiety symptoms (P = .005 for patients, P = .024 for caregivers), and poorer quality of life (P < .001 for patients, P = .003 for caregivers). A significant paired association was not found in PTSS (Pearson correlation coefficient [PCC], 0.23; 95% confidence interval [CI], -0.15 to 0.56). Financial toxicity was positively associated within dyads (PCC, 0.65; 95% CI, 0.36-0.83). CONCLUSIONS: At diagnosis, AYAO patients and caregivers exhibit substantial PTSS, which are associated with greater financial toxicity and other psychosocial distress.

Breastfeeding Difficulties Predict Mothers' Bonding with Their Infants from Birth to Age Six Months.

OBJECTIVES: We examined the association between breastfeeding difficulties and trajectories of bonding in the first 6 months postpartum. METHODS: Each month for the first 6 months following birth, 121 mothers of newborn infants (age = 23-45 years, M = 32.31 ± 4.79, 57% White, 23% Asian, 11% Hispanic, 9% Multiracial, 1% Black/African American) were invited to complete self-assessments of bonding. At the first postpartum assessment, mothers who intended to breastfeed also reported whether breastfeeding was more difficult than they had anticipated. We conducted linear mixed modelling to test whether early breastfeeding difficulty was associated with bonding trajectories and examined whether effects remained when accounting for postnatal depression symptoms. RESULTS: We found main effects of breastfeeding difficulty (ß = - .20, 95% CI [ -  .34, - .06]) and postpartum month (ß = .13, 95% CI [.07, .20]) on bonding. On average, women who reported breastfeeding difficulty reported lower bonding than women who did not (Cohen's d = - 0.44, 95% CI [- 0.81, - 0.06]). Additional analyses indicated that, independent of breastfeeding difficulties, women who reported higher postnatal depressive symptoms across the first 6 months postpartum reported lower levels of bonding, on average. Further, within-individual decreases in postnatal depressive symptoms across the first six months were associated with relative improvements in bonding across this period. CONCLUSIONS FOR PRACTICE: Our findings suggest that mothers who experience breastfeeding difficulties are at risk for reduced bonding with their infants in the first 6 months after birth. Moreover, while postnatal depressive symptoms are also associated with reduced bonding, the effect of breastfeeding difficulties on bonding persists over and above the effect of postnatal depressive symptoms.

Attachment Security in Pregnancy Mediates the Association Between Maternal Childhood Maltreatment and Emotional and Behavioral Problems in Offspring.

Attachment security may be a mechanism by which exposure to early life adversity affects subsequent generations. We used a prospective cohort design to examine this possibility in a convenience sample of 124 women (age = 23-45 years, M = 32.32 [SD = 4.83] years; 57.3% White, 22.6% Asian) who provided self-reports of attachment style during pregnancy using the Attachment Style Questionnaire, of whom 96 (age = 28-50 years, M = 36.67 [SD = 4.90] years; 60.4% White, 19.8% Asian) were reassessed when their child was preschool-age (M = 4.38 [SD = 1.29] years). Women self-reported on their own childhood maltreatment severity and their child's current emotional and behavioral problems using the Childhood Trauma Questionnaire and the Child Behavior Checklist for ages 1.5-5, respectively. Maternal childhood maltreatment severity was associated with less secure, and more avoidant and anxious attachment. Mediation analyses revealed further that less secure maternal attachment, but not avoidant or anxious attachment, mediated the associations between maternal childhood maltreatment and offspring emotional and behavioral problems. These findings suggest that improving maternal attachment security, which can be identified even prior to the child's birth, is an important target to consider for intervention efforts aimed at minimizing adverse intergenerational effects of early life adversity.

Prenatal stress exposure and multimodal assessment of amygdala-medial prefrontal cortex connectivity in infants.

Stressful experiences are linked to neurodevelopment. There is growing interest in the role of stress in the connectivity between the amygdala and medial prefrontal cortex (mPFC), a circuit that subserves automatic emotion regulation. However, the specific timing and mechanisms that underlie the association between stress and amygdala-mPFC connectivity are unclear. Many factors, including variations in fetal exposure to maternal stress, appear to affect early developing brain circuitry. However, few studies have examined the associations of stress and amygdala-mPFC connectivity in early life, when the brain is most plastic and sensitive to environmental influence. In this longitudinal pilot study, we characterized the association between prenatal stress and amygdala-mPFC connectivity in young infants (approximately age 5 weeks). A final sample of 33 women who provided data on preconception and prenatal stress during their pregnancy returned with their offspring for a magnetic resonance imaging scan session, which enabled us to characterize amygdala-mPFC structural and functional connectivity as a function of prenatal stress. Increased prenatal stress was associated with decreased functional connectivity and increased structural connectivity between the amygdala and mPFC. These results provide insight into the influence of prenatal maternal stress on the early development of this critical regulatory circuitry.

Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression.

Early life adversity and insecure attachment style are known risk factors for perinatal depression. The biological pathways linking these experiences, however, have not yet been elucidated. We hypothesized that overlap in patterns of DNA methylation in association with each of these phenomena could identify genes and pathways of importance. Specifically, we wished to distinguish between allostatic-load and role-transition hypotheses of perinatal depression. We conducted a large-scale analysis of methylation patterns across 5 × 106 individual CG dinucleotides in 54 women participating in a longitudinal prospective study of perinatal depression, using clustering-based criteria for significance to control for multiple comparisons. We identified 1580 regions in which methylation density was associated with childhood adversity, 3 in which methylation density was associated with insecure attachment style, and 6 in which methylation density was associated with perinatal depression. Shorter telomeres were observed in association with childhood trauma but not with perinatal depression or attachment insecurity. A detailed analysis of methylation density in the oxytocin receptor gene revealed similar patterns of DNA methylation in association with perinatal depression and with insecure attachment style, while childhood trauma was associated with a distinct methylation pattern in this gene. Clinically, attachment style was strongly associated with depression only in pregnancy and the early postpartum, whereas the association of childhood adversity with depression was time-invariant. We concluded that the broad DNA methylation signature and reduced telomere length associated with childhood adversity could indicate increased allostatic load across multiple body systems, whereas perinatal depression and attachment insecurity may be narrower phenotypes with more limited DNA methylation signatures outside the CNS, and no apparent association with telomere length or, by extension, allostatic load. In contrast, the finding of matching DNA methylation patterns within the oxytocin receptor gene for perinatal depression and attachment insecurity is consistent with the theory that the perinatal period is a time of activation of existing attachment schemas for the purpose of structuring the mother-child relationship, and that such activation may occur in part through specific patterns of methylation of the oxytocin receptor gene.

Self-reported neglect, amygdala volume, and symptoms of anxiety in adolescent boys.

Experiences of psychosocial neglect affect the developing brain and may place individuals at increased risk for anxiety. The majority of research in this area has focused on children who have experienced severe psychosocial deprivation; it is not clear whether typical variation in neglect experienced in community samples would have the same neurobiological consequences as those documented in extreme samples. The present study examined the associations among self-reported childhood neglect, amygdala volume, and anxiety symptoms in a community sample of 138 adolescents ages 9-15 years (43% male). Linear mixed modeling yielded a three-way interaction of neglect, sex, and brain hemisphere, reflecting a significant positive association between neglect and right amygdala volume in boys. Additional analyses indicated that right amygdala volume significantly mediated the association between neglect and anxiety symptoms in boys. These findings are consistent with previous reports of larger amygdala volumes in previously institutionalized children, and with documented associations between caregiving deprivation and anxiety symptoms. The results suggest that the effects of childhood neglect on limbic structures are sex-specific and lateralized, and provide support for a neural mechanism relating childhood neglect to later difficulties in emotional functioning.