Search

Background This study leveraged machine learning to evaluate the contribution of information from multiple developmental stages to prospective prediction of depression and anxiety in mid-adolescence. Methods A community sample (N = 374; 53.5% male) of children and their families completed tri-annual assessments across ages 3–15. The feature set included several important risk factors spanning psychopathology, temperament/personality, family environment, life stress, interpersonal relationships, neurocognitive, hormonal, and neural functioning, and parental psychopathology and personality. We used canonical correlation analysis (CCA) to reduce the large feature set to a lower dimensional space while preserving the longitudinal structure of the data. Ablation analysis was conducted to evaluate the relative contributions to prediction of information gathered at different developmental periods and relative to previous disorder status (i.e. age 12 depression or anxiety) and demographics (sex, race, ethnicity). Results CCA components from individual waves predicted age 15 disorder status better than chance across ages 3, 6, 9, and 12 for anxiety and 9 and 12 for depression. Only the components from age 12 for depression, and ages 9 and 12 for anxiety, improved prediction over prior disorder status and demographics. Conclusions These findings suggest that screening for risk of adolescent depression can be successful as early as age 9, while screening for risk of adolescent anxiety can be successful as early as age 3. Assessing additional risk factors at age 12 for depression, and going back to age 9 for anxiety, can improve screening for risk at age 15 beyond knowing standard demographics and disorder history.

Background: Childhood trauma is a common and potent risk factor for developing major depressive disorder in adulthood, associated with earlier onset, more chronic or recurrent symptoms, and greater probability of having comorbidities. Some studies indicate that evidence-based pharmacotherapies and psychotherapies for adult depression might be less efficacious in patients with a history of childhood trauma than patients without childhood trauma, but findings are inconsistent. Therefore, we examined whether individuals with major depressive disorder, including chronic forms of depression, and a reported history of childhood trauma, had more severe depressive symptoms before treatment, had more unfavourable treatment outcomes following active treatments, and were less likely to benefit from active treatments relative to a control condition, compared with individuals with depression without childhood trauma. Methods: We did a comprehensive meta-analysis (PROSPERO CRD42020220139). Study selection combined the search of bibliographical databases (PubMed, PsycINFO, and Embase) from Nov 21, 2013, to March 16, 2020, and full-text randomised clinical trials (RCTs) identified from several sources (1966 up to 2016–19) to identify articles in English. RCTs and open trials comparing the efficacy or effectiveness of evidence-based pharmacotherapy, psychotherapy, or combination intervention for adult patients with depressive disorders and the presence or absence of childhood trauma were included. Two independent researchers extracted study characteristics. Group data for effect-size calculations were requested from study authors. The primary outcome was depression severity change from baseline to the end of the acute treatment phase, expressed as standardised effect size (Hedges' g). Meta-analyses were done using random-effects models. Findings: From 10 505 publications, 54 trials met the inclusion criteria, of which 29 (20 RCTs and nine open trials) contributed data of a maximum of 6830 participants (age range 18–85 years, male and female individuals and specific ethnicity data unavailable). More than half (4268 [62%] of 6830) of patients with major depressive disorder reported a history of childhood trauma. Despite having more severe depression at baseline (g=0·202, 95% CI 0·145 to 0·258, I2=0%), patients with childhood trauma benefitted from active treatment similarly to patients without childhood trauma history (treatment effect difference between groups g=0·016, –0·094 to 0·125, I2=44·3%), with no significant difference in active treatment effects (vs control condition) between individuals with and without childhood trauma (childhood trauma g=0·605, 0·294 to 0·916, I2=58·0%; no childhood trauma g=0·178, –0·195 to 0·552, I2=67·5%; between-group difference p=0·051), and similar dropout rates (risk ratio 1·063, 0·945 to 1·195, I2=0%). Findings did not significantly differ by childhood trauma type, study design, depression diagnosis, assessment method of childhood trauma, study quality, year, or treatment type or length, but differed by country (North American studies showed larger treatment effects for patients with childhood trauma; false discovery rate corrected p=0·0080). Most studies had a moderate to high risk of bias (21 [72%] of 29), but the sensitivity analysis in low-bias studies yielded similar findings to when all studies were included. Interpretation: Contrary to previous studies, we found evidence that the symptoms of patients with major depressive disorder and childhood trauma significantly improve after pharmacological and psychotherapeutic treatments, notwithstanding their higher severity of depressive symptoms. Evidence-based psychotherapy and pharmacotherapy should be offered to patients with major depressive disorder regardless of childhood trauma status. Funding: None.

The rates of suicide in youth have increased dramatically, leading to increased interest in routinely screening youth for suicidality. However, data on suicidal ideation (SI) in younger children are sparse, especially with brief self-report measures that can easily be used for screening non-referred samples.We evaluated a community sample of 497 6-year-old children and their parents and followed them into adolescence. SI was assessed via child self-report at ages 6 and 9 using an item from the Children's Depression Inventory, and via parent-report at age 6 using an item from the Early Childhood Inventory. Child psychopathology and functioning were assessed via semi-structured interviews every 3 years from age 6 through 15.Child endorsement of SI at age 6 did not predict later psychopathology or functioning. Child endorsement of SI at age 9 was associated with attention deficit hyperactivity disorder (ADHD) and disruptive behavior disorders (DBD) diagnoses across the adolescent follow-up assessments. Parent endorsement of child SI predicted an increased likelihood of later SI and non-suicidal self-injury, a higher rate of DBD and externalizing symptoms, and poorer global functioning in adolescence.Our results support recommendations against administering SI screening measures to children under the age of 10.

There is an extensive literature documenting associations between dimensions of temperament and depressive and anxiety disorders. However, much of the research in this area relies on cross-sectional and monomethod designs, uses samples of older youth and adults, and examines only the main effects of temperament. We examined longitudinal associations between temperamental positive emotionality (PE) and negative emotionality (NE) in early childhood and depressive and anxiety symptoms in adolescence. We assessed temperament using laboratory observations and parent reports, and symptoms using youth and parent report. We also examined potential moderators of these associations, including maternal and paternal history of depressive and anxiety disorders, youth experience of stressful life events, and parenting styles. Early childhood NE was associated with both adolescent depression and anxiety. Additionally, life events and psychological controlling and firm parenting moderated the associations between NE and depression symptoms, and maternal depression, paternal anxiety, and psychological controlling and firm parenting moderated the associations between NE and anxiety symptoms. Interaction effects were largely consistent with diathesis-stress interpretations. These findings show that temperamental NE, but not PE, is prospectively associated with risk for depressive and anxiety symptoms in adolescence, and that multiple additional factors potentiate these associations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Our study aimed at assessing the anatomical feasibility of using the nerve supplying the Gantzer muscle (GM) to supercharge the ulnar nerve following injury. The GM nerve was dissected and measured in 36 forearms. The distance between its origin and the lateral epicondyle of humerus and between the GM nerve and the ulnar nerve was measured. The GM was present in 15 forearms (47%). The average distance between the origin of the GM nerve and the lateral epicondyle was 7.34 cm (range 3.3-9.1 cm). The average length of the GM nerve was 3.05 cm (range 1.6-4.5 cm) from origin to neuromuscular junction. The average distance from the ulnar nerve was 2.56 cm (range 1.8-13 3.4 cm). The length of the GM nerve was significantly greater (p 0.05) than the perpendicular distance between its origin and the ulnar nerve, allowing ample margin for side-to-side or end-to-side supercharging of the ulnar nerve with minimal or no need for further translocation or dissection. The use of the GM nerve as donor following ulnar nerve injury may provide an alternative to the pronator quadratus nerve for supercharged end-to-side transfer, or as an addition, thus supercharging the ulnar nerve twice.

Irritability is a common and clinically important problem in children and adolescents and a risk factor for later psychopathology and impairment. Irritability can manifest in both tonic (e.g., irritable, touchy mood) and phasic (e.g., temper outburst) forms, and recent studies of adolescents suggest that they predict different outcomes. However, no studies have examined whether tonic and phasic irritability are empirically distinguishable in 6-year-old children and whether they have distinct correlates and outcomes.We utilized data from a longitudinal study of an unselected community sample of four hundred fifty-two 6-year-olds followed at 3-year intervals to age 15. We conducted confirmatory factor analysis (CFA) using relevant items from a diagnostic interview and several parent-report inventories.The CFA identified dimensions that were consistent with tonic and phasic irritability. Tonic irritability was independently associated with concurrent parent-reported temperamental negative affectivity and internalizing and externalizing disorders at age 6 and predicted higher rates of internalizing psychopathology, and suicidal ideation, in adolescence. Phasic irritability was independently associated with concurrent parent-reported temperamental negative affectivity, surgency, and low effortful control, maladaptive parenting styles and practices, and externalizing disorders at age 6, and predicted higher rates of externalizing psychopathology in adolescence.Tonic and phasic irritability in 6-year-old children appear to be distinguishable constructs with different temperament and parenting correlates and psychopathological outcomes. Distinguishing these components has implications for research on the etiology and pathophysiology of irritability and developing effective treatments.

Background Preschool psychiatric symptoms significantly increase the risk for long-term negative outcomes. Transdiagnostic hierarchical approaches that capture general (‘p’) and specific psychopathology dimensions are promising for understanding risk and predicting outcomes, but their predictive utility in young children is not well established. We delineated a hierarchical structure of preschool psychopathology dimensions and tested their ability to predict psychiatric disorders and functional impairment in preadolescence. Methods Data for 1253 preschool children (mean age = 4.17, s.d. = 0.81) were drawn from three longitudinal studies using a similar methodology (one community sample, two psychopathology-enriched samples) and followed up into preadolescence, yielding a large and diverse sample. Exploratory factor models derived a hierarchical structure of general and specific factors using symptoms from the Preschool Age Psychiatric Assessment interview. Longitudinal analyses examined the prospective associations of preschool p and specific factors with preadolescent psychiatric disorders and functional impairment. Results A hierarchical dimensional structure with a p factor at the top and up to six specific factors (distress, fear, separation anxiety, social anxiety, inattention-hyperactivity, oppositionality) emerged at preschool age. The p factor predicted all preadolescent disorders (ΔR2 = 0.04–0.15) and functional impairment (ΔR2 = 0.01–0.07) to a significantly greater extent than preschool psychiatric diagnoses and functioning. Specific dimensions provided additional predictive power for the majority of preadolescent outcomes (disorders: ΔR2 = 0.06–0.15; functional impairment: ΔR2 = 0.05–0.12). Conclusions Both general and specific dimensions of preschool psychopathology are useful for predicting clinical and functional outcomes almost a decade later. These findings highlight the value of transdiagnostic dimensions for predicting prognosis and as potential targets for early intervention and prevention.

Background Adolescence is a key developmental period for the emergence of psychiatric disorders. However, there is still no consensus on the core mechanisms of dysfunction in youth. Neurobiological sensitivity to unpredictable threat has been associated with several psychiatric disorders in adults. The present study examined adolescent defensive motivation (startle reflex) and attention (event-related potentials) in anticipation of unpredictable threat in relation to both adolescent and maternal (i.e. familial risk) internalizing and externalizing spectra. Methods The sample included 395 15-year-old adolescents and their biological mothers. Adolescent startle potentiation and probe P300 suppression (indicating increased attention to threat) were measured in anticipation of predictable and unpredictable threat. Adolescent and maternal lifetime history of psychiatric disorders were assessed via semi-structured diagnostic interviews, and confirmatory factor analysis was used to model internalizing and externalizing spectra. Results The adolescent internalizing spectrum was positively associated with adolescent startle potentiation and probe P300 suppression to unpredictable threat. Conversely, the adolescent externalizing spectrum was negatively associated with adolescent P300 suppression to unpredictable threat. The maternal internalizing spectrum was positively associated with adolescent startle potentiation to unpredictable threat and P300 suppression to both predictable and unpredictable threat. The maternal externalizing spectrum was negatively associated with adolescent startle potentiation to unpredictable threat and P300 suppression to both predictable and unpredictable threat. Adolescent and maternal internalizing and externalizing spectra were independently related to adolescent startle potentiation and P300 suppression. Conclusions Adolescent neurobiological sensitivity to unpredictable threat is associated with both personal history and familial risk for the internalizing and externalizing spectra.

OBJECTIVE: Studies of the association between early childhood low temperamental fearfulness or behavioral inhibition (BI) and later externalizing symptoms are few and results are inconsistent, despite research from outside the temperament field that has linked fearlessness with externalizing problems. There is also a large literature showing that peer victimization (PV) predicts externalizing symptoms. However, no prior studies have examined the joint effect of low temperamental fearfulness/BI and PV on externalizing psychopathology. The current study examined the main and joint effects of low temperamental fearfulness/BI and PV on broad internalizing and externalizing problems, as well as more narrow forms of externalizing psychopathology. METHOD: Participants included 559 children (86.5% white, 54% male) assessed at ages 3, 6, 9, and 12. Temperamental fearfulness/BI was assessed using laboratory observations at age 3. PV was assessed via semi-structured interviews at ages 6 and 9. Finally, internalizing and externalizing psychopathology were each assessed at ages 3 and 12. RESULTS: After accounting for sex, race, and age 3 symptomatology, the joint effect of low temperamental fearfulness/BI and PV predicted higher levels of externalizing problems overall and specific externalizing symptom domains, but not internalizing problems. CONCLUSION: These results suggest that there is an association between low temperamental fearfulness/BI and later externalizing psychopathology, but that it depends on moderating factors such as PV.

Currently, no effective therapeutics exist for the treatment of incurable neurodegenerative diseases such as Alzheimer’s disease (AD). The cellular prion protein (PrPC) acts as a high-affinity receptor for amyloid beta oligomers (AβO), a main neurotoxic species mediating AD pathology. The interaction of AβO with PrPC subsequently activates Fyn tyrosine kinase and neuroinflammation. Herein, we used our previously developed peptide aptamer 8 (PA8) binding to PrPC as a therapeutic to target the AβO–PrP–Fyn axis and prevent its associated pathologies. Our in vitro results indicated that PA8 prevents the binding of AβO with PrPC and reduces AβO-induced neurotoxicity in mouse neuroblastoma N2a cells and primary hippocampal neurons. Next, we performed in vivo experiments using the transgenic 5XFAD mouse model of AD. The 5XFAD mice were treated with PA8 and its scaffold protein thioredoxin A (Trx) at a 14.4 µg/day dosage for 12 weeks by intraventricular infusion through Alzet® osmotic pumps. We observed that treatment with PA8 improves learning and memory functions of 5XFAD mice as compared to Trx-treated 5XFAD mice. We found that PA8 treatment significantly reduces AβO levels and Aβ plaques in the brain tissue of 5XFAD mice. Interestingly, PA8 significantly reduces AβO–PrP interaction and its downstream signaling such as phosphorylation of Fyn kinase, reactive gliosis as well as apoptotic neurodegeneration in the 5XFAD mice compared to Trx-treated 5XFAD mice. Collectively, our results demonstrate that treatment with PA8 targeting the AβO–PrP–Fyn axis is a promising and novel approach to prevent and treat AD.

Youth personality is hypothesized to mediate the intergenerational transmission of internalizing disorders. However, this has rarely been examined. We tested whether the intergenerational transmission of depressive and anxiety disorders is mediated by youth neuroticism and extraversion, and how parent personality influenced these relationships. Participants included 550 adolescent girls, aged 13-15 years at baseline (T1), and a coparticipating biological parent. Depressive and anxiety disorders were assessed by interview at T1, and adolescents were reinterviewed every 9 months for 3 years (T2-T5). Parent and youth personality was assessed at T1. Four path models examined direct and indirect effects of parent psychopathology and personality (neuroticism and extraversion) on youth outcomes, with youth neuroticism and extraversion as mediators in separate models. In the model examining the effects of parent psychopathology via T1 youth neuroticism, there were direct effects of parent depression on T2-T5 youth depressive disorders and indirect effects of parent anxiety disorders on T2-T5 youth depressive and anxiety disorders. When parent neuroticism was added, indirect effects of T1 parent anxiety disorders and neuroticism on T2-T5 youth depressive and anxiety disorders via T1 youth neuroticism were significant. In the model examining T1 youth extraversion as a mediator, there were significant direct effects of parent depressive and anxiety disorders on T2-T5 youth depressive and anxiety disorders, respectively. Finally, when adding parent extraversion, indirect effects of parent extraversion on T2-T5 youth depressive and anxiety disorders via youth extraversion were significant. Parent and youth personality play important roles in the intergenerational transmission of depressive and anxiety disorders. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background Life stress and blunted reward processing each have been associated with the onset and maintenance of major depressive disorder. However, much of this work has been cross-sectional, conducted in separate lines of inquiry, and focused on recent life stressor exposure, despite the fact that theories of depression posit that stressors can have cumulative effects over the lifespan. To address these limitations, we investigated whether acute and chronic stressors occurring over the lifespan interacted with blunted reward processing to predict increases in depression over time in healthy youth. Method Participants were 245 adolescent girls aged 8–14 years old (Mage = 12.4, s.d. = 1.8) who were evaluated at baseline and two years later. The reward positivity (RewP), an event-related potential measure of reward responsiveness, was assessed at baseline using the doors task. Cumulative lifetime exposure to acute and chronic stressors was assessed two years later using the Stress and Adversity Inventory for Adolescents (Adolescent STRAIN). Finally, depressive symptoms were assessed at both baseline and follow-up using the Children's Depression Inventory. Results As hypothesized, greater lifetime acute stressor exposure predicted increases in depressive symptoms over two years, but only for youth exhibiting a blunted RewP. This interaction, however, was not found for chronic stressors. Conclusions Lifetime acute stressor exposure may be particularly depressogenic for youth exhibiting a blunted RewP. Conversely, a robust RewP may be protective in the presence of greater acute lifetime stressor exposure.