Developmental pathway for first onset of depressive disorders in females: from adolescence to emerging adulthood.

BACKGROUND: Although risk markers for depressive disorders (DD) are dynamic, especially during adolescence, few studies have examined how change in risk levels during adolescence predict DD onset during transition to adulthood. We compared two competing hypotheses of the dynamic effects of risk. The risk escalation hypothesis posits that worsening of risk predicts DD onset beyond risk level. The chronic risk hypothesis posits that persistently elevated risk level, rather than risk change, predicts DD onset. METHODS: Our sample included 393 girls (baseline age 13.5-15.5 years) from the adolescent development of emotions and personality traits project. Participants underwent five diagnostic interviews and assessments of risk markers for DD at 9-month intervals and were re-interviewed at a 6-year follow-up. We focused on 17 well-established risk markers. For each risk marker, we examined the prospective effects of risk level and change on first DD onset at wave six, estimated by growth curve modeling using data from the first five waves. RESULTS: For 13 of the 17 depression risk markers, elevated levels of risk during adolescence, but not change in risk, predicted first DD onset during transition to adulthood, supporting the chronic risk hypothesis. Minimal evidence was found for the risk escalation hypothesis. CONCLUSIONS: Participants who had a first DD onset during transition to adulthood have exhibited elevated levels of risk throughout adolescence. Researchers and practitioners should administer multiple assessments and focus on persistently elevated levels of risk to identify individuals who are most likely to develop DD and to provide targeted DD prevention.

General v. specific vulnerabilities: polygenic risk scores and higher-order psychopathology dimensions in the Adolescent Brain Cognitive Development (ABCD) Study.

BACKGROUND: Polygenic risk scores (PRSs) capture genetic vulnerability to psychiatric conditions. However, PRSs are often associated with multiple mental health problems in children, complicating their use in research and clinical practice. The current study is the first to systematically test which PRSs associate broadly with all forms of childhood psychopathology, and which PRSs are more specific to one or a handful of forms of psychopathology. METHODS: The sample consisted of 4717 unrelated children (mean age = 9.92, s.d. = 0.62; 47.1% female; all European ancestry). Psychopathology was conceptualized hierarchically as empirically derived general factor (p-factor) and five specific factors: externalizing, internalizing, neurodevelopmental, somatoform, and detachment. Partial correlations explored associations between psychopathology factors and 22 psychopathology-related PRSs. Regressions tested which level of the psychopathology hierarchy was most strongly associated with each PRS. RESULTS: Thirteen PRSs were significantly associated with the general factor, most prominently Chronic Multisite Pain-PRS (r = 0.098), ADHD-PRS (r = 0.079), and Depression-PRS (r = 0.078). After adjusting for the general factor, Depression-PRS, Neuroticism-PRS, PTSD-PRS, Insomnia-PRS, Chronic Back Pain-PRS, and Autism-PRS were not associated with lower order factors. Conversely, several externalizing PRSs, including Adventurousness-PRS and Disinhibition-PRS, remained associated with the externalizing factor (|r| = 0.040-0.058). The ADHD-PRS remained uniquely associated with the neurodevelopmental factor (r = 062). CONCLUSIONS: PRSs developed to predict vulnerability to emotional difficulties and chronic pain generally captured genetic risk for all forms of childhood psychopathology. PRSs developed to predict vulnerability to externalizing difficulties, e.g. disinhibition, tended to be more specific in predicting behavioral problems. The results may inform translation of existing PRSs to pediatric research and future clinical practice.

Do general and specific factors of preschool psychopathology predict preadolescent outcomes? A transdiagnostic hierarchical approach.

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.

Polygenic prediction of PTSD trajectories in 9/11 responders.

BACKGROUND: Genetics hold promise of predicting long-term post-traumatic stress disorder (PTSD) outcomes following trauma. The aim of the current study was to test whether six hypothesized polygenic risk scores (PRSs) developed to capture genetic vulnerability to psychiatric conditions prospectively predict PTSD onset, severity, and 18-year course after trauma exposure. METHODS: Participants were 1490 responders to the World Trade Center (WTC) disaster (mean age at 9/11 = 38.81 years, s.d. = 8.20; 93.5% male; 23.8% lifetime WTC-related PTSD diagnosis). Prospective longitudinal data on WTC-related PTSD symptoms were obtained from electronic medical records and modelled as PTSD trajectories using growth mixture model analysis. Independent regression models tested whether six hypothesized psychiatric PRSs (PTSD-PRS, Re-experiencing-PRS, Generalized Anxiety-PRS, Schizophrenia-PRS, Depression-PRS, and Neuroticism-PRS) are predictive of WTC-PTSD outcomes: lifetime diagnoses, average symptom severity, and 18-year symptom trajectory. All analyses were adjusted for population stratification, 9/11 exposure severity, and multiple testing. RESULTS: Depression-PRS predicted PTSD diagnostic status (OR 1.37, CI 1.17-1.61, adjusted p = 0.001). All PRSs, except PTSD-PRS, significantly predicted average PTSD symptoms (ß = 0.06-0.10, adjusted p < 0.05). Re-experiencing-PRS, Generalized Anxiety-PRS and Schizophrenia-PRS predicted the high severity PTSD trajectory class (ORs 1.21-1.28, adjusted p < 0.05). Finally, PRSs prediction was independent of 9/11 exposure severity and jointly accounted for 3.7 times more variance in PTSD symptoms than the exposure severity. CONCLUSIONS: Psychiatric PRSs prospectively predicted WTC-related PTSD lifetime diagnosis, average symptom severity, and 18-year trajectory in responders to 9/11 disaster. Jointly, PRSs were more predictive of subsequent PTSD than the exposure severity. In the future, PRSs may help identify at-risk responders who might benefit from targeted prevention approaches.

Discovery and replication of blood-based proteomic signature of PTSD in 9/11 responders.

Proteomics provides an opportunity to develop biomarkers for the early detection and monitoring of post-traumatic stress disorder (PTSD). However, research to date has been limited by small sample sizes and a lack of replication. This study performed Olink Proseek Multiplex Platform profiling of 81 proteins involved in neurological processes in 936 responders to the 9/11 disaster (mean age at blood draw = 55.41 years (SD = 7.93), 94.1% white, all men). Bivariate correlations and elastic net regressions were used in a discovery subsample to identify concurrent associations between PTSD symptom severity and the profiled proteins, and to create a multiprotein composite score. In hold-out subsamples, nine bivariate associations between PTSD symptoms and differentially expressed proteins were replicated: SKR3, NCAN, BCAN, MSR1, PVR, TNFRSF21, DRAXIN, CLM6, and SCARB2 (|r| = 0.08-0.17, p < 0.05). There were three replicated bivariate associations between lifetime PTSD diagnosis and differentially expressed proteins: SKR3, SIGLEC, and CPM (OR = 1.38-1.50, p < 0.05). The multiprotein composite score retained 38 proteins, including 10/11 proteins that replicated in bivariate tests. The composite score was significantly associated with PTSD symptom severity (ß = 0.27, p < 0.001) and PTSD diagnosis (OR = 1.60, 95% CI: 1.17-2.19, p = 0.003) in the hold-out subsample. Overall, these findings suggest that PTSD is characterized by altered expression of several proteins implicated in neurological processes. Replicated associations with TNFRSF21, CLM6, and PVR support the neuroinflammatory signature of PTSD. The multiprotein composite score substantially increased associations with PTSD symptom severity over individual proteins. If generalizable to other populations, the current findings may inform the development of PTSD biomarkers.

Longitudinal associations between PTSD and sleep disturbances among World Trade Center responders.

OBJECTIVE/BACKGROUND: Post-traumatic stress disorder (PTSD) is characterized by substantial disruptions in sleep quality, continuity, and depth. Sleep problems also may exacerbate PTSD symptom severity. Understanding how PTSD and sleep may reinforce one another is critical for informing effective treatments. PATIENTS/METHODS: In a sample of 452 World Trade Center 9/11 responders (mean age = 55.22, 89.4% male, 66.1% current or former police), we examined concurrent and cross-lagged associations between PTSD symptom severity, insomnia symptoms, nightmares, and sleep quality at 3 time points ∼1 year apart. Data were analyzed using random intercept cross-lagged panel models. RESULTS: PTSD symptom severity and sleep variables were relatively stable across time (intraclass correlation coefficients: 0.63 to 0.84). Individuals with more insomnia symptoms, more nightmares, and poorer sleep quality had greater PTSD symptom severity, on average. Within-person results revealed that greater insomnia symptoms and nightmares at Time 1 were concurrently associated with greater PTSD symptoms at Time 1. Insomnia symptoms were also concurrently associated with PTSD symptoms at Times 2 and 3, respectively. Cross-lagged and autoregressive results revealed that PTSD symptoms and nightmares predicted nightmares at the next timepoint. CONCLUSIONS: Overall, results suggest PTSD and sleep problems may be linked at the same point in time but may not always influence each other longitudinally. Further, individuals who experience more sleep disturbances on average may suffer from more debilitating PTSD. Evidence-based treatments for PTSD may consider incorporating treatment of underlying sleep disturbances and nightmares.

Is personality stable and symptoms fleeting? A longitudinal comparison in adolescence.

Few investigations have directly compared personality and internalizing symptoms stability within the same sample and have not included personality facets. This study examined rank-order stability and mean-level change of Big Five domains, facets of neuroticism and extraversion, and internalizing symptoms in a sample of 550 adolescent females. Personality and symptoms were assessed every nine months for three years. Three year rank-order stability was higher for personality domains and facets compared to symptoms. Notable exceptions included lower stability of depressivity and positive emotionality facets. Facets and symptoms showed similar mean level change. Overall, we observed modest and variable temporal differences between symptoms and traits; symptoms exhibited high rank-order stability and low mean-level change, but domains and facets were generally more stable.

Association of attention and memory biases for negative stimuli with post-traumatic stress disorder symptoms.

Cognitive models have highlighted the role of attentional and memory biases towards negatively-valenced emotional stimuli in the maintenance of post-traumatic stress disorder (PTSD). However, previous research has focused mainly on attentional biases towards distracting (task-irrelevant) negative stimuli. Furthermore, attentional and memory biases have been examined in isolation and the links between them remain underexplored. We manipulated attention during encoding of trauma-unrelated negative and neutral words and examined the differential relationship of their encoding and recall with PTSD symptoms. Responders to the World Trade Center disaster (N = 392) performed tasks in which they read negative and neutral words and reported the color of another set of such words. Subsequently, participants used word stems to aid retrieval of words shown earlier. PTSD symptoms were associated with slower response times for negative versus neutral words in the word-reading task (r = 0.170) but not color-naming task. Furthermore, greater PTSD symptom severity was associated with more accurate recall of negative versus neutral words, irrespective of whether words were encoded during word-reading or color-naming tasks (F = 4.11, p = 0.044, ηp2 = 0.018). Our results show that PTSD symptoms in a trauma-exposed population are related to encoding of trauma-unrelated negative versus neutral stimuli only when attention was voluntarily directed towards the emotional aspects of the stimuli and to subsequent recall of negative stimuli, irrespective of attention during encoding.

The Role of Personality in the Mental and Physical Health of World Trade Center Responders: Self- versus Informant-Reports.

Personality is linked to important health outcomes, but most prior studies have relied on self-reports, making it possible that shared-method variance explains the associations. The present study examined self- versus informant-reports of personality and multi-method outcomes. World Trade Center (WTC) responders and informants, 283 pairs, completed five-factor model personality measures and multi-method assessments of stressful events, functioning, mental disorders, 9/11-related treatment costs, BMI, and daily activity across three years. Self-reports were uniquely related to stressful events and functioning. Both self-reports and informant-reports showed incremental validity over one another for mental disorder diagnoses and treatment costs. For objective outcomes daily activity and BMI, informant-reports showed incremental validity over self-reports, accounting for all self-report variance and more. The findings suggest that informant-reports of personality provide better validity for objective health outcomes, which has implications for understanding personality and its role in mental and physical health.

Artificial intelligence language predictors of two-year trauma-related outcomes.

BACKGROUND: Recent research on artificial intelligence has demonstrated that natural language can be used to provide valid indicators of psychopathology. The present study examined artificial intelligence-based language predictors (ALPs) of seven trauma-related mental and physical health outcomes in responders to the World Trade Center disaster. METHODS: The responders (N = 174, Mage = 55.4 years) provided daily voicemail updates over 14 days. Algorithms developed using machine learning in large social media discovery samples were applied to the voicemail transcriptions to derive ALP scores for several risk factors (depressivity, anxiousness, anger proneness, stress, and personality). Responders also completed self-report assessments of these risk factors at baseline and trauma-related mental and physical health outcomes at two-year follow-up (including symptoms of depression, posttraumatic stress disorder, sleep disturbance, respiratory problems, and GERD). RESULTS: Voicemail ALPs were significantly associated with a majority of the trauma-related outcomes at two-year follow-up, over and above corresponding baseline self-reports. ALPs showed significant convergence with corresponding self-report scales, but also considerable uniqueness from each other and from self-report scales. LIMITATIONS: The study has a relatively short follow-up period relative to trauma occurrence and a limited sample size. CONCLUSIONS: This study shows evidence that ALPs may provide a novel, objective, and clinically useful approach to forecasting, and may in the future help to identify individuals at risk for negative health outcomes.