Search

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 Irritable mood is a transdiagnostic clinical feature that is present in multiple psychiatric disorders. Although irritability is frequently examined as a unitary construct, two dimensions of irritability, tonic (i.e., irritable mood) and phasic (i.e., temper outbursts), have been hypothesized. However, few studies have examined whether tonic and phasic irritability are empirically separable and predict different forms of psychopathology. METHODS We utilized data from a longitudinal study of a community sample of 550 girls (age 13.5-15.5 years) followed at 9-month intervals for 3 years. We conducted exploratory factor analysis (EFA) using items from three self-report inventories: the International Personality Item Pool Anger scale, Temperament and Affectivity Inventory Anger scale, and Buss-Perry Aggression Questionnaire Anger scale. RESULTS The EFA identified dimensions that were consistent with tonic and phasic irritability. Tonic irritability at baseline independently predicted the development of depressive disorders and generalized anxiety disorder (GAD) in subsequent waves. Phasic irritability independently predicted a decreased probability of GAD, but an increased probability of oppositional defiant, conduct, and substance use disorder, and greater risky sexual behavior and relational aggression during the follow-up. CONCLUSIONS Tonic and phasic irritability appear to be separable constructs with unique implications for later psychopathology and related behavior among adolescent girls. It is important to consider this distinction in research on the etiology and pathophysiology of irritability and developing effective treatments.

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 rankorder 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.

Objective Adolescent nonsuicidal self-injury (NSSI) is a significant risk factor for suicidal behavior and an important clinical marker of psychopathology. NSSI is especially common in adolescent girls. A number of psychosocial correlates of adolescent NSSI have been identified, including problems characterized by disinhibition and negative affectivity. However, it is unknown whether these characteristics prospectively predict first-onset NSSI, limiting our understanding of its etiology and prevention. The current study addresses this gap in the literature. Method Participants in the Adolescent Development of Emotion and Personality Traits (ADEPT) project at Stony Brook University who had not experienced NSSI at baseline (462 girls, mean age = 14.39 years, SD = 0.62 years) completed baseline measures of hypothesized risk factors related to problems with disinhibition and negative affectivity, including adolescent psychopathology, personality and clinical traits, and parental psychopathology. First onset of NSSI was monitored at 9-month intervals by in-person and telephone interviews over the next 36 months. Results There were 42 first onsets of NSSI (9.1%) in the 3 years since baseline. First-onset NSSI was independently predicted by adolescents’ low conscientiousness, high avoidance, and parental substance abuse at baseline. The composite risk index predicting first-onset NSSI demonstrated good accuracy for identifying girls who will start self-injuring (area under the curve = 0.78, sensitivity = 0.85, specificity = 0.57). Conclusion These results highlight the role of disinhibition and avoidance in the development of NSSI. The risk index predicting NSSI onset may help to guide the design and application of novel interventions to prevent this condition in adolescent girls.

Mismatch negativity (MMN) amplitude has been widely shown to be diminished in schizophrenia and, more recently, in other psychotic disorders. Although there is considerable evidence linking MMN reduction to cognitive and functional deficits in schizophrenia, there is little evidence of associations with specific psychotic symptoms. Further, it is unclear if MMN reductions relate to specific symptoms, cognitive, and functional deficits transdiagnostically across different psychotic disorders. The present study examines MMN amplitude in a large cohort of cases diagnosed with psychotic disorders including schizophrenia and schizoaffective disorder (N = 116); bipolar disorder and major depressive disorder (N = 75); and other psychotic disorders (N = 25), as well as individuals with no psychotic disorder diagnoses (N = 248). Furthermore, we examined the association of MMN with symptoms, cognitive functioning, and real-world functioning to determine whether these relationships differ by diagnosis. Results showed that MMN amplitude was reduced in cases overall compared to never-psychotic individuals, with no differences between psychotic disorders. Furthermore, there were transdiagnostic associations of reduced duration MMN (MMN-D) with worse auditory hallucinations (r = .14) and disorganization (r = .14), frequency MMN (MMN-F) with real-word functioning (r = .20) and episodic memory (r = -.22), and both components with executive functioning (MMN-D: r = -.17; MMN-F: r = -.15). Our findings relating MMN reductions with cognitive and real-world functioning replicate earlier research in schizophrenia and extend these relationships to other psychotic disorders. Furthermore, our correlations with MMN-D are consistent with computational modeling research and theoretical proposals that view MMN reduction, cognitive dysfunction, and psychotic symptoms as reflecting underlying predictive coding deficits. However, differences in relationships with MMN-F suggest that additional work is warranted on this topic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objective:At first hospitalization, a long duration of untreated psychosis (DUP) predicts illness severity and worse treatment outcomes. The mechanism of this association, however, remains unclear....

BackgroundRisk factors for depressive disorders (DD) change substantially over time, but the prognostic value of these changes remains unclear. Two basic types of dynamic effects are possible. The ‘Risk Escalation hypothesis’ posits that worsening of risk levels predicts DD onset above average level of risk factors. Alternatively, the ‘Chronic Risk hypothesis’ posits that the average level rather than change predicts first-onset DD.MethodsWe utilized data from the ADEPT project, a cohort of 496 girls (baseline age 13.5–15.5 years) from the community followed for 3 years. Participants underwent five waves of assessments for risk factors and diagnostic interviews for DD. For illustration purposes, we selected 16 well-established dynamic risk factors for adolescent depression, such as depressive and anxiety symptoms, personality traits, clinical traits, and social risk factors. We conducted Cox regression analyses with time-varying covariates to predict first DD onset.ResultsConsistently elevated risk factors (i.e. the mean of multiple waves), but not recent escalation, predicted first-onset DD, consistent with the Chronic Risk hypothesis. This hypothesis was supported across all 16 risk factors.ConclusionsAcross a range of risk factors, girls who had first-onset DD generally did not experience a sharp increase in risk level shortly before the onset of disorder; rather, for years before onset, they exhibited elevated levels of risk. Our findings suggest that chronicity of risk should be a particular focus in screening high-risk populations to prevent the onset of DDs. In particular, regular monitoring of risk factors in school settings is highly informative.

Background Evidence supports the notion that early-life stress and trauma impact cortical development and increase vulnerability to depression. However, it remains unclear whether common stressful life events in community-dwelling adolescents have similar consequences for cortical development. Methods A total of 232 adolescent girls (mean age 15.29 ± 0.65 years) were assessed with the Stressful Life Events Schedule (a semistructured interview of stressors in the previous 9 months) and underwent a magnetic resonance imaging scan. FreeSurfer 5.3.0 was used to perform whole-brain surface-based morphometry. Dysphoria was assessed at the time of imaging and prospectively at three 9-month follow-up appointments using the Inventory of Depression and Anxiety Symptoms II. Results At least one stressful life event was reported in 90% of the adolescent participants during the 9 months preceding imaging. Greater burden of recent life stress was associated with less left precuneus and left postcentral cortical thickness and smaller left superior frontal and right inferior parietal volume (all p Conclusions Consistent with evidence from imaging studies of trauma-exposed youths and preclinical stress models, a heavy burden of recent common life stress in community-dwelling adolescent girls was associated with altered frontal/parietal cortical morphology. Stress-linked precuneus cortical thickness represents a candidate prospective biomarker of adolescent depression.

Salivary markers of immune function are increasingly commonly used in studies of human health. Yet, few studies have examined the short-term or long-term reliability or stability of these biomarkers, making their measurement properties unclear. We addressed this issue in the present study by collecting two saliva samples, two hours apart, from 426 adolescent girls during a baseline laboratory visit. Then, eighteen months later, we collected the same samples again from a subset of these participants (n = 113). The correlations between the two samples collected at each session were generally high (mean r = 0.67). In contrast, although single saliva samples were only weakly correlated across 18 month (mean rs = 0.18), averaging the two quantifications within a session considerably improved the reliability (mean r = 0.27). In short, salivary immune markers exhibited strong short-term test-retest correlations, and averaging across multiple assessments notably improved long-term test-retest correlations. Additional research is needed to establish the health relevance and mechanisms underlying these potentially useful, non-invasive biomarkers.

Background Research on a putative link between apolipoprotein-e4 allele (APOE-e4) and schizophrenia has been inconclusive. However, prior studies have not investigated the association between APOE-e4 and symptom trajectories, nor has the existing literature taken into account the potentially moderating effect of age in genetic association studies. Methods The association between APOE-e4 and four symptom dimensions was investigated in a longitudinal study of 116 individuals with schizophrenia initially assessed during their first admission for psychosis and evaluated five times over the following 20 years. A meta-analysis identified 29 case-control studies of APOE-e4 allele frequency in schizophrenia, which were analyzed using random-effects meta-regression to test the potentially moderating effect of age. Results Longitudinal models identified a specific association between APOE-e4 and symptom trajectories, showing that APOE-e4 portends worsening severity of hallucinations and delusions in late adulthood among people with schizophrenia, at a rate of a 0.46 standard deviation increase per decade. Meta-analysis showed a significant effect of age: the association between APOE-e4 and schizophrenia was not detectable in younger people but became pronounced with age, such that APOE-e4 increased the odds of diagnosis by 10% per decade. Conclusions Taken together, the meta-analysis and longitudinal analysis implicate APOE-e4 as an age-related risk factor for worsening hallucinations and delusions, and suggest APOE-e4 may play an age-mediated pathophysiological role in schizophrenia. The presence of an APOE-e4 allele may also identify a subgroup of patients who require intensive monitoring and additional targeted interventions, especially in mid-to late-life.

Mismatch negativity (MMN) amplitude is reliably reduced in psychotic disorders. While several studies have examined this effect in first-degree relatives of individuals with schizophrenia, few have sought to quantify deficits in relatives of individuals with other psychotic disorders. While some conclude that, compared to healthy subjects, first-degree relatives of schizophrenia show reduced MMN, others contradict this finding. Furthermore, though MMN is often shown to be associated with cognitive impairments and clinical symptoms in psychotic disorders, to our knowledge no studies have sought to fully examine these relationships in studies of first-degree relatives. The present study sought to clarify the extent of MMN amplitude reductions in a large sample of siblings of individuals with diverse psychotic disorders (n = 67), compared to probands with psychosis (n = 221) and never psychotic comparison subjects (n = 251). We further examined associations of MMN amplitude with cognition and schizotypal symptoms across these groups. We found that MMN amplitude was intact in siblings compared to probands. MMN amplitude was associated with cognition and schizotypal symptoms dimensionally across levels of familial risk. The present results imply that MMN reductions do not reflect genetic risk for psychotic disorders per se, and instead emerge as a result of, or in conjunction with, clinical features associated with psychosis. Such findings carry important implications for the utility of MMN amplitude as an indicator of inherited risk, and suggest that this component may be best conceptualized as an endophenotype for clinical symptoms and cognitive impairments, rather than risk for psychosis per se.

Past psychiatric diagnoses are central to patient case formulation and prognosis. Recently, alternative classification models such as the Hierarchical Taxonomy of Psychopathology (HiTOP) proposed to assess traits to predict clinically relevant outcomes. In the current study, we directly compared personality traits and past diagnoses as predictors of future mental health and functioning in three independent, prospective samples. Regression analyses found that personality traits significantly predicted future first onsets of psychiatric disorders (change in [∆] R2 = .06–.15), symptom chronicity (∆ R2 = .03–.06), and functioning (∆ R2 = .02–.07), beyond past and current psychiatric diagnoses. Conversely, past psychiatric diagnoses did not provide an incremental prediction of outcomes when personality traits and other concurrent predictors were already included in the model. Overall, personality traits predicted a variety of outcomes in diverse settings beyond diagnoses. Past diagnoses were generally not informative about future outcomes when personality was considered. Together, these findings support the added value of personality traits assessment in case formulation, consistent with the HiTOP model.

Highlights • A clinically relevant method of predicting MDD treatment efficacy is needed. • The present investigation applies dynamic FDG-PET using blood as a reference. • FDG-PET was assessed in the raphe nuclei, ventral prefrontal cortex and insula. • Regional pretreatment metabolism does not relate to symptom severity decrease. • Predictive FDG-PET signal may not be generalizable to heterogeneous MDD cohorts., There is critical need for a clinically useful tool to predict antidepressant treatment outcome in major depressive disorder (MDD) to reduce suffering and mortality. This analysis sought to build upon previously reported antidepressant treatment efficacy prediction from 2-[18F]-fluorodeoxyglucose - Positron Emission Tomography (FDG-PET) using metabolic rate of glucose uptake (MRGlu) from dynamic FDG-PET imaging with the goal of translation to clinical utility. This investigation is a randomized, double-blind placebo-controlled trial. All participants were diagnosed with MDD and received an FDG-PET scan before randomization and after treatment. Hamilton Depression Rating Scale (HDRS-17) was completed in participants diagnosed with MDD before and after 8 weeks of escitalopram, or placebo. MRGlu (mg/(min*100 ml)) was estimated within the raphe nuclei, right insula, and left ventral Prefrontal Cortex in 63 individuals. Linear regression was used to examine the association between pretreatment MRGlu and percent decrease in HDRS-17. Additionally, the association between percent decrease in HDRS-17 and percent change in MRGlu between pretreatment scan and post-treatment scan was examined. Covariates were treatment type (SSRI/placebo), handedness, sex, and age. Depression severity decrease (n = 63) was not significantly associated with pretreatment MRGlu in the raphe nuclei (β = -2.61e-03 [-0.26, 0.25], p = 0.98), right insula (β = 0.05 [-0.23, 0.32], p = 0.72), or ventral prefrontal cortex (β = 0.06 [-0.23, 0.34], p = 0.68) where β is the standardized estimated coefficient, with a 95% confidence interval, or in whole brain voxelwise analysis (family-wise error correction, alpha = 0.05). MRGlu percent change was not significantly associated with depression severity decrease (n = 58) before multiple comparison correction in the RN (β = 0.20 [-0.07, 0.47], p = 0.15), right insula (β = 0.24 [-0.03, 0.51], p = 0.08), or vPFC (β = 0.22 [-0.06, 0.50], p = 0.12). We propose that FDG-PET imaging does not indicate a clinically relevant biomarker of escitalopram or placebo treatment response in heterogeneous major depressive disorder cohorts. Future directions include focusing on potential biologically-based subtypes of major depressive disorder by implementing biomarker stratified designs.

Background: Mismatch negativity (MMN) amplitude is reliably reduced in psychotic disorders. While several studies have examined this effect in first-degree relatives of individuals with schizophrenia, few have sought to quantify deficits in relatives of individuals with other psychotic disorders. While some studies conclude that, compared to healthy subjects, first-degree relatives of schizophrenia show reduced MMN, others contradict this finding, a discrepancy which extends to two recent meta-analyses. Furthermore, though MMN is often shown to be associated with cognitive impairments and clinical symptoms in psychotic disorders, to our knowledge no studies have sought to examine these relationships in studies of first-degree relatives. Method: The present study sought to clarify the extent of MMN amplitude reductions in a large sample of siblings of individuals with diverse psychotic disorders (n=65), compared to cases with psychosis (n=220) and never psychotic comparison subjects (n=252). We further examined associations of MMN amplitude with cognition and schizotypal symptoms across these groups. Results: We found that MMN amplitude was intact in siblings compared to cases with psychosis. MMN amplitude was associated with cognition and schizotypal symptoms dimensionally across levels of familial risk. Conclusions: The present results imply that MMN amplitude reductions emerge as a result of, or in conjunction with, clinical features associated with psychosis. Such findings carry important implications for the utility of MMN amplitude as an indicator of inherited risk, and suggest that this component may be best conceptualized as a marker for clinical symptoms and cognitive impairments, rather than risk for psychosis per se.

Background Adolescent-onset depressive disorders (DDs) are associated with deficits in the regulation of negative affect across modalities (self-report, behavioral paradigms, and neuroimaging), which may manifest prior to first-onset DDs. Whether the neurocircuitry governing emotional regulation predates DDs is unclear. This study tested whether a critical pathway for emotion regulation (rostral anterior cingulate cortex–amygdala structural connectivity) predicts first-onset DDs in adolescent females. Methods Diffusion tensor imaging data were acquired on adolescent females (n = 212) without a history of DDs and the cohort was reassessed for first-onset DDs over the next 27 months. Results A total of 26 girls developed first onsets of DDs in the 27 months after imaging. Multivariate logistic regression showed that lower weighted average fractional anisotropy of uncinate fasciculus tracts between the rostral anterior cingulate cortex and amygdala prospectively predicted first onset of DDs (adjusted odds ratio = 0.44, p = .005), above and beyond established risk factors including baseline depression symptom severity, history of anxiety disorders, parental history of depression, parental education, and age. Conclusions This study provides evidence for the first time showing that aberrant structural connectivity between the rostral anterior cingulate cortex and amygdala prospectively predates first onset of DDs in adolescent females. These results highlight the importance of a well-established neural circuit implicated in the regulation of negative affect as a likely etiological factor and a promising target for intervention and prevention of DDs.

Background: First onsets of depression are especially common in adolescent females and often develop into chronic/recurrent illness. Surprisingly few studies have comprehensively evaluated multiple domains of etiologically-informative risk factors for first onset in adolescents from the community. We investigated whether clinical, cognitive, personality, interpersonal, and biological risk factors prospectively predict a first onset of depressive disorder (DD), and of DD with a chronic/recurrent course, in a community sample of adolescent girls. Methods: 479 girls (13.5–15.5 years) with no history of DD completed baseline assessments of risk factors and five diagnostic assessments over 3 years. Baseline measures were analyzed separately and jointly to prospectively predict first-onset DD and first-onset chronic/recurrent DD. Results: Most risk factors predicted first-onset DD (n = 93), including depressive symptoms, anxiety disorders, rumination, personality traits, blunted neural response (late positive potential [LPP]) to unpleasant pictures, peer victimization, parental criticism, and parental mood disorder. Depressive symptoms, rumination, parental mood disorder, and parental criticism were independently associated with first onsets. Nearly all measures, including a blunted neural response to rewards (reward positivity [RewP]), also predicted first-onset chronic/recurrent DD (n = 52), with depressive symptoms, low extraversion, poor peer relationships, and blunted RewP emerging as independent risk factors. Limitations: This study focused on adolescent females and therefore does not provide information on males. Conclusions: Multiple domains of risk factors in early adolescence are prospectively associated with first-onset DD and chronic/recurrent DD. A smaller subset of risk factors uniquely contributing to first onsets may represent core vulnerabilities for adolescent-onset depression and promising prevention targets.

BackgroundPerformance monitoring entails rapid error detection to maintain task performance. Impaired performance monitoring is a candidate pathophysiological process in psychotic disorders, which may explain the broader deficit in executive function and its known associations with negative symptoms and poor functioning. The current study models cross-sectional pathways bridging neurophysiological measures of performance monitoring with executive function, symptoms, and functioning.MethodsData were from the 20-year assessment of the Suffolk County Mental Health Project. Individuals with psychotic disorders (N = 181) were originally recruited from inpatient psychiatric facilities. Data were also collected from a geographically and demographically matched group with no psychosis history (N = 242). Neural measures were the error-related negativity (ERN) and error positivity (Pe). Structural equation modeling tested mediation pathways.ResultsBlunted ERN and Pe in the clinical cohort related to impaired executive function (r = 0.26–0.35), negative symptom severity (r = 0.17–0.25), and poor real-world functioning (r = 0.17–0.19). Associations with executive function were consistent across groups. Multiple potential pathways were identified in the clinical cohort: reduced ERN to inexpressivity was mediated by executive function (β = 0.10); reduced Pe to global functioning was mediated by executive function and avolition (β = 0.10).ConclusionsThis supports a transdiagnostic model of psychotic disorders by which poor performance monitoring contributes to impaired executive function, which contributes to negative symptoms and poor real-world functioning. If supported by future longitudinal research, these pathways could inform the development of targeted interventions to address cognitive and functional deficits that are central to psychotic disorders.

Individual with substance use disorders have well-recognized impairments in cognitive control, including in behavioral adaptation after mistakes. One way in which this impairment manifests is via diminished post-error slowing, the increase in reaction time following a task-related error that is posited to reflect cautionary or corrective behavior. Yet, in the substance use disorder literature, findings with regard to post-error slowing have been inconsistent, and thus could benefit from quantitative integration. Here, we conducted a meta-analysis of case-control studies examining post-error slowing in addiction. Twelve studies with 15 unique comparisons were identified, comprising 567 substance users and 384 healthy controls across three broad types of inhibitory control paradigms (go-no/go, conflict resolution, and stop signal tasks, respectively). Results of the random-effects meta-analysis revealed a moderate group difference across all studies (Cohen's d = 0.31), such that the individuals with substance use disorder had diminished post-error slowing compared with controls. Despite this omnibus effect, there was also large variability in the magnitude of the effects, explained in part by differences between studies in task complexity. These findings suggest that post-error slowing may serve as a promising and easy-to-implement measure of cognitive control impairment in substance use disorder, with potential links to aberrant brain function in cognitive control areas such as the anterior cingulate cortex.

OBJECTIVE: An increased neural response to making mistakes has emerged as a potential biomarker of anxiety across development. The error-related negativity is an event-related potential elicited when people make mistakes on simple laboratory-based reaction time tasks that has been associated with risk for anxiety. The present study examined whether the error-related negativity prospectively predicted the first onset of generalized anxiety disorder (GAD) over 1.5 years in adolescent girls. METHODS: The sample included 457 girls between the ages of 13.5 and 15.5 years, with no history of GAD. At baseline, the error-related negativity was measured using a flankers task. Psychiatric history of the adolescent and biological parent were assessed with diagnostic interviews, and the adolescent completed a self-report questionnaire regarding anxiety symptoms. Approximately 1.5 years later, adolescents completed the same interview. RESULTS: An increased neural response to errors at baseline predicted first-onset GAD over 1.5 years. The error-related negativity was a significant predictor independent of other prominent risk factors, including baseline anxiety and depression symptoms and parental lifetime psychiatric history. Jointly the error-related negativity and social anxiety symptoms provided the greatest power for predicting first-onset GAD. CONCLUSIONS: The current study provides evidence for the utility of the error-related negativity as a biomarker of risk for GAD during a key developmental period.

People diagnosed with schizophrenia and other psychoses demonstrate impaired neuropsychological performance. Their unaffected siblings exhibit mild impairments relative to unrelated controls, suggesting genetic and shared environmental risk for psychosis account for some portion of cognitive impairments observed in cases. However, most sibling studies were conducted early in illness course. Studying cases and unaffected siblings later in life is valuable because diagnostic misclassification is common early in illness, possibly leading to spurious conclusions. This study compared neuropsychological performance of individuals with psychotic disorders (schizophrenia and other psychoses), their unaffected siblings, and controls. Assessments were conducted 20 years after case enrollment in the Suffolk County Mental Health Project, when siblings and controls were added to the protocol. Results showed individuals with schizophrenia and other psychoses performed worse than their matched siblings across domains. Relative to controls, siblings of participants with schizophrenia showed mild deficits in executive function and processing speed, while no significant differences were observed between siblings of those with other psychoses and controls. These findings suggest pre- and post-onset factors impact cognitive deficits in psychosis, but pre-onset factors are more salient in schizophrenia. Additionally, schizophrenia and other psychoses exist on a neurodevelopmental continuum, with schizophrenia being a more severe manifestation.

Purpose The aim of present study was to test the diathesis-stress model of depression using baseline cortisol, prospective assessment of depression symptoms, and stressful life events. Methods The sample consisted of 527 adolescent girls aged 13.5–15.5 years without major depressive disorder. At baseline, saliva samples were collected at waking, 30 minutes after waking, and 8 p.m. on 3 consecutive days. Diurnal cortisol was indexed by cortisol awakening response (CAR) and area under the curve with respect to ground (AUCg). Stressful events during the preceding interval and current depressive symptoms were assessed 18 months following baseline. Results Stressful events and the interaction of CAR or AUCg with stressful events predicted depressive symptoms at 18 months, even after controlling for baseline depressive symptoms. Specifically, in the face of high levels of stress, baseline blunted CAR or smaller AUCg were associated with future depressive symptoms. This was more apparent for CAR than AUCg. The effect was reversed at low levels of stress, with heightened CAR associated with more severe depressive symptoms. Conclusions Blunted CAR and less daily cortisol output at baseline appear to accentuate the depressogenic effects of stressful events after 18 months, consistent with the diathesis-stress model of hypothalamic-pituitary-adrenal axis function in depression.

There is substantial evidence that personality traits, such as self-criticism and dependency, predict the development of depression and anxiety symptoms, as well as depressive episodes. However, it is unknown whether self-criticism and dependency predict the first onset of depressive and anxiety disorders, and unclear how to characterize dynamic mechanisms by which these traits, stressful life events, and psychopathology influence one another over time. In this study, 550 female adolescents were assessed at baseline, 528 and 513 of whom were assessed again at Waves 2 and 3, respectively, over the course of 18 months. Self-criticism and dependency were assessed with self-report inventories, depressive and anxiety disorders were assessed with diagnostic interviews, and stressful life events were assessed via semistructured interview. Logistic regression analyses showed that self-criticism and dependency significantly predicted the first onset of nearly all depressive and anxiety disorders (significant polychoric rs ranged from .15-.42). Subsequent path analyses focused on prediction of depression, and supported several conceptual models of personality-stress-psychopathology relationships. In particular, Personality × Stress interactions were evident for both dependency and self-criticism. These interactions took the form of dual vulnerability, such that stressful life events predicted an increased probability of a later depressive disorder only at low levels of each trait. Results suggest the traits of self-criticism and dependency are important to consider in understanding who is at risk for depressive and anxiety disorders. (PsycINFO Database Record

Background Major depressive disorder is a leading cause of disability worldwide; however, little is known about pathological mechanisms involved in its development. Research in adolescent depression has focused on reward sensitivity and striatal mechanisms implementing it. The contribution of loss sensitivity to future depression, as well as the orbitofrontal cortex (OFC) mechanisms critical for processing losses and rewards, remains unexplored. Furthermore, it is unclear whether OFC functioning interacts with familial history in predicting future depression. Methods In this longitudinal study, we recorded functional magnetic resonance imaging data while 229 female adolescents with or without parental history of depression completed a monetary gambling task. We examined whether OFC blood oxygen level–dependent response and functional connectivity during loss and win feedback was associated with depression symptoms concurrently and prospectively (9 months later) and whether this relationship was moderated by parental history of depression. Results Reduced OFC response during loss was associated with higher depression symptoms concurrently and prospectively, even after controlling for concurrent depression, specifically in adolescents with parental history of depression. Similarly, increased OFC-posterior insula connectivity during loss was associated with future depression symptoms, but this relationship was not moderated by parental history of depression. Conclusions This study provides the first evidence for loss-related alterations in OFC functioning and its interaction with familial history of depression as possible mechanisms in the development of depression. While the current functional magnetic resonance imaging literature has mainly focused on reward, the current findings underscore the need to include prefrontal loss processing in existing developmental models of depression.

BackgroundIndividual differences in neuroticism, extraversion, and conscientiousness are associated with, and may predict onset of, internalizing disorders. These general traits can be parsed into facets, but there is a surprising paucity of research on facet risk for internalizing disorders. We examined general traits and facets of neuroticism, extraversion, and conscientiousness in predicting first onsets of depressive and anxiety disorders.MethodsA community sample of 550 adolescent females completed general and facet-level personality measures and diagnostic interviews. Interviews were re-administered 18 months later.ResultsFirst onsets of depressive disorders were predicted by neuroticism, extraversion, and conscientiousness. Facets predicting first onset of depression included depressivity (neuroticism facet) and lower positive emotionality and sociability (extraversion facets). First onsets of generalized anxiety disorder (GAD) were predicted by neuroticism, and particularly the facet of anxiousness. First onsets of social phobia were predicted at the facet level by anxiousness. First onsets of specific phobia were predicted by neuroticism, low conscientiousness, and all neuroticism facets. In multivariate analyses, first onsets of depression were uniquely predicted by depressivity, and onsets of GAD and social phobia were uniquely predicted by anxiousness over and above the general trait of neuroticism.ConclusionsGeneral traits predict first onsets of depressive and anxiety disorders. In addition, more specific associations are evident at the facet level. Facets can refine our understanding of the links between personality and psychopathology risk, and provide finer-grained targets for personality-informed interventions.

Understanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnosis and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically- and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms (β = 0.21), greater illness severity (β = 0.28), and worse cognition (β = −0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20 years (AUC = 0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a tool for diagnosis and treatment planning.

Effective suicide prevention is hindered by a limited understanding of the natural progression and neurobiology of the suicidal process. Our objective was to characterize the duration of the suicidal process and its relation to possible determinants: time judgment and cognitive impulsivity. In four groups of adults of both sexes including recent suicide attempters (n=57), suicidal ideators (n=131), non-suicidal depressed controls (n=51) and healthy controls (n=48) we examined time estimation and production, impulsivity and other cognitive variables. Duration of the suicidal process was recorded in suicide attempters. The suicide process duration, suicide contemplation and action intervals, had a bimodal distribution, ~40% of attempters took less than 5 minutes from decision to attempt. Time slowing correlated negatively with the suicidal action interval (time from the decision to kill oneself to suicide attempt) (p=.003). Individuals with suicide contemplation interval shorter than three hours showed increased time slowing, measured as shorter time production at 35 seconds (p=.011) and 43 seconds (p=.036). Delay discounting for rewards correlated with time estimation at 25 minutes (p=0.02) and 90 seconds (p=.01). Time slowing correlated positively with suicidal ideation severity, independently of depression severity (p

BackgroundClassic conceptual frameworks explaining the relationship of personality traits to depression include the precursor and predisposition models. The former hypothesizes that depression is predicted by traits alone whereas the latter hypothesizes that stress, together with personality, predicts depression. Dynamic vulnerability models (DVM) expand on these perspectives by incorporating fluctuations in personality over time. The stress generation model provides an alternative view, positing that depression generates stress, creating a self-perpetuating cycle. However, these conceptual models are rarely directly compared.MethodWe tested these models, focusing on neuroticism and stressful life events that the participant may have contributed to, using path analysis in a sample of 550 never-depressed, adolescent females assessed five times over 3 years.ResultsA dynamic precursor model with stress generation was best supported. For the precursor component, neuroticism predicted subsequent depression across four assessment intervals. For the dynamic trait component, stressful life events predicted subsequent neuroticism at three of four intervals. Finally, in line with stress generation, depression consistently predicted subsequent stressful life events, and life events then predicted depression.ConclusionsFinding support for the DVM is noteworthy, as this is the first comprehensive test of this model. Moreover, results supported integrating stress generation with trait vulnerability. Continued use of integrated approaches and refining the statistical implementation of these theories is necessary to advance understanding of the development of depression.

Background Adolescence is characterized by affective and cognitive changes that increase vulnerability to depression, especially in females. Neurodevelopmental models attribute adolescent depression to abnormal responses in amygdala, striatum, and prefrontal cortex (PFC). We examined whether the strength of functional brain networks involving these regions predicts depression symptoms in adolescent females. Methods In this longitudinal study, we recorded resting-state functional connectivity (RSFC) in 174 adolescent females. Using a cross-validation strategy, we related RSFC profiles that included (a) a network consisting of amygdala, striatum, and PFC (within-circuit model), (b) connectivity of this network to the whole brain (extended-circuit model), and (c) a network consisting of the entire brain (whole-brain model) to depression symptoms assessed concurrently and 18 months later. Results In testing subsets, the within-circuit RSFC profiles were associated with depression symptoms concurrently and 18 months later, while the extended-circuit and whole-brain model did not explain any additional variance in depression symptoms. Connectivity related to anterior cingulate and ventromedial prefrontal cortex contributed most to the association. Conclusions Our results demonstrate that RSFC-based brain networks that include amygdala, striatum, and PFC are stable neural signatures of concurrent and future depression symptoms, representing a significant step toward identifying the neural mechanism of depression in adolescence.

BACKGROUND: Lithium, one of the few effective treatments for bipolar depression (BPD), has been hypothesized to work by enhancing serotonergic transmission. Despite preclinical evidence, it is unknown whether lithium acts via the serotonergic system. Here we examined the potential of serotonin transporter (5-HTT) or serotonin 1A receptor (5-HT(1A)) pre-treatment binding to predict lithium treatment response and remission. We hypothesized that lower pretreatment 5-HTT and higher pretreatment 5-HT(1A) binding would predict better clinical response. Additional analyses investigated group differences between BPD and healthy controls and the relationship between change in binding pre- to post-treatment and clinical response. 27 medication-free patients with BPD currently in a depressive episode received positron emission tomography (PET) scans using 5-HTT tracer [(11)C]DASB, a subset also received a PET scan using 5-HT(1A) tracer [(11)C]-CUMI-101 before and after eight weeks of lithium monotherapy. Metabolite-corrected arterial input functions were used to estimate binding potential, proportional to receptor availability. 14 patients with BPD with both [(11)C]DASB and [(11)C]-CUMI-101 pre-treatment scans and eight weeks of post treatment clinical scores were included in the prediction analysis examining the potential of either pre-treatment 5-HTT or 5-HT1A or the combination of both to predict post-treatment clinical scores. RESULTS: We found lower pre-treatment 5-HTT binding (p=0.003) and lower 5-HT(1A) binding (p=0.035) were both significantly associated with improved clinical response. Pre-treatment 5-HTT predicted remission with 71% accuracy (77% specificity, 60% sensitivity), while 5-HT(1A) binding was able to predict remission with 85% accuracy (87% sensitivity, 80% specificity). The combined prediction analysis using both 5-HTT and 5-HT(1A) was able to predict remission with 84.6% accuracy (87.5% specificity, 60% sensitivity). Additional analyses BPD and controls pre- or post-treatment, and the change in binding were not significant and unrelated to treatment response (p>0.05). CONCLUSIONS: Our findings suggest that while lithium may not act directly via 5-HTT or 5-HT(1A) to ameliorate depressive symptoms, pre-treatment binding may be a potential biomarker for successful treatment of BPD with lithium. CLINICAL TRIAL REGISTRATION: PET and MRI Brain Imaging of Bipolar Disorder Identifier: NCT01880957; URL: https://clinicaltrials.gov/ct2/show/NCT01880957

Blunted reward sensitivity and life stress are each depressogenic. Additionally, individuals with clinical and psychosocial vulnerabilities are prone to experience or evoke dependent life stressors (e.g., interpersonal conflict) that, in turn, increase depression risk. However, no previous study has investigated the role of neural vulnerability factors in generating life stress. Therefore, the current study investigated whether a neural measure of reward sensitivity prospectively predicts the generation of life stress, which in turn mediates effects of these neural processes on subsequent depression. Participants were 467 never-depressed adolescent girls. Using event-related potentials, neural sensitivity to the difference between monetary reward and loss (the Reward Positivity [RewP]) was assessed at baseline. Negative life events were assessed twice via interview over the ensuing 18 months, yielding an index of total life stress over the follow-up period. A self-report dimensional measure of depression symptoms was administered at baseline and follow-up. After accounting for baseline age, depression, and race, a blunted RewP predicted greater dependent, but not independent, life stress over the follow-up. Mediation analyses revealed a significant indirect effect of the RewP on follow-up depression through dependent, but not independent, life stress. Our results suggest that neural processing reward and loss plays a crucial role in depressogenic stress generation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

BackgroundThe effect of life stress on suicidal symptoms during adolescence is well documented. Stressful life events can trigger suicidality, but most adolescents are resilient and it is unclear which factors protect against the deleterious impact of stress. Social support is thought to be one such factor. Therefore, we investigated the buffering effect of specific sources of social support (parental and peer) on life stress (interpersonal and non-interpersonal) in predicting suicidal symptoms during adolescence. In order to test the specificity of this stress buffering, we also examined it with regard to dysphoric mood.MethodData come from the Adolescent Development of Emotions and Personality Traits (ADEPT) Project, a cohort of 550 adolescent females aged 13.5–15.5 recruited from Long Island. Self-reported social support, suicidality, and dysphoria were assessed at baseline and suicidality and dysphoria were assessed again at 9-month follow-up. Life stress was assessed by interview at the follow-up.ResultsHigh levels of parental support protected adolescent girls from developing suicidal symptoms following a stressor. This effect was less pronounced for peer support. Also, social support did not buffer the pathogenic effects of non-interpersonal stress. Finally, social support did not buffer the effect of life stress on dysphoric symptoms.ConclusionsAltogether, our results highlight a distinct developmental pathway for the development of suicidal symptoms involving parental support that differs from the development of dysphoria, and signifies the importance and specificity of social support in protecting against suicidality in adolescent girls.

Error processing is impaired in psychosis, and numerous event-related potential studies have found reductions in the error-related negativity (ERN) and, more recently, the error positivity (Pe). The stability of reduced ERN/Pe in psychosis, however, is unknown. In a previous cross-sectional report, reduced ERN was associated with negative symptom severity and reduced Pe with a diagnosis of schizophrenia versus other psychosis. Here, we test the stability of impaired error processing over a four-year follow-up and relationships with subdimensions of negative symptoms. The ERN and Pe were recorded from individuals with psychotic disorders twice: 79 individuals were assessed 15 years after first hospitalization, and 69 were assessed at 19 years; 59 (26 with schizophrenia, 33 with other psychotic disorders) had data at both assessments. At 19 years the Pe was blunted in schizophrenia. The ERN and Pe exhibited temporal stability over the four years (r=.59 and .60, respectively). Reduced ERN and Pe correlated with the negative symptom subdimensions of inexpressivity and avolition, respectively, and not with psychotic or disorganized symptoms. Moreover, 15-year ERN predicted an increase in inexpressivity by year 19. No evidence was found for the reverse: negative symptoms did not predict change in ERN/Pe. Similar to non-clinical samples, the ERN and Pe show impressive four-year stability in late-phase psychosis. The ERN and Pe are promising neural measures for capturing individual differences in psychotic disorders, particularly with regard to negative symptomatology. They may prove to be useful clinically for forecasting illness course and as treatment targets.

Offspring with maternal PTSD are at increased risk of developing PTSD themselves. Alterations in the hypothalamus-pituitary-adrenal (HPA) axis may play a role and have been noted in offspring, although evidence is mostly from adult offspring with PTSD symptoms themselves. The present study of adolescent girls (N=472) and their mothers (n = 18 with lifetime PTSD versus n = 454 with no PTSD) sought to determine whether healthy, non-affected offspring of mothers with PTSD would exhibit altered HPA axis function. Saliva samples were collected from the adolescent girls at waking, 30 minutes after waking, and 8 pm on 3 consecutive days. Offspring whose mothers were diagnosed with PTSD demonstrated higher cortisol awakening response (CAR; Cohen's d = .58) and greater total cortisol output (Cohen's d = .62). In this preliminary study, higher cortisol levels during adolescence among offspring of mothers with PTSD may index a vulnerability in these at-risk youth.

The error-related negativity (ERN) currently appears as a physiological measure in relation to three Research Domain Criteria (RDoC) constructs: Cognitive Control, Sustained Threat, and Reward Learning. We propose a conceptual model in which variance in the ERN reflects individual differences in the degree to which errors are evaluated as threatening. We also discuss evidence for the placement of the ERN in the "Sustained Threat" construct, as well as evidence that the ERN may more specifically reflect sensitivity to endogenous threat. Following this, we present data from a sample of 515 adolescent females demonstrating a larger ERN in relation to self-reported checking behaviors, but only in older adolescents, suggesting that sensitivity to internal threat and the ERN-checking relationship may follow a developmental course as adolescents develop behavioral control. In contrast, depressive symptoms were linked to a smaller ERN, and this association was invariant with respect to age. Collectively, these data suggest that the magnitude of the ERN is sensitive both to specific anxiety-related processes and depression, in opposing directions that may reflect variation in internal threat sensitivity. We discuss directions for future research, as well as ways in which findings for the ERN complement and challenge aspects of the current RDoC matrix.

Abnormal patterns of attention to threat and reward have been proposed as potential mechanisms of dysfunction in anxiety and unipolar depressive disorders. However, few studies have simultaneously examined whether these patterns of attention are shared among disorders or distinguish between them. In the present study, we recorded the Late Positive Potential (LPP), an event-related potential and putative index of motivated attention, from 145 patients with anxiety and unipolar depressive disorders and 32 controls, as they viewed blocks of rewarding and threatening images, respectively. We found that a current diagnosis of depression was associated with a reduced LPP to rewarding visual stimuli. This appeared to be specific to a subgroup of individuals with early onset depression; this subgroup was also characterized by a reduced LPP to threatening images. Anxiety diagnosis and age of onset of anxiety, whether comorbid with depression or not, was unrelated to the magnitude of the LPP. Finally, a transdiagnostic symptom dimension measuring current severity of suicidal ideation was related to a reduced LPP to both rewarding and threatening images. These data suggest that dysfunction in neural markers of attention to threat and reward can effectively distinguish features of depression from anxiety, particularly early onset depression, and may track suicidal ideation across disorders.