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Background: Research on a putative link between apolipoprotein-ε4 allele (APOE-ε4) and schizophrenia has been inconclusive. However, prior studies have not investigated the association between APOE-ε4 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-ε4 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 20years. A meta-analysis identified 29 case-control studies of APOE-ε4 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-ε4 and symptom trajectories, showing that APOE-ε4 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-ε4 and schizophrenia was not detectable in younger people but became pronounced with age, such that APOE-ε4 increased the odds of diagnosis by 10% per decade., Conclusions: Taken together, the meta-analysis and longitudinal analysis implicate APOE-ε4 as an age-related risk factor for worsening hallucinations and delusions, and suggest APOE-ε4 may play an age-mediated pathophysiological role in schizophrenia. The presence of an APOE-ε4 allele may also identify a subgroup of patients who require intensive monitoring and additional targeted interventions, especially in mid-to late-life., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Posttraumatic stress disorder (PTSD) increases risk of future respiratory illness. However, mechanisms that underpin the association between these common and debilitating conditions remain unknown. The aim of this study was to identify modifiable, health-related behaviors they may explain the link between PTSD and respiratory problems., Methods: World Trade Center responders (N = 452, 89% male, mean age = 55 years) completed baseline PTSD and sleep questionnaires, followed by 2-weeks of daily diaries, actigraphy and ambulatory spirometry to monitor lower respiratory symptoms, pulmonary function, activity levels, stressors, and sleep. Lipid levels were obtained from electronic medical records., Results: Cross-sectional mediation analyses revealed that the association between PTSD and self-reported respiratory symptoms was explained by poor sleep, low activity, and daily stressors. The association between PTSD symptoms and pulmonary function was explained by insomnia and low activity., Conclusions: A range of health-related daily behaviors and experiences, especially sleep disturbances and inactivity, may explain excess respiratory illness morbidity in PTSD. The findings were generally consistent across daily self-report and spirometry measures of respiratory problems. Targeting these behaviors might enhance prevention of and intervention in respiratory problems in traumatized populations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background : This study sought to examine whether handgrip strength (HGS), a measure of muscle strength and a biomarker of aging, was associated with post-traumatic stress disorder (PTSD) in a cohort of World Trade Center (WTC) responders at midlife. Methods : HGS was assessed utilizing a computer-assisted hand dynamometer administered to a consecutive sample of men and women ( n = 2016) who participated in rescue and recovery efforts following the World Trade Center (WTC) attacks and subsequently attended monitoring appointments in Long Island, NY. PTSD symptom severity and depressive symptoms were assessed using the PTSD specific-trauma checklist (PCL-S) and the Patient Health Questionnaire (PHQ-9). General linear models were used to examine the association of WTC-related PTSD with HGS after adjusting for confounders. Results : The sample was at midlife (mean age = 53.3) when assessed, and 91.3% were men. Nearly 10% of the sample had probable PTSD (PCL ≥ 44) with concomitant depression (PHQ ≥ 10), while 5.1% had probable PTSD without depression. Average HGS was 57.4 lbs. (95% confidence interval (95% CI): 56.6⁻58.1) among men and 36.1 lbs. (95% CI = 33.8⁻38.5) among women. Mean HGS of those with probable PTSD with concomitant depression was lower (45.9 lbs., 95% CI = 43.6⁻48.2) than responders with only PTSD (49.1 lbs., 95% CI = 46.0⁻52.4) and those without PTSD or depression (57.5 lbs., 95% CI = 56.2⁻57.8). Subdomain analyses of PTSD symptoms revealed that re-experiencing symptoms at enrollment ( p = 0.003) was associated with lower HGS after adjusting for depressive symptoms and other confounders. Discussion : Results suggested that higher WTC-related PTSD symptom severity was associated with lower HGS. Results support ongoing work suggesting that PTSD may be associated with more rapid physical aging. The potential for developing interventions that might simultaneously improve physical and mental health in the aftermath of trauma may be considered.

Introduction: Chronic posttraumatic stress disorder (PTSD) is associated with poor memory and increased burden of various degenerative cerebral neuropathologies. The goal of this pilot study was to determine whether PTSD was associated with changes in plasma-based neuropathological biomarkers of neurodegeneration among World Trade Center (WTC) responders., Methods: Thirty-four WTC responders had blood drawn and flash-frozen within 15 minutes of retrieval. PTSD symptoms were assessed at that time. Age, sex, and WTC exposure duration were obtained from medical records. Plasma was assayed in duplicate using an ultra-sensitive single-molecule enzyme-linked immunosorbent assay to examine the distribution of amyloid-β (Aβ) 42/40 ratios, total Aβ, total tau, and neurofilament light (NfL). The comparison group was drawn from a bank of healthy controls collected and assayed at the same facility., Results: The average age of WTC responders at blood draw was 53 years. Half were PTSD positive (PTSD+) as indicated by symptom severity. WTC responders had lower Aβ42/Aβ40 ratios but higher total tau and NfL levels in the plasma than healthy controls. PTSD+ status was associated with lower plasma Aβ load and higher Aβ42/Aβ40 ratios., Discussion: Findings suggest that PTSD may be associated with alterations in plasma markers related to Aβ, tau, and NfL, highlighting the potential association between PTSD status and neurodegenerative neuropathology in WTC responders.

Posttraumatic stress disorder (PTSD), a chronic disorder resulting from severe trauma, has been linked to immunologic dysregulation. Gene expression profiling has emerged as a promising tool for understanding the pathophysiology of PTSD. However, to date, all but one gene expression study was based on whole blood or unsorted peripheral blood mononuclear cell (PBMC), a complex tissue consisting of several populations of cells. The objective of this study was to utilize RNA sequencing to simultaneously profile the gene expression of four immune cell subpopulations (CD4T, CD8T, B cells, and monocytes) in 39 World Trade Center responders (20 with and 19 without PTSD) to determine which immune subsets play a role in the transcriptomic changes found in whole blood. Transcriptome-wide analyses identified cell-specific and shared differentially expressed genes across the four cell types. FKBP5 and PI4KAP1 genes were consistently upregulated across all cell types. Notably, REST and SEPT4, genes linked to neurodegeneration, were among the top differentially expressed genes in monocytes. Pathway analyses identified differentially expressed gene sets involved in mast cell activation and regulation in CD4T, interferon-beta production in CD8T, and neutrophil-related gene sets in monocytes. These findings suggest that gene expression indicative of immune dysregulation is common across several immune cell populations in PTSD. Furthermore, given notable differences between cell subpopulations in gene expression associated with PTSD, the results also indicate that it may be valuable to analyze different cell populations separately. Monocytes may constitute a key cell type to target in research on gene expression profile of PTSD.

Emotion dysfunction has long been considered a cardinal feature across psychotic disorders, including schizophrenia and affective psychosis. However, few studies have used objective markers of emotional function to compare psychotic disorders to one another, and fewer studies have examined such markers within a longitudinal framework. Here, we examine one objective marker of emotional responsivity, the late positive potential (LPP), which is a centro-parietal event-related potential (ERP) that tracks the dynamic allocation of attention to emotional vs. neutral stimuli. We used the LPP to characterize abnormal emotional responsivity by relating it to negative, depressive, and psychotic symptoms among two clinical groups: individuals diagnosed with affective psychosis and individuals with schizophrenia. We also used a long-term longitudinal framework, examining concurrent associations between LPP amplitude and symptom severity, as well as prospective associations with symptoms 4 years later. Participants were 74 individuals with psychotic illness: 37 with schizophrenia spectrum disorders and 37 with a primary affective disorder (psychotic bipolar disorder, psychotic depression). There were no mean-level differences in LPP amplitude between the schizophrenia spectrum and primary affective psychosis group. In the primary affective psychosis group, reduced LPP amplitude was associated with greater depressive, negative, and psychotic symptom severity, both concurrently and at follow-up; associations between LPP and symptoms were not observed within the schizophrenia spectrum group. This pattern of results suggests that the neural correlates of emotion dysfunction may differ across psychotic disorders. One possibility is that schizophrenia is characterized by a decoupling of symptom severity and emotional processing. Such findings underscore the importance of analyzing transdiagnostic samples to determine common or specific symptom relationships across various patient populations.

Objective: An increased neural response to making mistakes has emerged as a potential biomarker of anxiety across development. The error-related negativity (ERN) 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. This study examined whether the ERN 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 ERN was measured using a flankers task. Psychiatric history of the adolescent and biological parent was 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 ERN was a significant predictor independent of other prominent risk factors, including baseline anxiety and depression symptoms and parental lifetime psychiatric history. Jointly the ERN and social anxiety symptoms provided the greatest power for predicting first-onset GAD., Conclusions: This study provides evidence for the utility of the ERN as a biomarker of risk for GAD during a key developmental period., (© 2018 Association for Child and Adolescent Mental Health.)

Adolescent non-suicidal self-injury (aNSSI) is associated with abnormal scores on personality traits, such as high neuroticism. However, no studies to date have examined personality facets of self-injury in a cohort younger than college-age. Plus, adolescent psychopathologies, especially Depressive Disorders, are associated with a similar personality profile and are highly comorbid with aNSSI. Consequently, it remains unclear whether personality provides insights about aNSSI in youth beyond that due to underlying psychopathology. 550 community-dwelling 13- to 15-year-old never-depressed adolescent girls were interviewed for lifetime aNSSI and lifetime psychopathology. Personality traits, broad domains and specific facets, were assessed by self-report. Never-depressed adolescent girls who endorse aNSSI often met lifetime criteria for psychiatric disorders (NSSI: 20/43; 46.5% vs. non-aNSSI: 131/507; 26.1%). aNSSI and lifetime psychopathology were each independently associated with several traits (e.g., high neuroticism and conscientiousness), whereas some traits only discriminated aNSSI (e.g., high melancholia, a facet of neuroticism related to sadness and negative self-evaluation) or lifetime psychopathology independent of each other (e.g., low positive emotionality; low agreeableness). Furthermore, a multivariate model identified high melancholia, high openness to experience, and low conscientiousness as incrementally independent correlates of lifetime aNSSI over and above psychiatric illness. Proneness to melancholia, interest in new things, and poor self-control incrementally track aNSSI in never-depressed adolescent girls. Importantly, this emerges early in course (13-15 years of age) and is independent of lifetime psychiatric diagnosis. Implications for updating etiological models and clinical utility of personality assessment are discussed.

The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural equation modeling approaches. In the last 50 years, efforts in both psychiatry and psychological science have moved toward (1) a dimensional model of psychopathology (eg, the current Hierarchical Taxonomy of Psychopathology [HiTOP] initiative), (2) an integration of methods and measures across traits and units of analysis (eg, the RDoC initiative), and (3) powerful, impactful study designs maximizing sample size to detect subtle genomic variation relating to complex traits (the Psychiatric Genomics Consortium [PGC]). These movements are important to the future study of the psychosis spectrum, and to resolving heterogeneity with respect to instrument and population. The International Consortium of Schizotypy Research is composed of over 40 laboratories in 12 countries, and to date, members have compiled a body of schizotypy- and psychosis-related phenotype data from more than 30000 individuals. It has become apparent that compiling data into a protected, relational database and crowdsourcing analytic and data science expertise will result in significant enhancement of current research on the structure and biological substrates of the psychosis spectrum. The authors present a data-sharing infrastructure similar to that of the PGC, and a resource-sharing infrastructure similar to that of HiTOP. This report details the rationale and benefits of the phenotypic data collective and presents an open invitation for participation.

Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is generally more dimensional than categorical. When the discreteness versus continuity of psychopathology is treated as a research question, as opposed to being decided as a matter of tradition, the evidence clearly supports the hypothesis of continuity. In addition, a related body of literature shows how psychopathology dimensions can be arranged in a hierarchy, ranging from very broad "spectrum level" dimensions, to specific and narrow clusters of symptoms. In this way, a quantitative approach solves the "problem of comorbidity" by explicitly modeling patterns of co-occurrence among signs and symptoms within a detailed and variegated hierarchy of dimensional concepts with direct clinical utility. Indeed, extensive evidence pertaining to the dimensional and hierarchical structure of psychopathology has led to the formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium. This is a group of 70 investigators working together to study empirical classification of psychopathology. In this paper, we describe the aims and current foci of the HiTOP Consortium. These aims pertain to continued research on the empirical organization of psychopathology; the connection between personality and psychopathology; the utility of empirically based psychopathology constructs in both research and the clinic; and the development of novel and comprehensive models and corresponding assessment instruments for psychopathology constructs derived from an empirical approach., (© 2018 World Psychiatric Association.)

Background: Anxious youth are at increased risk for later depressive disorders, but not all anxious youth develop depression. Sequential comorbidity models emphasize shared risk factors and anxiety sequelae, but some anxious youth who later develop depression may have risk factors that are relatively specific to depression, in addition to a liability to anxiety. We examined several variables that appear relatively specific to risk for depression-the personality traits of low positive affectivity and high sadness, and an electrophysiological measure of blunted response to reward - in predicting first-onset depressive disorders and depressive symptoms in clinically anxious adolescent girls., Methods: A sample of 114 adolescents with baseline anxiety disorders completed personality and psychopathology measures, psychophysiology tasks, and diagnostic interviews. Interviews and a measure of depressive symptoms were re-administered over 27 months., Results: After controlling for baseline depressive symptoms, blunted reward sensitivity uniquely predicted first-onset depressive disorders and depressive symptoms 27 months later. Post-hoc analyses indicated that blunted reward sensitivity only predicted first-onset depressive disorders and depressive symptoms in girls with high social anxiety symptoms., Limitations: Analyses were unable to account for concurrent anxiety symptoms and disorders., Conclusions: The depression-specific risk factor, blunted reward sensitivity, may comprise one pathway to subsequent depressive disorders and symptoms in anxious youth and indicate which anxious youth need intervention to prevent later depression, particularly in socially anxious girls., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Personality is a major predictor of many mental and physical disorders, but its contributions to illness course are understudied., Purpose: The current study aimed to explore whether personality is associated with a course of psychiatric and medical illness over 10 years following trauma., Methods: World Trade Center (WTC) responders (N = 532) completed the personality inventory for DSM-5, which measures both broad domains and narrow facets. Responders' mental and physical health was assessed in the decade following the WTC disaster during annual monitoring visits at a WTC Health Program clinic. Multilevel modeling was used in an exploratory manner to chart the course of health and functioning, and examine associations of maladaptive personality domains and facets with intercepts (initial illness) and slopes (course) of illness trajectories., Results: Three maladaptive personality domains-negative affectivity, detachment and psychoticism-were uniquely associated with initial posttraumatic stress disorder (PTSD); detachment and psychoticism were also associated with initial functional impairment. Five facets-emotional lability, anhedonia, callousness, distractibility and perceptual dysregulation-were uniquely associated with initial mental and physical health and functional impairment. Anxiousness and depressivity facets were associated with worse initial levels of psychiatric outcomes only. With regard to illness trajectory, callousness and perceptual dysregulation were associated with the increase in PTSD symptoms. Anxiousness was associated with greater persistence of respiratory symptoms., Conclusions: Several personality domains and facets were associated with initial levels and long-term course of illness and functional impairment in a traumatized population. Results inform the role of maladaptive personality in the development and maintenance of chronic mental-physical comorbidity. Personality might constitute a transdiagnostic prognostic and treatment target.

Affective personality traits, such as extraversion and neuroticism, are associated with individual differences in reward system functioning. The reward positivity (ΔRewP) is an event-related potential (ERP) component that indexes sensitivity to reward, and can be elicited by feedback indicating monetary gains relative to losses. In a sample of 508 adolescent girls, the current study examined the relationship between extraversion, neuroticism, and their respective facets and the ΔRewP. Results indicated an Extraversion × Neuroticism interaction, such that greater extraversion was associated with an increased ΔRewP, but only in the context of low neuroticism. This association was primarily due to the extraversion facet positive emotionality-high levels of positive emotionality were associated with an increased ΔRewP, but only in the context of low neuroticism. In addition, increased neuroticism diminished the age-related increase in the ΔRewP. The current study suggests that both extraversion and neuroticism are associated with reward system function in adolescence., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Individual 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., Methods: A community sample of 550 adolescent females completed general and facet-level personality measures and diagnostic interviews. Interviews were re-administered 18 months later., Results: First 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., Conclusions: General 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.

This study examined whether exposure to Hurricane Sandy-related stressors altered children's brain response to emotional information. An average of 8 months (M age  = 9.19) before and 9 months after (M age  = 10.95) Hurricane Sandy, 77 children experiencing high (n = 37) and low (n = 40) levels of hurricane-related stress exposure completed a task in which the late positive potential, a neural index of emotional reactivity, was measured in response to pleasant and unpleasant, compared to neutral, images. From pre- to post-Hurricane Sandy, children with high stress exposure failed to show the same decrease in emotional reactivity to unpleasant versus neutral stimuli as those with low stress exposure. Results provide compelling evidence that exposure to natural disaster-related stressors alters neural emotional reactivity to negatively valenced information., (© 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.)

Background: A blunted reward positivity (RewP), an event-related potential elicited by feedback indicating monetary gain relative to loss, was recently shown to prospectively predict the development of adolescent-onset depression. Time-frequency-based representations of this activity (e.g., reward-related delta) have also been associated with depression. This study is a reanalysis of the time-domain RewP investigation to examine the incremental value of time-frequency indices in the prediction of adolescent-onset depression., Methods: The sample included 444 13- to 15-year-old girls with no lifetime history of a depressive disorder. At baseline, adolescents completed a monetary guessing task, and both time-domain and time-frequency analyses were conducted on the event-related potential response to gain and loss feedback. Lifetime psychiatric history in the adolescent and a biological parent were evaluated with diagnostic interviews, and adolescents' current depressive symptoms were assessed using a self-report questionnaire. Adolescents were interviewed again approximately 18 months later to identify first-onset depressive disorder., Results: Blunted reward-related delta predicted first-onset depressive disorder 18 months later, independent of the time-domain RewP and psychosocial risk factors (i.e., adolescent baseline depressive symptoms, adolescent and parental psychiatric history). In contrast, loss-related theta did not predict the development of depression. Reward-related delta increased sensitivity (73.8% to 82.8%) and positive predictive value (45.0% to 70.9%) for first-onset depressive disorder when applied in parallel and in series, respectively, with baseline depressive symptoms and the time-domain RewP., Conclusions: This study provides evidence that frequency-based representations of event-related potentials provide incremental value in the prediction of psychiatric disorders., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The gene expression approach has provided promising insights into the pathophysiology of posttraumatic stress disorder (PTSD). However, few studies used hypothesis-free transcriptome-wide approach to comprehensively understand gene expression underpinning PTSD. A transcriptome-wide expression study using RNA sequencing of whole blood was conducted in 324 World Trade Center responders (201 with never, 81 current, 42 past PTSD). Samples from current and never PTSD reponders were randomly split to form discovery (N = 195) and replication (N = 87) cohorts. Differentially expressed genes were used in pathway analysis and to create a polygenic expression score. There were 448 differentially expressed genes in the discovery cohort, of which 99 remained significant in the replication cohort, including FKBP5, which was found to be up-regulated in current PTSD regardless of the genotypes. Several enriched biological pathways were found, including glucocorticoid receptor signaling and immunity-related pathways, but these pathways did not survive FDR correction. The polygenic expression score computed by aggregating 30 differentially expressed genes using the elastic net algorithm achieved sensitivity/specificity of 0.917/0.508, respectively for identifying current PTSD in the replication cohort. Polygenic scores were similar in current and past PTSD, with both groups scoring higher than trauma-exposed controls without any history of PTSD. Together with the pathway analysis results, these findings point to HPA-axis and immune dysregulation as key biological processes underpinning PTSD. A novel polygenic expression aggregate that differentiates PTSD patients from trauma-exposed controls might be a useful screening tool for research and clinical practice, if replicated in other populations.

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., (Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: The current study examined whether the interaction of lower respiratory symptoms and anxiety sensitivity is related to smoking lapse in the context of smoking cessation., Method: Participants were adult daily smokers (N=60) exposed to the World Trade Center (WTC) disaster who were in a smoking cessation treatment program (75.0% male, 50.6years old [SD=9.2], and current smoking rate was 17.6 cigarettes per day (SD=10.6)., Results: Results indicated that the interaction between lower respiratory symptoms and anxiety sensitivity was a significant predictor of greater risk for lapse (i.e., lower survival time; B=0.005, OR=1.01, p=0.039). Follow-up analysis showed that greater respiratory symptoms were a significant predictor of lapse risk among those with high (B=0.116, OR=1.12, p=0.025), but not those with low (B=-0.048, OR=0.95, p=0.322), levels of anxiety sensitivity., Discussion: The findings from the current study suggest that smokers with greater respiratory symptoms and higher levels of anxiety sensitivity may be associated with early lapse to smoking following smoking cessation treatment. Future work has the potential to inform the development of tailored cessation interventions for smokers who experience varying levels of lower respiratory symptoms and anxiety sensitivity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Traditional categorization of emotional disorders suffers from within-disorder heterogeneity and excessive comorbidity. Quantitative nosology instead proposes grouping homogenous components of these disorders within a higher order internalizing dimension. However, the precise number, composition, and hierarchical structure of these components remains unclear and varies based on assessment tools., Methods: The present study jointly examined two assessment systems with the broadest coverage of homogeneous emotional disorder components-the revised Interview for Mood and Anxiety Symptoms (IMAS-R) and the self-report-based expanded version of the Inventory of Depression and Anxiety Symptoms (IDAS-II)-to map their convergent and discriminant validity and joint structure in outpatient (N=426) and treated student (N=306) samples., Results: Results identified 33 non-redundant components of emotional disorders. Most demonstrated strong convergent and discriminant validity between these two instruments. However, the IMAS-R provided more detailed and differentiated characterization of the content subsumed within three IDAS-II scales, and seven of the 33 components were unique to one measure or the other. Joint analysis of scales from both measures supported a four factor (i.e., distress, fear, OCD, mania) mid-level structure of emotional disorders., Conclusions: Using multiple measures, methods, and samples, the present study provided evidence for the validity of core lower order components of the internalizing dimension and suggested they cluster into as many as four distinct factors reflecting distress, fear, OCD, and mania., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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 r s 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, ((c) 2017 APA, all rights reserved).)

Objective: Social impairment is a long-recognized core feature of schizophrenia and is common in other psychotic disorders. Still, to date the long-term trajectories of social impairment in psychotic disorders have rarely been studied systematically., Methods: Data came from the Suffolk County Mental Health Project, a 20-year prospective study of first-admission patients with psychotic disorders. A never-psychotic comparison group was also assessed. Latent class growth analysis was applied to longitudinal data on social functioning from 485 respondents with schizophrenia spectrum disorders and psychotic mood disorders, and associations of the empirically derived trajectories with premorbid social adjustment, diagnosis, and 20-year outcomes were examined., Results: Four mostly stable trajectories of preserved (N=82; 59th percentile of comparison group sample distribution), moderately impaired (N=148; 17th percentile), severely impaired (N=181; 3rd percentile), and profoundly impaired (N=74; 1st percentile) functioning best described the 20-year course of social functioning across diagnoses. The outcome in the group with preserved functioning did not differ from that of never-psychotic individuals at 20 years, but the other groups functioned significantly worse. Differences among trajectories were already evident in childhood. The two most impaired trajectories started to diverge in early adolescence. Poorer social functioning trajectories were strongly associated with other real-world outcomes at 20 years. Multiple trajectories were represented within each disorder. However, more participants with schizophrenia spectrum disorders had impaired trajectories, and more with mood disorders had better functioning trajectories., Conclusions: The results highlight substantial variability of social outcomes within diagnoses-albeit overall worse social outcomes in schizophrenia spectrum disorders-and show remarkably stable long-term impairments in social functioning after illness onset across all diagnoses.

Background: A large body of research has focused on identifying the optimal number of dimensions - or spectra - to model individual differences in psychopathology. Recently, it has become increasingly clear that ostensibly competing models with varying numbers of spectra can be synthesized in empirically derived hierarchical structures., Methods and Materials: We examined the convergence between top-down (bass-ackwards or sequential principal components analysis) and bottom-up (hierarchical agglomerative cluster analysis) statistical methods for elucidating hierarchies to explicate the joint hierarchical structure of clinical and personality disorders. Analyses examined 24 clinical and personality disorders based on semi-structured clinical interviews in an outpatient psychiatric sample (n=2900)., Results: The two methods of hierarchical analysis converged on a three-tier joint hierarchy of psychopathology. At the lowest tier, there were seven spectra - disinhibition, antagonism, core thought disorder, detachment, core internalizing, somatoform, and compulsivity - that emerged in both methods. These spectra were nested under the same three higher-order superspectra in both methods: externalizing, broad thought dysfunction, and broad internalizing. In turn, these three superspectra were nested under a single general psychopathology spectrum, which represented the top tier of the hierarchical structure., Conclusions: The hierarchical structure mirrors and extends upon past research, with the inclusion of a novel compulsivity spectrum, and the finding that psychopathology is organized in three superordinate domains. This hierarchy can thus be used as a flexible and integrative framework to facilitate psychopathology research with varying levels of specificity (i.e., focusing on the optimal level of detailed information, rather than the optimal number of factors)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Although practice guidelines are based on disorders specified in diagnostic manuals, such as the DSM, practitioners appear to follow symptoms when making treatment decisions. Psychiatric medication is generally prescribed in a transdiagnostic manner, further highlighting how symptoms, not diagnoses, often guide clinical practice. A quantitative approach to nosology promises to provide better guidance as it describes psychopathology dimensionally and its organization reflects patterns of covariation among symptoms., Aim: To investigate whether a quantitative classification of emotional disorders can account for naturalistic medication prescription patterns better than traditional diagnoses., Methods: Symptom dimensions and DSM diagnoses of emotional disorders, as well as prescribed medications, were assessed using interviews in a psychiatric outpatient sample (N=318, mean age 42.5years old, 59% female, 81% Caucasian)., Results: Each diagnosis was associated with prescription of multiple medication classes, and most medications were associated with multiple disorders. This was largely due to heterogeneity of clinical diagnoses, with narrow, homogenous dimensions underpinning diagnoses showing different medication profiles. Symptom dimensions predicted medication prescription better than DSM diagnoses, irrespective of whether this was examined broadly across all conditions, or focused on a specific disorder and medication indicated for it., Conclusions: Psychiatric medication was prescribed in line with symptoms rather than DSM diagnoses. A quantitative approach to nosology may better reflect treatment planning and be a more effective guide to pharmacotherapy than traditional diagnoses. This adds to a diverse body of evidence about superiority of the quantitative system in practical applications and highlights its potential to improve psychiatric care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Kraepelin considered declining course a hallmark of schizophrenia, but others have suggested that outcomes usually stabilize or improve after treatment initiation. The authors investigated this question in an epidemiologically defined cohort with psychotic disorders followed for 20 years after first hospitalization., Method: The Suffolk County Mental Health Project recruited first-admission patients with psychosis from all inpatient units of Suffolk County, New York (response rate, 72%). Participants were assessed in person six times over two decades; 373 completed the 20-year follow-up (68% of survivors); 175 had schizophrenia/schizoaffective disorder. Global Assessment of Functioning (GAF), psychotic symptoms, and mood symptoms were rated at each assessment. Month 6, when nearly all participants were discharged from the index hospitalization, was used as a reference., Results: In the schizophrenia group, mean GAF scores declined from 49 at month 6 to 36 at year 20. Negative and positive symptoms also worsened (Cohen's d values, 0.45-0.73). Among participants without schizophrenia, GAF scores were higher initially (a mean of approximately 64) but declined by 9 points over the follow-up period. Worsening began between years 5 and 8. Neither aging nor changes in antipsychotic treatment accounted for the declines. In all disorders, depression improved and manic symptoms remained low across the 20 years., Conclusions: The authors found substantial symptom burden across disorders that increased with time and ultimately may undo initial treatment gains. Previous studies have suggested that better health care delivery models may preempt this decline. In the United States, these care needs are often not met, and addressing them is an urgent priority.

Introduction: This study examined whether World Trade Center (WTC)-related exposures and posttraumatic stress disorder (PTSD) were associated with cognitive function and whether WTC responders' cognition differed from normative data., Methods: A computer-assisted neuropsychological battery was administered to a prospective cohort study of 1193 WTC responders with no history of stroke or WTC-related head injuries. Data were linked to information collected prospectively since 2002. Sample averages were compared to published norms., Results: Approximately 14.8% of sampled responders had cognitive dysfunction. WTC responders had worse cognitive function compared to normative data. PTSD symptom severity and working >5 weeks on-site was associated with lower cognition., Discussion: Results from this sample highlight the potential for WTC responders to be experiencing an increased burden of cognitive dysfunction and linked lowered cognitive functioning to physical exposures and to PTSD. Future research is warranted to understand the extent to which cognitive dysfunction is evident in neural dysfunction.

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, remain 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 (fMRI) data while 229 adolescent females with or without parental history of depression completed a monetary gambling task. We examined if OFC blood-oxygen-level-dependent (BOLD) 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 fMRI literature has mainly focused on reward, the present findings underscore the need to include prefrontal loss processing in existing developmental models of depression.

Posttraumatic stress disorder (PTSD) is associated with self-reported difficulties navigating the social and physical world and may also be associated with risk of functional limitations. The Short Physical Performance Battery (SPPB), an objective functional assessment, was administered during monitoring exams between January and December 2015 to a consecutive sample of 1,268 rescue workers, volunteers, and other responders who had aided in response, recovery, and cleanup efforts at the World Trade Center (WTC) in New York after the September 11, 2011 attacks. Data were linked with diagnostic and longitudinal data from the WTC monitoring study. Multivariable analyses were used to examine predictors of functional limitations. Prevalence estimates weighted to the general responder population revealed a relatively high prevalence of functional limitations, SPPB ≤ 9; 16.0%, 95% CI [13.7, 18.4]. Current PTSD was associated with a twofold increased risk of functional limitations after controlling for predisposing factors, trauma severity, behavioral factors, and WTC-related medical conditions, adjusted risk ratio (aRR) = 2.11, 95% CI [1.48, 3.01]. Exposure to ergonomic risk factors at the WTC also increased the risk of functional impairments, aRR = 1.34 95% CI [1.05, 1.70]. Longitudinal results suggest that individuals with current functional limitations experienced high baseline PTSD severity, B = 2.94, SE = 1.33, and increasing PTSD symptom severity, B = 0.29, SE = 0.10, since September 11, 2001. This study identified a cross-sectional relationship between functional limitations and PTSD and a worsening of PTSD symptoms in persons who eventually demonstrated functional limitations. Results highlight the potential role of chronic PTSD in functional limitations., (Copyright © 2017 International Society for Traumatic Stress Studies.)

Introduction: Proton pump inhibitors (PPIs), a common treatment for gastroesophageal reflux disease (GERD), were recently associated with increased risk of dementia. However, severe or chronic stress including, for example, posttraumatic stress disorder (PTSD) was not accounted for. This study examined whether PPI use was associated with severe cognitive impairment (SCI) and whether PTSD explained this association in a cohort of World Trade Center (WTC) responders., Method: A prospective cohort study of 3779 WTC responders attending a university-based monitoring and treatment program. Prescriptions for PPIs and SCI determined using the Montreal Cognitive Assessment were the focus of the analysis., Results: Overall, 1451 (38.4%) responders were dispensed PPIs, and 83 (2.2%) had SCI. Bivariable analyses revealed significant associations between being-dispensed PPIs in relation to SCI. After adjusting for PTSD, major depressive disorder, WTC exposures, age, and sex, being-dispensed PPIs were significantly associated with odds of SCI (adjusted odds ratio = 1.67 95% confidence interval = 1.054-2.643)., Conclusions: Being-dispensed PPIs were associated with SCI in this analysis of WTC responders. Results suggest that clinicians treating GERD seek to both understand patients' mental health history and monitor cognitive functioning when designing treatment routines. Overall, results confirmed that this is an important area of investigation with potential direct clinical implications.

Introduction: The main objective was to evaluate the efficacy of an 8-session, group-based comprehensive smoking cessation and trauma management (CSC-T) treatment among daily smokers (≥5 cigarettes/day) exposed to the World Trade Center (WTC) disaster with elevated WTC-related post-traumatic stress disorder (PTSD) symptoms., Methods: Participants (N = 90) were randomly assigned to CSC-T (N = 44; 63.6% white; 27.3% female; mean age = 51.32 ± 7.87) or comprehensive smoking cessation (CSC) alone (N = 46; 71.7% white; 28.3% female; mean age = 48.74 ± 10.66), which was comparable in length and time. Assessments included a diagnostic clinical interview and self-report measures of PTSD and respiratory symptoms, and smoking behavior, and biologically confirmed smoking abstinence. Evaluations occurred at a baseline visit, each treatment session, and at 1-, 2-, 4-, 12-, and 26-weeks post-treatment., Results: The two treatments did not differ in regard to PTSD symptom improvement. After quit day (week 6), the two groups had similar 7-day (~15%) and 6-month (~20%) abstinence rates as well as average number of cigarettes smoked, and PTSD and respiratory symptoms., Conclusions: It is possible that the Cognitive Behavioral Therapy skills specific to quitting smoking, group-based support, and degree of therapist contact, that were available in both treatments may have played a role in equalizing the abstinence rates between the two conditions. Although the current study found no evidence that the CSC-T was superior to the CSC alone treatment, the abstinence rates observed were high relative to previous trials of smokers with diagnosed PTSD. Further development of smoking cessation programs tailored to the needs of smokers with PTSD symptoms continues to be needed., Implications: This study suggests that a CSC program aids in smoking abstinence for smokers with PTSD symptoms and that incorporating trauma management skills, may not add additional benefits for abstinence and PTSD and respiratory symptom relief. Further work is needed to improve smoking cessation efforts for smokers with PTSD symptoms., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: There is an increased prevalence of obesity in schizophrenia and bipolar disorder, leading to a disproportionate risk of adverse health conditions. Prospective, long-term weight gain data, however, are scarce., Methods: We analyzed data from the Suffolk County Mental Health Project cohort of consecutive first admissions with psychosis recruited from September 1989 to December 1995 and subsequently followed for 20 years, focusing on people with schizophrenia (n=146) and bipolar disorder (n=87). The time course of weight gain was examined using a 2 (group)×5 (time) mixed-model repeated measures ANOVA, and body mass index (BMI) scores at the first (6 months) and second (2 years) assessments were compared to examine whether early overweight predicted later obesity., Results: There was a statistically significant effect of time (F(1,210)=68.06, P<.001) and diagnosis (F(1,210)=29.18, P<.001) on BMI, but not the interaction of time×diagnosis (F(1,210)=0.88, P=.48). Most participants had normal BMIs at the first two assessments. Early overweight was a predictor of eventual obesity for both groups. At the 20-year follow-ups, approximately 50% of the bipolar and 62% of the schizophrenia sample were obese, with a greater prevalence of obesity in schizophrenia at each assessment (all P<.02), except for years 4 (P=.12) and 20 (P=.27)., Conclusions: Nearly two-thirds of the participants with schizophrenia and over half of those with bipolar disorder were obese 20 years after first hospitalization for psychosis, considerably higher than the rate for adults in New York State (27%). Early intervention may be required to prevent long-term consequences of obesity-related morbidity and mortality., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the clinical neuroscience literature, between-subjects differences in neural activity are presumed to reflect reliable measures-even though the psychometric properties of neural measures are almost never reported. The current article focuses on the critical importance of assessing and reporting internal consistency reliability-the homogeneity of "items" that comprise a neural "score." We demonstrate how variability in the internal consistency of neural measures limits between-subjects (i.e., individual differences) effects. To this end, we utilize error-related brain activity (i.e., the error-related negativity or ERN) in both healthy and generalized anxiety disorder (GAD) participants to demonstrate options for psychometric analyses of neural measures; we examine between-groups differences in internal consistency, between-groups effect sizes, and between-groups discriminability (i.e., ROC analyses)-all as a function of increasing items (i.e., number of trials). Overall, internal consistency should be used to inform experimental design and the choice of neural measures in individual differences research. The internal consistency of neural measures is necessary for interpreting results and guiding progress in clinical neuroscience-and should be routinely reported in all individual differences studies. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Classification of emotional disorders faces challenges of within-disorder heterogeneity and between-disorder comorbidity. The current study addressed these issues by analyzing all emotional disorder symptoms to identify homogeneous dimensions that characterize this domain. These dimensions were, in turn, used to define coherent syndromes and higher order factors. All of the emotional disorder symptoms specified in diagnostic manuals were assessed by interview in 2 treatment-seeking samples (N = 426 and 305), alongside clinical diagnoses and functioning measures. Exploratory and confirmatory factor analyses were employed to elucidate replicable lower and higher order structures. We found 31 homogenous symptom dimensions that clustered, at different levels of generality, into 8 syndromes (Vegetative Symptoms, Cognitive Depression, Posttraumatic Stress Disorder, Panic, Social Anxiety, Phobia, Obsessive-Compulsive Disorder [OCD], and Mania), 3 subfactors (Distress, Fear, and OCD/Mania), and a single Internalizing spectrum. This structure replicated in both samples. Identified dimensions showed considerable convergence with categorical diagnoses, but provided more information about global functioning than diagnoses. Overall, current results propose a novel comprehensive description of the lower order structure of emotional disorders. The empirical syndromes generally paralleled disorders listed in diagnostic manuals, although several differences were notable. The higher order results also confirmed previously reported Distress, Fear, and Mania subfactors of the Internalizing spectrum using homogeneous dimensional markers. Taken together, results highlight a bottom-up approach to constructing an empirical nosology that does not rely on analysis of diagnostic categories. The resulting hierarchical system can be used clinically and to facilitate research on the pathophysiology of emotional disorders, which, in turn, can inform intervention and prevention. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Two competing models of personality psychopathology are included in the fifth edition of the Diagnostic Statistical Manual of Mental Disorders ( DSM-5 ; American Psychiatric Association, 2013); the traditional personality disorder (PD) model included in Section II and an alternative trait-based model included in Section III. Numerous studies have examined the validity of the alternative trait model and its official assessment instrument, the Personality Inventory for DSM-5 (PID-5; Krueger, Derringer, Markon, Watson, & Skodol, 2012). However, few studies have directly compared the trait-based model to the traditional PD model empirically in the same dataset. Moreover, to our knowledge, only a single study (Suzuki, Griffin, & Samuel, 2015) has examined the dependability of the PID-5, which is an essential component of construct validity for traits (Chmielewski & Watson, 2009; McCrae, Kurtz, Yamagata, & Terracciano, 2011). The current study directly compared the dependability of the DSM-5 traits, as assessed by the PID-5, and the traditional PD model, as assessed by the Personality Diagnostic Questionnaire-4 (PDQ-4+), in a large undergraduate sample. In addition, it evaluated and compared their associations with functioning, another essential component of personality pathology. In general, our findings indicate that most DSM-5 traits demonstrate high levels of dependability that are superior to the traditional PD model; however, some of the constructs assessed by the PID-5 may be more state like. The models were roughly equivalent in terms of their associations with functioning. The current results provide additional support for the validity of PID-5 and the DSM-5 Section III personality pathology model. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

There is considerable variation in negative and positive symptoms of psychosis, global functioning, and emotional face perception (EFP), not only in schizophrenia but also in other psychotic disorders and healthy individuals. However, EFP impairment and its association with worse symptoms and global functioning have been examined largely in the domain of schizophrenia. The present study adopted a dimensional approach to examine the association of behavioral and neural measures of EFP with symptoms of psychosis and global functioning across individuals with schizophrenia spectrum (SZ; N = 28) and other psychotic (OP; N = 29) disorders, and never-psychotic participants (NP; N = 21). Behavioral and functional MRI data were recorded as participants matched emotional expressions of faces and geometrical shapes. Lower accuracy and increased activity in early visual regions, hippocampus, and amygdala during emotion versus shape matching were associated with higher negative, but not positive, symptoms and lower global functioning, across all participants. This association remained even after controlling for group-related (SZ, OP, and NP) variance, dysphoria, and antipsychotic medication status, except in amygdala. Furthermore, negative symptoms mediated the relationship between behavioral and brain EFP measures and global functioning. This study provides some of the first evidence supporting the specific relationship of EFP measures with negative symptoms and global functioning across psychotic and never-psychotic samples, and transdiagnostically across different psychotic disorders. Present findings help bridge the gap between basic EFP-related neuroscience research and clinical research in psychosis, and highlight EFP as a potential symptom-specific marker that tracks global functioning. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Objective: Respiratory illness and posttraumatic stress disorder (PTSD) are common debilitating conditions that frequently co-occur. Observational studies indicate that PTSD, independently of smoking, is a major risk and maintenance factor for lower respiratory symptoms (LRS). The current study experimentally tested this etiologic pathway by investigating whether LRS can be reduced by treating PTSD symptoms., Method: Ninety daily smokers exposed to the World Trade Center (WTC) disaster (mean age 50 years, 28% female; 68% White) completed 8-session group-based weekly comprehensive trauma management and smoking cessation treatment that focused on skills to alleviate PTSD symptoms. LRS, PTSD symptoms, and smoking were assessed weekly. Data was analyzed using multilevel models of within-person associations between LRS, PTSD symptoms, smoking, and treatment dose across 8 weekly sessions with concurrent and lagged outcomes., Results: LRS improved significantly with treatment (reduction of .50 standard deviations). Reduction in PTSD symptoms uniquely predicted improvement in LRS at consecutive sessions 1 week apart and fully accounted for the treatment effect on LRS. The effect of PTSD symptoms was stronger than that of smoking, and the only effect to remain significant when both entered the model. Notably, reduction in LRS did not predict future improvement in PTSD symptoms., Conclusions: The results are in line with the etiologic pathway suggesting that PTSD symptoms are a risk and maintenance factor for chronic LRS and that treatment of PTSD can help to alleviate LRS in trauma-exposed populations. PTSD is emerging as a novel and important treatment target for chronic respiratory problems. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

The reliability and validity of traditional taxonomies are limited by arbitrary boundaries between psychopathology and normality, often unclear boundaries between disorders, frequent disorder co-occurrence, heterogeneity within disorders, and diagnostic instability. These taxonomies went beyond evidence available on the structure of psychopathology and were shaped by a variety of other considerations, which may explain the aforementioned shortcomings. The Hierarchical Taxonomy Of Psychopathology (HiTOP) model has emerged as a research effort to address these problems. It constructs psychopathological syndromes and their components/subtypes based on the observed covariation of symptoms, grouping related symptoms together and thus reducing heterogeneity. It also combines co-occurring syndromes into spectra, thereby mapping out comorbidity. Moreover, it characterizes these phenomena dimensionally, which addresses boundary problems and diagnostic instability. Here, we review the development of the HiTOP and the relevant evidence. The new classification already covers most forms of psychopathology. Dimensional measures have been developed to assess many of the identified components, syndromes, and spectra. Several domains of this model are ready for clinical and research applications. The HiTOP promises to improve research and clinical practice by addressing the aforementioned shortcomings of traditional nosologies. It also provides an effective way to summarize and convey information on risk factors, etiology, pathophysiology, phenomenology, illness course, and treatment response. This can greatly improve the utility of the diagnosis of mental disorders. The new classification remains a work in progress. However, it is developing rapidly and is poised to advance mental health research and care significantly as the relevant science matures. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Objective: Although most people will experience a traumatic event at some point in their life, only some will develop significant psychological symptoms in the aftermath. In the current study, we use a preexisting longitudinal study located in Long Island to examine the impact of Hurricane Sandy on internalizing symptoms in a large sample of children. We focused on temperamental fear and a biomarker of risk for anxiety, the error-related negativity (ERN). The ERN is a negative deflection in the event-related potential (ERP) occurring when individuals make mistakes and is increased in anxious individuals., Method: The final sample consisted of 223 children who had undergone an observational assessment of fear at age 3 years and an electroencephalogram assessment of the ERN at age 6 years. At the age 9 year assessment, internalizing symptoms were assessed, and then again after the hurricane (∼65 weeks later)., Results: A significant three-way interaction among fearfulness, hurricane stressors, and the ERN in predicting posthurricane increases in internalizing symptoms suggested that children who were high in fear at age 3 years and experienced elevated hurricane stressors were characterized by subsequent increases in internalizing symptoms, but only when they were also characterized by an increased ERN at age 6 years., Conclusion: These findings support a diathesis-stress model, suggesting that early temperament and prestressor biological markers confer risk for increased psychological symptoms following environmental stressors., (Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

The psychological consequences of a second disaster on populations exposed to an earlier disaster have rarely been studied prospectively. Using a pre- and postdesign, we examined the effects of Hurricane Sandy on possible World Trade Center (WTC) related posttraumatic stress disorder (PTSD Checklist score of ≥ 50) and overall depression (major depressive disorder [MDD]; Patient Health Questionnaire depression score of ≥ 10) among 870 WTC responders with a follow-up monitoring visit at the Long Island WTC Health Program during the 6 months post-Hurricane Sandy. The Hurricane Sandy exposures evaluated were damage to home (8.3%) and to possessions (7.8%), gasoline shortage (24.1%), prolonged power outage (42.7%), and filing a Federal Emergency Management Agency claim (11.3%). A composite exposure score also was constructed. In unadjusted analyses, Hurricane Sandy exposures were associated with 1.77 to 5.38 increased likelihood of PTSD and 1.58 to 4.13 likelihood of MDD; odds ratios for ≥ 3 exposures were 6.47 for PTSD and 6.45 for MDD. After adjusting for demographic characteristics, WTC exposure, pre-Hurricane Sandy mental health status, and time between assessments, reporting ≥ 3 Hurricane Sandy exposures was associated with a 3.29 and 3.71 increased likelihood of PTSD and MDD, respectively. These findings underscore the importance of assessing the impact of a subsequent disaster in ongoing responder health surveillance programs., (Copyright © 2017 International Society for Traumatic Stress Studies.)

Respiratory problems and posttraumatic stress disorder (PTSD) are the signature health consequences associated with the September 11, 2001 (9/11), World Trade Center disaster and frequently co-occur. The reasons for this comorbidity, however, remain unknown. Anxiety sensitivity is a transdiagnostic trait that is associated with both PTSD and respiratory symptoms. The present study explored whether anxiety sensitivity could explain the experience of respiratory symptoms in trauma-exposed smokers with PTSD symptoms. Participants (N = 135; M age = 49.18 years, SD = 10.01) were 9/11-exposed daily smokers. Cross-sectional self-report measures were used to assess PTSD symptoms, anxiety sensitivity, and respiratory symptoms. After controlling for covariates and PTSD symptoms, anxiety sensitivity accounted for significant additional variance in respiratory symptoms (ΔR 2 = .04 to .08). This effect was specific to the somatic concerns dimension (β = .29, p = .020); somatic concerns contributed significantly to accounting for the overlap between PTSD and respiratory symptoms, b = 0.03, 95% CI [0.01, 0.07]. These findings suggest that the somatic dimension of anxiety sensitivity is important in understanding respiratory symptoms in individuals with PTSD symptoms. These findings also suggest that it may be critical to address anxiety sensitivity when treating patients with comorbid respiratory problems and PTSD., (Copyright © 2017 International Society for Traumatic Stress Studies.)

Adolescent non-suicidal self-injury (NSSI), a significant risk factor for suicidal behavior, is strongly associated with adolescent psychopathology and personality traits, particularly those characterized by poor self-regulation. Some parental psychopathology and personality traits have also been identified as risk factors for adolescent NSSI, but specific parental characteristics and mechanisms involved in this association have not been systematically examined. The current study comprehensively investigated the contribution of parental psychopathology and personality to adolescent NSSI using data from the baseline wave of the Adolescent Development of Emotion and Personality Traits (ADEPT) study of 550 adolescent girls (mean age = 14.39 years, SD = 0.63) and their biological parents. We first investigated whether parental lifetime psychiatric diagnoses, and personality and clinical (rumination, self-criticism, emotional reliance) traits were associated with adolescent NSSI. We also tested whether adolescent history of psychiatric illness, personality, and clinical traits mediated the associations between parental characteristics and adolescent NSSI. Parental substance use disorder, adult-ADHD symptoms, self-criticism, and lower agreeableness and conscientiousness were associated with offspring's NSSI. These associations were mediated through adolescent characteristics. In contrast, parental mood and anxiety disorders and neuroticism were unrelated to adolescent NSSI. The results suggest that parental traits and disorders characterized by self-regulatory difficulties and lack of support constitute risk factors for self-injury in adolescent girls, acting via adolescent traits. This demonstrates that parental influences play a significant role in the etiology of adolescent NSSI., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Many previous studies have indicated that individuals who are depressed or at risk for depression are characterized by increased levels of morning cortisol and a greater cortisol awakening response (CAR). However, despite the high comorbidity between depressive and anxiety disorders, fewer studies have examined whether these diurnal cortisol abnormalities are also characteristic of anxiety or risk for anxiety., Methods: In the present study we examined cortisol in a community sample of 476 female adolescents and related it to maternal history of depression and/or anxiety disorders. Salivary cortisol was collected at waking, 30min post waking, and in the evening on three weekdays., Results: Contrary to prior results, offspring at risk for depression did not have increased morning cortisol or CAR. However, offspring at risk for anxiety disorders had elevated 30min cortisol and total cortisol produced throughout the day; this effect was primarily driven by offspring of mothers with panic disorder or agoraphobia. Additionally, levels of cortisol were highest among offspring of mothers with multiple anxiety diagnoses., Limitations: The study is limited to female adolescents and maternal diagnostic history. Additionally, some diagnoses could not be examined as a result of too few cases (e.g. GAD)., Conclusions: Overall, these results underscore the importance of considering anxiety when examining the association of diurnal cortisol abnormalities with risk for psychopathology, as it may have influenced prior observations of elevated morning cortisol in depression., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: A blunted neural response to rewards has recently emerged as a potential mechanistic biomarker of adolescent depression. The reward positivity, an event-related potential elicited by feedback indicating monetary gain relative to loss, has been associated with risk for depression. The authors examined whether the reward positivity prospectively predicted the development of depression 18 months later in a large community sample of adolescent girls., Method: The sample included 444 girls 13.5-15.5 years old with no lifetime history of a depressive disorder, along with a biological parent for each girl. At baseline, the adolescents' reward positivity was measured using a monetary guessing task, their current depressive symptoms were assessed using a self-report questionnaire, and the adolescents' and parents' lifetime psychiatric histories were evaluated with diagnostic interviews. The same interview and questionnaire were administered to the adolescents again approximately 18 months later., Results: A blunted reward positivity at baseline predicted first-onset depressive disorder and greater depressive symptom scores 18 months later. The reward positivity was also a significant predictor independent of other prominent risk factors, including baseline depressive symptoms and adolescent and parental lifetime psychiatric history. The combination of a blunted reward positivity and greater depressive symptom scores at baseline provided the greatest positive predictive value for first-onset depressive disorder., Conclusions: This study provides strong converging evidence that a blunted neural response to rewards precedes adolescent-onset depression and symptom emergence. Blunted neural response may therefore constitute an important target for screening and prevention.

Posttraumatic stress disorder (PTSD) is a debilitating and often chronic psychiatric disorder. Following the 9/11/2001 World Trade Center (WTC) attacks, thousands of individuals were involved in rescue, recovery and clean-up efforts. While a growing body of literature has documented the prevalence and correlates of PTSD in WTC responders, no study has evaluated predominant typologies of PTSD in this population. Participants were 4352 WTC responders with probable WTC-related DSM-IV PTSD. Latent class analyses were conducted to identify predominant typologies of PTSD symptoms and associated correlates. A 3-class solution provided the optimal representation of latent PTSD symptom typologies. The first class, labeled "High-Symptom (n = 1,973, 45.3%)," was characterized by high probabilities of all PTSD symptoms. The second class, "Dysphoric (n = 1,371, 31.5%)," exhibited relatively high probabilities of emotional numbing and dysphoric arousal (e.g., sleep disturbance). The third class, "Threat (n = 1,008, 23.2%)," was characterized by high probabilities of re-experiencing, avoidance and anxious arousal (e.g., hypervigilance). Compared to the Threat class, the Dysphoric class reported a greater number of life stressors after 9/11/2001 (OR = 1.06). The High-Symptom class was more likely than the Threat class to have a positive psychiatric history before 9/11/2001 (OR = 1.7) and reported a greater number of life stressors after 9/11/2001 (OR = 1.1). The High-Symptom class was more likely than the Dysphoric class, which was more likely than the Threat class, to screen positive for depression (83% > 74% > 53%, respectively), and to report greater functional impairment (High-Symptom > Dysphoric [Cohen d = 0.19], Dysphoric > Threat [Cohen d = 0.24]). These results may help inform assessment, risk stratification, and treatment approaches for PTSD in WTC and disaster responders., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Heterogeneity of psychosis presents significant challenges for classification. Between 2 and 12 symptom dimensions have been proposed, and consensus is lacking. The present study sought to identify uniquely informative models by comparing the validity of these alternatives. An epidemiologic cohort of 628 first-admission inpatients with psychosis was interviewed 6 times over 2 decades and completed an electrophysiological assessment of error processing at year 20. We first analyzed a comprehensive set of 49 symptoms rated by interviewers at baseline, progressively extracting from 1 to 12 factors. Next, we compared the ability of resulting factor solutions to (a) account for concurrent neural dysfunction and (b) predict 20-year role, social, residential, and global functioning, and life satisfaction. A four-factor model showed incremental validity with all outcomes, and more complex models did not improve explanatory power. The 4 dimensions-reality distortion, disorganization, inexpressivity, and apathy/asociality-were replicable in 5 follow-ups, internally consistent, stable across assessments, and showed strong discriminant validity. These results reaffirm the value of separating disorganization and reality distortion, are consistent with recent findings distinguishing inexpressivity and apathy/asociality, and suggest that these 4 dimensions are fundamental to understanding neural abnormalities and long-term outcomes in psychosis. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Trajectories of disaster-related posttraumatic stress disorder (PTSD) symptoms are often heterogeneous, and associated with common and unique risk factors, yet little is known about potentially modifiable psychosocial characteristics associated with low-symptom and recovering trajectories in disaster responders. A total of 4487 rescue and recovery workers (1874 police and 2613 non-traditional responders) involved during and in the aftermath of the unprecedented World Trade Center (WTC) attacks, were assessed an average of 3, 6, 8, and 12 years post-9/11/2001. Among police responders, WTC-related PTSD symptoms were characterized by four trajectories, including no/low-symptom (76.1%), worsening (12.1%), improving (7.5%), and chronic (4.4%) trajectories. In non-traditional responders, a five-trajectory solution was optimal, with fewer responders in a no/low-symptom trajectory (55.5%), and the remainder in subtly worsening (19.3%), chronic (10.8%), improving (8.5%), and steeply worsening (5.9%) trajectories. Consistent factors associated with symptomatic PTSD trajectories across responder groups included Hispanic ethnicity, pre-9/11 psychiatric history, greater WTC exposure, greater medical illness burden, life stressors and post-9/11 traumas, and maladaptive coping (e.g., substance use, avoidance coping). Higher perceived preparedness, greater sense of purpose in life, and positive emotion-focused coping (e.g., positive reframing, acceptance) were negatively associated with symptomatic trajectories. Findings in this unique cohort indicate considerable heterogeneity in WTC-related PTSD symptom trajectories over 12 years post-9/11/2001, with lower rates of elevated PTSD symptoms in police than in non-traditional responders. They further provide a comprehensive risk prediction model of PTSD symptom trajectories, which can inform prevention, monitoring, and treatment efforts in WTC and other disaster responders., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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 15years after first hospitalization, and 69 were assessed at 19years; 59 (26 with schizophrenia, 33 with other psychotic disorders) had data at both assessments. At 19years the Pe was blunted in schizophrenia. The ERN and Pe exhibited temporal stability over the four years (r=0.59 and 0.60, 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., (Copyright © 2016 Elsevier B.V. All rights reserved.)