Genome-wide association study identifies four pan-ancestry loci for suicidal ideation in the Million Veteran Program.

Suicidal ideation (SI) often precedes and predicts suicide attempt and death, is the most common suicidal phenotype and is over-represented in veterans. The genetic architecture of SI in the absence of suicide attempt (SA) is unknown, yet believed to have distinct and overlapping risk with other suicidal behaviors. We performed the first GWAS of SI without SA in the Million Veteran Program (MVP), identifying 99,814 SI cases from electronic health records without a history of SA or suicide death (SD) and 512,567 controls without SI, SA or SD. GWAS was performed separately in the four largest ancestry groups, controlling for sex, age and genetic substructure. Ancestry-specific results were combined via meta-analysis to identify pan-ancestry loci. Four genome-wide significant (GWS) loci were identified in the pan-ancestry meta-analysis with loci on chromosomes 6 and 9 associated with suicide attempt in an independent sample. Pan-ancestry gene-based analysis identified GWS associations with DRD2, DCC, FBXL19, BCL7C, CTF1, ANNK1, and EXD3. Gene-set analysis implicated synaptic and startle response pathways (q's<0.05). European ancestry (EA) analysis identified GWS loci on chromosomes 6 and 9, as well as GWS gene associations in EXD3, DRD2, and DCC. No other ancestry-specific GWS results were identified, underscoring the need to increase representation of diverse individuals. The genetic correlation of SI and SA within MVP was high (rG = 0.87; p = 1.09e-50), as well as with post-traumatic stress disorder (PTSD; rG = 0.78; p = 1.98e-95) and major depressive disorder (MDD; rG = 0.78; p = 8.33e-83). Conditional analysis on PTSD and MDD attenuated most pan-ancestry and EA GWS signals for SI without SA to nominal significance, with the exception of EXD3 which remained GWS. Our novel findings support a polygenic and complex architecture for SI without SA which is largely shared with SA and overlaps with psychiatric conditions frequently comorbid with suicidal behaviors.

Correlates of suicidal behaviors and genetic risk among United States veterans with schizophrenia or bipolar I disorder.

Persons diagnosed with schizophrenia (SCZ) or bipolar I disorder (BPI) are at high risk for self-injurious behavior, suicidal ideation, and suicidal behaviors (SB). Characterizing associations between diagnosed health problems, prior pharmacological treatments, and polygenic scores (PGS) has potential to inform risk stratification. We examined self-reported SB and ideation using the Columbia Suicide Severity Rating Scale (C-SSRS) among 3,942 SCZ and 5,414 BPI patients receiving care within the Veterans Health Administration (VHA). These cross-sectional data were integrated with electronic health records (EHRs), and compared across lifetime diagnoses, treatment histories, follow-up screenings, and mortality data. PGS were constructed using available genomic data for related traits. Genome-wide association studies were performed to identify and prioritize specific loci. Only 20% of the veterans who reported SB had a corroborating ICD-9/10 EHR code. Among those without prior SB, more than 20% reported new-onset SB at follow-up. SB were associated with a range of additional clinical diagnoses, and with treatment with specific classes of psychotropic medications (e.g., antidepressants, antipsychotics, etc.). PGS for externalizing behaviors, smoking initiation, suicide attempt, and major depressive disorder were associated with SB. The GWAS for SB yielded no significant loci. Among individuals with a diagnosed mental illness, self-reported SB were strongly associated with clinical variables across several EHR domains. Analyses point to sequelae of substance-related and psychiatric comorbidities as strong correlates of prior and subsequent SB. Nonetheless, past SB was frequently not documented in health records, underscoring the value of regular screening with direct, in-person assessments, especially among high-risk individuals.

Computerized Cognitive and Skills Training in Older People With Mild Cognitive Impairment: Using Ecological Momentary Assessment to Index Treatment-Related Changes in Real-World Performance of Technology-Dependent Functional Tasks.

OBJECTIVES: Cognitive and functional skills training improves skills and cognitive test performance, but the true test of efficacy is real-world transfer. We trained participants with mild cognitive impairment (MCI) or normal cognition (NC) for up to 12 weeks on six technology-related skills using remote computerized functional skills assessment and training (FUNSAT) software. Using ecological momentary assessment (EMA), we measured real-world performance of the technology-related skills over 6 months and related EMA-identified changes in performance to training gains. DESIGN: Randomized clinical trial with post-training follow-up. SETTING: A total of 14 Community centers in New York City and Miami. PARTICIPANTS: Older adults with normal cognition (n = 72) or well-defined MCI (n = 92), ranging in age from 60 to 90, primarily female, and racially and ethnically diverse. INTERVENTION: Computerized cognitive and skills training. MEASUREMENTS: EMA surveys measuring trained and untrained functional skills 3 or more days per week for 6 months and training gains from baseline to end of training. RESULTS: Training gains in completion times across all 6 tasks were significant (p <0.001) for both samples, with effect sizes more than 1.0 SD for all tasks. EMA surveys detected increases in performance for both trained (p <0.03) and untrained (p <0.001) technology-related skills for both samples. Training gains in completion times predicted increases in performance of both trained and untrained technology-related skills (all p <0.001). CONCLUSIONS: Computerized training produces increases in real-world performance of important technology-related skills. These gains continued after the end of training, with greater gains in MCI participants.

Early prediction of mastery of a computerized functional skills training program in participants with mild cognitive impairment.

BACKGROUND: Cognition in MCI has responded poorly to pharmacological interventions, leading to use of computerized training. Combining computerized cognitive training (CCT) and functional skills training software (FUNSAT) produced improvements in 6 functional skills in MCI, with effect sizes >0.75. However, 4% of HC and 35% of MCI participants failed to master all 6 tasks. We address early identification of characteristics that identify participants who do not graduate, to improve later interventions. METHODS: NC participants (n = 72) received FUNSAT and MCI (n = 92) participants received FUNSAT alone or combined FUNSAT and CCT on a fully remote basis. Participants trained twice a week for up to 12 weeks. Participants "graduated" each task when they made one or fewer errors on all 3-6 subtasks per task. Tasks were no longer trained after graduation. RESULTS: Between-group comparisons of graduation status on baseline completion time and errors found that failure to graduate was associated with more baseline errors on all tasks but no longer completion times. A discriminant analysis found that errors on the first task (Ticket purchase) uniquely separated the groups, F = 41.40, p < .001, correctly classifying 94% of graduators. An ROC analysis found an AUC of .83. MOCA scores did not increase classification accuracy. CONCLUSIONS: More baseline errors, but not completion times, predicted failure to master all FUNSAT tasks. Accuracy of identification of eventual mastery was exceptional. Detection of risk to fail to master training tasks is possible in the first 15 minutes of the baseline assessment. This information can guide future enhancements of computerized training.

Novel measures of cognition and function for the AD spectrum in the Novel Measures for Alzheimer's Disease Prevention Trials (NoMAD) project: Psychometric properties, convergent validation, and contrasts with established measures.

INTRODUCTION: This study derived composite scores for two novel cognitive measures, the No Practice Effect (NPE) battery and the Miami Computerized Functional Skills Assessment and Training system for use in early-stage Alzheimer's disease (AD) clinical trials. Their psychometric properties and associations with AD risk markers were compared to those of well-established measures. METHODS: For 291 older adults with healthy cognition or early mild cognitive impairment, Exploratory factor analyses were used to identify the factor structure of the NPE. Factor and total scores were examined for their psychometric properties and associations with AD risk biomarkers. RESULTS: Composite scores from the novel cognitive and functional measures demonstrated better psychometric properties (distribution and test-retest reliability) and stronger associations with AD-related demographic, genetic, and brain risk markers than well-established measures, DISCUSSION: These novel measures have potential for use as primary cognitive and functional outcomes in early-stage AD clinical trials. HIGHLIGHTS: Well-established cognitive tests may not accurately detect subtle cognitive changes. No Practice Effect (NPE) and Computerized Functional Skills Assessment and Training are novel measures designed to have improved psychometric properties. NPE had Executive Function, Cognitive Control/Speed, and Episodic Memory domains. Novel measures had better psychometric properties compared to established measures. Significant associations with Alzheimer's disease biomarkers were found with novel measures.

Confidence, accuracy judgments and feedback in schizophrenia and bipolar disorder: a time series network analysis.

BACKGROUND: Inaccurate self-assessment of performance is common among people with serious mental illness, and it is associated with poor functional outcomes independent from ability. However, the temporal interdependencies between judgments of performance, confidence in accuracy, and feedback about performance are not well understood. METHODS: We evaluated two tasks: the Wisconsin Card Sorting Test (WCST) and the Penn Emotion recognition task (ER40). These tasks were modified to include item-by-item confidence and accuracy judgments, along with feedback on accuracy. We evaluated these tasks as time series and applied network modeling to understand the temporal relationships between momentary confidence, accuracy judgments, and feedback. The sample constituted participants with schizophrenia (SZ; N = 144), bipolar disorder (BD; N = 140), and healthy controls (HC; N = 39). RESULTS: Network models for both WCST and ER40 revealed denser and lagged connections between confidence and accuracy judgments in SZ and, to a lesser extent in BD, that were not evidenced in HC. However, associations between feedback regarding accuracy with subsequent accuracy judgments and confidence were weaker in SZ and BD. In each of these comparisons, the BD group was intermediate between HC and SZ. In analyses of the WCST, wherein incorporating feedback is crucial for success, higher confidence predicted worse subsequent performance in SZ but not in HC or BD. CONCLUSIONS: While network models are exploratory, the results suggest some potential mechanisms by which challenges in self-assessment may impede performance, perhaps through hyperfocus on self-generated judgments at the expense of incorporation of feedback.

Reading the mind in the eyes and cognitive ability in schizophrenia- and autism spectrum disorders.

BACKGROUND: Schizophrenia (SZ) and autism spectrum disorders (ASD) are characterized by difficulties in theory of mind (ToM). We examined group differences in performance on a ToM-related test and associations with an estimated IQ. METHODS: Participants [N = 1227, SZ (n = 563), ASD (n = 159), and controls (n = 505), 32.2% female] completed the Reading the Mind in the Eyes Test (RMET) and assessments of cognitive ability. Associations between IQ and group on RMET were investigated with regression analyses. RESULTS: SZ (d = 0.73, p < 0.001) and ASD (d = 0.37, p < 0.001) performed significantly worse on the RMET than controls. SZ performed significantly worse than ASD (d = 0.32, p = 0.002). Adding IQ to the model, SZ (d = 0.60, p < 0.001) and ASD (d = 0.44, p < 0.001) continued to perform significantly worse than controls, but no longer differed from each other (d = 0.13, p = 0.30). Small significant negative correlations between symptom severity and RMET performance were found in SZ (PANSS positive: r = -0.10, negative: r = -0.11, both p < 0.05). A small non-significant negative correlation was found for Autism Diagnostic Observation Schedule scores and RMET in ASD (r = -0.08, p = 0.34). CONCLUSIONS: SZ and ASD are characterized by impairments in RMET. IQ contributed significantly to RMET performance and accounted for group differences in RMET between SZ and ASD. This suggests that non-social cognitive ability needs to be included in comparative studies of the two disorders.

Life engagement in people living with schizophrenia: predictors and correlates of patient life engagement in a large sample of people living in the community.

BACKGROUND: Life engagement represents a holistic concept that encompasses outcomes reflecting life-fulfilment, well-being and participation in valued and meaningful activities, which is recently gaining attention and scientific interest. Despite its conceptual importance and its relevance, life engagement represents a largely unexplored domain in schizophrenia. The aims of the present study were to independently assess correlates and predictors of patient life engagement in a large and well-characterized sample of schizophrenia patients. METHODS: To assess the impact of different demographic, clinical, cognitive and functional parameters on life engagement in a large sample of patients with schizophrenia, data from the social cognition psychometric evaluation project were analyzed. RESULTS: Overall schizophrenia and depressive symptom severity, premorbid IQ, neurocognitive performance, social cognition performance both in the emotion processing and theory of mind domains, functional capacity, social skills performance and real-world functioning in different areas all emerged as correlates of patient life engagement. Greater symptom severity and greater impairment in real-world interpersonal relationships, social skills, functional capacity and work outcomes emerged as individual predictors of greater limitations in life engagement. CONCLUSIONS: Life engagement in people living with schizophrenia represents a holistic and complex construct, with several different clinical, cognitive and functional correlates. These features represent potential treatment targets to improve the clinical condition and also facilitate the process of recovery and the overall well-being of people living with schizophrenia.

A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci.

To identify pan-ancestry and ancestry-specific loci associated with attempting suicide among veterans, we conducted a genome-wide association study (GWAS) of suicide attempts within a large, multi-ancestry cohort of U.S. veterans enrolled in the Million Veterans Program (MVP). Cases were defined as veterans with a documented history of suicide attempts in the electronic health record (EHR; N = 14,089) and controls were defined as veterans with no documented history of suicidal thoughts or behaviors in the EHR (N = 395,064). GWAS was performed separately in each ancestry group, controlling for sex, age and genetic substructure. Pan-ancestry risk loci were identified through meta-analysis and included two genome-wide significant loci on chromosomes 20 (p = 3.64 × 10-9) and 1 (p = 3.69 × 10-8). A strong pan-ancestry signal at the Dopamine Receptor D2 locus (p = 1.77 × 10-7) was also identified and subsequently replicated in a large, independent international civilian cohort (p = 7.97 × 10-4). Additionally, ancestry-specific genome-wide significant loci were also detected in African-Americans, European-Americans, Asian-Americans, and Hispanic-Americans. Pathway analyses suggested over-representation of many biological pathways with high clinical significance, including oxytocin signaling, glutamatergic synapse, cortisol synthesis and secretion, dopaminergic synapse, and circadian rhythm. These findings confirm that the genetic architecture underlying suicide attempt risk is complex and includes both pan-ancestry and ancestry-specific risk loci. Moreover, pathway analyses suggested many commonly impacted biological pathways that could inform development of improved therapeutics for suicide prevention.

Mild Cognitive Impairment, But Not HIV Status, is Related to Reduced Awareness of Level of Cognitive Performance Among Older Adults.

OBJECTIVE: Self-assessment of cognitive abilities can be an important predictor of clinical outcomes. This study examined impairments in self-assessments of cognitive performance, assessed with traditional neuropsychological assessments and novel virtual reality tests among older persons with and without human immunodeficiency virus (HIV) and mild cognitive impairment (MCI). METHODS: One hundred twenty-two participants (82 persons with HIV; 79 MCI+) completed a traditional neuropsychological battery, DETECT virtual reality cognitive battery, and self-reported their general cognitive complaints, depressive symptoms, and perceptions of DETECT performance. Relationships between DETECT performance and self-assessments of performance were examined as were the correlations between general cognitive complaints and performance. These relations were evaluated across HIV and MCI status, considering the associations of depressive symptoms, performance, and self-assessment. RESULTS: We found no effect of HIV status on objective performance or self-assessment of DETECT performance. However, MCI+ participants performed worse on DETECT and traditional cognitive tests, while also showing a directional bias towards overestimation of their performance. MCI- participants showed a bias toward underestimation. Cognitive complaints were reduced compared to objective performance in MCI+ participants. Correlations between self-reported depressive symptoms and cognitive performance or self-assessment of performance were nonsignificant. CONCLUSIONS: MCI+ participants underperformed on neuropsychological testing, while overestimating performance. Interestingly, MCI- participants underestimated performance to approximately the same extent as MCI+ participants overestimated. Practical implications include providing support for persons with MCI regarding awareness of limitations and consideration that self-assessments of cognitive performance may be overestimated. Similarly, supporting older persons without MCI to realistically appraise their abilities may have clinical importance.

The Tripartite Model of Depression in Schizophrenia and Bipolar Disorder: A Secondary Analysis.

ABSTRACT: Models of affect, like the tripartite model, suggest that positive affect (PA) and negative affect (NA) are independent between subjects and negatively correlated within. Correlations may differ in bipolar disorder (BD) and schizophrenia. Using ecological momentary assessment (EMA) and clinical ratings, this secondary analysis evaluated the tripartite model by examining PA and NA. Two hundred eighty-one participants with BD or a psychotic disorder completed 30 days of EMA of PA and NA, and clinical raters assessed depression. PA and NA were more related between subjects and less related within subjects among participants with schizophrenia. In BD, lower momentary PA was positively associated with clinical ratings of depression, although greater momentary NA was not significantly associated with clinical ratings. In schizophrenia, the inverse was found. These results suggest that the tripartite model was not confirmed in people with schizophrenia or BD. However, PA and NA manifested associations in BD that were more congruent with population studies than in schizophrenia. These findings may have implications for clinical interventions targeting depression, PA, and NA in these populations.

Immediate post performance judgements about cognitive performance in schizophrenia and bipolar disorder: associations with test performance and subjective overall judgments regarding abilities.

INTRODUCTION: The study explored associations between the accuracy of post assessment judgements of cognitive performance with global self-assessments of psychosocial functioning compared to evaluations generated by observers in schizophrenia and bipolar disorder. METHODS: An abbreviated cognitive assessment based on the MATRICS Consensus Cognitive Battery was administered to 122 individuals with schizophrenia and 113 with bipolar disorder. They provided self-estimates of their performance after each subtest. In addition, self-reports on cognition, social cognition, and everyday functioning were collected and compared to observer ratings. RESULTS: Both groups overestimated their cognitive function, but in bipolar disorder, there was 30% shared variance between task performance and self-rated task performance (vs. 5% in schizophrenia). Significant correlations were found between self-reported everyday outcomes and both actual and self-assessed performance. In schizophrenia, immediate judgements were only related to self-rated functioning, not to observer rated functioning. In bipolar disorder, impairments in self-assessment of performance correlated with observer ratings of cognitive ability, which was not observed in schizophrenia. CONCLUSIONS: While both groups showed correlations between cognitive performance and introspective accuracy, individuals with bipolar disorder showed higher accuracy in assessing their cognitive performance and other outcomes. Notably, impairments in introspective accuracy were associated with observer-rated functioning exclusively in bipolar disorder.

Specific Associations Between Type of Childhood Abuse and Elevated C-Reactive Protein in Young Adult Psychiatric Rehabilitation Participants.

BACKGROUND: Early-life adversity such as childhood emotional, physical, and sexual trauma is associated with later-life psychiatric and chronic medical conditions, including elevated inflammatory markers. Although previous research suggests a role for chronic inflammatory dysfunctions in several disease etiologies, specific associations between childhood trauma types and later-life inflammation and health status are poorly understood. METHODS: We studied patients (n = 280) admitted to a psychiatric rehabilitation center. Self-reported histories of childhood emotional, physical, and sexual trauma were collected with a standard instrument. At the time of admission, we also assessed individuals' body mass index and collected blood samples used to examine inflammatory marker C-reactive protein (CRP) levels. RESULTS: The prevalence of all 3 types of abuse was relatively high at 21% or more. Fifty percent of the sample had elevations in CRP, with clinically significant elevations in 26%. We found that compared with a history of emotional or physical abuse, a history of childhood sexual trauma was more specifically associated with elevated CRP. This result held up when using linear regressions to examine the contribution of body mass index. LIMITATION: Our sample was relatively young, with an average age of 27.2 years and minimal representation of ethnic and racial minority participants. CONCLUSION: Relative to childhood emotional and physical trauma, childhood sexual trauma may lead to elevated inflammatory responses, as confirmed in our finding of an association between CRP and sexual abuse. Future studies need to assess the causal link between childhood sexual trauma and poorer health outcomes later in life.

Ecological momentary facial emotion recognition in psychotic disorders.

BACKGROUND: Cognitive tasks delivered during ecological momentary assessment (EMA) may elucidate the short-term dynamics and contextual influences on cognition and judgements of performance. This paper provides initial validation of a smartphone task of facial emotion recognition in serious mental illness. METHODS: A total of 86 participants with psychotic disorders (non-affective and affective psychosis), aged 19-65, were administered in-lab 'gold standard' affect recognition, neurocognition, and symptom assessments. They subsequently completed 10 days of the mobile facial emotion recognition task, assessing both accuracy and self-assessed performance, along with concurrent EMA of psychotic symptoms and mood. Validation focused on task adherence and predictors of adherence, gold standard convergent validity, and symptom and diagnostic group variation. RESULTS: The mean rate of adherence to the task was 79%; no demographic or clinical variables predicted adherence. Convergent validity was observed with in-lab measures of facial emotion recognition, and no practice effects were observed on the mobile facial emotion recognition task. EMA reports of more severe voices, sadness, and paranoia were associated with worse performance, whereas mood more strongly associated with self-assessed performance. CONCLUSION: The mobile facial emotion recognition task was tolerated and demonstrated convergent validity with in-lab measures of the same construct. Social cognitive performance, and biased judgements previously shown to predict function, can be evaluated in real-time in naturalistic environments.

Integration of peripheral transcriptomics, genomics, and interactomics following trauma identifies causal genes for symptoms of post-traumatic stress and major depression.

Posttraumatic stress disorder (PTSD) is a debilitating syndrome with substantial morbidity and mortality that occurs in the aftermath of trauma. Symptoms of major depressive disorder (MDD) are also a frequent consequence of trauma exposure. Identifying novel risk markers in the immediate aftermath of trauma is a critical step for the identification of novel biological targets to understand mechanisms of pathophysiology and prevention, as well as the determination of patients most at risk who may benefit from immediate intervention. Our study utilizes a novel approach to computationally integrate blood-based transcriptomics, genomics, and interactomics to understand the development of risk vs. resilience in the months following trauma exposure. In a two-site longitudinal, observational prospective study, we assessed over 10,000 individuals and enrolled >700 subjects in the immediate aftermath of trauma (average 5.3 h post-trauma (range 0.5-12 h)) in the Grady Memorial Hospital (Atlanta) and Jackson Memorial Hospital (Miami) emergency departments. RNA expression data and 6-month follow-up data were available for 366 individuals, while genotype, transcriptome, and phenotype data were available for 297 patients. To maximize our power and understanding of genes and pathways that predict risk vs. resilience, we utilized a set-cover approach to capture fluctuations of gene expression of PTSD or depression-converting patients and non-converting trauma-exposed controls to find representative sets of disease-relevant dysregulated genes. We annotated such genes with their corresponding expression quantitative trait loci and applied a variant of a current flow algorithm to identify genes that potentially were causal for the observed dysregulation of disease genes involved in the development of depression and PTSD symptoms after trauma exposure. We obtained a final list of 11 driver causal genes related to MDD symptoms, 13 genes for PTSD symptoms, and 22 genes in PTSD and/or MDD. We observed that these individual or combined disorders shared ESR1, RUNX1, PPARA, and WWOX as driver causal genes, while other genes appeared to be causal driver in the PTSD only or MDD only cases. A number of these identified causal pathways have been previously implicated in the biology or genetics of PTSD and MDD, as well as in preclinical models of amygdala function and fear regulation. Our work provides a promising set of initial pathways that may underlie causal mechanisms in the development of PTSD or MDD in the aftermath of trauma.

Improvements in Cognitive Performance With Computerized Training in Older People With and Without Cognitive Impairment: Synergistic Effects of Skills-Focused and Cognitive-Focused Strategies.

OBJECTIVES: Both cognitively impaired (CI) and nonimpaired (NC) older people have challenges in performing everyday tasks. Previous skills training efforts in NC individuals have led to improvements in both functional skills and cognitive functioning. We evaluated the cognitive benefits of combining computerized cognitive training (CCT) with a computer-based functional skills assessment and training (CFSAT) program in a sample of CI and NC older adults. DESIGN: Randomized parallel clinical trial with two treatment conditions: up to 24 sessions of CFSAT training alone or CFSAT plus speed focused CCT. PARTICIPANTS: NC (n = 62) and CI (n = 55) older adults, ranging in age from 60-86 years (M = 73.12), primarily female (90%), and ethnically diverse (21% Hispanic, 52% African American). Participants were divided based on Montreal Cognitive Assessment scores and cognitive complaints. SETTING: Three different community centers in Miami, FL. MEASUREMENTS: The Brief Assessment of Cognition, app version, was used to measure cognitive performance across six different cognitive domains before and after training. RESULTS: All six cognitive domains improved from baseline. Multivariate analyses found the effects of the combined CFSAT and CCT to be superior. The interaction of training condition and cognitive status was not statistically significant, indicating no global impact of cognitive status on improvements in cognition across training conditions. CONCLUSIONS: CFSAT training was associated with cognitive benefits, particularly in CI participants. The combined intervention led to greater improvements. Consistent with results of previous studies, there is considerable evidence of cognitive plasticity in older adults, including those with CI.

Childhood Trauma Associations With the Interpersonal Psychological Theory of Suicide and Social Cognitive Biases in Psychotic Disorders.

ABSTRACT: Childhood trauma (CT) is associated with suicidal ideation and behaviors (SI/SB) in people with psychosis. The interpersonal psychological theory of suicide (IPTS) suggests that there are four factors that increase suicide risk: thwarted belongingness, perceived burdensomeness, acquired capacity for suicide, and hopelessness. The IPTS constructs and social cognitive biases are associated with SI/SB in psychotic disorders. However, the role of CT in IPTS constructs and social cognitive biases has not been examined in psychosis. In an outpatient community sample of persons with psychotic disorders (N = 96) assessed with the Childhood Trauma Questionnaire, the aims of this study were to a) evaluate rates of CT in this sample, b) determine the relationship between CT types and lifetime SI/SB, and c) explore the relationship between CT types, IPTS constructs, and social cognitive biases. All participants reported experiencing CT. Emotional abuse was associated with greater SI severity and higher rates of lifetime suicide attempts, as well as with greater perceived burdensomeness and more severe negative social cognitive biases. Other CT types were minimally associated with SI/SB or IPST constructs; hopelessness was not associated. Overall, negative interpersonal beliefs and social cognitive biases may explain how CT increases suicide risk in psychosis.

The association of momentary sad moods, concurrent productive behaviour, and global functional outcomes: a 30-day ecological momentary assessment study of people with bipolar illness.

BACKGROUND: Previous weekly sampling studies found that persistent sad moods are associated with disability in bipolar illness. However, those data were collected retrospectively. We examined the momentary quality of activities (productive, unproductive, and passive recreation) in an ecological momentary assessment (EMA) study and related sadness at each survey to quality of momentary activities and overall everyday functioning. METHODS: Participants with bipolar illness (N = 91) were sampled three times per day for 30 days. Each survey queried participants as to where they were, with whom, what they were doing, and their mood state. Activities were characterised according to predetermined criteria and related to momentary sadness. Observer ratings of everyday functioning were related to daily reports of sadness and activities. RESULTS: Sadness was associated with the quality of activities. Momentary reports of unproductive activities were associated with the most sadness (p < .001), followed by passive recreation, and productive activities. Momentary sadness and momentary unproductive activities correlated with observer ratings of competence in work, everyday activities, and social outcomes (p < .001). Using both predictors led to the best model. CONCLUSIONS: This study on the course of sad moods in people with bipolar illness to EMA found that momentary sadness correlatesdwith the quality of concurrent activities and that both sadness and the quality of everyday activities predicted observer ratings of everyday functioning. Although we cannot determine the causal direction, these findings support the hypothesis that momentary sadness leads to reductions in productive activities and impairments in everyday functioning.

Pathways from performance monitoring to negative symptoms and functional outcomes in psychotic disorders.

BACKGROUND: Performance 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. METHODS: Data 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. RESULTS: Blunted 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 (ß = 0.10); reduced Pe to global functioning was mediated by executive function and avolition (ß = 0.10). CONCLUSIONS: This 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.

Efficacy of Vortioxetine Monotherapy for Posttraumatic Stress Disorder: A Randomized, Placebo-Controlled Trial.

PURPOSE/BACKGROUND: There are few efficacious pharmacological treatments for posttraumatic stress disorder (PTSD) and many patients fail to benefit from existing treatments. Vortioxetine, a recently developed antidepressant, acts as a serotonin modulator through inhibition of the serotonin transporter and actions at multiple types of serotonin receptors. Its unique pharmacodynamic profile suggests it may have efficacy for the treatment of PTSD. METHODS/PROCEDURES: We conducted a 12-week placebo-controlled, randomized clinical trial of vortioxetine (flexibly dosed from 10 to 20 mg/d) versus placebo in adults with PTSD. The primary outcome was change from baseline in the past-month version of the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), analyzed using a mixed-model repeated-measures analysis of variance. FINDINGS/RESULTS: Forty-one patients were randomized, and 32 (78%) completed the 12 weeks of treatment. The mean reduction in CAPS-5 scores at week 12 did not significantly differ between the 2 arms; the effect size for the difference in changes between vortioxetine and placebo on CAPS-5 total scores at week 12 was Cohen d = 0.29. However, at week 8, the drug-placebo difference was d = 0.78, which met the multivariate criteria for statistical significance, P = 0.014. IMPLICATIONS/CONCLUSIONS: In this study of 41 patients, vortioxetine did not demonstrate superiority over placebo for adults with PTSD. Future PTSD trials may benefit from stratifying the randomization based on number of years since the index traumatic event and a history of failure to respond to treatment.