Psychiatric Controls Research Articles

Infection preventionists’ challenges in psychiatric clinical settings

Infection preventionists (IPs) play an important role in preventing health care-associated infections in a health care system. However, the limitations of the clinical setting and the unique characteristics of psychiatric patients could be barriers to effective infection prevention. The purpose of this study was to understand how IPs perceived their challenges and how these challenges negatively affect their infection prevention work in psychiatric clinical settings. A descriptive, qualitative research approach was used in this study. Thirteen Taiwanese psychiatric IPs were interviewed in semistructured interviews. Data were transcribed and then analyzed by thematic analysis. This analysis identified 6 themes: (1) lack of preservice training in psychiatric infection control, (2) insufficient staffing in practice, (3) working within environmental limits, (4) patient noncompliance, (5) undervaluation of the importance of infection control by professionals, and (6) involvement of hospital administrators. The implementation of effective infection prevention in psychiatric clinical settings may be strongly related to the factors of sufficient training and IP staffing while relying on collaboration among patients and clinical professionals and on the full support of administrators.

Elevated expression of a minor isoform of ANK3 is a risk factor for bipolar disorder

Ankyrin-3 (ANK3) is one of the few genes that have been consistently identified as associated with bipolar disorder by multiple genome-wide association studies. However, the exact molecular basis of the association remains unknown. A rare loss-of-function splice-site SNP (rs41283526*G) in a minor isoform of ANK3 (incorporating exon ENSE00001786716) was recently identified as protective of bipolar disorder and schizophrenia. This suggests that an elevated expression of this isoform may be involved in the etiology of the disorders. In this study, we used novel approaches and data sets to test this hypothesis. First, we strengthen the statistical evidence supporting the allelic association by replicating the protective effect of the minor allele of rs41283526 in three additional large independent samples (meta-analysis p-values: 6.8E–05 for bipolar disorder and 8.2E–04 for schizophrenia). Second, we confirm the hypothesis that both bipolar and schizophrenia patients have a significantly higher expression of this isoform than controls (p-values: 3.3E–05 for schizophrenia and 9.8E–04 for bipolar type I). Third, we determine the transcription start site for this minor isoform by Pacific Biosciences sequencing of full-length cDNA and show that it is primarily expressed in the corpus callosum. Finally, we combine genotype and expression data from a large Norwegian sample of psychiatric patients and controls, and show that the risk alleles in ANK3 identified by bipolar disorder GWAS are located near the transcription start site of this isoform and are significantly associated with its elevated expression. Together, these results point to the likely molecular mechanism underlying ANK3´s association with bipolar disorder.

Social desirability, deceptive reporting, and awareness of problematic aggression in intermittent explosive disorder compared with non-aggressive healthy and psychiatric controls

Individuals with DSM-5 Intermittent Explosive Disorder (IED) are often suspected of minimizing the nature of their recurrent, problematic, impulsive aggressive behavior due to the social undesirability of these behaviors. Our first study involved 400 study participants categorized as Healthy Controls (HC), Psychiatric Controls (PC) and as having IED and included the Crowne-Marlowe Social Desirability Scale (SDS), the Lie Scale from the Eysenck Personality Questionnaire-Revised (EPQ-R Lie), and the Readiness to Change (Anger) Questionnaire (RTC). IED study participants had lower SDS and lower EPQ-R Lie scores, while having higher RTC scores, compared with both HC and PC study participants. Thus, when studied in a clinical research setting, IED study participants do not provide socially desirable answers to questions and do not engaging in deceptive reporting; likely because they have recognized their need/interest in reducing their own impulsive aggressive behavior. The second study, part of a family study of 70 probands and their first-degree relatives revealed a very high positive (96.3%), but substantially lower negative (55.8%), predictive power for IED based on informant report. This suggests that, while interview of close informants can confirm the diagnosis of IED, informant interviews cannot rule out IED when such informants provide a negative report.

Risk of Major Malformations in Infants Following First-Trimester Exposure to Quetiapine.

Second-generation antipsychotics are commonly prescribed to reproductive-age women for the treatment of a spectrum of psychiatric disorders. Quetiapine is the most commonly prescribed medication in this class, and therefore a better understanding of its reproductive safety profile is critical. The goal of this study was to determine the risk of major malformations among infants exposed to quetiapine during pregnancy compared with a group of infants whose mothers had a history of psychiatric morbidity but who did not use a second-generation antipsychotic during pregnancy. The National Pregnancy Registry for Atypical Antipsychotics interviews pregnant women ages 18-45 during pregnancy and the postpartum period. Obstetric, labor, and delivery medical records and pediatric medical records from the first 6 months of life were screened for evidence of major malformations, followed by adjudication by a blinded dysmorphologist. Women with first-trimester exposure to quetiapine were compared with control subjects without exposure to second-generation antipsychotics. As of March 2017, 888 women had enrolled prospectively and 357 were eligible for analysis. Of these, 152 women with first-trimester exposure to quetiapine were compared with 205 control subjects without any second-generation antipsychotic exposure. For the 155 infants born to women in the exposed group (including three sets of twins), two major malformations were confirmed (1.3%), compared with three major malformations among the 210 infants born in the unexposed group (including five sets of twins) (1.4%). The unadjusted odds ratio for major malformations between infants with and without quetiapine exposure was 0.90 (95% CI=0.15, 5.46), which is consistent with the pooled estimate of the available controlled data on fetal exposure to quetiapine. These data regarding the safety of fetal exposure to quetiapine in a small sample of well-characterized participants are reassuring given that the confidence interval does not exceed a fivefold increased risk of major malformations relative to psychiatric control subjects. Future analyses based on ongoing data collection will produce more precise estimates.

Comorbidity of personality disorder with intermittent explosive disorder

There is ambiguity in how recurrent anger and aggression are accounted for by psychiatric nosology. One area of uncertainty is the extent to which Intermittent Explosive Disorder (IED) overlaps with and is distinct from Personality Disorder (PD). Accordingly, we conducted a study of individuals with IED and PD in order to understand the nature of comorbidity relationships seen across these two areas of psychopathology. One-thousand-five-hundred-twenty-one adults were studied (441 Healthy Controls (HC), 430 Psychiatric Controls (PC), and 650 IED subjects) and assessed for DSM-5 psychiatric disorders, life history of aggressive behavior, trait aggression, state and trait anger reactivity, and impulsivity. While nearly half of IED study participants had a comorbid PD diagnosis, nearly half with a Cluster B PD, almost as many had other personality disorders. IED predicted anger symptoms and history of aggressive behavior above and beyond a PD diagnosis. Comorbidity between IED and either Antisocial (AsPD) or Borderline (BPD) PD was associated with the highest levels of aggressive behavior. However, having IED comorbid with either AsPD and/or BPD PD was not associated with higher levels of impulsivity. Underlying personality traits related to anger, affect, and social behavior, but not identity disturbance, contribute to the shared symptom profile of IED and PD. IED is usually comorbid with PD, but does not have a unique relationship with any single PD. When comorbid with PD, a diagnosis of IED predicts more severe anger and aggression, but not necessarily increased impulsivity. These results suggest that IED and PD diagnoses retain clinical utility when made in cases meeting criteria for both.

P4431The effect of schizophrenia on length of in-hospital stay and major adverse cardiac events following acute coronary syndrome in Denmark

Background: The relationship between schizophrenia and acute coronary syndrome (ACS) has already been established. This study aims to investigate the difference in length of in-hospital stay (LoS) between a population with schizophrenia and a psychiatric healthy control (PHC) population following admission for a first ACS. Methods: Data for this retrospective study was collected from three nationwide databases in Denmark; The Danish Civil Registration System, the National Patient register and the Danish Psychiatric Central Register. Patients diagnosed with a first ACS (unstable angina ICD-10 I20.0, NSTEMI ICD-10 I21.4 and STEMI ICD-10 I21.0-I21.3) between 2000–2014 were identified and screened for an additional diagnosis of narrow spectrum schizophrenia ICD-10 F20. The patients were matched 1:2 to a PHC population on gender, age and year of first ACS diagnosis. The LoS, as well as the effect of schizophrenia on major adverse cardiac events (MACE: stroke, reinfarction and all-cause mortality) was investigated using cox regression analyses. Results: A total of 1,572 patients were analysed (schizophrenia: n=524), 65.27% of the population were males and the mean age was 61.13 years. There was no difference in LoS (p>0.05) between the populations. Patients with schizophrenia had a higher prevalence of cardiac risk factors such as anemia and diabetes mellitus. Having schizophrenia had a significant effect on stroke (HR 1.47, 95% CI: 1.29–1.68)) and all-cause mortality rates (HR 2.69, 95% CI: 2.25–3.20). The results for the individual ACS diagnoses can be found in Table 1. (Less)

Cardiovascular and metabolic comorbidities in patients with Alzheimer's disease and vascular dementia compared to a psychiatric control cohort

Multimorbidity in dementia is associated with an increased risk of complications and a higher need for care. Having knowledge of cardiovascular and metabolic comorbidities is crucial when making decisions about diagnostic procedures and therapies. We compared the prevalence of comorbidities in hospitalized patients with Alzheimer's disease (AD), vascular dementia, and psychiatric diseases other than dementia. Additionally, we compared clinically relevant health-care indicators (length of hospital stay, rate of re-hospitalization) between these groups. We used information from a database of treatment-relevant indicators from psychiatric and psychosomatic hospitals throughout Germany. This database contains routinely recorded data collected from 85 German hospitals from 2011 to 2015. In total, 14 411 AD cases, 7156 vascular dementia cases, and 34 534 cases involving non-demented psychiatric patients (used as controls) were included. To analyze comorbidities and health-care indicators, χ2 tests and t-tests were used. Diabetes mellitus, lipoprotein disorders, coronary artery diseases, cardiac arrhythmia and insufficiency, and atherosclerosis were significantly more prevalent in patients with vascular dementia than in those with AD and psychiatric controls. Hypertension and coronary artery diseases were less frequently associated with AD than with non-demented psychiatric controls (P < 0.001). Additionally, dementia patients with cardiovascular or metabolic diseases exhibited longer hospital stays (+ 1.4 days, P < 0.001) and were more often re-hospitalized within 3 weeks (P < 0.001) and 1 year (P < 0.001) compared to dementia patients without these comorbidities. Awareness of somatic comorbidities in patients with dementia is crucial to avoid complications during inpatient treatment. The occurrence of comorbid disorders was associated with longer and more frequent hospital stays, which potentially lead to higher health-care costs. Further studies should evaluate the causative association between somatic comorbidities and inpatient costs in dementia patients.

Медикализация преступности в советской судебной психиатрии, 1918–1936 гг.

Михаил Александрович Погорелов – аспирант Школы исторических наук и стажер-исследователь Центра источниковедения Национального исследовательского университета «Высшая школа экономики», Москва, Россия. Электроннаяпочта: mikhail.alex.pogorelov@gmail.com&#x0D; В статье рассматривается история раннесоветской судебной психиатрии, которая появляется как полноценная академическая дисциплина и судебно-медицинская практика в 1920–1930-е гг. На материалах профессиональных совещаний и съездов, научных работ, законодательных и ведомственных документов рассмотрено, как складывалась профессиональная юрисдикция новой дисциплины и профессии. На короткий период психиатры получили возможность самостоятельно определять задачи и сферу компетенции собственной деятельности. Это, а также неоднозначность раннесоветского уголовного законодательства, привело к значительной экспансии «биосоциального» понимания преступности в судебно-психиатрической практике и теории. Некоторые советские психиатры сформулировали концепции, связывающие антисоциальные действия правонарушителей с их патологической предрасположенностью. Благодаря этому множество «пограничных» случаев – в частности, широко трактуемые психопатии – были включены в юрисдикцию судебной психиатрии. Медикализируя преступность, представители этой дисциплины претендовали на повсеместное проникновение в пенитенциарные учреждения. Ситуация изменилась в 1930-е гг.: реагируя на политические вызовы «социалистического наступления», дисциплина начинает перестраивать собственную профессиональную юрисдикцию. Во-первых, переопределена и сужена категория «психопатов». Невменяемыми и подлежащими принудительному лечению признавались только подсудимые с «тяжелыми» органическими заболеваниями, а все «пограничные» случаи передавались в ведение общей юстиции. Во-вторых, были переформулированы задачи дисциплины: если в 1920-х гг. исследования психиатров охватывали широкий спектр тем, связанных с изучением связей преступности и душевной болезни, а основная цель декларировалась как социальная экспертиза, то в середине 1930-х гг. судебная психиатрия ограничивается узкопрактической задачей – предоставлением экспертных заключений судебно-следственным органам. Эти процессы были связаны со стабилизацией профессиональной юрисдикции и институциализацией судебной психиатрии как академической дисциплины и профессии с четко очерченной сферой компетенции и набором задач, что происходило в условиях «сталинизации» науки и ужесточения юстиции.&#x0D;

Ultrahigh risk for developing psychosis and psychotic personality organization.

Childhood adversities combined with unsafe parenting may disturb personality development. This study investigated whether psychotic personality organization as defined by Kernberg and assessed with de Dutch Short Form of the MMPI (DSFM) is more prevalent in ultrahigh risk (UHR) for psychosis compared with non-psychotic psychiatric control patients (NPPC). A total of 73 UHR and 119 NPPC patients were assessed with the DSFM and the Comprehensive Assessment of at Risk Mental States (CAARMS). The results showed that the psychotic personality organization (PPO) was not associated to UHR status. The UHR group showed more severe symptoms, particularly higher scores on DSFM subscales negativism (negative affect) and somatization (vague somatic complaints) and severe psychopathology (psychotic symptoms and dissociation). The PPO profile is not associated to the risk of developing psychosis.

Obsessive compulsive disorder prevalence increases with latitude

Many individuals with obsessive compulsive disorder (OCD) report difficulty falling asleep until later than desired. This may reflect a misalignment between the sleep-wake cycle and the natural light dark cycle. Delayed bedtimes are related to disruptions in cognitive processes, increases in repetitive negative thinking, and OCD symptoms. Misalignment is more common in higher latitudes. AIMS: We hypothesized that the prevalence of OCD would be positively correlated with latitude. A systematic review of the literature identified peer-reviewed publications with estimates of OCD prevalence in the general population. Twenty-four estimates of the lifetime prevalence of OCD were identified and showed that the prevalence of OCD was significantly positively correlated with latitude. Other potential alternative individual, community and study specific factors were not significantly correlated with OCD prevalence. Finally, parallel analyses of a “psychiatric control” (panic disorder) failed to find a significant relationship between panic disorder and latitude. Findings from this study support a relation between latitude and OCD and suggest potential specificity of the relation to OCD vs factors related to mental health concerns broadly. These findings are consistent with recent results suggesting that the timing of sleep may be important in OCD. Future work in this area is warranted.

The physiological orienting response in female adolescents with borderline personality disorder

BackgroundThe reflexive startle- and orienting-response have been widely studied in psychiatric disorders. Existing evidence in patients with borderline personality disorder (BPD) is mixed, and limited to adults. The present study addressed clinical correlates of the psychophysiological orienting response in adolescents with BPD. MethodsFemale adolescents (13–19 years) with BPD (n = 30), healthy controls (HC; n = 34), and psychiatric clinical controls (CC; n = 53) participated in the trial. Orienting response was induced using acoustic startle-probes (sinus tones) while heart rate (HR) and skin conductance (SCR) were continuously recorded. Besides clinical interviews, the assessment included self-reports on depressive symptoms, anxiety, dissociation and psychopathological distress. ResultsOn a group level, relative habituation of the HR-response (regression slope) significantly differed between groups (F(2,114) = 3.74, p = 0.027), with significant contrasts (p = 0.026, Sidak corrected) comparing CC (slope 0.04 ± 0.41) and BPD (slope 0.28 ± 0.40). On a dimensional level, relative HR habituation was significantly correlated with the number of BPD diagnostic criteria endorsed (r(117) = 0.183, p = 0.049) and symptoms of dissociation (r(116) = 0.193, p = 0.038), indicating that delayed HR habituation across probes was associated with greater BPD symptom severity. Analyses of SCR showed no significant findings. ConclusionFindings provide preliminary support for altered habituation of the HR orienting response in adolescent BPD, associated with BPD severity – in particular dissociative experiences. Dissociative experiences may alter the automatic defensive response early in the course of BPD, providing a potential pathway to exaggerated emotional responding in BPD.

Objective and quantitative equilibriometric evaluation of individual locomotor behaviour in schizophrenia: Translational and clinical implications.

Psychiatry is the only medical specialty that lacks clinically applicable biomarkers for objective evaluation of the existing pathology at a single-patient level. On the basis of an original translational equilibriometric method for evaluation of movement patterns, we have introduced in the everyday clinical practice of psychiatry an easy-to-perform computerized objective quantification of the individual locomotor behaviour during execution of the Unterberger stepping test. For the last 20years, we have gradually collected a large database of more than 1000 schizophrenic patients, their relatives, and matched psychiatric, neurological, and healthy controls via cross-sectional and longitudinal investigations. Comparative analyses revealed transdiagnostic locomotor similarities among schizophrenic patients, high-risk schizotaxic individuals, and neurological patients with multiple sclerosis and cerebellar ataxia, thus suggesting common underlying brain mechanisms. In parallel, intradiagnostic dissimilarities were revealed, which allow to separate out subclinical locomotor subgroups within the diagnostic categories. Prototypical qualitative (dysmetric and ataxic) locomotor abnormalities in schizophrenic patients were differentiated from 2 atypical quantitative ones, manifested as either hypolocomotion or hyperlocomotion. Theoretical analyses suggested that these 3 subtypes of locomotor abnormalities could be conceived as objectively measurable biomarkers of 3 schizophrenic subgroups with dissimilar brain mechanisms, which require different treatment strategies. Analogies with the prominent role of locomotor measures in some well-known animal models of mental disorders advocate for a promising objective translational research in the so far over-subjective field of psychiatry. Distinctions among prototypical, atypical, and diagnostic biomarkers, as well as between neuromotor and psychomotor locomotor abnormalities, are discussed. Conclusions are drawn about the translational and clinical implications of the new approach and its future perspectives.

Prenatal exposure to maternal depression and anxiety on imprinted gene expression in placenta and infant neurodevelopment and growth.

BackgroundDepression and/or anxiety during pregnancy have been associated with impaired fetal growth and neurodevelopmental. Because placental imprinted genes play a central role in fetal development and respond to environmental stressors, we hypothesized that imprinted gene expression would be affected by prenatal depression and anxiety.MethodsPlacental gene expression was compared between mothers with prenatal depression and/or anxiety/obsessive compulsive disorder/panic and control mothers without psychiatric history (n=458) in the Rhode Island Child Health Study.ResultsTwenty-nine genes were identified as being significantly differentially expressed between placentae from infants of mothers with both depression and anxiety (n=54), with depression (n=89), or who took perinatal psychiatric medications (n=29) and control mother/infant pairs, with most genes having decreased expression in the stressed group. Among placentae from infants of mothers with depression, we found no differences in expression by medication use, indicating that our results are related to the stressor rather than the treatments. We did not find any relationship between the stress-associated gene expression and neonatal neurodevelopment as measured using the Neonatal Intensive Care Unit Network Neurobehavioral Scale.ConclusionsThis variation in expression may be part of an adaptive mechanism by which the placenta buffers the infant from the effects of maternal stress.

F54. PHARMACOLOGICAL ENHANCEMENT OF COGNITION AND SOCIAL COGNITION IN THE PSYCHOSIS SPECTRUM

BackgroundAbnormalities in cognition and social cognition represent a core feature of the schizophrenia spectrum disorders. Schizotypal personality disorder (SPD) is a milder disorder within the schizophrenia spectrum, characterized by attenuated, schizophrenia-like traits without overt psychosis.Study 1: Working memory impairments are a core cognitive deficit in schizophrenia and SPD. The dopamine D1 receptor is a promising target to enhance working memory. We aimed to test the effect of the D1 agonist dihydrexidine (DAR-0100A) to enhance working memory in patients with SPD.Study 2: Oxytocin modulates social cognition. However, oxytocin’s effect on social cognitive errors in the schizophrenia spectrum remains unexplored. We aimed to: 1) characterize social cognitive (mentalizing) errors in SPD patients and test their relationship with positive and negative symptoms of psychosis; 2) test the effect of intranasal oxytocin on mentalizing errors.MethodsStudy 1: We performed a randomized, double blind, placebo-controlled trial of DAR-0100A (15 mg/150 ml of normal saline i.v. over 30 min) in medication-free SPD patients (n=16). Study 2: Subjects: 15 SPD patients, 15 healthy controls [HC], and 15 psychiatric controls (PC). Intervention: intranasal oxytocin 24/40IU/placebo. Measures: Movie for the Assessment of Social Cognition (MASC), a naturalistic video task measuring mentalizing accuracy, “no mentalizing” errors, “hypomentalizing” errors and “hypermentalizing” errors. The “hyper-hypomentalizing ratio” can be computed to capture the predominant mentalizing tendency; PANSS; Schizotypal Personality Questionnaire, SPQ. Mentalizing measures were compared across groups (SPD, HC, PC), and treatments (oxytocin 24IU/40IU vs placebo) using ANOVA. Pearson correlations assessed the relationship between social cognition and symptoms.ResultsStudy 1: Treatment with dihydrexidine (DAR-0100A) was associated with significantly improved working memory performance relative to placebo, with a very large effect size (Cohen’s d=1.14). Study 2: SPD patients had lower mentalizing accuracy (F=10.11;df=1;p=0.003), made more “No mentalizing” or “hypomentalizing” errors (F=12.92;df=1;p=0.001), and had lower hyper-hypomentalizing ratios than HCs (F=2.84; df=1;p=0.099,trend level). In a subset of patients –including 8 SPD-, a single dose of intranasal oxytocin significantly increased the hyper-hypomentalizing ratio (F=6.84, df=1,p=0.019) and increased visual attention to social cues.“No mentalizing” and “hypomentalizing” errors were significantly correlated with negative symptoms. “Hypermentalizing” errors were significantly correlated with positive symptoms and the “ideas of reference” and “suspiciousness” SPQ subscales.DiscussionStudy 1: These preliminary findings lend further clinical support to the potential of D1 receptor agonists to treat schizophrenia-spectrum working memory impairments.Study 2: As hypothesized, SPD patients had impaired, less accurate social cognition, and made more “no mentalizing” and “hypomentalizing” errors, correlated with negative symptoms. Conversely, “hypermentalizing errors” were correlated with positive symptoms. Oxytocin increased the tendency to hypermentalize. This effect may normalize the abnormalities found at baseline in SPD patients. These results support the role of social cognitive impairments as an underlying factor of positive and negative symptoms of psychosis, with specific associations with paranoid and delusional traits. Our results also suggest that intranasal oxytocin modulates social cognitive errors in the psychosis spectrum.

S12. THE ‘AUTOANTIBODYOME’ IN PSYCHOSIS: A PILOT STUDY AND BLUEPRINT FOR BIOMARKER DISCOVERY

BackgroundRecent studies seeking to describe the prevalence and significance of autoantibodies in psychotic disorders can be characterized as ‘top-down’ in theoretical approach; that is, autoantibodies to specific (usually CNS) antigens are sought based on a) the known function of the antigen (e.g. NMDAR) and its putative role in psychosis or b) the clinical observation that these autoantibodies can cause psychosis as part of a more complex neuropsychiatric presentation (e.g. autoimmune encephalitis). No candidate autoantibodies with a clear diagnostic or prognostic role have been definitively established.We sought to take an alternative, ‘bottom-up’ approach to the significance of autoantibodies in psychosis that remains agnostic as to the potential significance of any one antigen. Every individual harbours autoantibodies directed against many thousands of self-antigens and the vast majority are not disease-causing. Indeed production of autoantibodies may represent a physiological, antigen-specific ‘debris-clearing’ response to tissue destruction or damage. It follows that the autoantibody profile of any individual reflects any pathological process that is ongoing in that individual and can thus serve as a ‘readout’ of the disease state in question.MethodsSera from 20 patients with a first episode of psychosis (FEP) (males: n=16; mean age: 29.35 s.d.: 7.07) from the Genetics and Psychosis (GAP) study and 20 matched controls were analysed, using Invitrogen’s ProtoArray v5.1 Human Protein Microarrays, for the presence of IgG to 9486 unique human protein antigens which had been expressed as GST fusion proteins in insect cells, purified and spotted onto slides. Following application of a fluorescent secondary IgG, reactivity patterns were automatically read using a fluorescence scanner. Samples were split into testing and training sets, and the top 50 most differentially expressed and differentially depleted antibodies were then chosen as biomarkers.ResultsThe top 50 expressed biomarkers from the training set correctly identified 100% of psychosis subjects from the testing set, and 80% of healthy controls (OOB estimate of error rate 10%). When training and testing sets were swapped, biomarker overlap was 46% and 90% of psychosis subjects and 90% of controls were correctly identified (OOB estimate of error rate 10%). The top 50 depleted biomarkers from the training set correctly identified 90% of psychosis subjects from the testing set, and 90% of healthy controls (OOB estimate of error rate 10%). When training and testing sets were swapped, depletion biomarker overlap was 2% and 70% of psychosis subjects and 40% of controls were correctly identified (OOB estimate of error rate 45%).DiscussionThe autoantibodyome in FEP differs from that of healthy individuals. In this novel pilot study, a panel of 50 differentially expressed autoantibodies allowed confident discrimination between patients and controls, potentially paving the way for development of antibody-based diagnostics for psychosis using a simple blood test and fewer autoantibodies. Depletion biomarkers, thought to represent antibodies selectively depleted from the blood due to target binding in tissues, had less replicability and utility than expression biomarkers, which may offer insights into the active role of the adaptive immune system in psychosis. Further work will attempt to validate this approach in larger samples, using psychiatric disease controls. This autoantibodyomic approach may also show promise for the identification of predictive and prognostic biomarkers in psychotic disorders.

Psychosocial impairment in DSM-5 intermittent explosive disorder

The purpose of this study was to document the functional severity of DSM-5 IED in a clinical research sample. IED and control groups were compared on psychosocial functioning, life satisfaction, and on a variety of cognitive and behavioral issues. IED study participants reported significantly worse psychosocial function, quality of life, and higher job dysfunction than both psychiatric and healthy control study participants. The presence of DSM-5 IED is associated with significant psychosocial and functional impairment. Early intervention may aid in minimizing the consequences of impulsive aggressive behavior, and improving psychosocial functioning and quality of life.

Multivariate Pattern Analysis of Genotype-Phenotype Relationships in Schizophrenia.

Genetic risk variants for schizophrenia have been linked to many related clinical and biological phenotypes with the hopes of delineating how individual variation across thousands of variants corresponds to the clinical and etiologic heterogeneity within schizophrenia. This has primarily been done using risk score profiling, which aggregates effects across all variants into a single predictor. While effective, this method lacks flexibility in certain domains: risk scores cannot capture nonlinear effects and do not employ any variable selection. We used random forest, an algorithm with this flexibility designed to maximize predictive power, to predict 6 cognitive endophenotypes in a combined sample of psychiatric patients and controls (N = 739) using 77 genetic variants strongly associated with schizophrenia. Tenfold cross-validation was applied to the discovery sample and models were externally validated in an independent sample of similar ancestry (N = 336). Linear approaches, including linear regression and task-specific polygenic risk scores, were employed for comparison. Random forest models for processing speed (P = .019) and visual memory (P = .036) and risk scores developed for verbal (P = .042) and working memory (P = .037) successfully generalized to an independent sample with similar predictive strength and error. As such, we suggest that both methods may be useful for mapping a limited set of predetermined, disease-associated SNPs to related phenotypes. Incorporating random forest and other more flexible algorithms into genotype-phenotype mapping inquiries could contribute to parsing heterogeneity within schizophrenia; such algorithms can perform as well as standard methods and can capture a more comprehensive set of potential relationships.

Altered fear processing in adolescents with a history of severe childhood maltreatment: an fMRI study.

Children with a history of maltreatment suffer from altered emotion processing but the neural basis of this phenomenon is unknown. This pioneering functional magnetic resonance imaging (fMRI) study investigated the effects of severe childhood maltreatment on emotion processing while controlling for psychiatric conditions, medication and substance abuse. Twenty medication-naive, substance abuse-free adolescents with a history of childhood abuse, 20 psychiatric control adolescents matched on psychiatric diagnoses but with no maltreatment and 27 healthy controls underwent a fMRI emotion discrimination task comprising fearful, angry, sad happy and neutral dynamic facial expressions. Maltreated participants responded faster to fearful expressions and demonstrated hyper-activation compared to healthy controls of classical fear-processing regions of ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex, which survived at a more lenient threshold relative to psychiatric controls. Functional connectivity analysis, furthermore, demonstrated reduced connectivity between left vmPFC and insula for fear in maltreated participants compared to both healthy and psychiatric controls. The findings show that people who have experienced childhood maltreatment have enhanced fear perception, both at the behavioural and neurofunctional levels, associated with enhanced fear-related ventromedial fronto-cingulate activation and altered functional connectivity with associated limbic regions. Furthermore, the connectivity adaptations were specific to the maltreatment rather than to the developing psychiatric conditions, whilst the functional changes were only evident at trend level when compared to psychiatric controls, suggesting a continuum. The neurofunctional hypersensitivity of fear-processing networks may be due to childhood over-exposure to fear in people who have been abused.

Eveningness is associated with poor sleep quality and negative affect in obsessive-compulsive disorder.

BackgroundObsessive–compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive behaviors that severely encumber daily functioning. OCD patients seem to exhibit sleep disturbances, especially delayed bedtimes that reflect disrupted circadian rhythmicity. Morningness–eveningness is a fundamental factor reflecting individual variations in diurnal preferences related to sleep and waking activities. Eveningness reflecting a delayed sleep–wake timing has repeatedly been associated with sleep problems and negative affect (NA). Therefore, the aim of this study was to examine the associations between morningness–eveningness, sleep complaints, and symptom severity in OCD patients and compared with a mixed psychiatric control group.Materials and methodsThe data of 49 OCD and 49 mixed psychiatric inpatients (with unipolar depression and anxiety disorders) were analyzed. Patients completed questionnaires regarding morningness–eveningness, sleep quality, nightmare frequency, depression, anxiety, and affective states. Obsessive and compulsive symptom severity was also assessed within the OCD group by clinician-rated scales.ResultsEveningness preference was associated with impaired sleep quality and higher NA in OCD patients. In addition, impaired sleep quality showed a moderate correlation with anxiety and strong correlations with depressive symptoms and NA. Interestingly, in the mixed psychiatric group, eveningness was not linked to NA, and sleep quality also showed weaker associations with depressive symptoms and NA. Within the OCD group, eveningness preference was predictive of poorer sleep quality regardless the influence of depressive symptoms.ConclusionOur findings suggest that eveningness and sleep complaints are predictive of affective dysfunctions, and should be carefully considered in the evaluation and treatment of OCD patients.

Exploring metabolic factors and health behaviors in relation to suicide attempts: A case-control study

BackgroundSuicide attempts are a serious public health concern with devastating global impact, thereby necessitating the development of an adequate prevention strategy. Few known risk factors of suicide attempts are directly modifiable. This study sought to investigate potential associations between health behaviors and suicide attempts, identifying novel opportunities for clinicians to help prevent suicidal behavior. MethodsA case-control study was conducted to compare body weight, serum total cholesterol, physical activity, tobacco use, and dietary food groups among adults who had made a suicide attempt (n = 84) to psychiatric inpatients (n = 104) and community controls (n = 93) without history of suicide attempt. Multivariable binary logistic regression analyses were used to investigate the association between metabolic risk factors and attempted suicide. ResultsPsychiatric inpatients who had attempted suicide were less likely to be physically active [moderate/strenuous (OR 0.42, 95% CI 0.19–0.95) and mild (OR 0.35, 95% CI 0.16–0.76)] compared to controls. Psychiatric inpatients who attempted suicide were more likely to use tobacco (OR 2.25, 95% CI 1.07–4.73) compared to controls. Contrary to prior research, obesity, serum total cholesterol, and diet were not significantly associated with risk of attempted suicide. LimitationsOur study was limited by its cross-sectional design, which precludes the identification of causal or temporal relationships between the risk of attempted suicide and factors such as physical activity and tobacco use. ConclusionsStudy results suggest that a history of attempted suicide is associated with a decreased likelihood of being physically active and an increased risk of tobacco use. Further investigation is warranted to understand the role of exercise and tobacco use in suicide intervention and prevention strategies.