Consensus Statement on Ethical & Safety Practices for Conducting Digital Monitoring Studies with People at Risk of Suicide and Related Behaviors.

OBJECTIVE: Digital monitoring technologies (e.g., smart-phones and wearable devices) provide unprecedented opportunities to study potentially harmful behaviors such as suicide, violence, and alcohol/substance use in real-time. The use of these new technologies has the potential to significantly advance the understanding, prediction, and prevention of these behaviors. However, such technologies also introduce myriad ethical and safety concerns, such as deciding when and how to intervene if a participant's responses indicate elevated risk during the study? METHODS: We used a modified Delphi process to develop a consensus among a diverse panel of experts on the ethical and safety practices for conducting digital monitoring studies with those at risk for suicide and related behaviors. Twenty-four experts including scientists, clinicians, ethicists, legal experts, and those with lived experience provided input into an iterative, multi-stage survey, and discussion process. RESULTS: Consensus was reached on multiple aspects of such studies, including: inclusion criteria, informed consent elements, technical and safety procedures, data review practices during the study, responding to various levels of participant risk in real-time, and data and safety monitoring. CONCLUSIONS: This consensus statement provides guidance for researchers, funding agencies, and institutional review boards regarding expert views on current best practices for conducting digital monitoring studies with those at risk for suicide-with relevance to the study of a range of other potentially harmful behaviors (e.g., alcohol/substance use and violence). This statement also highlights areas in which more data are needed before consensus can be reached regarding best ethical and safety practices for digital monitoring studies.

Suicidal ideation and behavior in institutions of higher learning: A latent class analysis.

Suicide is the second leading cause of death among undergraduate students, with an annual rate of 7.5 per 100,000. Suicidal behavior (SB) is complex and heterogeneous, which might be explained by there being multiple etiologies of SB. Data-driven identification of distinct at-risk subgroups among undergraduates would bolster this argument. We conducted a latent class analysis (LCA) on survey data from a large convenience sample of undergraduates to identify subgroups, and validated the resulting latent class model on a sample of graduate students. Data were collected through the Interactive Screening Program deployed by the American Foundation for Suicide Prevention. LCA identified 6 subgroups from the undergraduate sample (N = 5654). In the group with the most students reporting current suicidal thoughts (N = 623, 66% suicidal), 22.5% reported a prior suicide attempt, and 97.6% endorsed moderately severe or worse depressive symptoms. Notably, LCA identified a second at-risk group (N = 662, 27% suicidal), in which only 1.5% of respondents noted moderately severe or worse depressive symptoms. When graduate students (N = 1138) were classified using the model, a similar frequency distribution of groups was found. Finding multiple replicable groups at-risk for suicidal behavior, each with a distinct prevalence of risk factors, including a group of students who would not be classified as high risk with depression-based screening, is consistent with previous studies that identified multiple potential etiologies of SB.

Assessment of Suicidal Ideation and Behavior: Report of the International Society for CNS Clinical Trials and Methodology Consensus Meeting.

OBJECTIVE: To develop consensus recommendations for assessment of suicidal ideation/suicidal behavior (SI/SB) in clinical trials. PARTICIPANTS: Stakeholders from academia, industry, regulatory agencies, National Institutes of Health, National Institute of Mental Health, and patient advocacy organizations participated in a consensus meeting that was sponsored by the International Society for CNS Clinical Trials and Methodology and held November 17-18, 2015. Prior to the meeting, teams of experts identified key areas of consensus and dissent related to SI/SB. The most critical issues were presented and discussed in the consensus meeting. EVIDENCE: Literature reviews and a pre-meeting survey were conducted. Findings were discussed in pre-meeting working group sessions and at the consensus meeting. CONSENSUS PROCESS: Five pre-meeting working groups reviewed (1) nomenclature and classification schemes for SI/SB, (2) detection and assessment of SI/SB, (3) analysis of SI/SB data, (4) design of clinical trials for new treatments of SI/SB, and (5) public health approaches to SI/SB. A modification of the RAND/UCLA Appropriateness Method was used to combine review of scientific evidence with the collective views of experts and stakeholders to reach the final consensus statements. After discussion, all attendees voted using an electronic interactive audience response system. Areas of agreement and areas of continuing dissent were recorded. CONCLUSIONS: All 5 working groups agreed that a major barrier to advancement of the field of SI/SB research and the development of new treatments for SI/SB remains the lack of a universally accepted standardized nomenclature and classification system. Achieving alignment on definitions and classification of suicide-related phenomena is critical to improving the detection and assessment of SI/SB, the design of clinical trials for new treatments, and effective public health interventions.

Reducing Suicide Risk: Challenges and Opportunities in the Emergency Department.

Emergency departments (ED) are prime locations for identifying individuals at high risk of suicide and for making life-saving interventions. In an ideal scenario, all ED patients at risk of suicide could be identified and connected with effective, feasible interventions, and this would occur in a supportive system not overburdened by screening or assessment requirements. In this review, we focus on challenges to achieving this ideal--along with potential solutions--at the level of patients, providers, the ED environment, and the larger health care system.

De novo mutations from sporadic schizophrenia cases highlight important signaling genes in an independent sample.

Schizophrenia is a debilitating syndrome with high heritability. Genomic studies reveal more than a hundred genetic variants, largely nonspecific and of small effect size, and not accounting for its high heritability. De novo mutations are one mechanism whereby disease related alleles may be introduced into the population, although these have not been leveraged to explore the disease in general samples. This paper describes a framework to find high impact genes for schizophrenia. This study consists of two different datasets. First, whole exome sequencing was conducted to identify disruptive de novo mutations in 14 complete parent-offspring trios with sporadic schizophrenia from Jerusalem, which identified 5 sporadic cases with de novo gene mutations in 5 different genes (PTPRG, TGM5, SLC39A13, BTK, CDKN3). Next, targeted exome capture of these genes was conducted in 48 well-characterized, unrelated, ethnically diverse schizophrenia cases, recruited and characterized by the same research team in New York (NY sample), which demonstrated extremely rare and potentially damaging variants in three of the five genes (MAF<0.01) in 12/48 cases (25%); including PTPRG (5 cases), SCL39A13 (4 cases) and TGM5 (4 cases), a higher number than usually identified by whole exome sequencing. Cases differed in cognition and illness features based on which mutation-enriched gene they carried. Functional de novo mutations in protein-interaction domains in sporadic schizophrenia can illuminate risk genes that increase the propensity to develop schizophrenia across ethnicities.

Olfactory performance segregates effects of anhedonia and anxiety on social function in patients with schizophrenia.

BACKGROUND: Social dysfunction is common among individuals with schizophrenia. While often attributed to anhedonia, social dysfunction could also result from unrecognized anxiety. We examined the contributions of anhedonia and anxiety to social function using olfactory function to examine whether the domains had separate underpinnings. METHODS: We assessed anhedonia, anxiety and social function as well as olfactory function in well-characterized patients with schizophrenia or schizoaffective disorder and healthy controls. RESULTS: We included 56 patients and 37 controls in our study. Patients exhibited significantly higher levels of anhedonia and anxiety than controls, and the domains were highly correlated in patients. The combination of anhedonia and anxiety more strongly predicted social dysfunction than either measure alone. Smell identification was differentially related to the symptoms, with better performance predicting less anhedonia but more social fear in male patients. LIMITATIONS: The use of self-report measures precludes differentiation between recollected or recounted experience. Aside from smell identification and odour threshold, additional measures of olfaction may be considered for future studies. CONCLUSION: Anhedonia and anxiety were strongly correlated and both negatively impacted social function. The olfactory biomarker results support the conclusion that these domains are separate. Social function in patients with schizophrenia may improve with interventions for anxiety, even in the presence of marked negative symptoms.

Frequent Comorbidity and Predictors of Social Anxiety in Persons With Schizophrenia: A Retrospective Cohort Study.

OBJECTIVE: To determine if symptoms of social anxiety are distinct from negative symptoms of schizophrenia. METHOD: Fifty-three patients with schizophrenia or schizoaffective disorder (diagnosed per DSM-IV criteria) and 37 healthy controls were examined with the Liebowitz Social Anxiety Scale (LSAS) for social anxiety disorder and for the severity of social anxiety. The Positive and Negative Syndrome Scale (PANSS) and the Chapman scales for physical and social anhedonia were also administered. Data were collected from 2005 to 2010 from inpatient and outpatient research centers at the New York State Psychiatric Institute, New York. RESULTS: Social anxiety disorder was elevated more than 10-fold in schizophrenia patients than in controls (37.7% of patients vs 2.9% of controls, P ≤ .001). Social anxiety and social fear were unrelated to the PANSS with few exceptions. A family history of psychosis was also a significant independent predictor of social anxiety as measured by LSAS total (P = .004) and the social fear subscale (P = .007). CONCLUSIONS: These data confirm social anxiety disorder as a prominent comorbid disorder in patients with schizophrenia. Future studies should focus on treatment trials of this phenomenon. Social anxiety cannot be explained by the negative symptomatology of the disease. This study suggests that a family history of psychosis is a significant predictor of social anxiety.

Aggressiveness across development and suicidal behavior in depressed patients.

The objective of this study was to determine differences in the pathway of aggressiveness across development between depressive subjects and normal controls, and to examine males and females separately with regard to level of aggression and suicidal behavior among depressed subjects. Participants were classified into 5 groups: depressed suicide attempters (DSA; n = 339), depressed non-suicide attempters (DNSA; n = 92), psychiatric controls who had attempted suicide (PSA; n = 188), psychiatric controls who had not attempted suicide (PNSA; n = 222), and normal controls (NC; n = 532). The level of aggressiveness across development in the different groups was examined using a 5 (DSA vs. DNSA vs. PSA vs. PNSA vs. NC)×3 (Childhood, Adolescence, and Adulthood) MANCOVA. Adjusted and separate models for males and females were conducted. Depressed subjects differed in severity of aggressiveness. The level of aggressiveness in individuals in the NC group remained stable across development, while subjects in the DSA and DNSA groups showed significantly higher levels of aggressiveness. This finding was also observed in subjects of the PSA and PNSA groups. The level of aggressiveness in males with depression significantly increased over time. In women, increasing levels of aggressiveness across development were only observed in depressed suicide attempters. Limitations of this study included use of semi-structured interview for the assessment of risk factors. We found significant differences in severity and in the pathway of aggressiveness across development between depressive subjects and normal controls. In addition, sex differences regarding level of aggression and suicidal behavior among depressed subjects were found.

Assessing depression in youth at clinical high risk for psychosis: a comparison of three measures.

Depressive symptoms are prevalent among individuals at clinical high-risk (CHR) for psychosis. Prior studies have used the Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS), and the "dysphoric mood" item of the Scale of Prodromal Symptoms (SOPS) to assess depressive symptoms in CHR samples. We compared the psychometric properties of these instruments in a CHR cohort, to support the selection of appropriate depressive symptoms measures in future studies and in clinical settings. Internal consistency was assessed using Cronbach's alpha. Construct validity was assessed through correlations with SOPS items that were expected or not expected to be related to depressive symptoms. Criterion validity was assessed by comparing scores between patients with and without a major depressive disorder diagnosis. We hypothesized based on the schizophrenia literature that the BDI would have superior internal consistency and discriminant validity compared to the HDRS, and that all three measures would show convergent validity and criterion validity. The BDI demonstrated superior internal consistency and construct validity in this at-risk sample. The BDI and HDRS differentiated patients with major depressive disorder, but SOPS dysphoria did not. This has implications for the choice of depression measures in future CHR studies and for the interpretation of past findings.

Clinical characteristics in schizophrenia patients with or without suicide attempts and non-suicidal self-harm--a cross-sectional study.

BACKGROUND: To investigate whether schizophrenia patients with both suicide attempts and non-suicidal self-harm have earlier age of onset of psychotic and depressive symptoms and higher levels of clinical symptoms compared to patients with only suicide attempts or without suicide attempt. METHODS: Using a cross-sectional design, 251 patients (18-61 years old, 58% men) with schizophrenia treated at hospitals in Oslo and Innlandet Hospital Trust, Norway, were assessed with a comprehensive clinical research protocol and divided into three groups based on their history of suicide attempts and non-suicidal self-harm. RESULTS: Suicide attempts were present in 88 patients (35%); 52 had suicide attempts only (29%) and 36 had both suicide attempts and non-suicidal self-harm (14%). When compared with nonattempters and those with suicide attempts without non-suicidal self-harm, patients with both suicide attempts and non-suicidal self-harm were more frequently women, younger at the onset of psychotic symptoms, had longer duration of untreated psychosis, and had higher levels of current impulsivity/aggression and depression. Patients with both suicide attempts and non-suicidal self-harm were more likely to repeat suicide attempts than patients with suicide attempts only. CONCLUSIONS: Patients with both suicide attempts and non-suicidal self-harm had different illness history and clinical characteristics compared to patients with only suicide attempts or patients without suicidal behavior. Our study suggests that patients with both suicide attempts and non-suicidal self-harm represent a distinct subgroup among patients with schizophrenia and suicidal behavior with their early onset of psychotic symptoms, high rate of repeated suicidal behavior and significant treatment delay.

Obsessive compulsive symptoms in individuals at clinical risk for psychosis: association with depressive symptoms and suicidal ideation.

Obsessive-compulsive symptoms, particularly aggressive obsessions, are prevalent in schizophrenia patients and associated with other symptom severity, suicidal ideation and functional impairment. In a psychosis-risk cohort, obsessive-compulsive diagnosis and symptoms were assessed in terms of prevalence and content, and for associations with clinical measures. Obsessive-compulsive symptoms were prevalent in the CHR cohort, as was suicidal ideation. The presence and severity of aggressive obsessions were associated with depression, suicidal ideation and social impairment. The high prevalence of aggressive obsessions and associated suicidal ideation in a clinical high risk cohort, and their relationship to depression, is relevant for risk assessment and treatment strategies.

Depression, aggression, and suicidal ideation in first graders: a school-based cross-sectional study.

OBJECTIVE: This study explored the clinical characteristics and risk factors of suicidal ideation in a sample of first graders from South Korea. Children's depression and aggression and maternal depression were examined as possible risk factors. METHODS: This study is a school-based, cross-sectional study of 5 elementary schools in Gunpo City, South Korea. Participants were 707 first graders (mean age, 6.54 years) and their mothers. We assessed children's depressive and aggressive symptoms using the Behavior Assessment System for Children-2 (BASC-2) and maternal depression using the Beck Depression Inventory (BDI). Two items from BASC-2 and 1 item from BDI identified children's and maternal suicidal ideation. RESULTS: Twenty-seven (3.8%) children evidenced suicidal ideation. Children with suicidal ideation had higher mean scores of depression domain (10.11 ± 5.34 vs 4.57 ± 3.44, P < .0001) and aggression domain (7.78 ± 3.84 vs 3.80 ± 2.85, P < .0001) on BASC-2 and maternal depression (9.78 ± 6.45 vs 7.28 ± 5.38, P = .02) on BDI. In regression analysis, children's depression (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.07-1.32; P = .001) and aggression (OR, 1.24; 95% CI, 1.08-1.41; P = .002) contributed significantly to children's suicidal ideation, whereas maternal depression was not significantly related to children's suicidal ideation (OR, 0.99; 95% CI, 0.92-1.06; P = .75). CONCLUSIONS: This study demonstrated that even first graders had a considerable prevalence of suicidal ideation and that depression and aggression were associated with suicidal ideation in young children.

Olfaction and cognition in schizophrenia: sex matters.

Cognitive and olfactory deficits occur in schizophrenia, but little is known whether sex modifies these deficits. We examined the relationship between olfaction and cognition in 55 schizophrenia patients and 32 healthy controls. Patients and controls demonstrated significant differences performing cognitive tasks. In patients, sex modified all relationships of odor identification to cognition. Female patients showed significantly stronger trends than male patients correlating better smell identification with higher scores on intelligence, memory, and attention, whereas their correlations of odor identification with executive functioning contradicted those of male patients. Odor acuity significantly correlated with several cognitive measures, especially in male patients, in whom better acuity was generally associated with better cognition. Female patients again differed significantly from males; odor acuity correlations with cognitive measures were weaker, or contradicted, those of male patients. These findings indicate significant sex differences in olfactory processing in schizophrenia. Combining the sexes in research analyses may obscure important differences.

A neurophysiological deficit in early visual processing in schizophrenia patients with auditory hallucinations.

Existing 67-channel event-related potentials, obtained during recognition and working memory paradigms with words or faces, were used to examine early visual processing in schizophrenia patients prone to auditory hallucinations (AH, n = 26) or not (NH, n = 49) and healthy controls (HC, n = 46). Current source density (CSD) transforms revealed distinct, strongly left- (words) or right-lateralized (faces; N170) inferior-temporal N1 sinks (150 ms) in each group. N1 was quantified by temporal PCA of peak-adjusted CSDs. For words and faces in both paradigms, N1 was substantially reduced in AH compared with NH and HC, who did not differ from each other. The difference in N1 between AH and NH was not due to overall symptom severity or performance accuracy, with both groups showing comparable memory deficits. Our findings extend prior reports of reduced auditory N1 in AH, suggesting a broader early perceptual integration deficit that is not limited to the auditory modality.

Personality disorder assessments in acute depressive episodes: stability at follow-up.

Assessment of personality disorders during the acute phase of major depression may be invalidated by the potential distortion of personality traits in depressed mood states. However, few studies have tested this assumption. We examined the stability of personality disorder diagnoses during and then after a major depressive episode (MDE). Subjects with major depression (N = 82) completed the 17-item Hamilton Depression Scale (HAM-17) and the Structured Clinical Interview for Axis II both at baseline during an MDE and at 3-month follow-up. We compared subjects who continued to meet DSM-IV criteria for the same Axis II diagnoses with patients whose diagnosis changed and patients with no DSM-IV personality disorder to determine the relationship to major depression and its severity. Sixty-six percent of subjects met DSM-IV criteria for at least one Axis II diagnosis at baseline and 80% had the same personality disorder diagnoses at follow-up. Thirty-four percent had a full remission of MDE at 3-month follow-up. Instability of Axis II diagnosis was associated with number of Axis II diagnoses at baseline (p = .036) and Hispanic ethnicity (p = .013). HAM-17 score change was unrelated to differences in the number of symptoms of personality disorders from baseline to follow-up, nor was remission from MDE on follow-up. Axis II diagnoses in acutely depressed patients reassessed after 3 months are often stable and not associated with remission of or improvement in major depression.

Self-harm in patients with schizophrenia spectrum disorders.

This study describes the prevalence, clinical characteristics, and gender profile of self-harm in a cross-sectional sample of 388 patients with schizophrenia spectrum disorders. All patients were interviewed and assessed with respect to lifetime self-harm and relevant clinical variables. An overall of 49% of the patients reported self-harm which was associated with female gender, having had a depressive episode, younger age at psychosis onset, alcohol abuse or dependence, current suicidality, awareness of illness, and low adherence to prescribed medication. Higher awareness of having a mental disorder was associated with self-harm in men only, while emotional dysregulation was associated with self-harm in women only. We conclude that while self-harm in patients with schizophrenia spectrum disorders is highly prevalent in both genders, risk factors in men and women differ in several important ways.

Schizophrenia comorbid with panic disorder: evidence for distinct cognitive profiles.

Patients with comorbid schizophrenia and panic symptoms share a distinct clinical presentation and biological characteristics, prompting some to propose panic psychosis as a separate subtype of schizophrenia. Less is known about these patients' neuropsychological profiles, knowledge of which may facilitate target-specific treatments and research into the etiopathophysiology for such cases. A total of 255 schizophrenia patients with panic disorder (n=39), non-panic anxiety disorder (n=51), or no anxiety disorder (n=165) were assessed with the Wechsler Adult Intelligence Scale-Revised, the Wisconsin Card Sorting Test, the Trail Making Test, the Controlled Oral Word Association Test, the Animal Naming subtest of the Boston Diagnostic Aphasia Examination, and the Wechsler Memory Scale-Revised. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale. Patients with panic disorder demonstrated a higher verbal IQ and better problem solving, set switching, delayed recall, attention, and verbal fluency as compared to schizophrenia patients without comorbid anxiety. The schizophrenia-panic group reported a higher level of dysthymia on stable medication. Our findings suggest that patients with schizophrenia and comorbid panic disorder exhibit distinct cognitive functioning when compared to other schizophrenia patients. These data offer further support for a definable panic-psychosis subtype and suggest new etiological pathways for future research.

Olfactory acuity is associated with mood and function in a pilot study of stable bipolar disorder patients.

OBJECTIVES: Olfactory dysfunction is described in several neuropsychiatric disorders but there is little research on olfactory processing in bipolar disorder. METHODS: We assessed odor detection threshold (sensitivity) and smell identification test scores, along with symptoms, cognition, and social function in 20 DSM-IV bipolar disorder patients and 44 control subjects. RESULTS: The patient and control groups had similar demographic measures, intelligence, and mean olfaction scores, but significantly differed in social domains, including adjustment, function, and anxiety. Odor detection sensitivity showed significantly opposite correlations for the depressive and manic mood domains in bipolar disorder (r to z = 2.83, p = 0.005). Depressive symptoms were related to increased sensitivity (the ability to detect odors at a lower concentration) and mania symptoms were related to decreased sensitivity for odor detection. Increased sensitivity for odor detection also predicted significantly better employment (r = -0.642, p = 0.024), whereas less sensitivity was associated with social avoidance (r = 0.702, p =0.024) and social fear (r = 0.610, p = 0.046). CONCLUSIONS: Diminished odor detection sensitivity predicted mania and social avoidance, whereas more sensitive odor detection predicted more depressive symptoms but better employment functioning in bipolar disorder patients. Odor acuity may be an illness state marker of mood syndromes in bipolar disorder. Alternatively, differences in odor acuity may identify heterogeneous subgroups within the bipolar spectrum. Longitudinal assessments in a large, sex-stratified sample are needed to understand the implications of odor sensitivity in patients with bipolar disorder.

Suicide attempts are associated with worse quality of life in patients with bipolar disorder type I.

BACKGROUND: The association between suicidal behavior and quality of life (QoL) in bipolar disorder (BD) is poorly understood. Worse QoL has been associated with suicide attempts and suicidal ideation in schizophrenic patients, but this relationship has not been investigated in BD. This study tested whether a history of suicide attempts was associated with poor QoL in a well-characterized sample of patients with BD, as has been observed in other psychiatric disorders and in the general population. METHODS: One hundred eight patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition BD type I (44 with previous suicide attempts, 64 without previous suicide attempts) were studied. Quality of life was assessed using the World Health Organization's Quality of Life Instrument-Short Version. Depressive and manic symptoms were assessed using the Hamilton Depression Rating Scale-17 items and the Young Mania Rating Scale. RESULTS: Patients with BD and previous suicide attempts had significantly lower scores in all the 4 domains of the World Health Organization's Quality of Life Instrument-Short Version scale than did patients with BD but no previous suicide attempts (physical domain P = .001; psychological domain P < .0001; social domain P = .001, and environmental domain P = .039). In the euthymic subgroup (n = 70), patients with previous suicide attempts had significantly lower scores only in the psychological and social domains (P = .020 and P = .004). LIMITATIONS: This was a cross-sectional study, and no causal associations can be assumed. CONCLUSIONS: Patients with BD and a history of previous suicide attempts seem to have a worse QoL than did patients who never attempted suicide. Poorer QoL might be a marker of poor copying skills and inadequate social support and be a risk factor for suicidal behavior in BD. Alternatively, poorer QoL and suicidal behavior might be different expressions of more severe BD.