Suicidal ideation and behavior in US veterans with schizophrenia or bipolar disorder.

OBJECTIVE: Using data from a Department of Veterans Affairs study of schizophrenia (SZ) and bipolar I disorder (BP), we evaluated lifetime risks for suicidal ideation and behavior. We were interested in the prevalence and correlates of these outcomes, in populations of patients with severe mental illness (SMI), who have not been compared directly in previous studies despite data on high risk in each group separately. METHOD: Data were collected on demographic factors, medical and psychiatric comorbidity, cognitive and functional status, and lifetime suicidal ideation or behavior in a study of veterans with SZ (N = 3942) or BP (N = 5414). In-person diagnosis and evaluation, including performance-based assessments of cognition and functional skills, make this study unique compared to studies of completed suicide. Multinomial logistic regression examined how risk factors, including major depression and negative symptoms in SCZ patients, correlated with ideation and behavior. RESULTS: A lifetime history of suicidal ideation or behavior was reported by a majority of Veterans with SZ (69.9%) or BP (82.3%). Lower risk was found for patients with SZ vs. BP (odds ratio [OR] = 0.82 for ideation; OR = 0.81 for behavior). The highest risk was found for patients with multiple psychiatric comorbidities (OR = 2.61 for ideation; OR = 3.82 for behavior). Clinical factors (e.g., psychiatric comorbidity) contributed more of the variance in the predictive model than demographic factors. CONCLUSIONS: A history of suicidal ideation or behavior is common among US Veterans with SZ or BP, and specific demographic and clinical attributes correlate with variation in risk. These findings underscore the need for continuous monitoring for suicidal ideation and behavior in veteran populations with SMI, as well as the development of better risk predictions, including genomic factors. Although PTSD is a major current focus in veteran populations, the large number of veterans with SZ or BP and their high suicide risk suggests a greater clinical focus may be warranted.

Validación de la versión en español de la Columbia-Suicide Severity Rating Scale (Escala Columbia para Evaluar el Riesgo de Suicidio) / Validation of a Spanish version of the Columbia-Suicide Severity Rating Scale (C-SSRS)

Objetivo. Examinar las propiedades psicométricas de la versión en español de la escala C-SSRS (Sp-CSSRS). Método. Estudio de validación naturalista, transversal y multicéntrico. Muestra: 467 pacientes psiquiátricos ambulatorios (242 con tentativa de suicidio previa). Instrumentos: C-SSRS; Escala de Hamilton para la Depresión (HDRS); Escala de Intencionalidad Suicida de Beck; Escala de Gravedad Médica de la Tentativa (MDS). Resultados. Validez del constructo: el coeficiente de Pearson entre la subescala de gravedad (C-Grave) y la de intensidad (C-Int) de la Sp-C-SSRS fue 0,44 (p < 0,000). El coeficiente de Pearson entre C-Grave y el ítem 3 de la HDRS fue 0,56 (p < 0,000). Para la submuestra de pacientes con tentativa de suicidio previa, se encontró una correlación estadísticamente significativa entre C-Grave y la Escala de Intencionalidad Suicida de Beck (r = 0,22; p = 0,001). Validez discriminante: se encontraron diferencias estadísticamente significativas entre las puntuaciones de C-Grave y de C-Int entre pacientes con tentativa de suicidio y sin ella (p < 0,000). La puntuación de la C-Grave clasificó adecuadamente a los pacientes en función de su puntuación en el ítem 3 de la HDRS (p < 0,009). Sensibilidad al cambio: la regresión lineal mostró que la disminución de una unidad en el ítem 3 de la HDRS se correspondió con la disminución de 5,08 unidades en la C-Grave (p = 0,141). El cambio de una unidad en el ítem 3 de la HDRS se correspondió con un cambio de 13,51 unidades en la C-Int (p = 0,007). El alfa de Cronbach fue 0,53. El análisis factorial de la C-Int identificó 2 componentes que explicaron el 55,66% de la varianza total. Conclusión. La Sp-C-SSRS es un instrumento fiable y válido para evaluar la ideación y la conducta suicidas en la práctica clínica y en contextos de investigación (AU)

Objective. To examine the psychometric properties of a Spanish version of the C-SSRS (Sp-CSSRS). Method. Data are from a naturalistic, cross-sectional, multicentre, validation study, including 467 psychiatric outpatients, 242 of whom had a history of suicide attempt. The study measures were: C-SSRS; the Hamilton Depression Rating Scale (HDRS); the Beck Suicide Intent Scale; the Medical Damage Scale. Results. Construct validity: Pearson coefficient between the C-SSRS severity (C-Sev) and intensity (C-Int) of ideation subscale scores was 0.44 (P < .000) for the total sample. Likewise, Pearson coefficient between C-Sev score and HDRS item 3 was 0.56 (P < .000). For the sub-sample of patients with suicide attempt, significant Pearson correlations were found between the C-Sev and the Beck Suicide Intent Scale scores (r = 0.22; P = .001). Discriminant validity: Significant differences were found in C-Sev and C-Int scores between patients with and without suicide attempt (P < .000). The C-Sev score discriminated between patients based on HDRS item 3 (P < .009). Sensitivity to change: Linear regression showed that a one-unit decrease in HDRS item 3 corresponded to a decrease of 5.08 units in the C-Sev score (P = .141). A one-unit change in HDRS item 3 corresponded to a change of 13.51 on the C-Int assessments (P = .007). Cronbach's alpha was 0.53 for C-Int. The principal component analysis identified 2 components that explain 55.66% of the total variance (C-Int). Conclusion. The data support that the Sp-C-SSRS is a reliable and valid instrument for assessing suicidal ideation and behaviour in daily clinical practice and research settings (AU)

Validation of a Spanish version of the Columbia-Suicide Severity Rating Scale (C-SSRS). / Validación de la versión en español de la Columbia-Suicide Severity Rating Scale (Escala Columbia para Evaluar el Riesgo de Suicidio).

OBJECTIVE: To examine the psychometric properties of a Spanish version of the C-SSRS (Sp-CSSRS). METHOD: Data are from a naturalistic, cross-sectional, multicentre, validation study, including 467 psychiatric outpatients, 242 of whom had a history of suicide attempt. The study measures were: C-SSRS; the Hamilton Depression Rating Scale (HDRS); the Beck Suicide Intent Scale; the Medical Damage Scale. RESULTS: Construct validity: Pearson coefficient between the C-SSRS severity (C-Sev) and intensity (C-Int) of ideation subscale scores was 0.44 (P<.000) for the total sample. Likewise, Pearson coefficient between C-Sev score and HDRS item 3 was 0.56 (P<.000). For the sub-sample of patients with suicide attempt, significant Pearson correlations were found between the C-Sev and the Beck Suicide Intent Scale scores (r=0.22; P=.001). Discriminant validity: Significant differences were found in C-Sev and C-Int scores between patients with and without suicide attempt (P<.000). The C-Sev score discriminated between patients based on HDRS item 3 (P<.009). Sensitivity to change: Linear regression showed that a one-unit decrease in HDRS item 3 corresponded to a decrease of 5.08 units in the C-Sev score (P=.141). A one-unit change in HDRS item 3 corresponded to a change of 13.51 on the C-Int assessments (P=.007). Cronbach's alpha was 0.53 for C-Int. The principal component analysis identified 2 components that explain 55.66% of the total variance (C-Int). CONCLUSION: The data support that the Sp-C-SSRS is a reliable and valid instrument for assessing suicidal ideation and behaviour in daily clinical practice and research settings.

Predictive Value of Baseline Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) Assessments for Identifying Risk of Prospective Reports of Suicidal Behavior During Research Participation.

OBJECTIVE: Examine the ability of baseline electronic Columbia-Suicide Severity Rating Scale lifetime suicidal ideation and behavior categories to predict prospective reports of suicidal behavior in psychiatric and non-psychiatric research participants. DESIGN: Meta-analysis of 74,406 eC-SSRS assessments completed between September 2009 and December 2012. SETTING: Thirty-three clinical research studies that used the electronic Columbia-Suicide Severity Rating Scale to assess suicidal ideation and behavior at baseline and prospectively during follow-up visits. PARTICIPANTS: Records from 6,760 patients with psychiatric disorders (opioid dependence, generalized anxiety, major depressive, and posttraumatic stress disorders) and 2,077 nonpsychiatric disorder patients (chronic obstructive pulmonary disease, epilepsy, fibromyalgia, human immunodeficiency virus, insomnia, multiple sclerosis, osteoarthritis, pain/back pain, Parkinson's disease, restless leg syndrome) were analyzed. MEASUREMENTS: Electronic Columbia-Suicide Severity Rating Scale assessment of lifetime suicidal ideation (5 severity levels) and suicidal behavior (4 types) at baseline and prospectively reported suicidal behavior during study participation. RESULTS: Increasingly more severe lifetime suicidal ideation at baseline was associated with a progressively greater likelihood of prospectively reported suicidal behavior during study participation. Intent to act on suicidal ideation was most predictive of reports of suicidal behavior. Reports of lifetime suicidal behaviors at baseline also predicted subsequent suicidal behavior, and multiple lifetime behaviors monotonically increased prospective risk of suicidal behavior. Baseline suicidal ideation and behavior predicted future suicidal behavior in both psychiatric and non-psychiatric trials. CONCLUSIONS: Lifetime reports of suicidal ideation and/or behavior at baseline significantly increased risk of prospectively reporting suicidal behavior during research trial participation in both psychiatric and nonpsychiatric patients. Lifetime prevalence of suicidal ideation and behavior is higher among psychiatric patients, but also presents a safety concern among nonpsychiatric patients when reported.

Abuse liability measures for use in analgesic clinical trials in patients with pain: IMMPACT recommendations.

Assessing and mitigating the abuse liability (AL) of analgesics is an urgent clinical and societal problem. Analgesics have traditionally been assessed in randomized clinical trials (RCTs) designed to demonstrate analgesic efficacy relative to placebo or an active comparator. In these trials, rigorous, prospectively designed assessment for AL is generally not performed. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) convened a consensus meeting to review the available evidence and discuss methods for improving the assessment of the AL of analgesics in clinical trials in patients with pain. Recommendations for improved assessment include: (1) performing trials that include individuals with diverse risks of abuse; (2) improving the assessment of AL in clinical trials (eg, training study personnel in the principles of abuse and addiction behaviors, designing the trial to assess AL outcomes as primary or secondary outcome measures depending on the trial objectives); (3) performing standardized assessment of outcomes, including targeted observations by study personnel and using structured adverse events query forms that ask all subjects specifically for certain symptoms (such as euphoria and craving); and (4) collecting detailed information about events of potential concern (eg, unexpected urine drug testing results, loss of study medication, and dropping out of the trial). The authors also propose a research agenda for improving the assessment of AL in future trials.

Prediction of suicidal behavior in clinical research by lifetime suicidal ideation and behavior ascertained by the electronic Columbia-Suicide Severity Rating Scale.

OBJECTIVE: To evaluate whether lifetime suicidal ideation with intention to act and/or suicidal behaviors reported at baseline predict risk of prospectively reporting suicidal behavior during subsequent study participation. METHOD: Data from studies using the electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) to prospectively monitor suicidal ideation and behaviors between September 2009 and May 2011 were analyzed. Studies included patients with major depressive disorder, insomnia, posttraumatic stress disorder, epilepsy, and fibromyalgia. Records for 35,224 eC-SSRS assessments were extracted. Incomplete assessments and eC-SSRS records from patients missing a baseline assessment or with no prospective follow-up assessments were excluded. Baseline lifetime eC-SSRS reports were categorized as negative (no lifetime ideation with intent to act or prior suicidal behavior) or positive (lifetime ideation with intent to act but no prior behavior, no ideation with intent to act but prior behavior, or both lifetime ideation with intent and prior behavior). RESULTS: 3,776 patients completed a baseline and 1 or more follow-up assessments. The mean follow-up period was 64 days. Of patients with negative lifetime reports, 2.4% subsequently reported suicidal behavior during study participation, compared to 12.0% of patients with lifetime ideation with intent only (OR = 5.55; 95% CI, 2.65-11.59), 9.6% of patients with lifetime behavior only (OR = 4.33; 95% CI, 2.94-6.39), and 18.3% of patients with both (OR = 9.13; 95% CI, 6.47-12.88). Sensitivity and specificity of positive reports for identifying suicidal behaviors were 0.67 and 0.76, respectively. CONCLUSIONS: Patients reporting lifetime suicidal ideation with intent to act and/or prior suicidal behavior at baseline are 4 to 9 times more likely to prospectively report suicidal behavior during study participation.

Suicidal ideation and behavior screening in intractable focal epilepsy eligible for drug trials.

PURPOSE: Three suicidal ideation and suicidal behavior instruments were used to assess the prevalence of lifetime and recent suicidal ideation and suicidal behavior in patients with frequent treatment-resistant focal seizures who would be eligible for randomized clinical trials. This was done to determine which instrument was optimal for use in epilepsy. METHODS: In a cross-sectional study, we compared lifetime and recent suicidal ideation and suicide attempt on the MINI International Neuropsychiatric Interview (MINI), Columbia Suicide Severity Rating Scale (C-SSRS), and Interactive Voice Response System CSSRS (E-CSSRS). A safety algorithm determined treatment referral. Coordinators and participants evaluated experiences with the C-SSRS. The proportion of participants that baseline assessment would exclude from clinical trial enrollment was determined. KEY FINDINGS: Among 208 participants, 1.6-3.9% had recent high risk suicidal ideation and 1.0-4.7% had a recent suicide attempt across all instruments. Lifetime high-risk suicidal ideation occurred in 12.1-14.1%. Lifetime suicide attempt occurred in 10.2-13.1% of participants. Of those with recent suicide attempt, 31.1% required referral to a health professional, and 3.9% needed urgent referral. Lifetime suicidal behavior (including aborted suicide attempt, interrupted suicide attempt, suicide attempt, preparatory acts or behavior, and nonsuicidal self-injurious behavior) was found in 21.1% on the E-CSSRS and 15.5% on the C-SSRS. Agreement (Kappa) was good to excellent for comparisons of all instruments. Fifty-two percent of subjects preferred either the CSSRS or E-CSSRS, whereas the rest had no preference; of those having a preference, 87.5% favored the CSSRS. Of the 18.9% of participants who might have been excluded from trials based on suicidal ideation and suicide attempt, the CSSRS identified high-risk suicidal ideation or suicide attempt in the preceding 2 years in only 4.4%. SIGNIFICANCE: Suicidality screening is feasible in people with epilepsy. Slightly more suicidal behavior is reported with the E-CSSRS than C-SSRS, suggesting the E-CSSRS may be optimal. The proportion of patients who may be excluded from clinical trials based on worrisome suicidal ideation or suicide attempt is small, suggesting that it is possible to enroll most eligible individuals.

The Preschool Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) 6-year follow-up.

OBJECTIVE: To describe the clinical course of attention-deficit/hyperactivity disorder (ADHD) symptom severity and diagnosis from ages 3 to 5 up to 9 to 12 years during a 6-year follow-up after the original Preschool ADHD Treatment Study (PATS). METHOD: A total of 207 participants (75% male) from the original PATS, assessed at baseline (mean age, 4.4 years, when all met criteria for ADHD) and 3 months later (before medication treatment), were re-evaluated in three follow-up assessment visits (year 3, mean age 7.4 years; year 4, 8.3 years; and year 6, 10.4 years). Parents and teachers rated symptom severity, and clinicians established psychiatric diagnoses. Analyses examined longitudinal changes in symptom severity and ADHD diagnosis. RESULTS: Parent- and teacher-rated symptom severity decreased from baseline to year 3 but remained relatively stable and in the moderate-to-severe clinical range through year 6. Girls showed generally steeper decreases in symptom T-scores. At year 6, 89% (160/180) of remaining participants met ADHD symptom and impairment diagnostic criteria. Comorbidity of oppositional defiant disorder and/or conduct disorder was associated with a 30% higher risk of having an ADHD diagnosis at year 6 in the multiple logistic model. Medication status during follow-up, on versus off, did not predict symptom severity change from year 3 to year 6 after adjustment for other variables. CONCLUSIONS: ADHD in preschoolers is a relatively stable diagnosis over a 6-year period. The course is generally chronic, with high symptom severity and impairment, in very young children with moderate-to-severe ADHD, despite treatment with medication. Development of more effective ADHD intervention strategies is needed for this age group.

Decreased suicidal ideation in depressed patients with or without comorbid posttraumatic stress disorder treated with selective serotonin reuptake inhibitors: an open study.

Comorbidity of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) is associated with higher morbidity including suicidal ideation and behavior. Selective serotonin reuptake inhibitors (SSRIs) are a known treatment for PTSD, MDD and comorbid PTSD and MDD. Since the patients with comorbid MDD and PTSD (PTSD-MDD) are sicker, we hypothesize a poorer response to treatment compared to patients with MDD only. Ninety-six MDD patients were included in the study: 76 with MDD only and 20 with PTSD-MDD. Demographic and clinical parameters at baseline were assessed. We examined clinical parameters before and after 3 months of open SSRI treatment in subjects with PTSD-MDD and compared this group to individuals with MDD only. At baseline, PTSD-MDD patients had higher Hamilton Depression Rating Scale and Buss-Durkee Hostility Scale scores compared with MDD only subjects. There was a significant decrease in scores on the Hamilton Depression Rating Scale, Beck Depression Inventory, Beck Hopelessness Scale, and Beck Scale for Suicidal Ideation after 3 months of treatment with SSRIs in both groups. The magnitude of improvement in Beck Scale for Suicidal Ideation scores was greater in the PTSD-MDD group compared to the MDD only subjects. Symptoms of depression including suicidal ideation improved in MDD patients with or without comorbid PTSD after 3 months of treatment with SSRIs but improvement in suicidal ideation was greater in the PTSD-MDD group. Our finding has not supported the hypothesis that a response to treatment is poorer in the PTSD-MDD group which may indicate that sicker patients benefit more from the treatment.

The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults.

OBJECTIVE: Research on suicide prevention and interventions requires a standard method for assessing both suicidal ideation and behavior to identify those at risk and to track treatment response. The Columbia-Suicide Severity Rating Scale (C-SSRS) was designed to quantify the severity of suicidal ideation and behavior. The authors examined the psychometric properties of the scale. METHOD: The C-SSRS's validity relative to other measures of suicidal ideation and behavior and the internal consistency of its intensity of ideation subscale were analyzed in three multisite studies: a treatment study of adolescent suicide attempters (N=124); a medication efficacy trial with depressed adolescents (N=312); and a study of adults presenting to an emergency department for psychiatric reasons (N=237). RESULTS: The C-SSRS demonstrated good convergent and divergent validity with other multi-informant suicidal ideation and behavior scales and had high sensitivity and specificity for suicidal behavior classifications compared with another behavior scale and an independent suicide evaluation board. Both the ideation and behavior subscales were sensitive to change over time. The intensity of ideation subscale demonstrated moderate to strong internal consistency. In the adolescent suicide attempters study, worst-point lifetime suicidal ideation on the C-SSRS predicted suicide attempts during the study, whereas the Scale for Suicide Ideation did not. Participants with the two highest levels of ideation severity (intent or intent with plan) at baseline had higher odds for attempting suicide during the study. CONCLUSIONS: These findings suggest that the C-SSRS is suitable for assessment of suicidal ideation and behavior in clinical and research settings.

Suicidality and risk of suicide--definition, drug safety concerns, and a necessary target for drug development: a consensus statement.

OBJECTIVE: To address issues concerning potential treatment-emergent "suicidality," a consensus conference was convened March 23-24, 2009. PARTICIPANTS: This gathering of participants from academia, government, and industry brought together experts in suicide prevention, clinical trial design, psychometrics, pharmacoepidemiology, and genetics, as well as research psychiatrists involved in studies of major depression, bipolar disorder, schizophrenia, substance abuse/dependence, and other psychiatric disorders associated with elevated suicide risk across the life cycle. The process involved reviews of the relevant literature, and a series of 6 breakout sessions focused on specific questions of interest. EVIDENCE: Each of the participants at the meeting received references relevant to the formal presentations (as well as the slides for the presentations) for their review prior to the meeting. In addition, the assessment instruments of suicidal ideation/behavior were reviewed in relationship to standard measures of validity, reliability, and clinical utility, and these findings were discussed at length in relevant breakout groups, in the final plenary session, and in the preparation of the article. Consensus and dissenting views were noted. CONSENSUS PROCESS: Discussion and questions followed each formal presentation during the plenary sessions. Approximately 6 questions per breakout group were prepared in advance by members of the Steering Committee and each breakout group chair. Consensus in the breakout groups was achieved by nominal group process. Consensus recommendations and any dissent were reviewed for each breakout group at the final plenary session. All plenary sessions were recorded and transcribed by a court stenographer. Following the transcript, with input by each of the authors, the final paper went through 14 drafts. The output of the meeting was organized into this scholarly article, which has been developed by the authors with feedback from all participants at the meeting and represents a consensus view. Any areas of disagreement have been noted. CONCLUSIONS: The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's effort to promote standard definitions and definable expectations for investigators and industry sponsors by endorsing the terminology in the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to build upon its new authority to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk within informative large health care-related databases in the United States and abroad. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the current Agency requirement that all CNS clinical drug trials must include a C-CASA-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed, and they need to be included to enable premarket assessments of the risks and benefits of medications related to suicidal ideation, suicidal behavior, and suicide in such patients.

Suicidality and risk of suicide--definition, drug safety concerns, and a necessary target for drug development: a brief report.

OBJECTIVE: To address issues concerning potential treatment-emergent "suicidality," a consensus conference was convened March 23-24, 2009. PARTICIPANTS: This gathering of participants from academia, government, and industry brought together experts in suicide prevention, clinical trial design, psychometrics, pharmacoepidemiology, and genetics, as well as research psychiatrists involved in studies in studies of psychiatric disorders associated with elevated suicide risk across the life cycle. The process involved reviews of the relevant literature, and a series of 6 breakout sessions focused on specific questions of interest. EVIDENCE: Each of the participants at the meeting received references relevant to the formal presentations (as well as the slides for the presentations) for their review prior to the meeting. In addition, the assessment instruments of suicidal ideation/behavior were reviewed in relationship to standard measures of validity, reliability, and clinical utility, and these findings were discussed at length in relevant breakout groups, in the final plenary session, and in the preparation of the article. Consensus and dissenting views were noted. CONSENSUS PROCESS: Discussion and questions followed each formal presentation during the plenary sessions. Approximately 6 questions per breakout group were prepared in advance by members of the Steering Committee and each breakout group chair. Consensus in the breakout groups was achieved by nominal group process. Consensus recommendations and any dissent were reviewed for each breakout group at the final plenary session. All plenary sessions were recorded and transcribed by a court stenographer. Following the transcript, with input by each of the authors, the final paper went through 14 drafts. The output of the meeting was organized into this brief report and the accompanying full article from which it is distilled. The full article was developed by the authors with feedback from all participants at the meeting and represents a consensus view. Any areas of disagreement at the conference have been noted in the text. CONCLUSIONS: The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's encouragement of standard definitions and definable expectations for investigators and industry sponsors. Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the requirement that all central nervous system clinical drug trials must include a Columbia Classification Algorithm of Suicide Assessment (C-CASA)-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed.

Short sleep duration as a risk factor for hypercholesterolemia: analyses of the National Longitudinal Study of Adolescent Health.

STUDY OBJECTIVES: To explore the relationship between sleep duration in adolescence and hypercholesterolemia in young adulthood. Experimental sleep restriction has been shown to significantly increase total cholesterol and LDL cholesterol levels in women. Short sleep duration has been found in cross sectional studies to be associated with higher total cholesterol and lower HDL cholesterol levels. Sleep deprivation could increase the risk for hypercholesterolemia by increasing appetite and dietary consumption of saturated fats, decreasing motivation to engage in regular physical activity, and increasing stress and resultant catecholamine induced lipolysis. No previous published population studies have examined the longitudinal relationship between sleep duration and high cholesterol. DESIGN: Multivariate longitudinal analyses stratified by sex of the ADD Health using logistic regression. SETTING: United States nationally representative, school-based, probability-based sample. PARTICIPANTS: Adolescents (n = 14,257) in grades 7 to 12 at baseline (1994-95) and ages 18 to 26 at follow-up (2001-02). MEASUREMENTS AND RESULTS: Among females, each additional hour of sleep was associated with a significantly decreased odds of being diagnosed with high cholesterol in young adulthood (OR = 0.85, 95% CI 0.75-0.96) after controlling for covariates. Additional sleep was associated with decreased, yet not statistically significant, odds ratios for hypercholesterolemia in males (OR = 0.91, 95% CI 0.79-1.05). CONCLUSIONS: Short sleep durations in adolescent women could be a significant risk factor for high cholesterol. Interventions that lengthen sleep could potentially serve as treatments and as primary preventative measures for hypercholesterolemia.

Earlier parental set bedtimes as a protective factor against depression and suicidal ideation.

STUDY OBJECTIVES: To examine the relationships between parental set bedtimes, sleep duration, and depression as a quasi-experiment to explore the potentially bidirectional relationship between short sleep duration and depression. Short sleep duration has been shown to precede depression, but this could be explained as a prodromal symptom of depression. Depression in an adolescent can affect his/her chosen bedtime, but it is less likely to affect a parent's chosen set bedtime which can establish a relatively stable upper limit that can directly affect sleep duration. DESIGN: Multivariate cross-sectional analyses of the ADD Health using logistic regression. SETTING: United States nationally representative, school-based, probability-based sample in 1994-96. PARTICIPANTS: Adolescents (n = 15,659) in grades 7 to 12. MEASUREMENTS AND RESULTS: Adolescents with parental set bedtimes of midnight or later were 24% more likely to suffer from depression (OR = 1.24, 95% CI 1.04-1.49) and 20% more likely to have suicidal ideation (1.20, 1.01-1.41) than adolescents with parental set bedtimes of 10:00 PM or earlier, after controlling for covariates. Consistent with sleep duration and perception of getting enough sleep acting as mediators, the inclusion of these variables in the multivariate models appreciably attenuated the associations for depression (1.07, 0.88-1.30) and suicidal ideation (1.09, 0.92-1.29). CONCLUSIONS: The results from this study provide new evidence to strengthen the argument that short sleep duration could play a role in the etiology of depression. Earlier parental set bedtimes could therefore be protective against adolescent depression and suicidal ideation by lengthening sleep duration.

Insomnia and sleep duration as mediators of the relationship between depression and hypertension incidence.

BACKGROUND: Depression has been found to predict the incidence of hypertension and other adverse cardiovascular events in prospective studies. Insomnia and short sleep duration, which are typical symptoms of depression, have also been shown to increase the risk for hypertension incidence. Insomnia is associated with increased activation of the hypothalamic-pituitary-adrenal axis, and short sleep duration raises average 24-h blood pressure, which over time could lead to structural adaptations that gradually reset the entire cardiovascular system to operate at an elevated pressure equilibrium. No previous published population studies have examined whether insomnia and sleep duration mediate the relationship between depression and hypertension incidence. METHODS: We conducted multivariate longitudinal (1982-1992) analyses stratified by age of the First National Health and Nutrition Examination Survey (NHANES I) (n = 4,913) using Cox proportional hazards models. RESULTS: Middle-aged subjects who suffered from depression at baseline were 44% more likely to be diagnosed with hypertension over the follow-up period after controlling for covariates (hazard ratio (HR) = 1.44, 95% confidence interval (CI) 1.15-1.80). Both short sleep duration and insomnia were also significantly associated with hypertension incidence. Consistent with insomnia and sleep duration acting as mediators of the relationship between depression and hypertension incidence, the inclusion of these variables in the multivariate models appreciably attenuated the association (HR = 1.27, 95% CI 1.00-1.61). Depression, sleep duration, and insomnia were not significantly associated with hypertension incidence in elderly subjects. CONCLUSIONS: These results suggest the hypothesis that treatment of sleep problems in middle-aged individuals suffering from depression could reduce their risk for developing hypertension, and its vascular and cardiac complications.

Childhood onset diagnoses in a case series of teens at clinical high risk for psychosis.

REASONS: Schizophrenia is typically an adult neurodevelopmental disorder that has its antecedents in childhood and adolescence. Little is known about disorders "usually first diagnosed in infancy, childhood and adolescence" (e.g., childhood-onset disorders) in "prodromal" teens at heightened clinical risk for psychotic disorder. MAIN FINDINGS: Childhood-onset disorders were prevalent in putatively prodromal teens, including anxiety and disruptive disorders, attention-deficit/hyperactivity disorder (ADHD), and, surprisingly, elimination disorders. These may reflect developmental antecedents in psychotic disorders such as schizophrenia. KEY DATA AND STATISTICS: A case series of 9 teens (ages 13-17) identified as prodromal to psychosis were evaluated with the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL). Childhood-onset diagnoses commonly endorsed (threshold or subthreshold) included ADHD (5/9), oppositional defiant disorder (5/9), enuresis or encopresis (4/9), conduct disorder (2/9), separation anxiety (3/9), and transient tic disorder (2/9). Enuresis was identified in 3 of the 4 older teens (ages 15-17). MAJOR CONCLUSIONS: An understanding of the childhood-onset disorders that occur in teens at risk for psychotic illnesses, such as schizophrenia, can shed light on the pathophysiology of schizophrenia and potentially inform early identification and intervention.

The Treatment of Adolescent Suicide Attempters study (TASA): predictors of suicidal events in an open treatment trial.

OBJECTIVE: To identify the predictors of suicidal events and attempts in adolescent suicide attempters with depression treated in an open treatment trial. METHOD: Adolescents who had made a recent suicide attempt and had unipolar depression (n =124) were either randomized (n = 22) or given a choice (n = 102) among three conditions. Two participants withdrew before treatment assignment. The remaining 124 youths received a specialized psychotherapy for suicide attempting adolescents (n = 17), a medication algorithm (n = 14), or the combination (n = 93). The participants were followed up 6 months after intake with respect to rate, timing, and predictors of a suicidal event (attempt or acute suicidal ideation necessitating emergency referral). RESULTS: The morbid risks of suicidal events and attempts on 6-month follow-up were 0.19 and 0.12, respectively, with a median time to event of 44 days. Higher self-rated depression, suicidal ideation, family income, greater number of previous suicide attempts, lower maximum lethality of previous attempt, history of sexual abuse, and lower family cohesion predicted the occurrence, and earlier time to event, with similar findings for the outcome of attempts. A slower decline in suicidal ideation was associated with the occurrence of a suicidal event. CONCLUSIONS: In this open trial, the 6-month morbid risks for suicidal events and for reattempts were lower than those in other comparable samples, suggesting that this intervention should be studied further. Important treatment targets include suicidal ideation, family cohesion, and sequelae of previous abuse. Because 40% of events occurred with 4 weeks of intake, an emphasis on safety planning and increased therapeutic contact early in treatment may be warranted.

Suicidal events in the Treatment for Adolescents With Depression Study (TADS).

OBJECTIVE: The Treatment for Adolescents with Depression Study (TADS) database was analyzed to determine whether suicidal events (attempts and ideation) occurred early in treatment, could be predicted by severity of depression or other clinical characteristics, and were preceded by clinical deterioration or symptoms of increased irritability, akathisia, sleep disruption, or mania. METHOD: TADS was a 36-week randomized, controlled clinical trial of pharmacologic and psychotherapeutic treatments involving 439 youths with major depressive disorder (DSM-IV criteria). Suicidal events were defined according to the Columbia Classification Algorithm of Suicidal Assessment. Patients were randomly assigned into the study between spring 2000 and summer 2003. RESULTS: Forty-four patients (10.0%) had at least 1 suicidal event (no suicide occurred). Events occurred 0.4 to 31.1 weeks (mean +/- SD = 11.9 +/- 8.2) after starting TADS treatment, with no difference in event timing for patients receiving medication versus those not receiving medication. Severity of self-rated pretreatment suicidal ideation (Suicidal Ideation Questionnaire adapted for adolescents score > or = 31) and depressive symptoms (Reynolds Adolescent Depression Scale score > or = 91) predicted occurrence of suicidal events during treatment (P < .05). Patients with suicidal events were on average still moderately ill prior to the event (mean +/- SD Clinical Global Impressions-Severity of Illness scale score = 4.0 +/- 1.3) and only minimally improved (mean +/- SD Clinical Global Impressions-Improvement scale score = 3.2 +/- 1.1). Events were not preceded by increased irritability, akathisia, sleep disturbance, or manic signs. Specific interpersonal stressors were identified in 73% of cases (N = 44). Of the events, 55% (N = 24) resulted in overnight hospitalization. CONCLUSIONS: Most suicidal events occurred in the context of persistent depression and insufficient improvement without evidence of medication-induced behavioral activation as a precursor. Severity of self-rated suicidal ideation and depressive symptoms predicted emergence of suicidality during treatment. Risk for suicidal events did not decrease after the first month of treatment, suggesting the need for careful clinical monitoring for several months after starting treatment.

Effect of acute alcohol use on the lethality of suicide attempts in patients with mood disorders.

Acute alcohol use is an important risk factor for attempted and completed suicide. We evaluated the effect of acute alcohol intake on the lethality of suicide attempts to test the hypothesis that acute alcohol intoxication is associated with more lethal suicide attempts. This retrospective study included 317 suicide attempters enrolled in mood disorders protocols. Demographic and clinical parameters were assessed. The use of alcohol at the time of the most lethal suicide attempt was determined. On the basis of their responses participants were classified into three groups: participants who reported "Enough alcohol intake to impair judgment, reality testing and diminish responsibility" or "Intentional intake of alcohol in order to facilitate implementation of attempt" were included in the group "Alcohol" (A); participants who reported "Some alcohol intake prior to but not related to attempt, reportedly not enough to impair judgment, reality testing" were included in the group "Some Alcohol" (SA); and participants who reported "No alcohol intake immediately prior to attempt" were included in the group "No Alcohol" (NA). Lethality of the most lethal suicide attempts was higher in the A group compared to the SA and NA groups. Prevalence of patients with alcohol use disorders was higher in the A group compared to the SA and NA groups. SA participants reported more reasons for living and lower suicide intent scores at the time of their most lethal suicide attempt compared to the A and NA groups. Acute alcohol use increases the lethality of suicide attempts in individuals with mood disorders.