Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis.

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric = 1.28E-09 and 4.10E-18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.

Characterizing the Variation of Alcohol Cessation Pharmacotherapy in Primary Care.

BACKGROUND: Alcohol use disorder (AUD) imposes a high mortality and economic burden. Effective treatment is available, though underutilized. OBJECTIVE: Describe trends in AUD pharmacotherapy, variation in prescribing, and associated patient factors. DESIGN: Retrospective cohort using electronic health records from 2010 to 2019. PARTICIPANTS: Primary care patients from 39 clinics in Ohio and Florida with diagnostic codes for alcohol dependence or abuse plus social history indicating alcohol use. PCPs in family or internal medicine with at least 20 AUD patients. MAIN MEASURES: Pharmacotherapy for AUD (naltrexone, acamprosate, and disulfiram), abstinence from alcohol, patient demographics, and comorbidities. Generalized linear mixed models were used to identify patient factors associated with prescriptions and the association of pharmacotherapy with abstinence. KEY RESULTS: We identified 13,250 patients; average age was 54 years, 66.9% were male, 75.0% were White, and median household income was $51,776 per year. Over 10 years, the prescription rate rose from 4.4 to 5.6%. Patients who were Black (aOR 0.74; 95% CI 0.58, 0.94) and insured by Medicare versus commercial insurance (aOR 0.61; 95% CI 0.48, 0.78) were less likely to be treated. Higher median household income ($10,000 increment, aOR 1.06; 95% CI 1.03, 1.10) and Medicaid versus commercial insurance (aOR 1.52; 95% CI 1.24, 1.87) were associated with treatment. Receiving pharmacotherapy was associated with subsequent documented abstinence from alcohol (aOR 1.60; 95% CI 1.33, 1.92). We identified 236 PCPs. The average prescription rate was 3.6% (range 0 to 24%). The top decile prescribed to 14.6% of their patients. The bottom 4 deciles had no prescriptions. Family physicians had higher rates of pharmacotherapy than internists (OR 1.50; 95% CI 1.21, 1.85). CONCLUSIONS: Medications for AUD are infrequently prescribed, but there is considerable variation among PCPs. Increasing the use of pharmacotherapy by non-prescribers may increase abstinence from alcohol.

Clinical predictors of non-response to lithium treatment in the Pharmacogenomics of Bipolar Disorder (PGBD) study.

BACKGROUND: Lithium is regarded as a first-line treatment for bipolar disorder (BD), but partial response and non-response commonly occurs. There exists a need to identify lithium non-responders prior to initiating treatment. The Pharmacogenomics of Bipolar Disorder (PGBD) Study was designed to identify predictors of lithium response. METHODS: The PGBD Study was an eleven site prospective trial of lithium treatment in bipolar I disorder. Subjects were stabilized on lithium monotherapy over 4 months and gradually discontinued from all other psychotropic medications. After ensuring a sustained clinical remission (defined by a score of ≤3 on the CGI for 4 weeks) had been achieved, subjects were followed for up to 2 years to monitor clinical response. Cox proportional hazard models were used to examine the relationship between clinical measures and time until failure to remit or relapse. RESULTS: A total of 345 individuals were enrolled into the study and included in the analysis. Of these, 101 subjects failed to remit or relapsed, 88 achieved remission and continued to study completion, and 156 were terminated from the study for other reasons. Significant clinical predictors of treatment failure (p < 0.05) included baseline anxiety symptoms, functional impairments, negative life events and lifetime clinical features such as a history of migraine, suicidal ideation/attempts, and mixed episodes, as well as a chronic course of illness. CONCLUSIONS: In this PGBD Study of lithium response, several clinical features were found to be associated with failure to respond to lithium. Future validation is needed to confirm these clinical predictors of treatment failure and their use clinically to distinguish who will do well on lithium before starting pharmacotherapy.

Longitudinally Measured Changes in Somnolence Severity With a Visual Analog Scale in a Randomized Lithium Versus Quetiapine-IR Study in Bipolar Disorder.

OBJECTIVE: The aim of this study was to use a visual analog scale (VAS) longitudinally measuring somnolence severity in patients with bipolar disorder. METHODS: A data set of patients with bipolar spectrum disorders who were randomized to lithium or quetiapine-IR for 16 weeks was used. The somnolence severity was measured with a VAS from 0 to 100 (VAS based), and somnolence frequency was recorded according to incident report (incidence based) at each visit. The rates of VAS-based and incidence-based somnolence and changes in somnolence severity from baseline to the end of study were compared between the lithium and quetiapine groups. Longitudinal changes in somnolence severity were analyzed with linear regression analysis. RESULTS: Of 42 patients randomized, only 3 scored 0 on the VAS at baseline. The rates of incidence-based and VAS-based somnolence were similar in the lithium and quetiapine-IR groups. The VAS change scores from baseline to each visit varied in both groups with significant decreases at weeks 6 and 12 in the quetiapine-IR group only. The decrease at week 6 in the quetiapine-IR group was significantly different from that in the lithium group. Patterns of changes in somnolence severity were inconsistent in both groups. A significant interaction between time course and the decrease in VAS scores was observed in the quetiapine-IR group, but not in the lithium group. CONCLUSIONS: Baseline somnolence was highly prevalent in patients with bipolar disorder. The change in somnolence severity was different between lithium-treated and quetiapine-treated patients. Quantifying somnolence longitudinally is important in clinical trials and practice.

A Pilot Study of the Effectiveness of Lithium Versus Quetiapine Immediate Release Monotherapy in Patients With Bipolar Spectrum Disorders.

OBJECTIVE: The aim of this study was to compare the effectiveness of lithium versus quetiapine immediate release (IR) monotherapy in patients with bipolar I, II, or subthreshold bipolar disorder at any phase. METHODS: Eligible patients were randomized to lithium or quetiapine IR for 16 weeks. The difference in the time to discontinuation from study due to "all causes" between lithium and quetiapine IR groups and changes from baseline to 8 and 16 weeks in depression, mania, anxiety, quality of life (QOL), metabolic profiles, and proinflammatory markers were compared. RESULTS: Of the 42 patients randomized to lithium (n = 18) and quetiapine IR (n = 24), the median time to discontinuation due to "all causes" was 6 weeks (95% confidence interval, 2-12 weeks) in the lithium group and 8 weeks (95% confidence interval, 6 weeks to not calculable) in the quetiapine IR group. The mean time to discontinuation due to "all causes" was 7.7 ± 1.1 weeks for lithium versus 8.4 ± 0.8 weeks for quetiapine IR (P = 0.54). There was no significant difference between lithium and quetiapine IR in changes in the severity of depression, mania/hypomania, anxiety, and QOL as a whole or only in patients with depressive index episode. The decrease in total cholesterol was significantly larger with lithium than with quetiapine IR (P = 0.05) as a whole, but not only in patients with depression index episode. There was no other significant difference in changes in metabolic panels and inflammatory markers between the 2 groups. CONCLUSIONS: The difference in effectiveness between lithium and quetiapine IR monotherapy in a real-world bipolar population was minimal. Large-sample studies are needed to support or refute this finding.

Association of Spirituality With Mental Health Conditions in Ohio National Guard Soldiers.

Research exploring spirituality in military populations is a relatively new field with limited published reports. This study used the Spiritual Well-Being Scale to examine the association of spiritual well-being with suicidal ideation/behavior, posttraumatic stress disorder (PTSD), and depression and alcohol use disorders in a randomized sample of Ohio Army National Guard soldiers. The participants were 418 soldiers, mostly white and male, with nearly three-quarters indicating that they had been deployed at least once during their careers. Higher spirituality, especially in the existential well-being subscale, was associated with significantly less lifetime PTSD, depression, and alcohol use disorders and with less suicidal ideation over the past year. Future research in this area may benefit from a longitudinal design that can assess spirituality and mental health behaviors in addition to diagnoses at different time points, to begin to explore spirituality in a larger context.

Onset of Alcohol Use Disorders and Comorbid Psychiatric Disorders in a Military Cohort: Are there Critical Periods for Prevention of Alcohol Use Disorders?

Alcohol use disorders (AUD) are commonly comorbid with anxiety and mood disorders; however, a strategy for AUD prevention remains unclear in the presence of three competing etiological models that each recommends different high-risk groups. Therefore, the investigation of the three hypotheses in a characteristically unique cohort is critical to identifying pervasive characteristics of AUD that can inform a universal prevention strategy. The current study evaluated the temporality and onset of comorbid AUD and psychiatric disorders in a representative sample of 528 Ohio Army National Guard soldiers using structured clinical interviews from 2009 to 2012. We examined temporality both statistically and graphically to identify patterns that could inform prevention. General estimating equations with dichotomous predictor variables were used to estimate odds ratios between comorbid psychiatric disorders and AUDs. An annualized rate of 13.5 % persons per year was diagnosed with any AUD between 2010 and 2012. About an equal proportion of participants with comorbid psychiatric disorders and AUD initiated the psychiatric disorder prior to the AUD and half initiated the psychiatric disorder after the AUD. Regardless of onset, however, the majority (80 %) AUD initiated during a short interval between the ages of 16 and 23. Focused primary prevention during this narrow age range (16-23 years) may have the greatest potential to reduce population mental health burden of AUD, irrespective of the sequencing of comorbid psychiatric disorder.

Patient Priorities-Aligned Care for Older Adults With Multiple Conditions: A Nonrandomized Controlled Trial.

Importance: Older adults with multiple conditions receive health care that may be burdensome, of uncertain benefit, and not focused on what matters to them. Identifying and aligning care with patients' health priorities may improve outcomes. Objective: To assess the association of receiving patient priorities care (PPC) vs usual care (UC) with relevant clinical outcomes. Design, Setting, and Participants: In this nonrandomized controlled trial with propensity adjustment, enrollment occurred between August 21, 2020, and May 14, 2021, with follow-up continuing through February 26, 2022. Patients who were aged 65 years or older and with 3 or more chronic conditions were enrolled at 1 PPC and 1 UC site within the Cleveland Clinic primary care multisite practice. Data analysis was performed from March 2022 to August 2023. Intervention: Health professionals at the PPC site guided patients through identification of values, health outcome goals, health care preferences, and top priority (ie, health problem they most wanted to focus on because it impeded their health outcome goal). Primary clinicians followed PPC decisional strategies (eg, use patients' health priorities as focus of communication and decision-making) to decide with patients what care to stop, start, or continue. Main Outcomes and Measures: Main outcomes included perceived treatment burden, Patient-Reported Outcomes Measurement Information System (PROMIS) social roles and activities, CollaboRATE survey scores, the number of nonhealthy days (based on healthy days at home), and shared prescribing decision quality measures. Follow-up was at 9 months for patient-reported outcomes and 365 days for nonhealthy days. Results: A total of 264 individuals participated, 129 in the PPC group (mean [SD] age, 75.3 [6.1] years; 66 women [48.9%]) and 135 in the UC group (mean [SD] age, 75.6 [6.5] years; 55 women [42.6%]). Characteristics between sites were balanced after propensity score weighting. At follow-up, there was no statistically significant difference in perceived treatment burden score between groups in multivariate models (difference, -5.2 points; 95% CI, -10.9 to -0.50 points; P = .07). PPC participants were almost 2.5 times more likely than UC participants to endorse shared prescribing decision-making (adjusted odds ratio, 2.40; 95% CI, 0.90 to 6.40; P = .07), and participants in the PPC group experienced 4.6 fewer nonhealthy days (95% CI, -12.9 to -3.6 days; P = .27) compared with the UC participants. These differences were not statistically significant. CollaboRATE and PROMIS Social Roles and Activities scores were similar in the 2 groups at follow-up. Conclusions and Relevance: This nonrandomized trial of priorities-aligned care showed no benefit for social roles or CollaboRATE. While the findings for perceived treatment burden and shared prescribing decision-making were not statistically significant, point estimates for the findings suggested that PPC may hold promise for improving these outcomes. Randomized trials with larger samples are needed to determine the effectiveness of priorities-aligned care. Trial Registration: ClinicalTrials.gov Identifier: NCT04510948.

Impact of Embedding a Venous Thromboembolism Risk Assessment Model in the Electronic Health Record Versus Usual Care: A Cluster-Randomized Trial.

BACKGROUND: There are multiple risk assessment models (RAMs) for venous thromboembolism prophylaxis, but it is unknown whether they increase appropriate prophylaxis. METHODS: To determine the impact of a RAM embedded in the electronic health record, we conducted a stepped-wedge hospital-level cluster-randomized trial conducted from October 1, 2017 to February 28, 2019 at 10 Cleveland Clinic hospitals. We included consecutive general medical patients aged 18 years or older. Patients were excluded if they had a contraindication to prophylaxis, including anticoagulation for another condition, acute bleeding, or comfort-only care. A RAM was embedded in the general admission order set and physicians were encouraged to use it. The decisions to use the RAM and act on the results were reserved to the treating physician. The primary outcome was the percentage of patients receiving appropriate prophylaxis (high-risk patients with pharmacological thromboprophylaxis plus low-risk patients without prophylaxis) within 48 hours of hospitalization. Secondary outcomes included total patients receiving prophylaxis, venous thromboembolism among high-risk patients at 14 and 45 days, major bleeding, heparin-induced thrombocytopenia, and length of stay. Mixed-effects models were used to analyze the study outcomes. RESULTS: A total of 26 506 patients (mean age, 61; 52% female; 73% White) were analyzed, including 11 134 before and 15 406 after implementation of the RAM. After implementation, the RAM was used for 24% of patients, and the percentage of patients receiving appropriate prophylaxis increased from 43.1% to 48.8% (adjusted odds ratio, 1.11 [1.00-1.23]), while overall prophylaxis use decreased from 73.5% to 65.2% (adjusted odds ratio, 0.87 [0.78-0.97]). Rates of venous thromboembolism among high-risk patients (adjusted odds ratio, 0.72 [0.38-1.36]), rates of bleeding and heparin-induced thrombocytopenia (adjusted odds ratio, 0.19 [0.02-1.47]), and length of stay were unchanged. CONCLUSIONS: Implementation of a RAM for venous thromboembolism increased appropriate prophylaxis use, but the RAM was used for a minority of patients. REGISTRATION: URL: https://www.clinicaltrials.gov/study/NCT03243708?term=nct03243708&rank=1; Unique identifier: NCT03243708.

Assisted ambulation to improve health outcomes for older medical inpatients (AMBULATE): study protocol for a randomized controlled trial.

BACKGROUND: Hospitalized older adults spend as much as 95% of their time in bed, which can result in adverse events and delay recovery while increasing costs. Observational studies have shown that general mobility interventions (e.g., ambulation) can mitigate adverse events and improve patients' functional status. Mobility technicians (MTs) may address the need for patients to engage in mobility interventions without overburdening nurses. There is no data, however, on the effect of MT-assisted ambulation on adverse events or functional status, or on the cost tradeoffs if a MT were employed. The AMBULATE study aims to determine whether MT-assisted ambulation improves mobility status and decreases adverse events for older medical inpatients. It will also include analyses to identify the patients that benefit most from MT-assisted mobility and assess the cost-effectiveness of employing a MT. METHODS: The AMBULATE study is a multicenter, single-blind, parallel control design, individual-level randomized trial. It will include patients admitted to a medical service in five hospitals in two regions of the USA. Patients over age 65 with mild functional deficits will be randomized using a block randomization scheme. Those in the intervention group will ambulate with the MT up to three times daily, guided by the Johns Hopkins Mobility Goal Calculator. The intervention will conclude at hospital discharge, or after 10 days if the hospitalization is prolonged. The primary outcome is the Short Physical Performance Battery score at discharge. Secondary outcomes are discharge disposition, length of stay, hospital-acquired complications (falls, venous thromboembolism, pressure ulcers, and hospital-acquired pneumonia), and post-hospital functional status. DISCUSSION: While functional decline in the hospital is multifactorial, ambulation is a modifiable factor for many patients. The AMBULATE study will be the largest randomized controlled trial to test the clinical effects of dedicating a single care team member to facilitating mobility for older hospitalized patients. It will also provide a useful estimation of cost implications to help hospital administrators assess the feasibility and utility of employing MTs. TRIAL REGISTRATION: Registered in the United States National Library of Medicine clinicaltrials.gov (# NCT05725928). February 13, 2023.

Manualized cognitive behavioral group therapy to treat vasomotor symptoms for women diagnosed with mood disorders.

OBJECTIVE: This 6-week, prospective, single-arm study examined the feasibility, acceptability, and preliminary efficacy of cognitive behavioral group therapy in peri- and postmenopausal women with mood disorders (major depression or bipolar) and problematic vasomotor menopausal symptoms. METHODS: 59 participants from an outpatient clinic with mood disorders and problematic vasomotor symptoms were enrolled. The primary outcomes were change from baseline to 6 weeks in Hot Flush Night Sweat Problem Rating, Hot Flash Related Daily Interference, and Quality of Life. Secondary outcomes were change in Hot Flush Frequency, depression, anxiety, perceived stress, anhedonia, beliefs and cognitive appraisals of menopause. ClinicalTrials.gov [identifier: NCT02860910]. RESULTS: On the Hot Flush Night Sweat Problem Rating, 39.3% improved 2 or more points, which was clinically relevant. Changes in Quality of Life (p = .001) and the Hot Flash Related Daily Interference Scale were also significant (p < .001). Significant results were found on most secondary outcomes (hot flush frequency on the Hot Flush Daily Diary, depression, anxiety, perceived stress (p < .001) and anhedonia (p = .001). One of six subscales (control subscale) on the cognitive appraisal of menopause significantly improved (p < .001). Three subscales on the beliefs measure did not change significantly (p = .05, p = .91, and p = .14). Six-week study retention was robust (N = 55, 93%) and 94.2% of individuals reported that cognitive behavioral group therapy sessions were useful. CONCLUSION: This exploratory study suggests that CBGT is acceptable, feasible, and efficacious in women with mood disorders and problematic menopause vasomotor symptoms. Further studies are needed using more rigorous and controlled methods.

The association between lithium use and neurocognitive performance in patients with bipolar disorder.

Lithium remains the gold standard for the treatment of bipolar disorder (BD); however, its use has declined over the years mainly due to the side effects and the subjective experience of cognitive numbness reported by patients. In the present study, we aim to methodically test the effects of lithium on neurocognitive functioning in the largest single cohort (n = 262) of BD patients reported to date by harnessing the power of a multi-site, ongoing clinical trial of lithium monotherapy. At the cross-sectional level, multivariate analysis of covariance (MANCOVA) was conducted to examine potential group differences across neurocognitive tests [California Verbal Learning Test (CVLT trials 1-5,CVLT delayed recall), Wechsler Digit Symbol, Trail-making Test parts A and B (TMT-A; TMT-B), and a global cognition index]. At the longitudinal level, on a subset of patients (n = 88) who achieved mood stabilization with lithium monotherapy, we explored the effect of lithium treatment across time on neurocognitive functioning. There were no differences at baseline between BD patients that were taking lithium compared with those that were not. At follow-up a significant neurocognitive improvement in the global cognitive index score [F = 31.69; p < 0.001], CVLT trials 1-5 [F = 29.81; p < 0.001], CVLT delayed recall [F = 15.27; p < 0.001], and TMT-B [F = 6.64, p = 0.012] was detected. The cross-sectional and longitudinal (on a subset of 88 patients) investigations suggest that lithium may be beneficial to neurocognitive functioning in patients with BD and that at the very least it does not seem to significantly impair cognition when used therapeutically.

Double-blind, placebo-controlled trial of pioglitazone for bipolar depression.

BACKGROUND: Objective of the present study was to conduct an 8-week double-blind, randomized, placebo-controlled trial to test the efficacy of pioglitazone in the treatment of bipolar depression. METHODS: 38 outpatients with bipolar disorder and current major depressive episode were randomized to pioglitazone (15-45 mg/day) or placebo. The use of concomitant mood stabilizers, antipsychotics, and antidepressants was permitted. The primary outcome measure was the 30-item Inventory of Depressive Symptomatology, Clinician Rated (IDS-C30) total score change from baseline to endpoint. Laboratory evaluations, including serum level of inflammatory and metabolic biomarkers, were conducted. RESULTS: 37 subjects were analyzed for efficacy (1 subject had no follow-up data). Mean reduction from baseline to week 8 in IDS-C30 score was-6.59 for pioglitazone and -11.63 for placebo. Mixed effects modeling indicated borderline statistically significant difference between the two groups (p = 0.056) in favor of placebo. On analysis of inflammatory and metabolic markers, a statistically significant negative correlation was noted between change in leptin levels and change in depression scores in the pioglitazone group (r = -0.61, p = 0.047) but not in the placebo group, the significance of which is unclear as the study failed to demonstrate antidepressant efficacy of pioglitazone over placebo. No serious adverse effects were reported, and pioglitazone was well-tolerated. LIMITATIONS: small sample size with inadequate power, concomitant use of other psychotropic medications, and lack of statistical adjustment for multiple testing. CONCLUSION: Current study does not support the antidepressant efficacy of pioglitazone in the treatment of bipolar depression. (240 words).

Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder.

Bipolar disorder (BD) is a serious mood disorder associated with circadian rhythm abnormalities. Risk for BD is genetically encoded and overlaps with systems that maintain circadian rhythms. Lithium is an effective mood stabilizer treatment for BD, but only a minority of patients fully respond to monotherapy. Presently, we hypothesized that lithium-responsive BD patients (Li-R) would show characteristic differences in chronotype and cellular circadian rhythms compared to lithium non-responders (Li-NR). Selecting patients from a prospective, multi-center, clinical trial of lithium monotherapy, we examined morning vs. evening preference (chronotype) as a dimension of circadian rhythm function in 193 Li-R and Li-NR BD patients. From a subset of 59 patient donors, we measured circadian rhythms in skin fibroblasts longitudinally over 5 days using a bioluminescent reporter (Per2-luc). We then estimated circadian rhythm parameters (amplitude, period, phase) and the pharmacological effects of lithium on rhythms in cells from Li-R and Li-NR donors. Compared to Li-NRs, Li-Rs showed a difference in chronotype, with higher levels of morningness. Evening chronotype was associated with increased mood symptoms at baseline, including depression, mania, and insomnia. Cells from Li-Rs were more likely to exhibit a short circadian period, a linear relationship between period and phase, and period shortening effects of lithium. Common genetic variation in the IP3 signaling pathway may account for some of the individual differences in the effects of lithium on cellular rhythms. We conclude that circadian rhythms may influence response to lithium in maintenance treatment of BD.

Retrospective age-of-onset and projected lifetime prevalence of psychiatric disorders among U.S. Army National Guard soldiers.

BACKGROUND: The study of military-related mental health has been disproportionately focused on current symptomology rather than potentially more informative life course mental health. Indeed, no study has assessed age-of-onset and projected lifetime prevalence of disorders among reservists. METHODS: Age-of-onset and projected lifetime DSM-IV anxiety, mood, and substance use disorders were assessed in 671 Ohio Army National Guard soldiers aged 17-60 years. Between 2008 and 2012, face-to-face clinical assessments and surveys were conducted using the Structured Clinical Interview for DSM-IV and Clinician-Administered PTSD Scale. RESULTS: Lifetime prevalence of psychiatric disorders was 61%. Alcohol abuse/dependence (44%) and major depressive disorder (23%) were the most common disorders. The majority (64%) of participants reported disorders antedating enlistment. Median age-of-onset varied with anxiety disorders - particularly phobias and OCD - having the earliest (median=15 years) and mood disorders the latest median age-of-onset (median=21 years). LIMITATIONS: The study was limited by both the retrospective investigation of age-of-onset and the location of our sample. As our sample may not represent the general military population, our findings need to be confirmed in additional samples. CONCLUSIONS: Each psychiatric disorder exhibited a distinct age-of-onset pattern, such that phobias and OCD onset earliest, substance use disorders onset during a short interval from late-adolescence to early-adulthood, and mood disorders onset the latest. Our finding that the majority of participants reported disorders antedating enlistment suggests that an assessment of lifetime psychopathology is essential to understanding the mental health burden of both current and former military personnel.

Lifetime and 12-month use of psychiatric services among U.S. Army National Guard soldiers in Ohio.

OBJECTIVE: The individual and economic burden of psychiatric illnesses is substantial. Although treatment of psychiatric disorders mitigates the burden of illness, over half of military personnel with disorders do not receive mental health care. However, there is a paucity of research examining the relationship between psychiatric disorder categories and treatment-seeking behavior in representative military populations. This study aimed to document, by psychiatric disorder category, the annualized rate of Guard members who obtained psychiatric services and the factors associated with service utilization. METHODS: Face-to-face clinical assessments were conducted between 2008 and 2012 to assess lifetime and current psychiatric disorders and recent psychiatric service use among 528 Ohio Army National Guard soldiers. RESULTS: An annualized rate of 31% of persons per year accessed psychiatric services between 2010 and 2012. Persons with substance use disorders had the lowest annualized rate of service use, and these were the only disorders not predictive of accessing services. Current mood disorder, current anxiety disorder, and lifetime history of service use were the strongest predictors of recent service use. There were no socioeconomic or other group predictors of psychiatric service use. CONCLUSIONS: About half of the soldiers who could benefit from mental health services used them, yet soldiers with substance use disorders were predominantly going untreated. There were no differences in treatment utilization by group characteristics, suggesting no systematic barriers to care for particular groups. Efforts to encourage broader adoption of treatment seeking, particularly among persons with substance use disorders, are necessary to mitigate psychiatric health burden in this population.

Baseline prevalence of Axis I diagnosis in the Ohio Army National Guard.

The goal of this study is to determine the pre-existing lifetime and current prevalence of DSM-IV Axis I disorders within the Ohio Army National Guard (OHARNG). Data was analyzed from the clinical subsample of the Ohio Army National Guard Mental Health Initiative (OHARNG MHI). Five hundred participants were provided with an in-depth clinical assessment using the Clinician-Administered PTSD Scale (CAPS) and the Structured Clinical Interview for DSM-IV-TR (SCID). Logistic regression examined the relationship between Axis I disorders and the number of deployments and gender. Prevalence of at least one DSM-IV lifetime disorder was 66.2%; substance use disorders were 52.2%, followed by mood disorders (30.0%) and anxiety disorders (22.0%). Prevalence of at least one current disorder was 24.8%; anxiety disorders (13.2%), mood disorders (7.6%), and substance use disorders (7.0%) were most frequent. Number of deployments was associated with PTSD (OR=8.27, 95% CI 2.10-32.59, p=0.003), alcohol use disorder (OR=1.77, 95% CI 1.07-2.92, p=0.025), and any substance use disorder (OR=1.85, 95% CI 1.12-3.05, p=0.016). Gender (OR=2.02, 95% CI 1.10-3.73, p=0.024) was associated with any mood disorder. The results provide baseline information on the most prevalent mental disorders within the OHARNG.

A review of the history of traumatic stress studies in Japan: from traumatic neurosis to PTSD.

Based on available literature, this review article investigates traumatic stress studies in Japan from the late 19th century to the present for English speaking audiences. First, traumatic neuroses of war victims, A-bomb survivors, and victims of work-related accidents are discussed. Second, traumatic stress studies of victims of other manmade disasters, such as the sarin gas attacks in Tokyo, domestic violence, and burn injuries. Third, psychological outcomes of natural disaster studies are discussed in relation to social support and help-seeking tendencies of Japan disaster victims.

PTSD, depression and help-seeking patterns following the Miyake Island volcanic eruption.

Assessing help-seeking patterns following disaster provides useful information about who needs professional help the most, who is willing to seek help, and who is reluctant to seek help. 231 Japanese evacuees from the Miyake Island volcanic eruption (2000) participated in this study (ages 20-93, average age 59.52). Ten months after the evacuation, participants were mailed questionnaires which elicited demographic data, disaster experiences, help-seeking patterns, and psychological symptoms (Post-traumatic stress disorder and depression). Help-seeking patterns were categorized as: professionals (physicians, nurses, psychotherapists/counselors, telephone consultation, social workers, priests and monks, and others); or informal (family, relatives, friends, neighbors, and others) and, (information, advice, tangible, and emotional). The findings indicate that younger and/or female victims frequently sought help from informal sources while male and/or older victims frequently sought help from professionals. Severity of PTSD and depression symptoms were positively correlated with help-seeking from physicians, but not psychologists or mental health professionals. Very high rates of utilizing medical assistance rather than mental health treatment were also identified among these disaster victims, and appeared related to cultural norms regarding shame and self disclosure of emotional distress.

Validation of lay-administered mental health assessments in a large Army National Guard cohort.

To report the reliability and validity of key mental health assessments in an ongoing study of the Ohio Army National Guard (OHARNG). The 2616 OHARNG soldiers received hour-long structured telephone surveys including the post-traumatic stress disorder (PTSD) checklist (PCV-C) and Patient Health Questionnaire - 9 (PHQ-9). A subset (N = 500) participated in two hour clinical reappraisals, using the Clinician-Administered PTSD Scale (CAPS) and the Structured Clinical Interview for DSM (SCID). The telephone survey assessment for PTSD and for any depressive disorder were both highly specific [92% (standard error, SE 0.01), 83% (SE 0.02)] with moderate sensitivity [54% (SE 0.09), 51% (SE 0.05)]. Other psychopathologies assessed included alcohol abuse [sensitivity 40%, (SE 0.04) and specificity 80% (SE 0.02)] and alcohol dependence [sensitivity, 60% (SE 0.05) and specificity 81% (SE 0.02)].The baseline prevalence estimates from the telephone study suggest alcohol abuse and dependence may be higher in this sample than the general population. Validity and reliability statistics suggest specific, but moderately sensitive instruments.