Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci.

Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6, DALRD3, CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index.. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder.

Prevalence and correlates of lifetime suicide attempt in obsessive-compulsive disorder with major depression.

BACKGROUND: Little is known about specific obsessive-compulsive clinical features associated with lifetime history of suicide attempt in individuals with obsessive-compulsive disorder (OCD) and major depression. METHODS: The study sample included 515 adults with OCD and a history of major depression. In exploratory analyses, we compared the distributions of demographic characteristics and clinical features in those with and without a history of attempted suicide and used logistic regression to evaluate the association between specific obsessive-compulsive clinical features and lifetime suicide attempt. RESULTS: Sixty-four (12%) of the participants reported a lifetime history of suicide attempt. Those who had attempted suicide were more likely to report having experienced violent or horrific images (52% vs. 30%; p < 0.001). The odds of lifetime suicide attempt were more than twice as great in participants with versus without violent or horrific images (O.R. = 2.46, 95%, CI = 1.45-4.19; p < 0.001), even after adjustment for other risk correlates of attempted suicide, including alcohol dependence, post-traumatic stress disorder, parental conflict, excessive physical discipline, and number of episodes of depression. The association between violent or horrific images and attempted suicide was especially strong in men, 18-29 year olds, those with post-traumatic stress disorder, and those with particular childhood adversities. CONCLUSIONS: Violent or horrific images are strongly associated with lifetime suicide attempts in OCD-affected individuals with a history of major depression. Prospective clinical and epidemiological studies are needed to elucidate the basis of this relationship.

Impact of early, weekly drinking on latent classes of alcohol involvement progression and recovery: Evidence from the NESARC Waves 1 and 2.

INTRODUCTION: Early drinkers have been found to have higher risk of developing alcohol use disorder; however, the association of early drinking with progression to problematic alcohol involvement that does not meet disorder criteria (i.e., subclinical problems) or to severe stages of alcohol involvement, sex-specific associations, and relationship of early drinking with alcohol recovery have rarely been investigated. METHODS: Using data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), we applied latent transition analyses to investigate the impact of weekly drinking before age 18 on alcohol progression and recovery operationalized as three classes of alcohol involvement using abuse and dependence indicators. We analyzed data separately for male (n = 12,276) and female (n = 14,750) drinkers and applied propensity score methods to address confounding. RESULTS: We observed significant associations between early, weekly drinking and alcohol involvement class membership at Wave 1 for both males and females. For males, early, weekly drinking was also associated with greater odds of transitioning from moderate to severe alcohol problems (aOR = 3.19, 95% CI = 1.72, 5.35). For females, early, weekly drinking predicted the transition from no to severe problems (aOR = 2.98, 95% CI = 1.11-8.00). Contrary to our hypothesis, early, weekly drinking was associated with greater likelihood of transition from severe to no problems for males (aOR = 3.23, 95% CI = 1.26, 8.26). DISCUSSION: Frequent, early drinking seems to be an important indicator of drinking progression with differential associations by sex. This information is useful to identify those at greater risk of progressing to severe drinking problems to intervene appropriately.

The relationship between social and environmental factors and symptom severity in the seriously mentally ill population.

BACKGROUND: The goal of this article is to investigate the relationship of psychiatric symptom severity with internalised stigma, neighbourhood environment, and social support among individuals with serious mental illness. METHOD: Using a longitudinal study design we examined the relationship between psychiatric symptom severity with internalised stigma, neighbourhood environment, and social support among 271 adults with serious mental illness recruited from new admissions to two urban mental health clinics. RESULTS: After controlling for demographics increased stigma levels predicted greater symptom severity, as measured by the Positive and Negative Syndrome Scale (PANSS) Positive, Negative, and General Psychopathology scales over a 4-year period (p < .05). In adjusted models, individuals who reported living in more disadvantaged neighbourhoods also reported higher PANSS Negative and General scores over time (p < .05). Social support from friends and relatives was not significantly related to PANSS Positive, Negative, or General Psychopathology scores among individuals with serious mental illness. CONCLUSIONS: Individuals with serious mental illness who experience internalised stigma and neighbourhood disadvantage experience greater symptom severity over time. Targeting stigma and housing during treatment could potentially impact symptom severity in this population.

Assessing Self-reported Recovery in a Community Psychiatry Setting.

OBJECTIVE: This study examined demographic and diagnostic characteristics associated with self-reported recovery in patients with serious mental illness. METHODS: Patient demographics and diagnoses were obtained from a retrospective review of charts from 981 patients attending a community psychiatry outpatient program between January 2015 and December 2016. All patients completed the Recovery Assessment Scale-Revised (RAS-R), a self-report recovery questionnaire consisting of 5 subscales, approximately every 6 months. Generalized estimating equation models were used to assess change in RAS-R scores over time and to test for associations with demographic characteristics, clinical diagnoses, and appointment adherence. RESULTS: RAS-R scores increased among all demographic and diagnostic groups during the study period. A primary diagnosis of a psychotic disorder (including schizophrenia) was associated with higher 2-year average RAS-R total scores and scores on the Personal Confidence and Hope, Goal and Success Orientation, and Not Dominated by Symptoms subscales. African American race was associated with higher 2-year average scores on the Personal Confidence and Hope subscale. Increasing age was associated with higher total RAS-R scores and multiple subscale scores. No significant associations were found between sex or appointment adherence and RAS-R total scores or any of the subscale scores. CONCLUSIONS: While certain demographic and diagnostic groups were associated with higher RAS-R scores, study results suggest that time in treatment is itself associated with higher self-reported recovery among all demographic groups. Age, race, and diagnosis were all associated with higher scores on the Personal Confidence and Hope subscale, highlighting the need for individualized treatment that takes multiple patient characteristics into account.

Stressful life events and transitions in problematic alcohol use involvement among US adults.

OBJECTIVE: We investigated the impact of stressful life events (SLEs) for males and females on transitions in problematic alcohol involvement, both progression and recovery, over a 3-year interval. METHOD: Participants of both Wave 1 (2001-2002) and Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were stratified by sex (14,233 males and 19,550 females). Latent transition analysis estimated the impact of experiencing ≥3 SLE in the year preceding the Wave 1 interview on the probability of transitioning between three empirically-derived stages of alcohol involvement (patterns of alcohol use disorder [AUD] symptoms), across waves. Propensity score methods adjusted for confounding. RESULTS: For males, three or more SLEs were associated with progression from the moderate to the severe problem stage (odds ratio [OR] = 2.23, 95% confidence interval [CI] = 1.17, 4.26). Among those in the severe problem stage, SLEs negatively impacted recovery regardless of sex. Employment/Financial SLEs were associated with a higher odds of transition from the moderate to the no problem stage (OR = 1.60, 95% CI = 1.03, 2.46) and lower odds of transitions from the severe to the moderate problem stage (OR = 0.40, 95% CI = 0.16, 0.99) among males, and from the severe to the no problem stage (OR = 0.26, 95% CI = 0.07, 0.88) among females. CONCLUSION: Stressful life events appear to affect transitions in alcohol involvement over time among those who already have alcohol problems, rather than impacting a transition among those without AUD problems.

Symptom Severity and Care Delay among Patients with Serious Mental Illness.

PURPOSE: This study investigated associations between psychiatric symptom severity and delay in seeking general medical services among individuals with serious mental illness. METHODS: The association of psychiatric symptom severity, measured by the Positive and Negative Syndrome Scale (PANSS), and general medical care delay was examined among 271 patients at two urban, outpatient psychiatric clinics. RESULTS: Higher scores for PANSS paranoid/belligerence were associated with delays in accessing general medical care (adjusted odds ratio [AOR]=1.46, 95% confidence interval [CI]=1.04-2.01, p=.025). Higher scores on the depression symptom cluster were also associated with care delay (AOR=1.43, 95% CI=1.06-1.93, p=.018). Other symptom types showed no associations with care delay. CONCLUSION: Severity of specific psychiatric symptoms was associated with delays in seeking general medical care among people with serious mental illness. Increased focus on psychiatric symptom management may reduce medical care delay, thereby reducing the elevated morbidity and mortality among this population.

Symptom severity and medication-assisted treatment for individuals with serious mental illness and a history of heroin use.

The study examined associations between medication assisted treatment (MAT) and psychiatric symptom severity, measured by Positive and Negative Symptom Scale (PANSS), among individuals with serious mental illness and a history of heroin use. Of 271 participants, 32% (n=87) reported a history of heroin use and, of those, 14.9% (n=13) reported MAT. Higher scores in PANSS Total, Negative, and Disordered subscales were associated with lower odds, while being on an antipsychotic with higher odds, of receiving MAT. This supports the greater need for clinician attention to different symptom clusters and targeted multidimensional interventions as a way to increase MAT participation.

A Model for Advancing Scale-Up of Complex Interventions for Vulnerable Populations: the ALACRITY Center for Health and Longevity in Mental Illness.

Many of the most pressing health issues in the USA and worldwide require complex, multi-faceted solutions. Delivery of such solutions is often complicated by the need to reach and engage vulnerable populations facing multiple barriers to care. While the fields of quality improvement and implementation science have made valuable gains in the development and spread of individual strategies to improve evidence-based practice delivery, models for coordinated deployment of numerous strategies to simultaneously implement multiple evidence-based interventions in vulnerable populations are lacking. In this Perspective, we describe a model for this type of comprehensive research-practice translation effort: the Johns Hopkins ALACRITY Center for Health and Longevity in Mental Illness, which is focused on reducing premature mortality in the population with serious mental illness. We describe the Center's conceptual framework, which is built upon an integrated set of quality improvement and implementation science frameworks, provide an overview of the Center's organizational structure and core research-practice translation activities, and discuss our vision for how the Center may evolve over time. Lessons learned from this Center's efforts could inform models to address other critical health issues in vulnerable populations that require multi-component solutions at the policy, system, provider, and patient levels.

Clinical outcomes from the texting for relapse prevention (T4RP) in schizophrenia and schizoaffective disorder study.

This 6 month randomized control trial investigated whether a novel text-messaging program impacted targeted clinical outcomes in patients with schizophrenia and schizoaffective disorder (SAD). Forty patients were enrolled and completed baseline, 3-month and 6-month assessments. The intervention group received daily symptom check-in text messages, plus, a medication reminder or, inspirational quote text. The control group had treatment as usual. At 6 months the Positive and Negative Syndrome Scale mean positive score was significantly lower and injectable medication compliance was significantly higher in the intervention group. Recovery scores were significantly higher at 3 months. Results suggest that this program may benefit individuals with schizophrenia/SAD who use text messaging. Further investigation in a larger sample appears warranted.

Design and Implementation of a Regional Inpatient Psychiatry Unit for Patients who are Positive for Asymptomatic SARS-CoV-2.

BACKGROUND: Patients with psychiatric illnesses are particularly vulnerable to highly contagious, droplet-spread organisms such as SARS-CoV-2. Patients with mental illnesses may not be able to consistently follow up behavioral prescriptions to avoid contagion, and they are frequently found in settings with close contact and inadequate infection control, such as group homes, homeless shelters, residential rehabilitation centers, and correctional facilities. Furthermore, inpatient psychiatry settings are generally designed as communal spaces, with heavy emphasis on group and milieu therapies. As such, inpatient psychiatry services are vulnerable to rampant spread of contagion. OBJECTIVE: With this in mind, the authors outline the decision process and ultimate design and implementation of a regional inpatient psychiatry unit for patients infected with asymptomatic SARS-CoV-2 and share key points for consideration in implementing future units elsewhere. CONCLUSION: A major takeaway point of the analysis is the particular expertise of trained experts in psychosomatic medicine for treating patients infected with SARS-CoV-2.

Adverse childhood experiences (ACEs) and transitions in stages of alcohol involvement among US adults: Progression and regression.

BACKGROUND: Adverse childhood experiences (ACEs) are associated with a number of medical comorbidities. However, there is a paucity of data on the role ACEs play in transitions in stages of alcohol involvement. OBJECTIVE: To examine the association between ACEs and transitions in alcohol problems progression and regression between No Problems, Moderate Problems and Severe Problems stages. PARTICIPANTS AND SETTING: Data from 14,363 male and 19,774 female participants in Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). METHODS: We used latent transition analysis (LTA) with propensity score adjustment to estimate the odds of transitioning across stages of alcohol involvement, between waves, based on the number of types of ACEs experienced. We hypothesized that ACEs would be associated with increased risk of progression and decreased risk of regression. RESULTS: ACEs were associated with progression to higher alcohol involvement stages, with greatest likelihood of progression from No Problems to Severe Problems for those reporting ≥3 ACEs (males: aOR = 4.78 [CI (1.84-12.44)]; females: aOR = 3.81 [CI (1.69-8.57)]). ACEs were also associated with decreased odds of regression to less problematic alcohol involvement stages, with some distinctive patterns of associations in males and in females. CONCLUSIONS: This study suggests that ACEs impact transitions in alcohol involvement in both males and females, affecting both progression and regression. The association is magnified for those with multiple types of ACE exposures. These results highlight the need for prevention, early identification and intervention to mitigate the risks associated with childhood maltreatment.

Trichotillomania comorbidity in a sample enriched for familial obsessive-compulsive disorder.

BACKGROUND: This study addresses the strength of associations between trichotillomania (TTM) and other DSM-IV Axis I conditions in a large sample (n = 2606) enriched for familial obsessive-compulsive disorder (OCD), to inform TTM classification. METHODS: We identified participants with TTM in the Johns Hopkins OCD Family Study (153 families) and the OCD Collaborative Genetics Study, a six-site genetic linkage study of OCD (487 families). We used logistic regression (with generalized estimating equations) to assess the strength of associations between TTM and other DSM-IV disorders. RESULTS: TTM had excess comorbidity with a number of conditions from different DSM-IV chapters, including tic disorders, alcohol dependence, mood disorders, anxiety disorders, impulse-control disorders, and bulimia nervosa. However, association strengths (odds ratios) were highest for kleptomania (6.6), pyromania (5.8), OCD (5.6), skin picking disorder (4.4), bulimia nervosa (3.5), and pathological nail biting (3.4). CONCLUSIONS: TTM is comorbid with a number of psychiatric conditions besides OCD, and it is strongly associated with other conditions involving impaired impulse control. Though DSM-5 includes TTM as an OCD-related disorder, its comorbidity pattern also emphasizes the impulsive, appetitive aspects of this condition that may be relevant to classification.

Developing Texting for Relapse Prevention: A Scalable mHealth Program for People With Schizophrenia and Schizoaffective Disorder.

Symptom relapse in people with schizophrenia and schizoaffective disorder is common and has a negative impact on the course of illness. Here, we describe the development of Texting for Relapse Prevention, a scalable, cost-effective text messaging relapse prevention program that queries patients' "early warning signs" daily. Results of development focus groups and content advisory teams with 25 patients and 19 providers suggest that patients were enthusiastic about the program and thought that receiving daily messages about their symptoms would help them feel supported. Providers also were positive about the idea but worried that the program might interfere with patient-provider communication if patients thought that the messages were coming from providers. Patients found the content positive and actionable. The program was improved to address this feedback. This iterative development process that included multiple stakeholders ensured that the program is feasible and acceptable to both patients and providers.

The Effects of Marijuana Use on Transitions through Stages of Alcohol Involvement for Men and Women in the NESARC I and II.

Background: With the changing context of marijuana use, it is critical to identify effects of use. We extend previous work by examining whether marijuana use influences progression and remission through alcohol involvement stages for men and women. Methods: Data come from Waves I and II of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, n = 34,432). We assess the potential influence of marijuana use at Wave 1 on transitions across three latent statuses of alcohol involvement between waves. We apply propensity score weighting to account for shared risk factors. Results: Marijuana use was associated cross-sectionally and longitudinally with alcohol involvement statuses for both sexes. After propensity score adjustment, men with marijuana histories were 3.50 times as likely as men without such histories to transition from no to severe problems across waves relative to staying in the same status (p < .001). Women with marijuana histories were 1.74 times as likely as women without such histories to transition from no problems at Wave 1 to moderate problems at Wave 2 (p = .030) and 0.13 times as likely as women without such histories to transition from severe problems to no problems (p = .006). Conclusions: Results suggest that marijuana use impacts progression to more serious stages of alcohol involvement for both men and women, as well as hinders remission among women. Findings point to the importance of screening those with marijuana histories for alcohol problems, as well as the need to understand the mechanism of why marijuana use may increase the risk of alcohol problems.

Availability of Assertive Community Treatment in the United States: 2010 to 2016.

OBJECTIVE: The study examined change in availability of assertive community treatment (ACT) and associated services over time. METHODS: Change over time in the availability of facilities in the United States offering ACT and its associated services was examined by using 2010 and 2016 data from the National Mental Health Services Survey. RESULTS: The proportion of facilities that self-reported provision of ACT and its associated services declined between 2010 and 2016 (odds ratio [OR]=0.73, 95% confidence interval [CI]=0.63-0.86, p<0.001). Although a higher proportion of facilities that provided ACT reported offering all the required services in 2016 (OR=1.31, 95% CI=1.04-1.66, p=0.026) compared with 2010, this proportion accounted for less than 20% of the programs. Compared with 2010, in 2016 increases were observed in peer (OR=1.72, 95% CI=1.38-2.13, p<0.001) and co-occurring disorders services (OR=1.23, 95% CI=1.08-1.42, p=0.004) as well as in secondary services, such as tobacco cessation (OR=4.53, 95% CI=3.51-5.84, p<0.001) and telemedicine (OR=2.08, 95% CI=1.67-2.57, p<0.001). Continuous education for staff was required at more facilities with ACT in 2016 compared with 2010. CONCLUSIONS: Although the proportion of facilities with ACT that offer all the required core services has increased in recent years, such programs remain a minority, and the overall number of facilities with ACT has declined.

Distribution and Correlates of Assertive Community Treatment (ACT) and ACT-Like Programs: Results From the 2015 N-MHSS.

OBJECTIVE: The study examined the availability and characteristics of assertive community treatment (ACT) programs across mental health treatment facilities in the United States. METHODS: Prevalence and correlates of facilities that reported offering ACT, broadly defined as intensive community services for serious mental illness provided by multidisciplinary teams in the clients' natural settings and including both ACT and "ACT-like" programs, were examined by using data from the National Mental Health Services Survey. Availability of services essential to the ACT model in these facilities was also examined. RESULTS: Of the 12,826 surveyed facilities, 13.4% reported offering ACT, with significant variability among states. Of the facilities with ACT, 19.2% reported offering all core ACT services. Few facilities offered peer support, employment, and housing services. Compared with programs at facilities that did not offer all core ACT services, facilities with ACT programs that offered these services had higher odds of being publicly owned (odds ratio [OR]=2.12, 95% confidence interval [CI]=1.64-2.74) and of receiving federal (OR=3.60, CI=2.17-5.98) or grant funding (OR=1.87, CI=1.45-2.41). Facilities with ACT that offered all core services also had higher odds of offering other services important to individuals with serious mental disorders. CONCLUSIONS: Substantial differences existed in availability of ACT and ACT-like programs among states, with evidence of a large unmet need overall, even when a very broad and inclusive definition of ACT was used. Few ACT programs offered all core services. Legislative, administrative, and funding differences may explain some of the variability.

Altering the Attendance Rate Successfully for New Patients at an Outpatient Mental Health Clinic.

Show rates for psychiatric outpatient appointments are low among new patients, which affects all patients as well as providers and programs. This column describes two initiatives implemented to address this issue in a community psychiatry program: inpatient referrals and self-referrals. Inpatient referrals were scheduled for an orientation group within five days postdischarge, with initial evaluations within two working days. Biweekly walk-in screening clinics were established for community self-referrals, during which patients were screened and scheduled for an initial evaluation within three working days. Both initiatives significantly increased patient show rates and reduced unused scheduled physician time. Relatively simple initiatives can result in improvements in initial evaluation attendance, benefiting all involved.

Transitions through stages of alcohol involvement: The potential role of mood disorders.

INTRODUCTION: Although prior clinical and population-based studies have demonstrated comorbidity between mood and alcohol use disorders (AUD), there is a paucity of research assessing whether mood disorders predict transition across stages of alcohol involvement. METHOD: Hypothesizing that mood disorders predict transition across sex-specific alcohol involvement stages, we used prospective data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative survey of US adults, which included male (n = 14,564) and female (n = 20,089) participants surveyed in 2001-2 and re-interviewed in 2004-5. Latent class (LCA) and latent transition analyses (LTA) were used to assess patterns of alcohol involvement in the US and the association of lifetime mood disorders at baseline with transition across stages of alcohol involvement during follow-up. RESULTS: A three-class model of AUD criteria was identified (No problems, Moderate problems and Severe problems) for both sexes. Positive cross-sectional associations between mood disorder and problem classes of alcohol involvement were found among both sexes, as were positive longitudinal associations. Propensity score adjustment mitigated the associations of baseline mood disorder with progressive transition for both sexes. However, among females, baseline mood disorder was consistently associated with reduction in remission from Severe to Moderate alcohol problems (aOR = 0.30, CI = 0.09-0.99, p = .048) over time. DISCUSSION: Our study provides evidence that mood disorders impact transition through stages of alcohol involvement and are most strongly associated with hindering remission among females. Findings advance our understanding of these comorbid relationships and have clinical implications for ongoing assessment of drinking patterns among individuals with mood disorders.

Delays in Seeking General Medical Services and Measurable Abnormalities Among Individuals With Serious Mental Illness.

OBJECTIVE: The study explored the association of delays in seeking general medical care with elevated blood pressure and metabolic abnormalities among individuals with serious mental illness. METHODS: Association of delays in medical care with blood pressure, serum hemoglobin A1c (HbA1C), and lipids was assessed among patients at two inner-city community mental health centers. RESULTS: Of 271 participants, 62% reported delays in seeking general medical care due to attitudinal and financial barriers. Care delay was associated with abnormalities in measured blood pressure (adjusted odds ratio [AOR]=2.14, p=.029) and HbA1c (AOR=3.18, p=.026). Care delay was not associated with abnormalities in lipid profiles. CONCLUSIONS: This study found that delays in seeking general medical care are common and are associated with clinical markers linked with common medical conditions. The results may help to explain the elevated morbidity and mortality associated with serious mental illness.