Current Major Depressive Disorder Research Articles

Excitatory brain stimulation over the left dorsolateral prefrontal cortex enhances voluntary distraction in depressed patients.

While implicit distraction could ameliorate negative feelings in patients with major depressive disorders (MDD), it remains unclear whether patients could benefit from explicit, voluntary distraction. Meanwhile, though the dorsolateral prefrontal cortex (DLPFC) is established as a crucial brain region involved in attentional control, the causal relationship between the DLPFC and voluntary distraction is unexplored in patients. Combing explicit distraction and transcranial magnetic stimulation (TMS), this study investigated whether TMS-activated DLPFC facilitates voluntary distraction in MDD patients. Eighty patients diagnosed with current MDD underwent either active (n = 40) or sham (n = 40) TMS sessions, followed by receiving negative social feedback from other patients, during which they were requied to use distraction strategy to down-regulate their painful feelings. Electroencephalogram was recorded during the task. Both the subjective emotional rating and the amplitude of late positive potential showed that depressed patients successfully down-regulate their negative emotions via voluntary distraction, and the TMS-activated left DLPFC produced a larger benefit of emotion regulation compared to the sham TMS group. Results also revealed that while emotion regulation effect was negatively associated with depressive symptoms in the sham TMS group, this correlation was largely diminished when patients' left DLPFC was activated by TMS during the voluntary distraction. These findings demonstrated that distraction is valuable for emotion regulation in MDD patients and they could be beneficial in voluntary distraction by activating their left DLPFC using neural modulation techniques. This study has valuable implications for clinical treatement of emotional dysregulation in MDD patients.

Passive and active suicidal ideation in a population-based sample of older adults: Associations with polygenic risk scores of relevance for suicidal behavior.

There are few studies investigating genetic factors related to suicidal ideation or behavior in older adult populations. Our aim was to test associations between passive and active suicidal ideation and polygenic risk scores (PRSs) for suicidality and other traits of relevance for suicidality in old age (i.e. depression, neuroticism, loneliness, Alzheimer's disease, cognitive performance, educational attainment, and several specified vascular diseases) in a population-based sample aged 70 years and older. Participants in the prospective H70 study in Gothenburg, Sweden, took part in a psychiatric examination that included the Paykel questions on active and passive suicidal ideation. Genotyping was performed with the Neurochip (Illumina). After quality control of the genetic data the sample included 3467 participants. PRSs for suicidality and other related traits were calculated based on summary statistics from recent GWASs of relevance. Exclusion of persons with dementia or incomplete data on suicidal ideation yielded 3019 participants, age range 70-101 years. Associations between past year suicidal ideation (any level) and selected PRSs were analysed using general estimation equation (GEE) models, adjusted for sex and age. We observed associations between passive/active suicidal ideation and PRSs for depression (three versions), neuroticism, and general cognitive performance. After excluding individuals with current major depressive disorder (MDD), similar associations were seen with PRS for neuroticism, general cognitive performance and two PRSs for depression. No associations were found between suicidal ideation and PRSs for suicidality, loneliness, Alzheimer's disease, educational attainment, or vascular disease. Our results could indicate which types of genetic susceptibility that are of importance for suicidality in old age, and these findings can help to shed light on potential mechanisms that may be involved in passive and active suicidal ideation in late-life, also in those with no current MDD. However, due to the limited sample size, the results need to be interpreted with caution until replicated in larger samples.

The association between trauma exposure, polygenic risk and individual depression symptoms

BackgroundTraumatic experiences are associated with increased risk for major depressive disorder (MDD). This study sought to determine the extent that trauma exposure, depression polygenic risk scores (PRS), and their interaction are associated with MDD and individual depression symptoms. MethodsData from 102,182 individuals from the large-scale UK Biobank population cohort was analysed. A series of regression analyses were conducted to estimate the association between trauma, depression PRS and 1) current depression, 2) lifetime MDD case-control status, 3) nine individual current depressive symptoms, and 4) thirteen individual symptoms experienced during a major depressive episode. Additive and multiplicative PRS-by-trauma interactions were also assessed. ResultsTrauma and depression PRS were significantly associated with both current depression and lifetime MDD. A positive, additive interaction effect was observed on depression, but multiplicative interactions were not significant. Trauma exposure and depression PRS were associated with specific patterns of depression symptoms; Trauma was associated with low self-esteem, suicidal ideation, and atypical (but not typical) neurovegetative symptoms. Additive interaction effects were observed on six out of nine current depressive symptoms. ConclusionsTrauma exposure and genetic predisposition to depression may lead to particular symptomatology, which may contribute to the extreme clinical heterogeneity observed in individuals with major depression.

Serotonin 4 Receptor Brain Binding in Major Depressive Disorder and Association With Memory Dysfunction

The cerebral serotonin 4 (5-HT4) receptor is a promising novel target for treatment of major depressive disorder (MDD), and pharmacological stimulation of the 5-HT4 receptor has been associated with improved learning and memory in healthy individuals. To map the neurobiological signatures of patients with untreated MDD compared with healthy controls and to examine the association between cerebral 5-HT4 receptor binding and cognitive functions in the depressed state. This case-control study used baseline data from the NeuroPharm clinical depression trial in Denmark. Adult participants included antidepressant-free outpatients with a current moderate to severe depressive episode and healthy controls. All participants completed positron emission tomography (PET) scanning with [11C]SB207145 for quantification of brain 5-HT4 receptor binding, but only the patients underwent cognitive testing. Data analyses were performed from January 21, 2020, to April 22, 2022. The main study outcome was the group difference in cerebral 5-HT4 receptor binding between patients with MDD and healthy controls. In addition, the association between 5-HT4 receptor binding and verbal memory performance in the patient group was tested. Other cognitive domains (working memory, reaction time, emotion recognition bias, and negative social emotions) were assessed as secondary outcomes. A total of 90 patients with untreated MDD (mean [SD] age, 27.1 [8.2] years; 64 women [71.1%]) and 91 healthy controls (mean [SD] age, 27.1 [8.0] years; 55 women [60.4%]) were included in the analysis. Patients with current MDD had significantly lower cerebral 5-HT4 receptor binding than healthy controls (-7.0%; 95% CI, -11.2 to -2.7; P = .002). In patients with MDD, there was a correlation between cerebral 5-HT4 receptor binding and verbal memory (r = 0.29; P = .02). Results of this study show that cerebral 5-HT4 receptor binding was lower in patients with MDD than in healthy controls and that the memory dysfunction in patients with MDD was associated with lower cerebral 5-HT4 receptor binding. The cerebral 5-HT4 receptor is a promising treatment target for memory dysfunction in patients with MDD.

Anhedonia modulates benzodiazepine and opioid demand among persons in treatment for opioid use disorder.

Benzodiazepine (BZD) misuse is a significant public health problem, particularly in conjunction with opioid use, due to increased risks of overdose and death. One putative mechanism underlying BZD misuse is affective dysregulation, via exaggerated negative affect (e.g., anxiety, depression, stress-reactivity) and/or impaired positive affect (anhedonia). Similar to other misused substances, BZD consumption is sensitive to price and individual differences. Although purchase tasks and demand curve analysis can shed light on determinants of substance use, few studies have examined BZD demand, nor factors related to demand. This ongoing study is examining simulated economic demand for alprazolam (among BZD lifetime misusers based on self-report and DSM-5 diagnosis; n = 23 total; 14 male, 9 female) and each participant's preferred-opioid/route using hypothetical purchase tasks among patients with opioid use disorder (n = 59 total; 38 male, 21 female) who are not clinically stable, i.e., defined as being early in treatment or in treatment longer but with recent substance use. Aims are to determine whether: (1) BZD misusers differ from never-misusers on preferred-opioid economic demand, affective dysregulation (using questionnaire and performance measures), insomnia/behavioral alertness, psychiatric diagnoses or medications, or urinalysis results; and (2) alprazolam demand among BZD misusers is related to affective dysregulation or other measures. Lifetime BZD misuse is significantly (p < 0.05) related to current major depressive disorder diagnosis, opioid-negative and methadone-negative urinalysis, higher trait anxiety, greater self-reported affective dysregulation, and younger age, but not preferred-opioid demand or insomnia/behavioral alertness. Alprazolam and opioid demand are each significantly positively related to higher anhedonia and, to a lesser extent, depression symptoms but no other measures of negative-affective dysregulation, psychiatric conditions or medications (including opioid agonist therapy or inpatient/outpatient treatment modality), or sleep-related problems. Anhedonia (positive-affective deficit) robustly predicted increased BZD and opioid demand; these factors could modulate treatment response. Routine assessment and effective treatment of anhedonia in populations with concurrent opioid and sedative use disorder may improve treatment outcomes. https://clinicaltrials.gov/ct2/show/NCT03696017, identifier NCT03696017.

Self-blame-selective hyper-connectivity between anterior temporal and subgenual cortices predicts prognosis in major depressive disorder

BackgroundSelf-blame-related fMRI measures were shown to predict subsequent recurrence in remitted major depressive disorder (MDD). Their role in current MDD, however, is unknown. We hypothesised that these neural signatures reflect a highly recurrent but remitting course of MDD and therefore predict favourable outcomes over a four-month follow-up period in current MDD. MethodsForty-five participants with current MDD and non-responders to at least two serotonergic antidepressants, were encouraged to optimise their medication and followed up after receiving four months of primary care treatment-as-usual. Prior to their medication review, participants completed an fMRI paradigm in which they viewed self- and other-blame emotion-evoking statements. Thirty-nine participants met pre-defined fMRI data minimum quality thresholds. Psychophysiological interaction analysis was used to determine baseline connectivity of the right superior anterior temporal lobe (RSATL), with an a priori BA25 region-of-interest for self-blaming vs other-blaming emotions, using Quick Inventory of Depressive Symptomatology (16-item) percentage change as a covariate. ResultsWe corroborated our pre-registered hypothesis that a favourable clinical outcome was associated with higher self-blame-selective RSATL-BA25 connectivity (Family-Wise Error-corrected p <.05 over the a priori BA25 region-of-interest; rs(34) = −0.47, p =.005). This generalised to the sample including participants with suboptimal fMRI quality (rs(39) = −0.32, p =.05). ConclusionsThis study shows that neural signatures of overgeneralised self-blame are relevant for prognostic stratification of current treatment-resistant MDD. Future studies need to confirm whether this neural signature indeed represents a trait-like feature of a fully remitting subtype of MDD, or whether it is also modulated by depressive state and related to treatment effects.

Mental health of U.S. combat veterans by war era: Results from the National health and Resilience in veterans study

Combat exposure is associated with elevated risk for adverse psychiatric outcomes in military veterans. However, few studies have examined psychiatric characteristics of veterans who served in different war eras. We analyzed data from the 2019–2020 National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 1257 US combat veterans including World War II or Korean War veterans (n = 61, weighted 4.9%), Vietnam War veterans (n = 767, weighted 44.5%), Gulf War veterans (n = 168, weighted 14.5%), and Iraq/Afghanistan War veterans (n = 261, weighted 36.2%). Sociodemographic, military, and mental health factors were examined. Gulf and Iraq/Afghanistan War era veterans were comprised of younger veterans and included more women and racial/ethnic minorities relative to previous era veterans. Overall, Gulf and Iraq/Afghanistan War veterans endorsed greater trauma burden, and were more likely to screen positive for lifetime and current major depressive disorder and posttraumatic stress disorder (PTSD), as well as current suicidal ideation. Among all war era groups, Iraq/Afghanistan war veterans reported the greatest lifetime trauma and combat exposure severity, and were most likely to screen positive for lifetime PTSD (weighted 29.3%), current alcohol use disorder (weighted 17.2%), and current drug use disorder (weighted 12.4%). Specifically, more than 1-in-4 Iraq/Afghanistan War veterans (weighted 26.3%) reported current suicidal thoughts. Collectively, these findings provide war-era specific characterization of the psychiatric status of US combat veterans, which may help inform era-specific assessment, monitoring, and treatment of psychiatric disorders in the combat veteran population.

Effects of Self-awareness and Cognitive Impairment on Depression Status in Adults with Traumatic Brain Injury

<h3>Research Objectives</h3> To examine the association of self-awareness and cognitive impairments on depression after controlling for potential covariates in a sample of adults with chronic complicated mild to severe traumatic brain injury. <h3>Design</h3> Secondary analysis of a cohort study. <h3>Setting</h3> Community. <h3>Participants</h3> The study included a volunteer sample of sixty-five community-dwelling individuals with a history of complicated-mild-to-severe TBI. Inclusion criteria were: 1) documented history of TBI; 2) over six months post-injury; 3) living in the community; 4) older than 18 years old. <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measures</h3> Depression status was measured using the Patient Health Questionnaire (PHQ9) questions and dichotomized as Current Major or Minor Depression and No Current Depression. Logistic regression models were formed using self-awareness, cognitive impairments, and their interaction as independent variables with dichotomized depression as the dependent variable. <h3>Results</h3> Sixty-three participants with complete data were included in the analysis. Participants were aged 18 to 83 years old (mean=45.51 + 15.90 years), were primarily men (79.37%), and 85.71% of participants had current major or minor depression. Disability was identified as a covariate based on a significant bivariate correlation with depression (r=.286, p < .05). The logistic regression revealed no significant associations of self-awareness and cognitive impairments on depression after controlling for disability, but disability was significantly associated with depression status (p < .05). <h3>Conclusions</h3> Cognitive impairment, self-awareness, and their interaction may not contribute to depression status in chronic TBI, but those with depression did have more disability. It is possible that more impaired cognition and self-awareness acutely after injury contribute to later disability and, subsequently, depression, but a longitudinal prospective study is required to test this hypothesis. <h3>Author(s) Disclosures</h3> The study was supported in part of the SHRS Dissertation Development Fund.

Coping in Mid- to Late Life and Risk of Mild Cognitive Impairment Subtypes and Dementia: A JPHC Saku Mental Health Study.

The relationship between coping in mid- to late life and cognitive functions remains unclear. To investigate the relationship between habitual coping behaviors of a large Japanese population in their mid- to late-lives and their risk of cognitive decline 15 years later. Overall 1,299 participants were assessed for coping behaviors (in 2000) and cognition (2014-2015). We used the Stress and Coping Inventory to assess the frequency of six coping behaviors (i.e., consulting, planning, positive reappraisal, avoidance, fantasizing, and self-blame). Logistic regression analyses were conducted to examine odds ratios (ORs) for the diagnosis of mild cognitive impairment (MCI), MCI subtypes (single- and multiple-domain MCI), and dementia for coping behaviors. Among the eligible 1,015 participants (72.6 [SD = 5.5] years old in 2014-2015), the numbers for cognitively normal, single-domain MCI, multiple-domain MCI, and dementia were 650 (64.0%), 116 (11.4%), 213 (21.0%), and 36 (3.5%), respectively. Among the six coping behaviors, avoidant coping was significantly associated with noticeable cognitive decline (multiple-domain MCI and dementia). This association remained significant after adjusting for sex, age, education, diagnosis of current major depressive disorder, past history of ischemic heart disease, diabetes, regular alcohol consumption, and smoking (OR = 2.52, 95% CI = 1.23 to 5.15). No significant association with other coping behaviors was found. Avoidant coping in mid- and late life is associated with cognitive decline among older people.

Decision-making biases in suicide attempters with major depressive disorder: A computational modeling study using the balloon analog risk task (BART).

In the last decade, suicidality has been increasingly theorized as a distinct phenomenon from major depressive disorder (MDD), with unique psychological and neural mechanisms, rather than being mostly a severe symptom of MDD. Although decision-making biases have been widely reported in suicide attempters with MDD, little is known regarding what components of these biases can be distinguished from depressiveness itself. Ninety-three patients with current MDD(40 with suicide attempts [SA group]and 53 without suicide attempts [NS group])and 65 healthy controls (HCs) completed psychometric assessments and the balloon analog risk task (BART). To analyze and compare decision-making components among the three groups, we applied a five-parameter Bayesian computational modeling. Psychological assessments showed that the SA group had greater suicidal ideation and psychological pain avoidance than the NS group. Computational modeling showed that both MDD groups had higher risk preference and lower ability to learn and adapt from within-task observations than HCs, without differences between the SA and NS patient groups. The SA group also had higher loss aversion than the NS and HC groups, which had similar loss aversion. Our BART and computational modeling findings suggest that psychological pain avoidance and loss aversion may be important suicide risk factor that are distinguishable from depression illness itself.

Economic burden and antidepressant treatment patterns among patients with major depressive disorder in the United States.

BACKGROUND: The prevalence of major depressive disorder (MDD) continues to rise year over year, resulting in significant economic implications. However, when patients are treated with contemporary standard-of-care antidepressant pharmacotherapies, a suboptimal response is often attained, resulting in frequent treatment changes. OBJECTIVE: To compare health care resource utilization (HCRU) and all-cause medical and pharmacy costs between commercially insured patients with an MDD diagnosis and matched non-MDD patients and explore treatment patterns among patients with MDD initiating antidepressant pharmacotherapy. METHODS: This was a retrospective, observational analysis of IBM MarketScan US commercial claims data. Adults aged 18 years and older with continuous enrollment 12 or more months before and after the patient's first MDD diagnosis from 2017 to 2018 were included in the analysis. HCRU and all-cause medical and pharmacy costs were compared among patients with MDD and a 1:1 exact-matched cohort of non-MDD patients during the same period (Objective 1). Treatment patterns (persistence, discontinuation, switch, combination, and augmentation) were analyzed for patients with MDD starting first-line antidepressant monotherapy for up to 12 months following their antidepressant initiation index date (Objective 2). Time to first treatment change or discontinuation was calculated and treatment patterns were graphically displayed in Sankey diagrams. RESULTS: 625,272 patients with MDD were matched 1:1 to a cohort of non-MDD patients in Objective 1. Patients with MDD had statistically significantly greater all-cause medical (20.4 vs 9.4; P < 0.0001), outpatient (19.5 vs 9.0; P < 0.0001), emergency department (0.51 vs 0.23; P < 0.0001), inpatient (0.35 vs 0.11; P < 0.0001), and any mental health-related (7.7 vs 0.58; P < 0.0001) visits compared with non-MDD patients. Mean all-cause medical costs were $6,809 (P < 0.0001) higher among patients with MDD than among patients without MDD ($13,183 vs $6,374, respectively). In Objective 2, 44,485 patients with MDD who received antidepressant monotherapy as their first-line MDD treatment were examined. Among the first treatment patterns observed following initiation, 19.3% of patients persisted with their first-line therapy, 56.2% discontinued antidepressant therapy, 24.5% experienced a treatment change (switching, adding a second antidepressant, or augmenting their existing therapy). The median days until first treatment change were 65 days for those discontinuing and 47 days for those switching antidepressants. Among the 24.5% of patients with a treatment change, 50.0% experienced another change in therapy within 30 days. CONCLUSIONS: The HCRU and costs accrued for patients with MDD is significantly greater than those for non-MDD patients. A large proportion of patients with MDD experienced treatment changes shortly after initiating their first-line antidepressant therapy. The results of this study highlight the need for reevaluation of the current MDD treatment paradigm. DISCLOSURES: Drs Zhu and Namjoshi are employees of Biogen Inc. and may hold stock. Dr Ferries and Ms Suthoff are employees of Sage Therapeutics, Inc., and may hold stock and/or stock options. Dr Bera has no potential conflicts of interest to disclose. This research was funded by Sage Therapeutics and Biogen. Manuscript editorial services were provided by Boston Strategic Partners, Inc., funded by Sage Therapeutics and Biogen. This work was supported by Sage Therapeutics, Inc., and Biogen. The authors had full editorial control of the manuscript and provided final approval on all content.

The Impact of Caregiver Depression on Child Asthma Outcomes: Pathways and Mechanisms

Depression is common in caregivers of children with asthma and is associated with poor outcomes in their child. No prior studies have longitudinally examined caregiver depression remission as a predictor of improvement in child asthma control. This 2-site study examined whether the proportion of time a caregiver was in depression remission predicted subsequent child asthma control at exit. Caregivers (n= 205) with current major depressive disorder and their children, ages 7 to 17, with persistent asthma were observed every 4 weeks for 52 weeks. Caregiver depressive symptoms were measured using the 17-item Hamilton Rating Scale for Depression (HRSD). Child asthma was assessed with the (Childhood) Asthma Control Test (cACT/ACT) and spirometry, and depression with the Children's Depression Inventory (CDI). Linear regression analyses were conducted with change in cACT/ACT, CDI, and forced expiratory volume in 1 second (FEV1)% predicted as outcomes and proportion of time the caregiver was in remission (HRSD score ≤ 7) as the predictor. Multilevel mediation analyses examined the role of child depressive symptoms and asthma controller medication adherence. Children were, on average, 54.1% female and 11 years old. Caregiver proportion of time in HRSD-assessed remission of depression was a significant predictor of improvement in cACT/ACT, CDI, and FEV1% predicted. Child CDI score, but not medication adherence, mediated the relationship between caregiver HRSD scores and child asthma control scores. Improvement in caregiver depression positively influences child asthma outcomes partially through improvement in child depressive symptom severity. Caregiver depression screening and treatment might lead to improvement in child asthma outcomes.

Suicidal ideation among Nigerian patients with epilepsy

BackgroundPatients with epilepsy are at increased risk of suicide which is often preceded by suicidal ideation. Suicidal ideation is rarely assessed in Nigerian patients with epilepsy and there are limited studies on prevalence and determinants. MethodsTwo-hundred and seventy patients with epilepsy attending the Neuropsychiatric Hospital, Abeokuta were recruited. Suicidal ideation was assessed with item 9 of the BDI-II. QOLIE-31, MINI-PLUS, and a sociodemographic questionnaire were also administered to the participants. ResultsTwenty-four patients reported having suicidal ideation with a prevalence of 8.9 %. Suicidal patients were younger, more likely to have a current or history of a mood disorder, and had a lower quality of life scores on all domains. In the multivariate analysis, current major depression (OR=26.26, p < 0.0001, CI= 8.51 – 81.05) and a lower score on the cognitive functioning subscale of the QOLIE-31 (OR=0.97, p = 0.003, CI=0.96 – 0.99) were the only independent predictors of suicidal ideation. ConclusionsSuicidal ideation is common among Nigerian patients with epilepsy. Comorbid depression and poor cognitive functioning are risk factors for suicidal ideation among them. Clinicians should screen for suicidal ideation and comorbid mood disorders among patients with epilepsy and identify patients at increased risk of suicide.

How well do Cognitive Behavioural Therapy and Behavioural Activation for depression repair anhedonia? A secondary analysis of the COBRA randomized controlled trial

A secondary analysis of the COBRA randomized controlled trial was conducted to examine how well Cognitive Behavioural Therapy (CBT) and Behavioural Activation (BA) repair anhedonia. Patients with current major depressive disorder (N = 440) were randomized to receive BA or CBT, and anhedonia and depression outcomes were measured after acute treatment (six months) and at two further follow up intervals (12 and 18 months). Anhedonia was assessed using the Snaith Hamilton Pleasure Scale (SHAPS; a measure of consummatory pleasure). Both CBT and BA led to significant improvements in anhedonia during acute treatment, with no significant difference between treatments. Participants remained above healthy population averages of anhedonia at six months, and there was no further significant improvement in anhedonia at 12-month or 18-month follow up. Greater baseline anhedonia severity predicted reduced repair of depression symptoms and fewer depression-free days across the follow-up period in both the BA and CBT arms. The extent of anhedonia repair was less marked than the extent of depression repair across both treatment arms. These findings demonstrate that CBT and BA are similarly and only partially effective in treating anhedonia. Therefore, both therapies should be further refined or novel treatments should be developed in order better to treat anhedonia.

Prevalence of Depression and Posttraumatic Stress Disorder in Flint, Michigan, 5 Years After the Onset of the Water Crisis

Environmental disasters, such as the Flint, Michigan, water crisis, are potentially traumatic events (PTEs) that may precipitate long-term psychiatric disorders. The water crisis was associated with acute elevations in mental health problems in the Flint community, but long-term psychiatric sequelae have not yet been evaluated using standardized diagnostic measures. To investigate the prevalence of and factors associated with current presumptive diagnostic-level major depression and posttraumatic stress disorder (PTSD) among Flint residents 5 years after the onset of the crisis. In this cross-sectional study, a household probability sample of 1970 adults living in Flint, Michigan, during the crisis were surveyed about their crisis experiences, their psychological symptoms 5 years later, and their access to and use of mental health services in the intervening years. Analyses were weighted to produce population-representative estimates. Presumptive Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) diagnostic-level past-year major depression and PTSD. Among 1970 respondents, 1061 of 1946 reporting sex (54.5%) were women; 1043 of 1951 reporting race (53.5%) were Black or African American and 829 (42.5%) were White; and 1895 of 1946 reporting ethnicity (97.4%) were non-Hispanic. Overall, 435 (22.1%) met DSM-5 criteria for presumptive past-year depression, 480 (24.4%) for presumptive past-year PTSD, and 276 (14.0%) for both disorders. Residents who believed that their or their family's health was harmed by contaminated water (eg, risk ratio [RR] for depression: 2.23; 95% CI, 1.80-2.76), who had low confidence in public-official information (eg, RR for PTSD, 1.44; 95% CI, 1.16-1.78), who had previous exposure to PTEs (eg, RR for both disorders: 5.06; 95% CI, 2.99-8.58), or who reported low social support (eg, RR for PTSD, 2.58; 95% CI, 1.94-3.43) had significantly higher risk for depression, PTSD, and comorbidity. PTEs involving prior physical or sexual assault were especially potent risk factors (eg, both disorders: RR, 7.30; 95% CI, 4.30-12.42). Only 685 respondents (34.8%) were ever offered mental health services to assist with water-crisis-related psychiatric symptoms; most (543 [79.3%]) who were offered services utilized them. In this cross-sectional study of psychiatric disorder in Flint, Michigan, presumptive depression and PTSD were highly prevalent 5 years after the onset of the water crisis. These findings suggest that public-works environmental disasters have large-scale, long-term psychological sequelae. The Flint community may require expanded mental health services to meet continued psychiatric need. National disaster preparedness and response programs should consider psychiatric outcomes.

The prevalence of comorbid serious mental illnesses and substance use disorders in prison populations: a systematic review and meta-analysis

SummaryBackgroundComorbid mental illnesses and substance use disorders are associated with adverse criminal, social, and health outcomes. Yet, their burden is not reliably known among prison populations. We therefore aimed to estimate the prevalence of comorbid serious mental illnesses and substance use disorders (dual disorders) among people in prison worldwide.MethodsIn this systematic review and meta-analysis, we searched 15 electronic databases (ASSIA, CAB s, Criminal Justice Database, Embase, Global Health, Global Index Medicus, IBSS, MEDLINE, NCJRS, PAIS Index, PsycINFO, Russian Science Citation Index, Scielo, Social Services s, and Web of Science) and the grey literature (Open Grey and ProQuest Dissertations & Theses Global) for studies reporting the prevalence of serious mental illnesses and substance use disorders in prison populations published between Jan 1, 1980, and Sept 25, 2021, and contacted the authors of relevant studies. Empirical studies among unselected adult prison populations that applied representative sampling strategies and validated diagnostic instruments, and either reported the prevalence of dual disorders or had authors who could provide prevalence data in correspondence, were included. Two reviewers (GB and SDL) independently extracted data from the eligible studies; both current (up to 1 year) and lifetime prevalence were extracted, if available. We sought summary estimates. Our primary outcomes were comorbid non-affective psychosis with substance use disorders and comorbid major depression with substance use disorders. We conducted a random-effects meta-analysis, explored between-sample heterogeneity with meta-regression, and calculated odds ratios (ORs) to assess bidirectional relationships between mental and substance use disorders. Risk of bias was assessed by use of a standard tool. The study protocol was registered with PROSPERO, CRD42020207301.FindingsOf 11 346 records screened, we identified 34 studies reporting the prevalence of dual disorders among individuals in prison and received unpublished prevalence data for 16 studies, totalling 50 eligible studies and 24 915 people. The mean quality score of included studies was 7·8 (SD 1·2). We found that 3·5% (95% CI 2·2–5·0) had current non-affective psychosis with any comorbid substance use disorder, representing 443 (49·2%) of 900 people with non-affective psychosis, and 9·1% (5·6–13·3) had current major depression and comorbid substance use disorders, representing 1105 (51·6%) of 2143 people with major depression. Between-sample heterogeneity was high (I2>80%). People in prison with current non-affective psychosis were significantly more likely to have substance use disorders compared with those without (OR 1·7, 95% CI 1·4–2·2). People with major depression had higher odds of substance use disorders than those without (1·6, 1·3–2·0).InterpretationAround half of the prison population with non-affective psychosis or major depression have a comorbid substance use disorder. Consideration should be given to screening for dual disorders and implementing integrated and scalable treatments.FundingEconomic and Social Research Council, Agencia Nacional de Investigación y Desarrollo (Chile), and the Wellcome Trust.

OROS-methylphenidate to reduce ADHD symptoms in male prisoners aged 16–25 years: a RCT

Background It is estimated that 20–30% of prisoners meet diagnostic criteria for attention deficit hyperactivity disorder (ADHD). Methylphenidate reduces ADHD symptoms, but its effect among prisoners remains uncertain. Objectives The primary objective was to estimate the efficacy of osmotic release oral system (OROS) methylphenidate in reducing ADHD symptoms in male prisoners aged 16–25 years who met diagnostic criteria for ADHD. Secondary objectives investigated change for associated clinical and behavioural problems and the role of ADHD symptoms in mediating change in behaviour. Design A Phase IV, 8-week, parallel-arm, double-blind, randomised, placebo-controlled trial of OROS-methylphenidate, compared with placebo, in young male adult prisoners with ADHD. Participants were randomised in a 1 : 1 ratio of OROS-methylphenidate to placebo, stratified by prison. Setting Participants were recruited from Her Majesty’s Prison and Young Offender Institution Isis (London, England) and Her Majesty’s Young Offender Institution Polmont (Falkirk, Scotland). Participants The participants were 200 male prisoners with ADHD aged 16–25 years who met the diagnostic criteria for ADHD. Exclusion criteria included moderate or severe learning disability; serious risk of violence to researchers; current major depression, psychosis, mania or hypomania, or a past history of bipolar disorder or schizophrenia; and drug-seeking behaviour that was of sufficient severity to affect the titration protocol. Intervention The intervention was overencapsulated OROS-methylphenidate (18 mg) or placebo capsules. Trial medication was titrated weekly for 5 weeks against symptom reduction and adverse effects to a final dose of one to four capsules per day, followed by a stable dose for 3 weeks. Main outcome measures The primary outcome was ADHD symptoms at 8 weeks using the investigator-rated Conners’ Adult ADHD Rating Scale-Observer. There were 13 secondary outcomes, including measures of emotional dysregulation, general psychopathology, reports of behaviour by prison staff and engagement with educational activities. Results For the primary outcome, the estimated improvement between the OROS-methylphenidate and placebo arms was 0.57 points on the Conners’ Adult ADHD Rating Scale-Observer (95% confidence interval –2.41 to 3.56) at 8 weeks, with a standardised effect size of 0.06. The difference was not statistically significant and was smaller than the difference the trial was powered to detect. Responder rate, defined as a 20% reduction in the Conners’ Adult ADHD Rating Scale-Observer score, was 48.3% for the OROS-methylphenidate arm and 47.9% for the placebo arm. None of the 13 secondary outcomes that could be formally compared between the trial arms showed a significant effect and no mediators of change in behaviour were identified. Limitations Low adherence to trial medication and low medication dose might have affected the results. Conclusion OROS-methylphenidate was not found to have an effect, compared with placebo, on the primary and secondary outcomes investigated. The findings indicate that ADHD symptoms do not respond to a standard treatment for ADHD following titration to low doses in young adults in prison. The findings do not support the routine treatment with OROS-methylphenidate of young adult prisoners meeting diagnostic criteria for ADHD. Future research Investigations of adequate, maintained dosing, non-pharmacological interventions and community studies are suggested. Trial registration This trial is registered as ISRCTN16827947 and EudraCT 2015-004271-78. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health and Care Research (NIHR) partnership. Janssen-Cilag Ltd supplied OROS-MPH (Concerta-XL). This will be published in full in Efficacy and Mechanism Evaluation; Vol. 9, No. 6. See the NIHR Journals Library website for further project information.

The Psychopathology of Worthlessness in Depression.

BackgroundDespite common dissatisfaction with the syndromic heterogeneity of major depression, investigations into its symptom structure are scarce. Self-worthlessness/inadequacy is a distinctive and consistent symptom of major depression across cultures.AimsWe investigated whether self-worthlessness is associated with self-blaming attribution-related symptoms or is instead an expression of reduced positive feelings overall, as would be implied by reduced positive affect accounts of depression.Methods44,161 undergraduate students in Study 1, and 215 patients with current Major Depressive Disorder (MDD) and 237 age-matched healthy control participants in Study 2 completed the well-validated Symptom Check List-90. Depression-relevant items were used to construct regularized partial correlation networks with bootstrap estimates of network parameter variability.ResultsWorthlessness co-occurred more strongly with other symptoms linked to self-blaming attributions (hopelessness, and self-blame), displaying a combined edge weight with these symptoms which was significantly stronger than the edge weight representing its connection with reduced positive emotion symptoms (such as reduced pleasure/interest/motivation, difference in edge weight sum in Study 1 = 2.95, in Study 2 = 1.64; 95% confidence intervals: Study 1: 2.6–3.4; Study 2: 0.02–3.5; Bonferroni-corrected p < 0.05).ConclusionsThis confirms the prediction of the revised learned helplessness model that worthlessness is most strongly linked to hopelessness and self-blame. In contrast, we did not find a strong and direct link between anhedonia items and a reduction in self-worth in either study. This supports worthlessness as a primary symptom rather than resulting from reduced positive affect.

Mental health of migrants with pre-migration exposure to armed conflict: a systematic review and meta-analysis

Exposure to armed conflict has been associated with negative mental health consequences. We aimed to estimate the prevalence of generalised anxiety disorder, major depressive disorder, and post-traumatic stress disorder among migrants exposed to armed conflict. In this systematic review and meta-analysis, we searched online databases (Cochrane Library, Embase, LILACS, PsycInfo [via Ovid], PubMed, and Web of Science Core Collection) for relevant observational studies published between Jan 1, 1994, and June 28, 2021. We included studies that used standardised psychiatric interviews to assess generalised anxiety disorder, major depressive disorder, or post-traumatic stress disorder among migrants (refugees or internally displaced persons; aged ≥18 years) with pre-migration exposure to armed conflict. We excluded studies in which exposure to armed conflict could not be ascertained, studies that included a clinical population or people with chronic diseases that can trigger the onset of mental disease, and studies published before 1994. We used a random effects model to estimate each mental health disorder's pooled prevalence and random effects meta-regression to assess sources of heterogeneity. Two independent reviewers assessed the risk of bias for each study using the Joanna Briggs Institute Checklist for Prevalence Studies. The protocol was registered with PROSPERO, CRD42020209251. Of the 13 935 studies identified, 34 met our inclusion criteria; these studies accounted for 15 549 migrants. We estimated a prevalence of current post-traumatic stress disorder of 31% (95% CI 23-40); prevalence of current major depressive disorder of 25% (17-34); and prevalence of generalised anxiety disorder of 14% (5-35). Younger age was associated with a higher prevalence of current post-traumatic stress disorder (odds ratio 0·95 [95% CI 0·90-0·99]), lifetime post-traumatic stress disorder (0·88 [0·83-0·92]), and current generalised anxiety disorder (0·87 [0·78-0·97]). A longer time since displacement was associated with a lower lifetime prevalence of post-traumatic stress disorder (0·88 [0·81-0·95]) and major depressive disorder (0·81 [0·77-0·86]). Migrating to a middle-income (8·09 [3·06-21·40]) or low-income (39·29 [11·96-129·70]) country was associated with increased prevalence of generalised anxiety disorder. Migrants who are exposed to armed conflict are at high risk of mental health disorders. The mental health-care needs of migrants should be assessed soon after resettlement, and adequate care should be provided, with particular attention paid to young adults. Marie Skłodowska-Curie Actions (Horizon 2020-COFUND), MinCiencias (Colombia), and Swiss National Science Foundation.

Cerebellum and nucleus caudatus asymmetry in major depressive disorder

Background/Aim: The relationship between major depressive disorder (MDD) and specific brain regions was investigated using neuroimaging methods. Although the findings show structural hemispheric asymmetry, research has often focused on the specific brain region involved in MDD. This study aimed to investigate asymmetry in the brain regions of MDD patients for the first time with volBrain, which is a fully automated segmentation technique. Methods: Our study was designed as a case-control study. Structural asymmetry was evaluated using the current web-based fully automated segmentation algorithm, volBrain, that analyzes volumetric T1 axial magnetic resonance imaging data. Sixteen cases with MDD and 14 healthy controls were analyzed. For comparison of continuous data between binary groups, an independent T-test was used for data that follow a normal distribution and Mann–Whitney U (MWU) test was used for data that did not follow a normal distribution while categorical data were evaluated using Chi-square test (or Fisher’s exact test when needed). Results: There was no significant difference in terms of gender (χ2 [1, n = 30] = 0.117, P = 0.732), education level (2 [1, n = 30] = 0.002; P = 0.961] and marital status (P = 0.596, Fisher exact chi-square test). However, both groups were found to be similar in terms of age (P = 0.608, MWU test). Right/left nucleus caudatus volume ratios (P = 0.028, MWU test) and right/left cerebellum volume ratios were significantly smaller in the case group (P = 0.006, independent T-test). When the volumes of the right and left parts were compared, only the volume of the right globus pallidus was larger (statistically significant) in the case group (P = 0.008, independent T-test). Conclusion: In line with our hypothesis, our study supports the notion of cortico–striatal–pallidal–thalamic circuit abnormalities in current MDD research and found that some regions in this phase may contain structural asymmetry. In addition, this study contributed to the literature consisting of studies that have examined the relationship between cerebellum and MDD by adding that the cerebellum may show structural asymmetry. The results of our study suggest that research using volBrain may be beneficial to patients with MDD. Current web-based fully automatic segmentation algorithms can restrict both the rater-induced differences in manual segmentation applications and the differences that various segmentation algorithms can create. The challenge of multicenter research can be overcome by using web-based fully automated segmentation volumetry systems and data containing the same standardized magnetic resonance imaging (MRI) acquisition parameters because it is easy for clinicians around the world to access web-based fully automated segmentation volumetry systems. Research on fully automatic segmentation techniques might be the driving force behind fully understanding biological foundations of MDD in the future.