Occurrence and characteristics of suicidal ideation in psychiatrically healthy individuals based on ecological momentary assessment.

Decedents with no known mental disorder comprise 5-40% of suicides, suggesting that suicide ideation (SI) and behavior may occur in the psychiatrically healthy with important implications for suicide risk screening. Healthy Volunteers (HV) and patients with Major Depressive Disorder (MDD) provided 7 days of Ecological Momentary Assessment (EMA) data about SI and stressors. Longitudinal mixed effects logistic regression models compared HV and patient SI and stressors. Mixed effects linear regression models compared HVs' and patients' SI score change from the previous epoch's SI score when each stressor occurred. HVs (n = 42) reported less frequent (p < 0.001) and less intense SI (p < 0.003) than patients (n = 80), yet did endorse SI and/or SI-related items in 44% of EMA epochs, endorsing SI items in 25% of epochs with non-zero SI scores. For 7 of 8 stressors, patients reported stressors more often than HVs (all p < 0.001) responding to them with increased SI (0.0001 < p < 0.0472). HVs were relatively resilient to stressors, reporting SI increases only in response to neglect (p < 0.0147). Although SI and SAs are documented among psychiatrically healthy individuals, scientific attention to these observations has been scant. Real-time SI measurement showed that HVs' SI was less pronounced than MDD patients', but was endorsed, nonetheless. Patients were more likely to report stressors than HVs, perhaps due to greater sensitivity to the environment, and reported SI in response to stressors, which was less common in HVs. Both MDD patients and HVs most often manifested passive SI (viz, "decreased wish to live"). However, passive SI (viz, "desire for death"), may predict suicide, even absent SI per se (thinking about killing yourself). This study validates the utility of real-time SI assessment, showing that HVs endorse SI items in 11% of epochs, which implies that suicide risk screening focused on those with mental disorders may be too narrow an approach.

Suicidal behavior across a broad range of psychiatric disorders.

Suicide is a leading cause of death worldwide. In 2020, some 12.2 million Americans seriously contemplated suicide, 3.2 million planned suicide attempts, and 1.2 million attempted suicide. Traditionally, the approach to treating suicidal behavior (SB) has been to treat the "underlying" psychiatric disorder. However, the number of diagnoses associated with SB is considerable. We could find no studies describing the range of disorders reported to be comorbid with SB. This narrative review summarizes literature documenting the occurrence of SB across the lifespan and the full range of psychiatric diagnoses, not only BPD and those that comprise MDE, It also describes the relevance of these observations to clinical practice, research, and nosology. The literature searches contained the terms "suicid*" and each individual psychiatric diagnosis and identified 587 studies. We did not include case reports, case series, studies only addressing suicidal ideation or non-suicidal self-injury (NSSI), studies on self-harm, not distinguishing between SB and NSSI and studies that did not include any individuals that met criteria for a specific DSM-5 diagnosis (n = 366). We found that SB (suicide and/or suicide attempt) was reported to be associated with 72 out of 145 diagnoses, although data quality varied. Thus, SB is not exclusively germane to Major Depressive Episode (MDE) and Borderline Personality Disorder (BPD), the only conditions for which it is a diagnostic criterion. That SB co-occurs with so many diagnoses reinforces the need to assess current and past SB regardless of diagnosis, and supports the addition of charting codes to the DSM-5 to indicate current or past SB. It also comports with new data that specific genes are associated with SB independent of psychiatric diagnoses, and suggests that SB should be managed with specific suicide prevention interventions in addition to treatments indicated for co-occurring diagnoses. SB diagnostic codes would help researchers and clinicians document and measure SB's trajectory and response to treatment over time, and, ultimately, help develop secondary and tertiary prevention strategies. As a separate diagnosis, SB would preclude situations in which a potentially life-threatening behavior is not accounted for by a diagnosis, a problem that is particularly salient when no mental disorder is present, as is sometimes the case.

Suicidal behaviour is pathological: implications for psychiatric euthanasia.

Some have challenged the validity of labelling suicidal thoughts and behaviours (STB) as pathological. In this paper, we argue that STB is indeed pathological, thereby, situating suicide prevention within the realm of medicine, complicating calls for the legalisation of medical assistance in dying for individuals whose sole condition is psychiatric (psychiatric medical assistance in dying (MAID)). Evidence shows STB predicts the risk of suicide; moreover, several mental illnesses are associated with STB, and 70%-90% of suicide deaths are linked to psychiatric illness. Treating psychiatric illnesses can prevent suicide. We contend that this clinical evidence not only warrants the classification of STB as pathological but also necessitates its treatment and prevention. This perspective poses a challenge to legislation that would legalise psychiatric MAID.

A cohort study of engagement in telehealth psychotherapy versus in-person services.

OBJECTIVE: Although telehealth psychotherapies have been studied for over 20 years, mental health services remained largely delivered in person until the COVID-19 pandemic forced clinics to reconsider the utility of telehealth psychotherapy. This study aims to compare patient engagement in in-person versus telehealth services in outpatient psychotherapy for mood and anxiety disorders. METHOD: A cohort investigation was conducted, using a propensity score matched sample, extracted from an electronic health record (EHR) to compare engagement in psychotherapy for 762 patients who used in-person services before the pandemic to a cohort of 762 patients who used telehealth psychotherapy after the onset of COVID-19. The authors compared cohorts on initial engagement in psychotherapy services following an initial intake, number of psychotherapy sessions attended, and the rate of missed sessions. RESULTS: There was a 26% increase in the total number of individual psychotherapy sessions attended when the clinics transitioned to telehealth services (p < .001). In addition, patients who received telehealth psychotherapy were five times more likely to not cancel or miss any scheduled sessions (p < .001). CONCLUSION: These results indicate that telehealth services may result in improved treatment engagement for outpatient centers focused on brief evidence-based psychotherapies for mood and anxiety disorders.

Brain serotonin 1A receptor binding: relationship to peripheral blood DNA methylation, recent life stress and childhood adversity in unmedicated major depression.

BACKGROUND: Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms. AIMS: We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT1A) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and in vivo 5-HT1A receptor binding potential (BPF) determined by positron emission tomography (PET) in 13 a priori brain regions, in participants with major depressive disorder (MDD) and healthy volunteers (controls). METHOD: Medication-free participants with MDD (n = 192: 110 female, 81 male, 1 other) and controls (n = 88: 48 female, 40 male) were interviewed about childhood adversity and recent stressors and genotyped for rs6295. DNA methylation was assayed at three upstream promoter sites (-1019, -1007, -681) of the 5-HT1A receptor gene. A subgroup (n = 119) had regional brain 5-HT1A receptor BPF quantified by PET. Multi-predictor models were used to test associations between diagnosis, recent stress, childhood adversity, genotype, methylation and BPF. RESULTS: Recent stress correlated positively with blood monocyte methylation at the -681 CpG site, adjusted for diagnosis, and had positive and region-specific correlations with 5-HT1A BPF in participants with MDD, but not in controls. In participants with MDD, but not in controls, methylation at the -1007 CpG site had positive and region-specific correlations with binding potential. Childhood adversity was not associated with methylation or BPF in participants with MDD. CONCLUSIONS: These findings support a model in which recent stress increases 5-HT1A receptor binding, via methylation of promoter sites, thus affecting MDD psychopathology.

Serotonin transporter binding in major depressive disorder: impact of serotonin system anatomy.

Serotonin transporter (5-HTT) binding deficits are reported in major depressive disorder (MDD). However, most studies have not considered serotonin system anatomy when parcellating brain regions of interest (ROIs). We now investigate 5-HTT binding in MDD in two novel ways: (1) use of a 5-HTT tract-based analysis examining binding along serotonergic axons; and (2) using the Copenhagen University Hospital Neurobiology Research Unit (NRU) 5-HT Atlas, based on brain-wide binding patterns of multiple serotonin receptor types. [11C]DASB 5-HTT PET scans were obtained in 60 unmedicated participants with MDD in a current depressive episode and 31 healthy volunteers (HVs). Binding potential (BPP) was quantified with empirical Bayesian estimation in graphical analysis (EBEGA). Within the [11C]DASB tract, the MDD group showed significantly lower BPP compared with HVs (p = 0.02). This BPP diagnosis difference also significantly varied by tract location (p = 0.02), with the strongest MDD binding deficit most proximal to brainstem raphe nuclei. NRU 5-HT Atlas ROIs showed a BPP diagnosis difference that varied by region (p < 0.001). BPP was lower in MDD in 3/10 regions (p-values < 0.05). Neither [11C]DASB tract or NRU 5-HT Atlas BPP correlated with depression severity, suicidal ideation, suicide attempt history, or antidepressant medication exposure. Future studies are needed to determine the causes of this deficit in 5-HTT binding being more pronounced in proximal axon segments and in only a subset of ROIs for the pathogenesis of MDD. Such regional specificity may have implications for targeting antidepressant treatment, and may extend to other serotonin-related disorders.

Does It Matter What Screener We Use? A Comparison of Ultra-brief PHQ-4 and E-mwTool-3 Screeners for Anxiety and Depression Among People With and Without HIV.

The burden of depression and anxiety disorders is high in sub-Saharan Africa, especially for people with HIV (PWH). The Patient Health Questionnaire-4 (PHQ-4) and Electronic Mental Wellness Tool-3 (E-mwTool-3) are ultra-brief screening tools for these disorders. We compared the performance of PHQ-4 and E-mwTool-3 for screening MINI-International Neuropsychiatric Interview diagnoses of depression and anxiety among a sample of individuals with and without HIV in two primary care clinics and one general hospital in Maputo City, Mozambique. Areas-under-the-curve (AUC) were calculated along with sensitivities and specificities at a range of cutoffs. For PWH, at a sum score cutoff of ≥ 1, sensitivities were strong: PHQ-4:Depression = 0.843; PHQ-4:Anxiety = 0.786; E-mwTool-3:Depression = 0.843; E-mwTool-3:Anxiety = 0.929. E-mwTool-3 performance was comparable to PHQ-4 among people with and without HIV.

Suicide in Global Mental Health.

PURPOSE OF REVIEW: We review recent research on the epidemiology and etiology of suicide in the global context. We focus on data from low- and middle-income countries (LMIC), with the goal of highlighting findings from these under-researched, over-burdened settings. RECENT FINDINGS: Prevalence of suicide in LMIC adults varies across region and country income-level, but is, on average, lower than in high-income countries. Recent gains in suicide reduction, however, have been smaller in LMIC compared to global rates. LMIC youth have much higher rates of suicide attempts than youth from high-income countries. Females as well as people with psychiatric disorders, those living with HIV, those who are LGBTQ + , and those with poor socioeconomic status are highly vulnerable populations in LMIC. Limited and low-quality data from LMIC hinder clear interpretation and comparison of results. A greater body of more rigorous research is needed to understand and prevent suicide in these settings.

Association between mental disorders and adherence to antiretroviral treatment in health facilities in two Mozambican provinces in 2018: a cross-sectional study.

INTRODUCTION: Lower adherence to antiretroviral treatment (ART) has been found among people with HIV (PWH) who have comorbid mental disorders like depression and alcohol use in Sub-Saharan African. However, there has been less exploration with regards to other mental disorders. METHODS: This study assessed the association of multiple mental disorders and adherence to ART based on the data from primary/tertiary health care facilities in Maputo and Nampula, Mozambique. We administered a sociodemographic questionnaire, Mini International Neuropsychiatric Interview (MINI) Plus 4.0.0 adapted for use in Mozambique to assess mental conditions, and a 3-item self-report to measure ART adherence. RESULTS: 395 HIV-positive (self-report) participants on ART, with an average age of 36.7 years (SD = 9.8), and 30.4% were male. The most common mental disorders were major depressive disorder (27.34%) followed by psychosis (22.03%), suicidal ideation/behavior (15.44%), and alcohol-use disorder (8.35%). Higher odds of missing at least one dose in the last 30 days (OR = 1.45, 95% CI: 1.01, 2.10) were found in participants with any mental disorder compared to those without a mental disorder. The highest levels of non-adherence were observed among those with drug use disorders and panic disorder. CONCLUSIONS: In Mozambique, PWH with any co-occurring mental conditions had a lower probability of ART adherence. Integrating comprehensive mental health assessment and treatment and ART adherence interventions tailored to PWH with co-occurring mental disorders is necessary to attain optimal ART adherence and reach the UNAIDS ART target.

A Multi-Site Study of Mental Disorders in the Mozambican Health Care System.

In Mozambique, human and financial resources for public mental health services are extremely limited. Understanding the mental health needs of those seeking healthcare can inform efficient targeting of mental health services. We examined if the frequency of mental disorders in a health facility varied based on the level of specialization of such facility, from primary care without mental health specialists (PrCMH -), to those with mental health specialists (PrCMH +) and tertiary care (TerC), where both inpatient and outpatient mental health services are available. Participants were adults (convenience sample) seeking health or mental health services at six facilities (2 PrCMH + , 3 PrCMH -, and 1 TerC) in the cities of Maputo and Nampula in Mozambique. Mental disorders were assessed by the MINI International Neuropsychiatric Interview (MINI) 4.0.0. We compared the sociodemographic characteristics and MINI diagnoses across the three types of health facilities. Multiple logistic regression models determined the likelihood that a person seeking services at each type of facility would have any mental disorder, common mental disorders (CMD), severe mental disorders (SMD), substance use disorders (SUD), and moderate-to-high suicide risk, adjusting for sociodemographic factors. Of the 612 total participants, 52.6% (n = 322) were positive for at least one mental disorder: 37.1% were positive for CMD, 28.9% for SMD, 13.2% for SUD, and 10.5% had suicide risk. Presence of any mental disorder was highest in TerC (62.5%) and lowest in PrCMH - (48.4%). Adjusting for sociodemographic covariates, participants in PrCMH + were significantly more likely to have SMD (OR 1.85, 95%CI 1.10-3.11) and SUD (OR 2.79, 95%CI 1.31-5.94) than participants in PrCMH -; participants in TerC were more likely to have CMD (OR 1.70, 95%CI 1.01-2.87) and SUD (OR 2.57, 95%CI 1.14-5.79) than in PrCMH -. Suicide risk was the only condition that did not differ across facility types. As anticipated, people with mental disorders were more likely to be cared for at facilities with mental health specialists. However, our study detected in this convenience sample a remarkably high frequency of mental disorders across different types of facilities within the Mozambican healthcare system. These results, if confirmed in representative samples, suggest a need to increase mental health services at the primary care level.

Exploration of baseline and early changes in neurocognitive characteristics as predictors of treatment response to bupropion, sertraline, and placebo in the EMBARC clinical trial.

BACKGROUND: Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner. METHODS: In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16. RESULTS: Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline. CONCLUSION: These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.

Sleep complaints are associated with increased suicide risk independently of psychiatric disorders: results from a national 3-year prospective study.

Prior research suggests that sleep disturbances are associated with increased risk of suicide. However, sleep disturbances are associated with a wide range of psychiatric disorders, and it is unknown whether this association is independent of psychopathology. In a large nationally representative prospective survey, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), we used structural equation modeling to examine the shared and specific effects of three sleep complaints (i.e., trouble falling asleep, early morning awakening, and hypersomnia) on the 3-year occurrence of attempting suicide. Because psychiatric disorders increase the risk of suicide attempt almost exclusively through a general psychopathology factor representing their shared effect, covariates included that factor, prior history of suicide attempt, and a wide range of sociodemographic and clinical characteristics. The 3-year prevalence rate of suicide attempt was 0.6% (n = 241). Compared with participants who did not attempt suicide between the two waves, those who did reported significantly more frequently having trouble falling asleep (44.6% vs. 16.6%), early morning awakening (38.9% vs. 12.7%), and hypersomnia (35.0% vs. 10.7%). Following adjustments, effects of sleep complaints on this risk were significant and exerted almost exclusively through a general sleep complaints factor representing the shared effect across all sleep complaints. There were no residual associations of any individual sleep complaint with attempting suicide above that association. Sleep complaints are associated with an increased risk of attempting suicide independently of psychopathology, and should be included in suicide risk assessments as these symptoms may provide targets for reducing the risks of suicidal behaviors.

Large-scale network dynamics in neural response to emotionally negative stimuli linked to serotonin 1A binding in major depressive disorder.

Serotonergic dysfunction is implicated in major depressive disorder (MDD), but the mechanisms of this relationship remain elusive. Serotonin 1A (5-HT1A) autoreceptors regulate brain-wide serotonin neuron firing and are positioned to assert large-scale effects on negative emotion. Here we investigated the relationship between raphe 5-HT1A binding and brain-wide network dynamics of negative emotion. 22 healthy-volunteers (HV) and 27 medication-free participants with MDD underwent positron emission tomography (PET) using [11C]CUMI-101 (CUMI) to quantify 5-HT1A binding in midbrain raphe nuclei and functional magnetic resonance imaging (fMRI) scanning during emotionally negative picture viewing. Causal connectivity across regions responsive to negative emotion was estimated in the fMRI data using a multivariate dynamical systems model. During negative picture viewing, MDD subjects demonstrated significant hippocampal inhibition of amygdala, basal-ganglia, thalamus, orbital frontal cortex, inferior frontal gyrus and dorsomedial prefrontal cortex (IFG, dmPFC). MDD-related connectivity was not associated with raphe 5-HT1A binding. However, greater hippocampal inhibition of amygdala, thalamus, IFG and dmPFC correlated with hippocampal 5-HT1A binding. Correlation between hippocampal 5-HT1A binding and the hippocampal inhibition network was specific to MDD but not HV. MDD and HV groups also differed with respect to the correlation between raphe and hippocampal 5-HT1A binding which was more pronounced in HV. These findings suggest that increased hippocampal network inhibition in MDD is linked to hippocampal serotonergic dysfunction which may in turn arise from disrupted linkage in raphe to hippocampus serotonergic circuitry.

Highly variable suicidal ideation: a phenotypic marker for stress induced suicide risk.

Suicidal behavior (SB) can be impulsive or methodical; violent or not; follow a stressor or no obvious precipitant. This study tested whether childhood trauma, affective lability, and aggressive and impulsive traits predicted greater SI variability. We also assessed whether affective lability, aggressive or impulsive traits explain childhood trauma's effects on SI variability and whether those with highly variable SI respond to stressful events with increases in SI. Finally, we assessed variable SI's trajectory over 2 years. Depressed participants (n = 51) had ecological momentary assessments (EMA) over 7 days at baseline, 3, 6, 12, 18, and 24 months. SI variability was assessed using the square Root of the Mean Square of Successive Deviations. Mixed Effects Models were fit as appropriate. Childhood trauma was associated with subsequent aggression. Physical abuse predicted both aggression and affective lability as well as SI variability, but not impulsivity. In two-predictor models, physical abuse's effect on SI variability was no longer significant, when controlling for the effect of higher aggression and impulsivity. Those with high SI variability exhibited greater increases in SI after stressors compared with those with less variability. We did not find that SI variability changed over time, suggesting it might be trait-like, at least over 2 years. Variable SI predisposes to marked SI increases after stressful events and may be a trait increasing risk for impulsive SB, at least over 2 years.

Structural brain measures linked to clinical phenotypes in major depression replicate across clinical centres.

Abnormalities in brain structural measures, such as cortical thickness and subcortical volumes, are observed in patients with major depressive disorder (MDD) who also often show heterogeneous clinical features. This study seeks to identify the multivariate associations between structural phenotypes and specific clinical symptoms, a novel area of investigation. T1-weighted magnetic resonance imaging measures were obtained using 3 T scanners for 178 unmedicated depressed patients at four academic medical centres. Cortical thickness and subcortical volumes were determined for the depressed patients and patients' clinical presentation was characterized by 213 item-level clinical measures, which were grouped into several large, homogeneous categories by K-means clustering. The multivariate correlations between structural and cluster-level clinical-feature measures were examined using canonical correlation analysis (CCA) and confirmed with both 5-fold and leave-one-site-out cross-validation. Four broad types of clinical measures were detected based on clustering: an anxious misery composite (composed of item-level depression, anxiety, anhedonia, neuroticism and suicidality scores); positive personality traits (extraversion, openness, agreeableness and conscientiousness); reported history of physical/emotional trauma; and a reported history of sexual abuse. Responses on the item-level anxious misery measures were negatively associated with cortical thickness/subcortical volumes in the limbic system and frontal lobe; reported childhood history of physical/emotional trauma and sexual abuse measures were negatively correlated with entorhinal thickness and left hippocampal volume, respectively. In contrast, the positive traits measures were positively associated with hippocampal and amygdala volumes and cortical thickness of the highly-connected precuneus and cingulate cortex. Our findings suggest that structural brain measures may reflect neurobiological mechanisms underlying MDD features.

Prevalence and correlates of suicidal behavior in primary care settings in Mozambique.

BACKGROUND: This study assessed the prevalence of suicidal behavior and associated risk factors in public primary health care in Mozambique. METHODS: The Mini International Neuropsychiatric Interview was used to evaluate suicidal behavior among 502 adults attending three Primary Health Care (PHC) settings. RESULTS: In the past month, 13% (n = 63) of PHC attendees expressed suicidal ideation, 8% (n = 40) had made a suicide plan, 4% (n = 20) had made a suicide attempt, and 5% (n = 25) reported a lifetime suicide attempt. Females had 2.8-fold increased odds of suicide plan (95% CI: 1.5, 5.5) and 3.3-fold increased odds of suicide attempt in the past month (95% CI: 1.2, 9.1). Each 10-year increase in age was associated with 0.61-fold the odds of suicide plan (95% CI: 0.38, 0.98) and 0.09-fold the odds of suicide attempt (95% CI: 0.01, 0.69) in the past month. People living with HIV (PLWHA) had 2.2-fold increased adjusted odds of past month suicide attempt (CI: 1.1, 4.1). CONCLUSION: Suicidal behaviors are common among adults attending PHC clinics in Mozambique. Screening and linkage to effective preventive interventions are urgently needed in PHC settings. Females, younger individuals, and PLWHA are at elevated risk for suicidal behavior in PHC.

Childhood trauma history is linked to abnormal brain connectivity in major depression.

Patients with major depressive disorder (MDD) present with heterogeneous symptom profiles, while neurobiological mechanisms are still largely unknown. Brain network studies consistently report disruptions of resting-state networks (RSNs) in patients with MDD, including hypoconnectivity in the frontoparietal network (FPN), hyperconnectivity in the default mode network (DMN), and increased connection between the DMN and FPN. Using a large, multisite fMRI dataset (n = 189 patients with MDD, n = 39 controls), we investigated network connectivity differences within and between RSNs in patients with MDD and healthy controls. We found that MDD could be characterized by a network model with the following abnormalities relative to controls: (i) lower within-network connectivity in three task-positive RSNs [FPN, dorsal attention network (DAN), and cingulo-opercular network (CON)], (ii) higher within-network connectivity in two intrinsic networks [DMN and salience network (SAN)], and (iii) higher within-network connectivity in two sensory networks [sensorimotor network (SMN) and visual network (VIS)]. Furthermore, we found significant alterations in connectivity between a number of these networks. Among patients with MDD, a history of childhood trauma and current symptoms quantified by clinical assessments were associated with a multivariate pattern of seven different within- and between-network connectivities involving the DAN, FPN, CON, subcortical regions, ventral attention network (VAN), auditory network (AUD), VIS, and SMN. Overall, our study showed that traumatic childhood experiences and dimensional symptoms are linked to abnormal network architecture in MDD. Our results suggest that RSN connectivity may explain underlying neurobiological mechanisms of MDD symptoms and has the potential to serve as an effective diagnostic biomarker.

Discovery and replication of cerebral blood flow differences in major depressive disorder.

Major depressive disorder (MDD) is a serious, heterogeneous disorder accompanied by brain-related changes, many of which are still to be discovered or refined. Arterial spin labeling (ASL) is a neuroimaging technique used to measure cerebral blood flow (CBF; perfusion) to understand brain function and detect differences among groups. CBF differences have been detected in MDD, and may reveal biosignatures of disease-state. The current work aimed to discover and replicate differences in CBF between MDD participants and healthy controls (HC) as part of the EMBARC study. Participants underwent neuroimaging at baseline, prior to starting study medication, to investigate biosignatures in MDD. Relative CBF (rCBF) was calculated and compared between 106 MDD and 36 HC EMBARC participants (whole-brain Discovery); and 58 MDD EMBARC participants and 58 HC from the DLBS study (region-of-interest Replication). Both analyses revealed reduced rCBF in the right parahippocampus, thalamus, fusiform and middle temporal gyri, as well as the left and right insula, for those with MDD relative to HC. Both samples also revealed increased rCBF in MDD relative to HC in both the left and right inferior parietal lobule, including the supramarginal and angular gyri. Cingulate and prefrontal regions did not fully replicate. Lastly, significant associations were detected between rCBF in replicated regions and clinical measures of MDD chronicity. These results (1) provide reliable evidence for ASL in detecting differences in perfusion for multiple brain regions thought to be important in MDD, and (2) highlight the potential role of using perfusion as a biosignature of MDD.

Reward related ventral striatal activity and differential response to sertraline versus placebo in depressed individuals.

Medications to treat major depressive disorder (MDD) are not equally effective across patients. Given that neural response to rewards is altered in MDD and given that reward-related circuitry is modulated by dopamine and serotonin, we examined, for the first time, whether reward-related neural activity moderated response to sertraline, an antidepressant medication that targets these neurotransmitters. A total of 222 unmedicated adults with MDD randomized to receive sertraline (n = 110) or placebo (n = 112) in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study completed demographic and clinical assessments, and pretreatment functional magnetic resonance imaging while performing a reward task. We tested whether an index of reward system function in the ventral striatum (VS), a key reward circuitry region, moderated differential response to sertraline versus placebo, assessed with the Hamilton Rating Scale for Depression (HSRD) over 8 weeks. We observed a significant moderation effect of the reward index, reflecting the temporal dynamics of VS activity, on week-8 depression levels (Fs ≥ 9.67, ps ≤ 0.002). Specifically, VS responses that were abnormal with respect to predictions from reinforcement learning theory were associated with lower week-8 depression symptoms in the sertraline versus placebo arms. Thus, a more abnormal pattern of pretreatment VS dynamic response to reward expectancy (expected outcome value) and prediction error (difference between expected and actual outcome), likely reflecting serotonergic and dopaminergic deficits, was associated with better response to sertraline than placebo. Pretreatment measures of reward-related VS activity may serve as objective neural markers to advance efforts to personalize interventions by guiding individual-level choice of antidepressant treatment.

Addressing Common Challenges in the Implementation of Collaborative Care for Mental Health: The Penn Integrated Care Program.

PURPOSE: We developed and implemented a new model of collaborative care that includes a triage and referral management system. We present initial implementation metrics using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. METHODS: Primary care clinicians in 8 practices referred patients with any unmet mental health needs to the Penn Integrated Care program. Assessments were conducted using validated measures. Patients were primarily triaged to collaborative care (26%) or specialty mental health care with active referral management (70%). We conducted 50 qualitative interviews to understand the implementation process and inform program refinement. Our primary outcomes were reach and implementation metrics, including referral and encounter rates derived from the electronic health record. RESULTS: In 12 months, 6,124 unique patients were referred. Assessed patients reported symptoms consistent with a range of conditions from mild to moderate depression and anxiety to serious mental illnesses including psychosis and acute suicidal ideation. Among patients enrolled in collaborative care, treatment entailed a mean of 7.2 (SD 5.1) encounters over 78.1 (SD 51.3) days. Remission of symptoms was achieved by 32.6% of patients with depression and 39.5% of patients with anxiety. Stakeholders viewed the program favorably and had concrete suggestions to ensure sustainability. CONCLUSIONS: The Penn Integrated Care program demonstrated broad reach. Implementation was consistent with collaborative care as delivered in seminal studies of the model. Our results provide insight into a model for launching and implementing collaborative care to meet the needs of a diverse group of patients with the full range of mental health conditions seen in primary care.