History Of Major Depressive Disorder Research Articles

A Case of Severe Kratom Addiction Contributing to a Suicide Attempt

Kratom is a plant product native to Southeast Asia that is surging in popularity in the United Statesas consumers look for natural remedies for ailments like chronic pain, anxiety, and even opioid addiction. Kratom's risks are largely unknown, and the market is poorly regulated. Americans typically get advice from online forums and purchase powder formulations from tobacco shops or obscure websites. These risks are highlighted in this case of a 38-year-old woman with a history of major depressive disorder and opioid use disorder who switched from Suboxone to kratom and became addicted, eventually consuming large quantities per day. Amplified by other stressors, she reached a breaking point and overdosed on her regular medications for depression. At the psychiatric hospital, she exhibited classic kratom withdrawal symptoms, including vague abdominal pain and restlessness. After eight days of treatment, her symptoms eventually abated, and she was discharged on Suboxone.

A transactional mediation model of risk for the intergenerational transmission of depression: The role of maternal criticism.

In this study, we sought to combine two lines of research to better understand risk for the intergenerational transmission of depression. The first focuses on the role of maternal criticism as a potential mechanism of risk for depression in youth while the second builds from interpersonal and stress generation models regarding the potential impact of youth depression on future escalations in maternal criticism. Specifically, we examined the role of maternal criticism within a transactional mediation model using data from a multi-wave study. Participants were 251 mother-offspring pairs consisting of mothers with (n = 129) and without (n = 122) a history of major depressive disorder (MDD) during their child's lifetime who completed assessments every 6 months for 2 years. We found support for the hypothesized transactional mediational model in which maternal expressed emotion-criticism (EE-Crit) mediated the link between maternal history of MDD and residual change in youth's depressive symptoms over the previous 6 months and, reciprocally, youth depressive symptoms mediated the relation between maternal MDD history and residual change in EE-Crit 6 months later. These results indicate that maternal criticism and offspring depressive symptoms may contribute to a vicious cycle of depression risk, which should be considered for interventions targeted toward youth at risk of developing MDD.

Circulating microRNA associated with future relapse status in major depressive disorder.

Major depressive disorder (MDD) is an episodic condition with relapsing and remitting disease course. Elucidating biomarkers that can predict future relapse in individuals responding to an antidepressant treatment holds the potential to identify those patients who are prone to illness recurrence. The current study explored relationships between relapse risk in recurrent MDD and circulating microRNAs (miRNAs) that participate in RNA silencing and post-transcriptional regulation of gene expression. Serum samples were acquired from individuals with a history of recurrent MDD who were followed longitudinally in the observational study, OBSERVEMDD0001 (ClinicalTrials.gov Identifier: NCT02489305). Circulating miRNA data were obtained in 63 participants who relapsed (“relapsers”) and 154 participants who did not relapse (“non-relapsers”) during follow-up. The miRNA was quantified using the ID3EAL™ miRNA Discovery Platform from MiRXES measuring 575 circulating miRNAs using a patented qPCR technology and normalized with a standard curve from spike-in controls in each plate. The association between miRNAs and subsequent relapse was tested using a linear model, adjusting for age, gender, and plate. Four miRNAs were nominally associated with relapse status during the observational follow-up phase with a false discover rate adjusted p-value < 0.1. Enrichment analysis of experimentally validated targets revealed 112 significantly enriched pathways, including neurogenesis, response to cytokine, neurotrophin signaling, vascular endothelial growth factor signaling, relaxin signaling, and cellular senescence pathways. These data suggest these miRNAs putatively associated with relapse status may have the potential to regulate genes involved in multiple signaling pathways that have previously been associated with MDD. If shown to be significant in a larger, independent sample, these data may hold potential for developing a miRNA signature to identify patients likely to relapse, allowing for earlier intervention.

Associations between depression-relevant genetic risk and youth stress exposure: Evidence of gene-environment correlations.

Familial risk for depression is associated with youth exposure to self-generated dependent stressful life events and independent events that are out of youth's control. Familial risk includes both genetic and environmental influences, raising the question of whether genetic influences, specifically, are associated with youth exposure to both dependent and independent stressful life events. To address this question, this study examined the relation between a genome-wide association study (GWAS)-derived depression-based polygenic risk score (DEP-PRS) and youth experiences of dependent and independent stress. Participants were 180 youth (ages 8 to 14, 52.2% female) of European ancestry and their biological mothers recruited based on the presence versus absence of a history of major depressive disorder (MDD) in the mothers. Youth and mothers were interviewed every 6 months for 2 years regarding the occurrence of stressful life events, which were coded as independent or dependent (self-generated). Results indicated that youth's DEP-PRS and maternal history of MDD were uniquely associated with increased exposure to both dependent and independent events. Similar results were observed when examining major versus minor events separately, with the additional finding of a DEP-PRS × mother MDD interaction for major dependent events such that levels of moderate to severe dependent life stressors were highest among youth with high DEP-PRSs who also had mothers with MDD. These results not only support the presence of depression-relevant gene-environment correlations (rGEs), but also highlight the possibility that rather than only capturing depression-specific genetic liability, GWAS-derived polygenic risk scores may also capture genetic variance contributing to stress exposure. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neural and peripheral markers of reward during positive social evaluation are associated with less clinician-rated depression symptom severity in adolescence

Although blunted sensitivity to reward is thought to play a key role in promoting risk for depression, most research on this topic has utilized monetary reward paradigms and focused on currently depressed adults. To address this issue, we analyzed neural reward and β-endorphin data from the Psychobiology of Stress and Adolescent Depression (PSY SAD) Study, which recruited a well-characterized sample of adolescent girls at high vs. low risk for major depressive disorder (MDD) (N = 52, Mage = 14.90, SD = 1.35) based on their mothers’ lifetime history of MDD. As hypothesized, greater striatal activity while receiving positive (vs. neutral) social evaluation was associated with lower depression symptom severity as independently assessed by the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). This association was present for girls at high but not low risk for MDD, suggesting that this neural response may represent a pre-clinical marker of risk for depression. Consistent with these results, higher post-social evaluation levels of a peripheral marker of reward sensitivity, β-endorphin, were related to lower clinician-rated depression symptom severity. Together, these results indicate that neural and peripheral markers of responsivity to social reward are both related to depression severity, which may have implications for understanding the pathophysiology of depression.

Reward-based reinforcement learning is altered among individuals with a history of major depressive disorder and psychomotor retardation symptoms

Reward-based reinforcement learning impairments are common in major depressive disorder, but it is unclear which aspects of reward-based reinforcement learning are disrupted in remitted major depression (rMDD). Given that the neurobiological substrates that implement reward-based RL are also strongly implicated in psychomotor retardation (PmR), the present study sought to test whether reward-based reinforcement learning is altered in rMDD individuals with a history of PmR. Three groups of individuals (1) rMDD with past PmR (PmR+, N = 34), (2) rMDD without past PmR (PmR-, N = 44), and (3) healthy controls (N = 90) completed a reward-based reinforcement learning task. Computational modeling was applied to test for group differences in model-derived parameters – specifically, learning rates and reward sensitivity. Compared to controls, rMDD PmR + exhibited lower learning rates, but not reduced reward sensitivity. By contrast, rMDD PmR- did not significantly differ from controls on either of the model-derived parameters. Follow-up analyses indicated that the results were not due to current psychopathology symptoms. Results indicate that a history of PmR predicts altered reward-based reinforcement learning in rMDD. Abnormal reward-related reinforcement learning may reflect a scar of past depressive episodes that contained psychomotor symptoms, or a trait-like deficit that preceded these episodes.

Autistic traits in trichotillomania.

IntroductionAlthough many variables have been examined as potentially contributing to the manifestation of trichotillomania (TTM), little research has focused on problems in social interactions. Hair pulling has many similarities to the stereotypies seen in autism spectrum disorders (ASD), and thus the present study examined autistic traits in adults with trichotillomania.MethodsFifty nontreatment‐seeking adults with DSM‐5 TTM were recruited. Participants completed standard diagnostic interviews, basic demographic information, and symptom inventories about TTM. Autistic traits were quantified using the Brief Autism‐ Spectrum Quotient (AQ‐10) which screens for autistic traits.ResultsThe sample comprised 50 participants, mean (standard deviation) age of 30.2 (5.6) years, 10% being male, 86% female, and 4% nonbinary. Eight of the participants had a history of major depressive disorder and six had a history of an anxiety disorder. No one had current or lifetime obsessive‐compulsive disorder. The mean AQ10 score was 3.5 (2.0), with 14.6% scoring 6 or greater. Autism scores correlated significantly only with family dysfunction and not with symptom severity or impulsivity.ConclusionsThis study examined autistic traits in a community‐based sample of adults with TTM and found elevated rates of probable ASD (based on a self‐report screening tool) among those with TTM. These results highlight the need to carefully screen for autistic traits in those with TTM. To what extent these traits may influence response to treatment, however, remains unclear.

Edible Mushrooms as a Potential Component of Dietary Interventions for Major Depressive Disorder.

Dietary interventions for people suffering from major depressive disorder (MDD) are an ongoing field of research. In this article, we present a comprehensive background for understanding the possibility of using edible medicinal mushrooms as an adjunctive treatment for MDD. We start with a brief history of MDD, its diagnosis, epidemiology and treatment, and the effects of diet on depression symptoms, followed by a review of neurobiological, behavioral, and clinical studies of medicinal mushrooms. We specifically highlight the results of preclinical and clinical studies on dietary supplementation with three selected mushroom species: Lion’s mane (Hericium erinaceus), Caterpillar mushroom (Cordyceps militaris), and Lingzhi/Reishi (Ganoderma lucidum). Preliminary small-sample clinical studies suggest that Lion’s mane can influence well-being of humans. In the case of Reishi, the results of clinical studies are equivocal, while in the case of Caterpillar Mushroom, such studies are underway. Edible mushrooms contain 5-hydroxy-L-tryptophan (5-HTP), which is a direct precursor of serotonin—a neurotransmitter targeted in pharmacotherapy of MDD. Therefore, in light of the well-recognized role of stress as a pathogenic factor of MDD, we also describe the neurobiological mechanisms of the interaction between stress and serotonergic neurotransmission; and summarize the current state of knowledge on dietary supplementation with 5-HTP in MDD.

Pupillary response in reward processing in adults with major depressive disorder in remission.

Major depressive disorder (MDD) is associated with impaired reward processing and reward learning. The literature is inconclusive regarding whether these impairments persist after remission. The current study examined reward processing during a probabilistic learning task in individuals in remission from MDD (n = 19) and never depressed healthy controls (n = 31) matched for age and sex. The outcome measures were pupil dilation (an indirect index of noradrenergic activity and arousal) and computational modeling parameters. Participants completed two versions (facial/nonfacial feedback) of probabilistic reward learning task with changing contingencies. Pupil dilation was measured with a corneal reflection eye tracker. The hypotheses and analysis plan were preregistered. Healthy controls had larger pupil dilation following losses than gains (p <.001), whereas no significant difference between outcomes was found in individuals with a history of MDD, resulting in an interaction between group and outcome (β = 0.81, SE = 0.34, t = 2.37, p = .018). The rMDD group also achieved lower mean score at the last trial (t[46.77] = 2.12, p = .040) as well as a smaller proportion of correct choices (t[46.70] = 2.09, p = .041) compared with healthy controls. Impaired reward processing may persist after remission from MDD and could constitute a latent risk factor for relapse. Measuring pupil dilation in a reward learning task is a promising method for identifying reward processing abnormalities linked to MDD. The task is simple and noninvasive, which makes it feasible for clinical research.

The burden associated with, and management of, difficult-to-treat depression in patients under specialist psychiatric care in the United Kingdom.

Background:Major depressive disorder (MDD) is common and often has sub-optimal response to treatment. Difficult-to-treat depression (DTD) is a new concept that describes ‘depression that continues to cause significant burden despite usual treatment efforts’.Aims:To identify patients with likely DTD in UK secondary care and examine demographic, disease and treatment data as compared with ‘non-DTD’ MDD patients.Methods:Anonymised electronic health records (EHRs) of five specialist mental health National Health Service (NHS) Trusts in the United Kingdom were analysed using a natural language processing model. Data on disease characteristics, comorbidities and treatment histories were extracted from structured fields and using natural language algorithms from unstructured fields. Patients with MDD aged ⩾18 years were included in the analysis; those with presumed DTD were identified on the basis of MDD history (duration and recurrence) and number of treatments prescribed.Results:In a sample of 28,184 patients with MDD, 19% met criteria for DTD. Compared to the non-DTD group, patients with DTD were more likely to have severe depression, suicidal ideation, and comorbid psychiatric and/or physical illness, as well as higher rates of hospitalisation. They were also more likely to be in receipt of unemployment and sickness/disability benefits. More intensive treatment strategies were used in the DTD group, including higher rates of combination therapy, augmentation, psychotherapy and electroconvulsive therapy.Conclusion:This study demonstrates the feasibility of identifying patients with probable DTD from EHRs and highlights the increased burden associated with MDD in these patients.

P244. Enhanced Frontal Midline Theta (fmTheta) Power After Mindfulness Training in Major Depressive Disorder (MDD) Patients Correlates With Improvements in Mindfulness, Depression, and Perceived Stress

Mindfulness based cognitive therapy (MBCT) has been shown effective for individuals with a history of MDD, significantly decreasing depressive episode relapse. These benefits may be related to mindfulness practice-related enhanced capacity for cognitive control, and decreased depressive rumination, and greater attentional engagement with the sensory surround. It is not yet clear what neural mechanisms may facilitate the benefits of mindfulness practice for MDD, however enhanced anterior cingulate cortex (ACC) activity has been demonstrated in previous studies of mindfulness interventions.

P326. Functional Neuroimaging of Remitted Major Depressive Disorder: A Meta-Analysis

Major depressive disorder (MDD) is a mental disorder characterized by abnormalities in brain function. Many neuroimaging studies have also documented abnormalities that persist during remission in individuals with a history of MDD (rMDD). However, these primary studies have reported inconsistent findings, which supports the utility of a meta-analysis to determine which of these neural abnormalities reliably persist in cases of rMDD. The present study seeks to improve our understanding of the neural basis of MDD by determining how neural abnormalities change across depressive states, particularly during remission.

Rhabdomyolysis in Young Adult Male Stabilized on Mirtazapine and with History of COVID-19 Infection

The purpose of this case study is to review the clinical presentation and medical workup of a young adult male presenting with rhabdomyolysis in the setting of suspected contributing factors, including treatment with mirtazapine and history of COVID-19 infection. This case study involves a 19-year-old male in a residential setting with a psychiatric history of major depressive disorder and post-traumatic stress disorder who had been stabilized on mirtazapine for 9months. Then, the patient exhibited fever, sore throat, cough, nausea, diarrhea, and malaise and was diagnosed with COVID-19 infection; he did not require hospitalization, was treated with supportive care, and signs and symptoms resolved uneventfully. Approximately 2months later, in the winter, the patient presented for clinical assessment due to hematuria and painful urination. History revealed that he had been exercising excessively exercising over the past 24hours, completing hundreds of push-ups and sit-ups. The patient presented to a nearby community hospital and was found to have creatine kinase of over 500,000. He was transferred to a large Midwestern university hospital for further evaluation and management. The patient's serum creatine kinase level was found to be 510,000 U/L. Patient's ALT, AST, and alkaline phosphatase were 283, 79, and 76 IU/L, respectively, while creatinine was 0.92. Patient received vigorous hydration, supportive care, and further evaluation. Treatment with mirtazapine was discontinued. The following week he developed severe nausea and vomiting; creatine kinase had decreased to 920, while hepatic function tests remained mildly elevated. Evaluation for hepatitis, cytomegalovirus, and Epstein-Barr virus were negative, as was Wilson's disease and hemochromatosis. Further medical workup for other potential causes of rhabdomyolysis was negative. The patient recovered and is asymptomatic with return to normal lab values. He remains in psychiatric follow-up. The patient's presentation of rhabdomyolysis may have been attributable to multiple factors. Independently, sustained excessive physical activity, COVID-19 infection, and treatment with mirtazapine have all been implicated in the development of rhabdomyolysis. Caution should be taken when prescribing mirtazapine in individuals at higher risk of developing rhabdomyolysis, including those engaged in excessive exercise or who have had COVID-19 infection. No funding.

Case Report: Multiple Courses of Electroconvulsive Therapy for Treatment Resistant Depression in a 68 year old male with a Cardiac Resynchronization Therapy Device with Defibrillator

<h3>Introduction</h3> Background: Electroconvulsive therapy (ECT) has been safely and successfully applied in patients with cardiac pacemakers and implantable cardiac devices, and reviewed in a number of case reports (1, 2). Cardiac Resynchronization Therapy Devices (CRT-D), available with and without defibrillation, benefit patients with Heart Failure with reduced ejection fraction (HfreF) by improving left ventricular function, optimizing ventricular filling, and confers benefits in quality of life and mortality (3). There are currently no case reports on the use of ECT in patients with cardiac resynchronization therapy devices. <h3>Methods</h3> Methods: Patient is a 68-year-old male with a history of major depressive disorder, PTSD, cluster B personality traits who presented in December 2019 for suicidal ideation in the context of a major depressive episode. His medical history is notable for atrial fibrillation on warfarin, DM2 on insulin, non-ischemic cardiomyopathy with HFREF. In 2015, patient's Implantable cardioverter-defribillator (ICD) was replaced with CRT-D. He has a history of 4 previous suicide attempts, most recently four years ago as well as a history of self-injurious behavior. His suicidal ideation on this admission was notable for newly observed command auditory hallucinations telling him to harm himself, suggestive of a mood-congruent psychosis. Patient was started on low-dose risperidone. His other psychotropic medications included bupropion, venlafaxine, and gabapentin with multiple failed medication trials in the past. Patient's initial MADRS was 30 on admission scoring highly for suicidal ideation. After initiation of risperidone, patient's MADRS lowered to 16 prior to first ECT session. Prior to ECT, anesthesia, cardiology, and electrophysiology were consulted. Patient's CRT-D device was interrogated and determined to be functioning and patient was medically optimized for ECT from cardiology standpoint. His ejection fraction was 30% approximately 6 months earlier. Anesthesia expressed concern about management of sympathetic and parasympathetic response to ECT. <h3>Results</h3> Results: Prior to first session, Electrophysiology reprogrammed device and patient had defibrillator pads placed. A brief seizure was achieved. Due to no observed bradycardia after first session, the electrophysiologist recommended patient can undergo further ECT with placement of magnet on CRT-D to disable defibrillator. For the following 3 sessions, an adequate seizure was obtained. Patient reported robust response with MADRS of 6 reported prior to his second session. During ECT therapy, patient underwent echocardiogram which indicated ejection fraction of 20-25%. Cardiology was again consulted and felt patient could continue with ECT if euvolemic and asymptomatic. After 4^th session, a collaborative decision was made with patient to forego further ECT given patient's improvement in mood. Patient returned for another course of 3 sessions of ECT 8 months later and one maintenance session 9 months later. For these sessions, a magnet was used exclusively to disable fibrillator with robust effect on depressive symptoms. <h3>Conclusions</h3> Conclusion: This case indicates ECT can be provided safely to patients with a CRT-D device over an extended period of time; placing device in electrocautery mode with defibrillator pads as well as disabling defibrillator function with a magnet both proved effective methods to provide ECT safely. Further study of ECT in patients with CRT is warranted, in particular, to observe patients who complete a number of sessions more typical in treatment resistant depression. ECT in patients with CRT-P devices have not been reported. <h3>This research was funded by</h3> none

Prevalence of mental health outcomes and effects of sex and mood or cognitive comorbidity in older adults during the COVID-19 pandemic

IntroductionOlder adults are at greater risk for developing severe illness from SARS-COV2 infection and may be more vulnerable to negative mental health outcomes as a result of public health guidelines that increase social isolation. In the current study, we assessed mental health outcomes in a cohort of older adults with normal cognition (NC), past history of major depressive disorder (i.e., remitted; rMDD), or mild cognitive impairment (MCI) to determine the prevalence of clinically significant symptoms of depression, anxiety, general stress, and post-traumatic stress. Additionally, we assessed the effects of mood or cognitive diagnosis and sex on symptom severity. Based on the pre-pandemic literature, we predicted that the presence of rMDD or MCI diagnosis would be associated with increased severity of psychiatric symptoms during the COVID-19 pandemic. We also predicted that women would experience greater severity of psychiatric symptoms compared to men.MethodsThe study included 108 older adults (37 males, mean age=72.1 years) who were participating in existing longitudinal studies. The sample included 71 older adults with normal cognition (NC) based on normal neuropsychological test performance and who were free of lifetime history of psychiatric illness, 21 rMDD participants based on DSM5 criteria, and 16 MCI participants based on the presence of memory concerns, impaired performance on neuropsychological assessments, and intact functional independence. Participants completed self-report measures of depression, anxiety, and stress through video- or teleconferencing with a research assistant. Measures included the Patient Health Questionnaire-9 (PHQ-9) to assess depression, the Patient-Reported Outcomes Measurement Information System (PROMIS) to measure anxiety, the Perceived Stress Scale (PSS) to measure stress, and the Impact of Events Scale-Revised (IES-R) to assess post-traumatic stress symptoms. Prevalence rates of clinically significant psychiatric symptoms were expressed as the percentage of participants with total scores that exceed the normal cut-offs for each respective measure. Separate MANOVAs were used to examine the effects of diagnosis and sex. Non-normally distributed data (PHQ-9 and PROMIS total scores) were rank-transformed and entered into MANOVA.ResultsWithin the sample of 108 participants, 33.7% exceeded the normal cut-off on the PHQ-9, 31.3% had clinically significant anxiety symptoms on the PROMIS-Anxiety, 35.5% had clinically significant stress scores on the PSS, and 38.3% had clinically significant post-traumatic stress scores on the IES-R. MANOVA showed statistically significant effects of diagnosis on all measures: PHQ-9 [F(2,90)=5.380, p=.006], PROMIS-Anxiety [F(2,90)=11.687, p<.001], PSS [F(2,90)=8.480, p<.001], and IES-R [F(2,90)=5.027, p=.009]. MDD participants scored higher on all measures compared to NC participants: PHQ-9 (p=.005), PROMIS-Anxiety (p<.001), PSS (p<.001), and IES-R (p=.004). In addition, MCI participants scored higher on the PSS compared to NC participants (p=.035). MANOVA showed significant effects of sex on all measures: PHQ-9 [F(1,91)=7.046, p=.009], PROMIS-Anxiety [F(1,91)=8.623, p=.004], PSS [F(1,91)=12.553, p<.001], and IES-R [F(1,91)=10.529, p=.002] such that women scored higher on all measures compared to men.ConclusionsOverall, over one-third of study participants reported clinically significant symptoms of depression, anxiety, general stress, and post-traumatic stress during the COVID-19 pandemic. These rates are higher than those described in population studies of older adults based on anonymous online surveys, which are reported to be 24.9% for depression, 19.4% for anxiety, 10.3% for stress, and 28.3% for post-traumatic stress; but are comparable to the prevalence rates of psychiatric symptoms in the general adult population. As predicted, presence of rMDD increased the severity of all psychiatric symptoms. However, MCI was also associated with increased stress compared to those with normal cognition, despite absence of current or past psychiatric illness. These findings suggest that older adults with previous depression or current MCI, as well as women overall, are particularly vulnerable to developing clinically significant psychiatric symptomatology during the COVID-19 pandemic. Limitations of the current study are the inclusion of participants in existing studies, as opposed to sampling from the general population and the relatively small sample size. Nevertheless, the current findings suggest that some clinical populations, including those with rMDD and MCI, as well as women overall, may benefit from receiving interventions for mental health during the current and future pandemics.This research was funded byThis study was funded by the Ontario Ministry of Health and Long-Term Care Alternative Funding Plan. The funders had no role in the design of the study, analysis, or preparation of the manuscript.

"Am I Not Allowed to be Comfortable?" The Doubled Edged Sword of Benzodiazepine Prescriptions in Older Adults

<h3>Introduction</h3> The treatment of anxiety, panic, depression, and insomnia symptoms in late life pose many challenges. The use of benzodiazepines for these symptoms offers often rapid relief in some domains but clearly poses risks. Second only to opioids, benzodiazepine prescriptions have become a major focus of public health concern and scrutiny. The use of electronic data base reporting and FDA warnings regarding abuse potential and withdrawal have lead to a movement to both deprescribe and not initiate benzodiazepine treatment in older adults. It is clear that concerns regarding side effects of falls, fractures, acute and chronic confusional states, abuse potential and drug-drug interactions are of great concern to clinicians. Patients often cite concerns regarding tapering of these agents including fear of relapse of anxiety and panic and a wish to maintain feelings of comfort with what is percieved as a stable medication regime in their advanced years of life. A challenge to clinicians is to work with aging patients over a treatment plan which balances medication safety with the therapuetic benefits of these agents. Management of older adults who have been treated chronically, often for many decades, with benzodiazepines poses a significant challenge. Many community providers no longer want to care for these patients and as a result, they present to hospital based clinics with stigma and disappointment over prior treatment. <h3>Methods</h3> Cases were identified from the patient population at Mount Sinai Beth Israel, an urban medical center serving a multicultural and socioeconomically diverse population. Mount Sinai Beth Israel has been serving the popultaion of Manhattan since 1889 and provides comprehensive behavioral health care services. Patients were identified from those who presented to the ambulatory care geriatric psychiatry service with care needs that included chronic benzodiazepine use. <h3>Results</h3> Case presentations: Ms. A: A 69 year old woman with history of Generalized Anxiety Disorder and Dysthymia whopresented for treatment after her long-term provider could no longer see her. Medication regime includes Citalopram 40mg once daily, Clonazepam 2.5mg daily in divided doses, Gabapentin 400mg daily in divided doses and Zolpidem 10mg at bedtime. The patient presents with complaints of nervousness and anxiety which impair her function. She is resistive toward any changes in her regime and also she is reluctant to engage in psychotherapy. Ms. B: A 69 year old woman has been enrolled in the clinic for many years. She has a history of Generalized Anxiety Disorder, Panic Disorder, Alcohol Use Disorder in sustained remission and Opioid Use Disorder in remission on Methadone 45mg daily. The patient has been treated with Mirtazapine 60mg at bedtime, Clonazepam 1mg three times daily and Gabapentin 200mg at bedtime. Her course has been complicated by her goal of ending her Opioid Treatment Program and undergoing a taper of her Methadone dose over time. She presents with many complaints of anxiety, abdominal pain and GI upset. While she is able to describe a history of significant childhood trauma and abuse, engaging in truama focused care has been a challenge and her visits focus on dose increases in current medications. Ms. C: A 70 year old woman with a history of Major Depressive Disorder and Generalized Anxiety Disorder has been stable for many years. He current medication regime incldues Venlafaxine 100mg daily, Gabapentin 100mg daily and Clonazepam 0.75mg daily in divided doses. The patient is very devoted to her medication regime, with specific times of the day when she takes her pills and how she divides the Clonazepam doses. She explains that she is very satisifed with this regime, has tolerated reduction from a higher does of Clonazepam in the past and feels does not want to risk any relapse at present. <h3>Conclusions</h3> The risk potential of benzodiazepines is exponentially higher in geriatric patients compared to younger adults. This does not imply that these medications should always be discontinued among those who have been treated chronically. It is clear that despite Beers Criteria inclusion and FDA warnings, patients and providers both have difficulties making long term treatment plans regarding individual risk verus benefit decisions. A finding from our hospital-based clinic population includes an increasing number of patients who enter treatment after prior providers have refused to continue prescribing controlled substances. This fracture in a prior relationship creates greater challenges in fostering the therapuetic alliance necessary to gain trust, offer adjuntive therapies and adequately discuss medication risks and benefits. Finding the best balance for the patient in mitigating risk while maintaining quality of life requires individual assessment and shared treatment goals. We want to reduce polypharmacy, maintain patient comfort and safety with a focus on harm reduction. <h3>This research was funded by</h3> Mount Sinai Beth Israel Department of Psychiatry

Familial aggregation and shared genetic loading for major psychiatric disorders and type 2 diabetes.

Psychiatric disorders, such as schizophrenia (SCZ), major depressive disorder (MDD) and bipolar disorder (BPD), are highly comorbid with type 2 diabetes. However, the mechanisms underlying such comorbidity are understudied. This study explored the familial aggregation of common psychiatric disorders and type 2 diabetes by testing family history association, and investigated the shared genetic loading between them by testing the polygenic risk score (PRS) association. A total of 105,184 participants were recruited from the Taiwan Biobank, and genome-wide genotyping data were available for 95,238 participants. The Psychiatric Genomics Consortium-derived PRS for SCZ, MDD and BPD was calculated. Logistic regression was used to estimate the OR with CIs between a family history of SCZ/MDD/BPD and a family history of type 2 diabetes, and between the PRS and the risk of type 2 diabetes. A family history of type 2 diabetes was associated with a family history of SCZ (OR 1.23, 95% CI 1.08, 1.40), MDD (OR 1.19, 95% CI 1.13, 1.26) and BPD (OR 1.26, 95% CI 1.15, 1.39). Compared with paternal type 2 diabetes, maternal type 2 diabetes was associated with a higher risk of a family history of SCZ. SCZ PRS was negatively associated with type 2 diabetes in women (OR 0.92, 95% CI 0.88, 0.97), but not in men; the effect of SCZ PRS reduced after adjusting for BMI. MDD PRS was positively associated with type 2 diabetes (OR 1.04, 95% CI 1.00, 1.07); the effect of MDD PRS reduced after adjusting for BMI or smoking. BPD PRS was not associated with type 2 diabetes. The comorbidity of type 2 diabetes with psychiatric disorders may be explained by shared familial factors. The shared polygenic loading between MDD and type 2 diabetes implies not only pleiotropy but also a shared genetic aetiology for the mechanism behind the comorbidity. The negative correlation between polygenic loading for SCZ and type 2 diabetes implies the role of environmental factors.

Relationship of the balloon analog risk task to neurocognitive impairment differs by HIV serostatus and history of major depressive disorder

HIV and major depressive disorder (MDD) commonly co-occur and are both linked to greater risk-taking behavior, possibly due to neurocognitive impairment (NCI). The present study examined the concordance of the Balloon Analog Risk Task (BART), a gold standard measure of risk-taking propensity, with NCI and real-world sexual risk behaviors in PWH with comorbid MDD. Participants included 259 adults, stratified by HIV serostatus (HIV + /HIV −) and lifetime MDD (MDD + /MDD −), who completed neuropsychological testing, the BART, and sexual risk behavior questionnaires. Logistic regression, stratified by HIV serostatus, examined joint effects of MDD and BART (linear and quadratic) on NCI. Follow-up linear regressions examined sexual risk behavior and neurocognitive domain T-scores as correlates of the BART. NCI prevalence was lowest in HIV − /MDD − , but BART scores did not differ by HIV/MDD status. In the HIV + group, BART performance predicted NCI such that high and low BART scores related to greater odds of NCI, but only in dual-risk HIV + /MDD + individuals. HIV + /MDD + individuals with both low and high BART scores exhibited poorer learning and recall, whereas processing speed and executive function were only poor in low BART risk-taking HIV + /MDD + . Higher BART scores linearly related to higher sexual risk behaviors only in MDD + individuals, independent of HIV serostatus. Low and high risk-taking on the BART may reflect discrete neurocognitive profiles in HIV + /MDD + individuals, with differential implications for real-world sexual risk behavior. HIV and comorbid MDD may disturb corticostriatal circuits responsible for integrating affective and neurocognitive components of decision-making, thereby contributing to risk-averse and risk-taking phenotypes.

Depressive symptoms and neuroticism-related traits are the main factors associated with wellbeing independent of the history of lifetime depression in the UK Biobank.

Wellbeing has a fundamental role in determining life expectancy and major depressive disorder (MDD) is one of the main modulating factors of wellbeing. This study evaluated the modulators of wellbeing in individuals with lifetime recurrent MDD (RMDD), single-episode MDD (SMDD) and no MDD in the UK Biobank. Scores of happiness, meaningful life and satisfaction about functioning were condensed in a functioning-wellbeing score (FWS). We evaluated depression and anxiety characteristics, neuroticism-related traits, physical diseases, lifestyle and polygenic risk scores (PRSs) of psychiatric disorders. Other than individual predictors, we estimated the cumulative contribution to FWS of each group of predictors. We tested the indirect role of neuroticism on FWS through the modulation of depression manifestations using a mediation analysis. We identified 47 966, 21 117 and 207 423 individuals with lifetime RMDD, SMDD and no MDD, respectively. Depression symptoms and personality showed the largest impact on FWS (variance explained ~20%), particularly self-harm, worthlessness feelings during the worst depression, chronic depression, loneliness and neuroticism. Personality played a stronger role in SMDD. Anxiety characteristics showed a higher effect in SMDD and no MDD groups. Neuroticism played indirect effects through specific depressive symptoms that modulated FWS. Physical diseases and lifestyle explained only 4-5% of FWS variance. The PRS of MDD showed the largest effect on FWS compared to other PRSs. This was the first study to comprehensively evaluate the predictors of wellbeing in relation to the history of MDD. The identified variables are important to identify individuals at risk and promote wellbeing.

Maladaptive blame-related action tendencies are associated with vulnerability to major depressive disorder

Biases towards self-blaming emotions, such as self-contempt/disgust, were previously associated with vulnerability to major depressive disorder (MDD). Self-blaming emotions are thought to prompt specific action tendencies (e.g. “feeling like hiding”), which are likely to be more important for psychosocial functioning than the emotions themselves. Systematic investigations, however, of these action tendencies in MDD are lacking. Here, we investigated the role of blame-related action tendencies for MDD vulnerability and their relationship with blame-related emotions. 76 participants with medication-free remitted MDD and 44 healthy control (HC) participants without a history of MDD completed the value-related moral sentiment task, which measured their blame-related emotions during hypothetical social interactions and a novel task to assess their blame-related action tendencies (feeling like hiding, apologising, creating a distance from oneself, attacking oneself, creating a distance from other, attacking other, no action). As predicted, the MDD group showed a maladaptive profile of action tendencies: a higher proneness to feeling like hiding and creating a distance from themselves compared with the HC group. In contrast, feeling like apologising was less common in the MDD than the HC group. Apologising for one's wrongdoing was associated with all self-blaming emotions including shame, guilt, self-contempt/disgust and self-indignation. Hiding was associated with both shame and guilt. Our study shows that MDD vulnerability was associated with specific maladaptive action tendencies which were independent of the type of emotion, thus unveiling novel cognitive markers and neurocognitive treatment targets.