History Of Major Depressive Disorder Research Articles

Impact of major depressive disorder on breast cancer outcomes: a national retrospective cohort study.

Establishing whether women with major depressive disorder (MDD) who develop breast cancer (BC) have poor outcomes is key to optimizing care for this population. To address this, we examined associations between MDD and BC recurrence and mortality. Using medical record data from the Veterans Affairs Healthcare System, we established a retrospective cohort of women with local or regional stage invasive BC between 2010 and 2019 and followed through 2022. We used a two-year window to identify women diagnosed with MDD prior to BC diagnosis. We used multivariable Cox-proportional hazards regression to estimate associations between MDD and BC recurrence and mortality while accounting for competing-risks and adjusting for sociodemographic, clinical, lifestyle, and tumor characteristics. We identified 6,051 women with BC, of whom 1,754 (29%) had MDD. The mean age at BC diagnosis was 57 years (standard deviation = 11). In multivariable analyses, women with MDD had a 37% (hazard ratio (HR)=1.37; 95% confidence interval (CI): 1.19-1.57) higher risk of recurrence and a 30% (HR = 1.30; 95% CI: 1.02-1.64) higher risk of BC mortality. The association between MDD and recurrence was stronger among women with estrogen receptor-positive BC. In secondary analyses, there were significant interactions between MDD and multiple exposures with respect to recurrence, including current smoking, substance abuse, and non-receipt of screening mammography. Women with MDD had inferior BC outcomes compared to women without a history of MDD. Research is needed to investigate underlying mechanisms linking depression to BC progression and evaluate interventions to improve outcomes in this high-risk population.

Genetic association of the kynurenine pathway to suicidal behavior

Suicidal behavior has been associated with dysfunctions in the kynurenine pathway, including alterations in the levels of neuroprotective and neurotoxic metabolites. Changes in the catalytic activity of enzymes within the pathway may contribute significantly. Variations in the genes encoding enzymes within the pathway can significantly affect their catalytic activity, playing a crucial role in the process. To explore this possibility, we hypothesized that these genetic variations would occur more frequently in patients with a history of suicidal behavior compared to non-suicidal individuals. Thus, we investigated the relationship between a history of suicide attempts and five single nucleotide polymorphisms (SNPs) within genes involved in the kynurenine pathway: IDO1 (rs7820268), IDO2 (rs10109853), KMO (rs1053230), KAT1 (rs10988134), and ACSMD (rs2121337). Our sample comprised 849 subjects: 325 individuals who had attempted suicide in their lifetime (SAs), 99 individuals with a history of major depression disorder but no previous suicide attempts (non-SAs), and 425 non-psychiatric controls (CTRL). We performed SNP association analyses using codominant, dominant, and recessive models. Adjustment for sex and multiple comparisons was applied. After adjustment, the analysis revealed that SAs showed a significantly higher frequency of T alleles and TT genotypes of the rs1053230 SNP compared to CTRL across nearly all models. Furthermore, in the recessive model, non-SAs displayed a higher prevalence of the TT genotype of the rs10109853 SNP compared to CTRL.The rs1053230 and rs10109853 SNPs could play a role in the previously observed metabolic dysregulation among SAs and non-SAs, respectively. To validate our findings, it is crucial to conduct functional analyses to investigate the impact of rs10109853 and rs1053230 SNPs on the expression and/or catalytic activity of the corresponding enzymes.

Acute Self-Harm Ideation as Presenting Adverse Event Associated with Adalimumab Treatment of Severe Scalp Psoriasis

We present a case of a 34-year-old woman with severe scalp psoriasis who developed acute self-harm ideations and major depressive symptoms shortly after initiating adalimumab treatment. The patient had a history of major depressive disorder, post-traumatic stress disorder, and anxiety, all well-controlled with multiple medications. Following the administration of adalimumab, she experienced intrusive thoughts of self-harm and exacerbation of depressive symptoms, prompting immediate discontinuation of the drug. The patient's symptoms resolved completely three weeks after discontinuation. This case highlights the potential psychiatric risks associated with adalimumab therapy for psoriasis, especially in patients with preexisting mental health conditions. Dermatologists should carefully evaluate patients for psychiatric disorders and suicide risk factors before initiating treatment and be vigilant in monitoring for adverse psychiatric events during therapy. Proper counseling and prompt identification of adverse events are crucial to prevent serious outcomes.

Prospective Relations Between Inferential Styles and Depressive Symptoms Among Children of Mothers with Major Depression

ABSTRACT Objective Current models of depression risk in children include both family history and cognitive models of risk; however, these models are rarely integrated. This study aimed to address this gap by examining how cognitive vulnerabilities featured in the hopelessness theory of depression – negative inferential styles for the causes, consequences, and self-characteristic implications of negative events – may increase risk for the intergenerational transmission of depression. Specifically, we examined whether children of mothers with a history of major depressive disorder (MDD), compared to children of never-depressed mothers, exhibit more negative inferential styles and whether maternal history of MDD moderates prospective relations between children’s inferential styles and depressive symptoms. Method Participants were 251 children (ages 8–14 at baseline; 51% girls; 81% Non-Hispanic White) of mothers with (n = 129) or without (n = 122) a history of MDD. Children’s inferential styles and depressive symptoms were assessed at baseline and then every 6 months for 2 years. Results Using random intercept cross-lagged panel models (RI-CLPMs), we found that children of mothers with a history of MDD, compared to children of never-depressed mothers, had more negative inferential styles for the causes and consequences of negative events, but not for self-characteristics, and higher depressive symptom levels, across the follow-up. In addition, there were reciprocal, transactional relations between children’s inferential styles for causes and their depressive symptoms across the follow-up, with no evidence for moderation by maternal MDD. Conclusions Children’s inferential styles for the causes of negative events may be a useful marker of risk for the intergenerational transmission of depression, which could be targeted to reduce risk for depression.

12586 A Case Of Ventricular Fibrillation In Thyroid Storm

Abstract Disclosure: A.A. Luzuriaga Chavez: None. N. Aamir: None. J.P. Hidalgo: None. A. Rao: None. N. Patel: None. Thyrotoxicosis is a life-threatening condition caused by an excessive level of circulating thyroid hormones. It can lead to high mortality and morbidity, even if diagnosed and treated in its early stages. Symptoms can include fever, irritability, tachycardia, diarrhea, and seizures. Levothyroxine is a medication commonly used for hypothyroidism, but cases of acute overdose have been reported worldwide. This is a case of a 55-year-old woman who was admitted after a cardiac arrest caused by a possible overdose of 8 mg of levothyroxine. Case presentation:A 55-year-old woman with a history of major depressive disorder was found unconscious by her boyfriend next to a bottle of levothyroxine (which contained a 3-month supply) and was rushed to the emergency department (ED) by EMS. According to the patient's medical chart and family, she did not have a history of hypothyroidism. In the field, she suffered a V-fib cardiac arrest but was successfully resuscitated and brought to the ED. However, she had another cardiac arrest upon arrival but was revived again after 20 minutes. During the physical examination, the patient did not exhibit any signs of thyroid enlargement, exophthalmos, or jaundice. The initial electrocardiogram showed concerning signs of ST-elevation myocardial infarction so the patient was started on heparin drip and continuing amiodarone. The patient was then transferred to the ICU for post-arrest care. Bloodwork revealed TSH <0.005, T3 15.74, and T4 1.57. The Burch-Wartofsky point scale indicated a score of 55, which is consistent with a high suspicion of thyroid storm. The patient's condition continued to worsen, with increasing vasopressor requirements and hyperthermia. Despite the amiodarone drip, the patient's heart rate continued to be less than 100 beats per minute, propranolol could not be started. Furthermore, the patient started bleeding from the nasogastric tube, and the medical team was unable to start any oral propylthiouracil or methimazole. Consequently, they administered hydrocortisone 300 mg, followed by 100mg every 8 hours. The patient was transitioned to comfort care measures. Discussion:Massive ingestion of levothyroxine can lead to excessive thyroid hormone levels and cause sympathetic excitation.Reports of adults ingesting levothyroxine are rare, and those who do generally experience more severe symptoms such as cardiac arrhythmias, malignant hyperthermia, and renal failure. Excessive thyroid hormone levels lead to increased beta adrenergic receptors within the myocardium, rendering it more susceptible to both vagal and sympathetic stimulation. A few isolated case reports show thyrotoxicosis was associated with ventricular fibrillation. Thyroid storm can occur a few days after an overdose of levothyroxine. However, in this case, the patient developed thyrotoxicosis within 6 to 8 hours of ingestion, making it an interesting case to study. Presentation: 6/1/2024

Excessive propagation of right frontal beta oscillations in patients with a history of major depressive disorder

Excessive propagation of right frontal beta oscillations in patients with a history of major depressive disorder

Proteogenomic signature of risk of Alzheimer's disease and related dementia risk in individuals with a history of major depression disorder.

The mechanisms linking a history of major depressive disorder (MDD) to an increased risk of Alzheimer's disease and related dementia (ADRD) are not fully understood. Using the UK Biobank available proteomic and genomic data, we evaluated the biological mechanisms linking both conditions. In participants with a history of MDD at baseline (n=3,615), we found that plasma levels of NfL, GFAP, PSG1 were associated with higher risk (HR=1.38; 1.37; 1.34, respectively; all adjusted p-values<0.05), while VGF, GET3, and HPGDS were associated with lower risk of incident ADRD (n=150) (HR=0.73; 0.71; 0.66, respectively; all adjusted p-values<0.05) during a mean follow-up of 13.7 years (SD=2.2). Two-sample Mendelian randomization analysis using cis-pQTLs genetic instruments revealed that a lower protein expression of apolipoprotein E and higher IL-10 receptor subunit B were causally linked to incident ADRD. Finally, we developed a Proteomic Risk Score (PrRSMDD-ADRD), which showed strong discriminative power (C-statistic = 0.84) to identify participants with MDD that developed ADRD upon follow-up. In addition to demonstrating an association between plasma proteins associated with inflammation and future ADRD risk in individuals with MDD, our findings include an element of causality using Mendelian Randomization (MR) and PrRSMDD-ADRD can be useful to identify individuals with the highest risk to develop ADRD in a highly vulnerable population.

How I think about how I feel: Personal beliefs about emotion prospectively predict suicide-related outcomes and depression symptoms

One transdiagnostic process that may be critical to depression and suicidal ideation is beliefs about the nature of one's own emotions, both concurrently and longitudinally. In a sample of community adults (n = 143), we assessed personal emotion beliefs about the degree to which one's own emotions are malleable, unique, and last a long time. There were significant associations between stronger views that one's own emotions were fixed, unique to you, and had a longer duration and higher clinical symptom severity, including higher levels of current suicidal ideation, and less adaptive emotion regulation. Mediation analyses using longitudinal data clarified that the differential engagement in emotion regulation, specifically rumination, represented the link tying specific personal emotion beliefs to clinical symptoms and that, in certain cases, the opposite pathway is also significant – differences in clinical symptoms mediated the relationship between specific personal emotion beliefs and emotion regulation (rumination) longitudinally. Additionally, personal emotion beliefs varied based on depression status, as determined using a semi-structured clinical interview. For example, individuals meeting current criteria for Major Depressive Disorder (MDD) held stronger views that their emotions were unique to them compared to individuals with remitted MDD or no history of MDD. The current study's findings highlight the important role of specific personal emotion beliefs in clinical symptoms concurrently and longitudinally and mechanisms in these relationships. These results could guide future research on interventions to promote more adaptive beliefs about emotion to improve clinical outcomes.

A Three-way Attack on the Gastrointestinal System- COVID-19, Ehler-Danlos Syndrome, and Anorexia Nervosa Leading to Severe Gastroparesis in a Young Female

A 28-year-old female with a past medical history of Major Depressive Disorder, Generalized Anxiety Disorder, Anorexia Nervosa, Chronic Pain Syndrome, and Gastro-esophageal Reflux presented to our clinic for establishing care in November 2022 with severe gastric dysmotility ever since contracting COVID-19 virus in December 2021. The patient’s symptoms were refractory to Erythromycin and metoclopramide therapy. A GI motility study in February 2022 showed delayed gastric emptying based on which the patient was diagnosed with Post COVID Gastroparesis. Based on an extensive clinical review of the patient’s past medical and surgical history, the patient was found to have cumulative symptoms of GERD, joint instability, abdominal hernia and chronic neuropathic pain, raising the suspicion of Ehler-Danlos syndrome- Hypermobility type. Given the failure of treatment with prokinetic agents and over 60 pounds of weight loss the patient underwent Percutaneous Endoscopic Gastrostomy-Jejunostomy in August 2022, the patient was started on Organic Tube Feeding Formula. To this date, the patient is using the PEG-J for feeding and remains nil per oral. Multiple trials of reintroducing oral feeding have been attempted but the patient still is unable to tolerate oral feeds completely and continues to complain of early satiety, nausea, and vomiting on reintroducing feeds.

Psychological state at the time of psychiatric genetic counseling impacts patient empowerment: A pre-post analysis.

Psychiatric genetic counseling (GC) has been associated with patient-reported increases in empowerment (perceived control, emotional regulation, and hope). We sought to evaluate the extent to which patients' psychological state at the time of GC is related to changes in empowerment. Participants with a history of major depressive disorder and/or bipolar disorder that had been refractory to treatment underwent psychiatric GC remotely from 2022 to 2023. GC was performed by four genetic counselors and included discussion of perceived causes of illness, multifactorial inheritance, and protective factors. Empowerment, depression, and anxiety were measured immediately prior to GC via online survey by the GCOS-16, PHQ-9, and GAD-7, respectively. Empowerment was re-assessed 2 weeks later. In total, 66/161 (41.0%) invited individuals completed both the baseline and follow-up surveys. Participants completing both surveys were 54.6% female, 84.8% white, and ranged in age from 22 to 78 years (mean = 54.8 years). Overall, a significant change in mean empowerment was not observed (p = 0.38); however, there were moderating effects by baseline psychological state. A multiple linear regression model incorporating PHQ-9, GAD-7 and baseline GCOS-16 score predicted change in empowerment with a large effect (F = 5.49, R2 = 0.21, p < 0.01). A higher score on the PHQ-9 was associated with decreases in empowerment from pre to post GC. Higher scores on the GAD-7 and lower baseline GCOS-16 scores were associated with increases in empowerment. Further, two-way ANOVA was conducted to assess change in empowerment between subgroups based on the level of anxiety and depression. Those with low depression and high anxiety reported significant increases in empowerment (F = 6.64, p = 0.01). These findings suggest that psychiatric GC may be especially helpful to individuals experiencing anxiety and low baseline empowerment. Alternative approaches may be needed to best meet the needs of those experiencing significant depression.

The mind wanders to dark places: Mind-wandering catalyzes rumination in the context of negative affect and impulsivity.

Spontaneous mind-wandering has been theorized to increase susceptibility for rumination, contributing to risk for major depressive disorder (MDD). Clarifying whether-and under what circumstances-mind-wandering leads to rumination could inform the development of targeted interventions to reduce risk for ruminative sequelae. Using intensively sampled data in 44 young adults with remitted MDD and 38 healthy volunteers with 1,558 total observations collected from 2018 to 2022, we conducted multilevel models to investigate temporal relationships between mind-wandering and rumination. Contextual factors (e.g., intensity of negative affect; momentary impulsivity) and individual factors (e.g., MDD history) were examined as moderators of these relationships. Mind-wandering predicted increased rumination, whereas rumination did not predict increased mind-wandering. When individuals experienced greater negative affect or acted more impulsively compared to their usual levels, they showed a stronger relationship between mind-wandering and subsequent rumination. Depression history did not significantly moderate temporal relationships between mind-wandering and rumination. Spontaneous mind-wandering may transition into rumination, particularly during moments when people experience more negative affect or impulsivity compared to usual. Delivering interventions in these moments could reduce risk for ruminative sequelae. The tendency to ruminate in response to mind-wandering is suggested to be consistent regardless of depression history, suggesting the transdiagnostic and dimensional nature of rumination as a possible consequence of mind-wandering. Future work is needed to determine whether these associations are generalizable across the lifespan. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Association between fatigue and depressive symptoms in persons with post-COVID-19 condition: a post hoc analysis

Objective Post-COVID-19 Condition (PCC) is a prevalent, persistent and debilitating phenomenon occurring three or more months after resolution of acute COVID-19 infection. Fatigue and depressive symptoms are commonly reported in PCC. We aimed to further characterize PCC by assessing the relationship between fatigue and depressive symptom severity in adults with PCC. Methods A post hoc analysis was conducted on data retrieved from a randomized, double-blinded, placebo-controlled study evaluating vortioxetine for cognitive deficits in persons with PCC. We sought to determine the relationship between baseline fatigue [i.e. Fatigue Severity Scale (FSS) total score] and baseline depressive symptom severity [i.e. 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR-16) total score] in adults with PCC. Results The statistical analysis included baseline data from 142 participants. After adjusting for age, sex, education, employment status, history of major depressive disorder (MDD) diagnosis, self-reported physical activity, history of documented acute SARS-CoV-2 infection and body mass index (BMI), baseline FSS was significantly correlated with baseline QIDS-SR-16 (β = 0.825, p = .001) Conclusion In our sample, baseline measures of fatigue and depressive symptoms are correlated in persons living with PCC. Individuals presenting with PCC and fatigue should be screened for the presence and severity of depressive symptoms. Guideline-concordant care should be prescribed for individuals experiencing clinically significant depressive symptoms. Fatigue and depressive symptom severity scores were not pre-specified as primary objectives of the study. Multiple confounding factors (i.e. disturbance in sleep, anthropometrics and cognitive impairment) were not collected nor adjusted for in the analysis herein. Trial registration Unrestricted Research Grant from H. Lundbeck A/S, Copenhagen, Denmark. ClinicalTrials.gov Identifier: NCT05047952

Perioperative Patient-Initiated Communication in Gender-Affirming Mastectomy.

Background: Gender-affirming mastectomy (GAM) improves the psychosocial functioning and quality of life of transgender and non-binary (TGNB) individuals. However, the perioperative period is often marked by emotional stress, concerns about surgical outcomes, and physical discomfort. While inpatient procedures provide multiple opportunities to engage with and educate patients, outpatient surgeries, such as GAM, pose a unique challenge as patients are followed for <24 h postoperatively. Given the heightened emotional and psychological distress related to gender dysphoria TGNB individuals often experience, addressing these gaps can significantly improve outcomes. This study aims to characterize patient and surgical characteristics associated with patient-initiated communication (PIC) frequency in this population. Methods: A single-center retrospective review of TGNB patients undergoing GAM from February 2018 to November 2022 was conducted. Demographics, surgical characteristics, and frequency of and reasons for perioperative PIC (30 days before and after surgery) were recorded. The primary outcome was the incidence of perioperative PIC. The secondary outcomes included (1) the rationale for PIC and (2) patient and surgical characteristics associated with PIC. Results: A total of 352 patients were included. Of these, 285 (74.6%) initiated communication in the perioperative period, totaling 659 PICs. The median age was 25.0 (interquartile range [IQR]: 9.0) years. The median body mass index (BMI) was 28.5 (IQR: 8.5) kg/m2. The mean number of PICs was 0.7 ± 1.3 preoperatively and 1.3 ± 1.7 postoperatively (p < 0.001). The most frequent preoperative PIC subjects were administrative issues (AI; n = 66, 30.7%), preoperative requirements (n = 43, 20.0%), and cost and insurance (n = 33, 15.0%). The most frequent postoperative PIC subjects were wound care (n = 77, 17.3%), AI (n = 70, 15.0%), activity restrictions (n = 60, 13.5%), drainage (n = 56, 12.6%), and swelling (n = 37, 8.3%). Collectively, older patients (β = 0.234, p = 0.001), those with a history of major depressive disorder or generalized anxiety disorder (2.4 ± 3.0 vs. 1.7 ± 1.9; p = 0.019), and those without postoperative drains (n = 16/17, 94.1% vs. n = 236/334, 70.7%; p = 0.025) engaged in higher levels of PIC. There were no significant associations between other patient characteristics, perioperative details, or complications and PIC frequency. Conclusions: Perioperative PIC is prevalent among the majority of GAM patients at our institution, with age, psychiatric diagnosis, and postoperative drain use identified as significant predictors. To mitigate PIC frequency, it is crucial to ensure adequate support staffing and provide comprehensive postoperative instructions, particularly concerning activity restrictions and drainage management. These interventions may reduce PICs in high-volume centers. Further research should investigate targeted interventions to further support TGNB patients during the perioperative period.

Vocal Emotional Expressions in Mothers with and without a History of Major Depressive Disorder

Vocal Emotional Expressions in Mothers with and without a History of Major Depressive Disorder

Serotonin Syndrome Following Low-Dose Sertraline: A Case Report

IntroductionSerotonin syndrome is a potentially life-threatening condition that is precipitated by the use of serotonergic medications, Selective Serotonin Reuptake Inhibitors (SSRIs) and Monoamine Oxidase Inhibitors (MAOIs). It usually occurs when high doses of serotonergic drugs are prescribed. It is a medical emergency that requires prompt recognition, cessation of offending drugs and supportive therapy.ObjectivesWe present a case of serotonin syndrome that occurred in a patient who was prescribed a low dose of sertraline, and aim to highlight the importance of early detection of this severe condition.MethodsDetails of the case were described. Information was gathered based on medical records.Results Patient M was a 29-year-old Malay male with a history of major depressive disorder, who was previously trialed on fluvoxamine 100mg every night but subsequently switched to and maintained on sertraline 75mg every night in 2020. He then defaulted follow up appointments. In 2023, he presented to the emergency services for a suicide attempt and was diagnosed with major depressive disorder with psychotic features. He was restarted on sertraline 50mg every night and risperidone 0.5mg every night was newly started. Two days later, sertraline was increased to 100mg every night. Two days following this increase, he was noted to have altered mental state, fever of 39.3-degree celcius, tachycardia of 120 beats per minute, ocular clonus and generalized hyperreflexia. Sertraline and risperidone were immediately stopped. Blood tests including creatine kinase, lumbar puncture and magnetic resonance imaging (MRI) of the brain did not show any abnormalities. After stopping of the medications, the patient’s symptoms resolved within 24 hours. Based on clinical symptoms and a normal creatine kinase level, neuroleptic malignant syndrome (NMS) was ruled out. Subsequently, he was restarted on risperidone 0.5mg and mirtazapine 7.5mg every night. He developed symptoms of serotonin syndrome with a low dose of sertraline. Symptoms resolved after the discontinuation of the SSRI.Conclusions In this case, differential diagnoses of serotonin syndrome were also considered, such as NMS, encephalitis, meningitis and thyroid storm. NMS was less likely due to the rapid onset of onset and resolution of symptoms. Encephalitis and meningitis were unlikely in view of normal MRI brain and lumbar puncture findings.There have been case reports of serotonin syndrome developing with lower doses of an SSRI in the pediatric population. There is, however, a lack of literature describing serotonin syndrome with low doses of SSRI in the adult population. To avoid a missed diagnosis, clinicians should monitor closely for SSRI toxicity, including serotonin syndrome, even when low doses of serotonergic drugs are used.Disclosure of InterestNone Declared

Risks Associated with Prescribing Zolpidem: A Case Report and Literature Review

Introduction Zolpidem is a nonbenzodiazepine, which acts as a sedative- hypnotic that binds to GABA (A) receptors at the same location as benzodiazepines and increases GABA effects in the central nervous system (Kovacic et al. Oxidative medicine and cellular longevity 2009, 2(1), 52–57). Literature shows that behavioral changes including amnesia, hallucinations, and other neurocognitive effects are some of the known side effects (Edinoff et al. Health psychology research 2021, 9(1), 24927). We present a case about Ms. A, a female in her sixties with a history of major depressive disorder with psychotic symptoms who was brought into the hospital by the EMS under police custody after stabbing her granddaughter with a knife. During the evaluation she was dissociating with impaired memory of the circumstances of her presentation. Collateral information about Ms. A revealed that she had no history of being violent, or any history of psychoactive substance use. Ms. A’s home psychiatric medications consisted of Sertraline 100mg, Bupropion 150 mg, Zolpidem 5mg.ObjectivesTo better understand the potential risks with prescribing zolpidem in patient with insomnia.MethodsIn depth literature review about zolpidem. In addition, observation of Ms. A in the emergency with a full medical workup including but not limited to urine drug screen, brain imaging, lumbar puncture, etc.Results Ms.A medical workup was positive for a urinalysis revealing asymptomatic bacteriuria and she was treated empirically with cefdinir. Her medication regimen consisted of Bupropion 150 mg and Sertraline 100m, both daily. Zolpidem was discontinued and changed to Clonazepam 0.5mg for insomnia. She was also started on Olanzapine 5mg in the AM and 10mg in the PM. Her mental status was noted to have improved after discontinuation of Zolpidem. Patient received one dose in the hospital but after two days since discontinuation her mental status improved. Upon literature review previous reports have been published citing cases of patients on Zolpidem physically acting out while sleeping in a parasomnia-like behavior, with no recollection of memories upon awakening. (Inagaki et al. Primary care companion to the Journal of clinical psychiatry 2010, 12(6)). There are case reports of Zolpidem associated homicide (Paradis et al.The primary care companion for CNS disorders 2012, 14(4).Conclusions One limitation of our study is the patient was noted to have a sudden change in behavior with altered mental status which may be attributed to an underlying asymptomatic bacteriuria. It should be noted that this may have been an incidental finding. This does not exclude the possibility of Zolpidem as the primary cause of the change of her altered mental status or further exacerbating the change in her mental status. Though Zolpidem can be therapeutic and safe, we as clinicians have to be aware of the potential side effects of Zolpidem when prescribing medications.Disclosure of InterestNone Declared

Identifying Depression Subtypes and Investigating their Consistency and Transitions in a 1-Year Cohort Analysis

Introduction Major Depressive Disorder (MDD) is a complex mental health condition characterized by a wide spectrum of symptoms. According to the Diagnostic Statistical Manual 5 (DSM-5) criteria, patients can present with up to 1,497 different symptom combinations, yet all receive the same MDD diagnosis. This diversity in symptom presentation poses a significant challenge to understanding the disorder in the wider population. Subtyping offers a way to unpick this phenotypic diversity and enable improved characterization of the disorder. According to reviews, MDD subtyping work to date has lacked consistency in results due to inadequate statistics, non-transparent reporting, or inappropriate sample choice. By addressing these limitations, the current study aims to extend past phenotypic subtyping studies in MDD.Objectives(1) To investigate phenotypic subtypes at baseline in a sample of people with MDD;(2) To determine if subtypes are consistent between baseline 6- and 12-month follow-ups; and(3) To examine how participants move between subtypes over time.Methods This was a secondary analysis of a one-year longitudinal observational cohort study. We collected data from individuals with a history of recurrent MDD in the United Kingdom, the Netherlands and Spain (N=619). The presence or absence of symptoms was tracked at three-month intervals through the Inventory of Depressive Symptomatology: Self-Report (IDS-SR) assessment. We used latent class and three-step latent transition analysis to identify subtypes at baseline, determined their consistency at 6- and 12-month follow-ups, and examined participants’ transitions over time.ResultsWe identified a 4-class solution based on model fit and interpretability, including (Class 1) severe with appetite increase, (Class 2), severe with appetite decrease, (Class 3) moderate, and (Class 4) low severity. The classes mainly differed in terms of severity (the varying likelihood of symptom endorsement) and, for the two more severe classes, the type of neurovegetative symptoms reported (Figure 1). The four classes were stable over time (measurement invariant) and participants tended to remain in the same class over baseline and follow-up (Figure 2).Image:Image 2:Conclusions We identified four stable subtypes of depression, with individuals most likely to remain in their same class over 1-year follow-up. This suggests a chronic nature of depression, with (for example) individuals in severe classes more likely to remain in the same class throughout follow-up. Despite the vast heterogeneous symptom combinations possible in MDD, our results emphasize differences across severity rather than symptom type. This raises questions about the meaningfulness of these subtypes beyond established measures of depression severity. Implications of these findings and recommendations for future research are made.Disclosure of Interest C. Oetzmann Grant / Research support from: C.O. is supported by the UK Medical Research Council (MR/N013700/1) and King’s College London member of the MRC Doctoral Training Partnership in Biomedical Sciences., N. Cummins: None Declared, F. Lamers: None Declared, F. Matcham: None Declared, K. White: None Declared, J. Haro: None Declared, S. Siddi: None Declared, S. Vairavan Employee of: S.V is an employee of Janssen Research &amp; Development, LLC and hold company stocks/stock options., B. Penninx : None Declared, V. Narayan: None Declared, M. Hotopf Grant / Research support from: M.H. is the principal investigator of the RADAR-CNS programme, a precompetitive public–private partnership funded by the Innovative Medicines Initiative and the European Federation of Pharmaceutical Industries and Associations. The programme received support from Janssen, Biogen, MSD, UCB and Lundbeck., E. Carr: None Declared

Cognitive function based on theta-gamma coupling vs. clinical diagnosis in older adults with mild cognitive impairment with or without major depressive disorder

Whether individuals with mild cognitive impairment (MCI) and a history of major depressive disorder (MDD) are at a higher risk for cognitive decline than those with MCI alone is still not clear. Previous work suggests that a reduction in prefrontal cortical theta phase-gamma amplitude coupling (TGC) is an early marker of cognitive impairment. This study aimed to determine whether using a TGC cutoff is better at separating individuals with MCI or MCI with remitted MDD (MCI+rMDD) on cognitive performance than their clinical diagnosis. Our hypothesis was that global cognition would differ more between TGC-based groups than diagnostic groups. We analyzed data from 128 MCI (mean age: 71.8, SD: 7.3) and 85 MCI+rMDD (mean age: 70.9, SD: 4.7) participants. Participants completed a comprehensive neuropsychological battery; TGC was measured during the N-back task. An optimal TGC cutoff was determined during the performance of the 2-back. This TGC cutoff was used to classify participants into low vs. high-TGC groups. We then compared Cohen’s d of the difference in global cognition between the high and low TGC groups to Cohen’s d between the MCI and MCI+rMDD groups. We used bootstrapping to determine 95% confidence intervals for Cohen’s d values using the whole sample. As hypothesized, Cohen’s d for the difference in global cognition between the TGC groups was larger (0.64 [0.32, 0.88]) than between the diagnostic groups (0.10 [0.004, 0.37]) with a difference between these two Cohen’s d’s of 0.54 [0.10, 0.80]. Our findings suggest that TGC is a useful marker to identify individuals at high risk for cognitive decline, beyond clinical diagnosis. This could be due to TGC being a sensitive marker of prefrontal cortical dysfunction that would lead to an accelerated cognitive decline.

Risk Factors, Prognosis, Influence on the Offspring, and Genetic Architecture of Perinatal Depression Classified Based on the Depressive Symptom Trajectory

This study is aimed at revealing the risk factors, prognosis, influence on offspring, and genetic architecture of perinatal depression (PD) classified based on the depressive symptom trajectory. Pregnant women with no history of major depressive disorder (MDD) were recruited and followed up with their offspring from 1 to 5 years postpartum. Using four self-report questionnaires in the perinatal period, PD was classified into four subtypes: pregnancy, early postpartum, late postpartum, and chronic PD. Risk factors, depressive symptom trajectory from 1 to 5 years postpartum, and child behavior problems were compared among the four PD subtypes. Genome-wide association studies (GWASs) were conducted for each subtype. The relationships between the PD subtypes and polygenic risk scores (PRS) for MDD, a psychiatric disorder, and premenstrual syndrome (PMS), a hormonal disorder, were examined. Among 12,338 participants, 1,145 (9.3%) developed pregnancy PD, 856 (6.9%) developed early postpartum PD, 382 (3.1%) developed late postpartum PD, and 1,048 (8.5%) developed chronic PD. Depressive symptoms decreased to 61.0%–73.3% in the 5 years postpartum. The relationship between risk factors and PD varied based on the PD subtype. Additionally, chronic PD increased the risk of child behavior problems by 2- to 3-fold. The GWASs uncovered five significant variants in different loci depending on PD subtypes, suggesting a subtype-specific genetic architecture. The PRS for MDD was related to pregnancy, early postpartum, and chronic PD, while that for PMS was related to late postpartum PD. It was concluded that PD is heterogeneous depending on the depressive symptom trajectory. Thus, specific prevention and treatment strategies are needed.

Polygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk

BackgroundSuicide is a leading cause of death worldwide. Whereas some studies have suggested that a direct measure of common genetic liability for suicide attempts (SA), captured by a polygenic risk score for SA (SA-PRS), explains risk independent of parental history, further confirmation would be useful. Even more unsettled is the extent to which SA-PRS is associated with lifetime non-suicidal self-injury (NSSI). MethodsWe used summary statistics from the largest available GWAS study of SA to generate SA-PRS for two non-overlapping cohorts of soldiers of European ancestry. These were tested in multivariable models that included parental major depressive disorder (MDD) and parental SA. ResultsIn the first cohort, 417 (6.3 %) of 6573 soldiers reported lifetime SA and 1195 (18.2 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.26, 95%CI:1.13–1.39, p < 0.001] per standardized unit SA-PRS]. In the second cohort, 204 (4.2 %) of 4900 soldiers reported lifetime SA, and 299 (6.1 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.20, 95%CI:1.04–1.38, p = 0.014]. A combined analysis of both cohorts yielded similar results. In neither cohort or in the combined analysis was SA-PRS significantly associated with NSSI. ConclusionsPRS for SA conveys information about likelihood of lifetime SA (but not NSSI, demonstrating specificity), independent of self-reported parental history of MDD and parental history of SA. LimitationsAt present, the magnitude of effects is small and would not be immediately useful for clinical decision-making or risk-stratified prevention initiatives, but this may be expected to improve with further iterations. Also critical will be the extension of these findings to more diverse populations.