Underlying Mood Disorders Research Articles

Myelin Transcription Factor 1 (MyT1) overexpression mitigates social isolation-induced behavioral deficits: Insights into cortical synaptotagmin 1 regulation and antidepressant-like effects

Social isolation (SI) stress is increasingly recognized as a concern, associated with detrimental effects on mood and emotional well-being. Myelin Transcription Factor 1 (MyT1) is known for its pivotal role in nervous system development and mood regulation. This study delves into the potential of MyT1 to mitigate SI-induced behavioral abnormalities in mice. Utilizing a chronic SI model involving neonatal and post-weaning SI, male and female mice were subjected to lentiviral overexpression of MyT1 specifically in the medial prefrontal cortex (mPFC). A battery of behavioral assessments, including novelty-suppressed feeding, sucrose preference, sucrose splash, tape grooming, tail suspension, and forced swim tests, revealed notable antidepressant-like effects in both sexes upon MyT1 overexpression. Enhanced MyT1 expression corresponded with increased feeding initiation, sucrose preference, and self-grooming, alongside decreased immobility time. Importantly, the upregulation of MyT1 was accompanied by a significant reduction in cortical synaptotagmin 1 (Syt1) level. These findings underscore the involvement of MyT1 in mitigating SI-induced depression-like behavior. Moreover, the observed alterations in behavior are closely associated with changes in cortical Syt1 expression, suggesting its potential role as a target for unraveling the molecular mechanisms underlying mood disorders induced by SI. This study sheds light on the intricate interplay between MyT1 and cortical function in modulating responses to SI, paving the way for potential therapeutic interventions targeting these pathways.

The major biogenic amine metabolites in mood disorders.

Mood disorders, including major depressive disorder and bipolar disorder, have a profound impact on more than 300 million people worldwide. It has been demonstrated mood disorders were closely associated with deviations in biogenic amine metabolites, which are involved in numerous critical physiological processes. The peripheral and central alteration of biogenic amine metabolites in patients may be one of the potential pathogeneses of mood disorders. This review provides a concise overview of the latest research on biogenic amine metabolites in mood disorders, such as histamine, kynurenine, and creatine. Further studies need larger sample sizes and multi-center collaboration. Investigating the changes of biogenic amine metabolites in mood disorders can provide biological foundation for diagnosis, offer guidance for more potent treatments, and aid in elucidating the biological mechanisms underlying mood disorders.

Implications of depressive mood in OSAHS patients: insights from event-related potential

BackgroundObstructive sleep apnea-hypopnea syndrome (OSAHS) is a chronic breathing disorder characterized by recurrent upper airway obstruction during sleep. Although previous studies have shown a link between OSAHS and depressive mood, the neurobiological mechanisms underlying mood disorders in OSAHS patients remain poorly understood. This study aims to investigate the emotion processing mechanism in OSAHS patients with depressive mood using event-related potentials (ERPs).MethodsSeventy-four OSAHS patients were divided into the depressive mood and non-depressive mood groups according to their Self-rating Depression Scale (SDS) scores. Patients underwent overnight polysomnography and completed various cognitive and emotional questionnaires. The patients were shown facial images displaying positive, neutral, and negative emotions and tasked to identify the emotion category, while their visual evoked potential was simultaneously recorded.ResultsThe two groups did not differ significantly in age, BMI, and years of education, but showed significant differences in their slow wave sleep ratio (P = 0.039), ESS (P = 0.006), MMSE (P < 0.001), and MOCA scores (P = 0.043). No significant difference was found in accuracy and response time on emotional face recognition between the two groups. N170 latency in the depressive group was significantly longer than the non-depressive group (P = 0.014 and 0.007) at the bilateral parieto-occipital lobe, while no significant difference in N170 amplitude was found. No significant difference in P300 amplitude or latency between the two groups. Furthermore, N170 amplitude at PO7 was positively correlated with the arousal index and negatively with MOCA scores (both P < 0.01).ConclusionOSAHS patients with depressive mood exhibit increased N170 latency and impaired facial emotion recognition ability. Special attention towards the depressive mood among OSAHS patients is warranted for its implications for patient care.

The effect of sleep disorders on quality of life in patients with epilepsy: A multicenter study from Turkey

ObjectiveWe aimed to investigate sleep disorders in patients with epilepsy (PWE) and to investigate the effects of sleep disorders on quality of life. MethodsIn our multicenter study conducted in Turkey, 1358 PWE were evaluated. The demographic and clinical data of the patients were recorded. The Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), and Quality of Life in Epilepsy Inventory-10 (QOLIE-10) were administered. ResultsThe mean age of 1358 patients was 35.92 ± 14.11 (range, 18–89) years. Seven hundred fifty-one (55.30 %) were women. Some 12.7 % of the patients had insomnia (ISI > 14), 9.6 % had excessive daytime sleepiness (ESS > 10), 46.5 % had poor sleep quality (PSQI > 5), and 354 patients (26.1 %) had depressive symptoms (BDI > 16). The mean QOLIE-10 score was 22.82 ± 8.14 (10–48). Resistant epilepsy was evaluated as the parameter with the highest risk affecting quality of life Adjusted odds ratio (AOR = 3.714; 95 % confidence interval (CI): [2.440–5.652] < 0.001)). ISI (AOR = 1.184; 95 % CI: [1.128–1.243]; p < 0.001), ESS (AOR = 1.081; 95 % CI: [1.034–1.130]; p < 0.001), PSQI (AOR = 0.928; 95 % CI: [0.867 – 0.994]; p = 0.034), BDI (AOR = 1.106; 95 % CI: [1.084–1.129]; p < 0.001), epilepsy duration (AOR = 1.023; 95 % CI: [1.004–1.041]; p = 0.014), were determined as factors affecting quality of life. SignificanceSleep disorders are common in PWE and impair their quality of life. Quality of life can be improved by controlling the factors that may cause sleep disorders such as good seizure control, avoiding polypharmacy, and correcting the underlying mood disorders in patients with epilepsy.

TREK-1 inhibition promotes synaptic plasticity in the prelimbic cortex

Synaptic plasticity is one of the putative mechanisms involved in the maturation of the prefrontal cortex (PFC) during postnatal development. Early life stress (ELS) affects the shaping of cortical circuitries through impairment of synaptic plasticity supporting the onset of mood disorders. Growing evidence suggests that dysfunctional postnatal maturation of the prelimbic division (PL) of the PFC might be related to the emergence of depression. The potassium channel TREK-1 has attracted particular interest among many factors that modulate plasticity, concerning synaptic modifications that could underlie mood disorders. Studies have found that ablation of TREK-1 increases the resilience to depression, while rats exposed to ELS exhibit higher TREK-1 levels in the PL. TREK-1 is regulated by multiple intracellular transduction pathways including the ones activated by metabotropic receptors. In the hippocampal neurons, TREK-1 interacts with the serotonergic system, one of the main factors involved in the action of antidepressants. To investigate possible mechanisms related to the antidepressant role of TREK-1, we used brain slice electrophysiology to evaluate the effects of TREK-1 pharmacological blockade on synaptic plasticity at PL circuitry. We extended this investigation to animals subjected to ELS. Our findings suggest that in non-stressed animals, TREK-1 activity is required for the reduction of synaptic responses mediated by the 5HT1A receptor activation. Furthermore, we demonstrate that TREK-1 blockade promotes activity-dependent long-term depression (LTD) when acting in synergy with 5HT1A receptor stimulation. On the other hand, in ELS animals, TREK-1 blockade reduces synaptic transmission and facilitates LTD expression. These results indicate that TREK-1 inhibition stimulates synaptic plasticity in the PL and this effect is more pronounced in animals subjected to ELS during postnatal development.

Ndufs4 KO mice: A model to study comorbid mood disorders associated with mitochondrial dysfunction

The Ndufs4 knockout (KO) mouse is a validated and robust preclinical model of mitochondrial diseases (specifically Leigh syndrome), that displays a narrow window of relative phenotypical normality, despite its inherent mitochondrial complex I dysfunction and severe phenotype. Preclinical observations related to psychiatric comorbidities that arise in patients with mitochondrial diseases and indeed in Leigh syndrome are, however, yet to be investigated in this model. Strengthening this narrative is the fact that major depression and bipolar disorder are known to present with deficits in mitochondrial function. We therefore screened the behavioural profile of male and female Ndufs4 KO mice (relative to heterozygous; HET and wildtype; WT mice) between postnatal days 28 and 35 for locomotor, depressive- and anxiety-like alterations and linked it with selected brain biomarkers, viz. serotonin, kynurenine, and redox status in brain areas relevant to psychiatric pathologies (i.e., prefrontal cortex, hippocampus, and striatum). The Ndufs4 KO mice initially displayed depressive-like behaviour in the tail suspension test on PND31 but not on PND35 in the forced swim test. In the mirror box test, increased risk resilience was observed. Serotonin levels of KO mice, compared to HET controls, were increased on PND36, together with increased tryptophan to serotonin and kynurenine turnover. Kynurenine to kynurenic acid turnover was however decreased, while reduced versus oxidized glutathione ratio (GSH/GSSG) was increased. When considering the comorbid psychiatric traits of patients with mitochondrial disorders, this work elaborates on the neuropsychiatric profile of the Ndufs KO mouse. Secondly, despite locomotor differences, Ndufs4 KO mice present with a behavioural profile not unlike rodent models of bipolar disorder, namely variable mood states and risk-taking behaviour. The model may elucidate the bio-energetic mechanisms underlying mood disorders, especially in the presence of mitochondrial disease. Studies are however required to further validate the model's translational relevance.

A 24-h restraint with food and water deprivation: a potential method to establish a model of depression in pigs.

Adverse stress, such as the long-term restriction of food intake and activity in intensive production, leads to a depression-like mental state in sows. Mood disorder, such as depression, is a widely concerned animal welfare issue. However, little is known about the biological mechanisms that underlie mood disorders in pigs. This study is the first attempt to establish a pig depression model by acute stress. A total of 16 adult Bama pigs were divided into the control and model groups, with 8 pigs (half male and half female) per group. The pigs in the model group were restrained for 24 h in a dark and ventilated environment, with food and water deprivation. After the restraint, behavioral tests (feed intake, sucrose preference test, open field test, and novel object test) were used to evaluate apparent indicators. The levels of COR and ACTH in the serum and the levels of 5-HT, NE, and BDNF in the hippocampus and medial prefrontal cortex were detected using ELISA to identify the physiological state. After acute stress, pigs exhibited decreased feed intake and sucrose preference, increased serum COR levels, decreased hippocampal 5-HT levels, and exhibited more fear. Finally, the model was evaluated according to the weight of the test indicators. The overall score of the model was 0.57, indicating that modeling was feasible. Although the reliability and stability require further verification, this novel model revealed typical depression-like changes in behavior and provided a potential method to establish a model of depression in pigs.

PREVALENCE OF DEPRESSION OR ANXIETY DURING ANTEPARTUM HOSPITALIZATIONS FOR OBSTETRIC COMPLICATIONS : A SYSTEMATIC REVIEW

Introduction: Women with pregnancy problems are more likely to develop perinatal mood disorders or relapse into underlying mood disorders. &#x0D; Objective: This study aimed to look at the prevalence of prenatal depression and anxiety in women admitted to an antepartum ward for obstetric problems. &#x0D; Methods: We searched Pubmed, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and ClinicalTrials.gov for English-language papers published between establishing the database in July 2023. The cross-sectional, cohort, case-control, quasi-experimental, and randomized-controlled designs used in the selected studies were all related to the research goal. &#x0D; Results: We discovered 8.799 papers and reviewed 7.918, included in the primary outcome systematic review. Using a 14-question checklist is used to assess the quality of each study. Depression was 34% (95% CI 27-41%), while anxiety was 29% (95% CI 16-43%). Significant clinical and methodologic heterogeneity between trials was expected, and it persisted even after planned a priori subgroup analysis and meta-regression. Nonetheless, the effect direction was constant across trials. There was no evidence of publication bias. &#x0D; Conclusion: According to the current systematic review, one in every three pregnant women hospitalized for obstetric difficulties has clinical depression or anxiety symptoms, double the reported prevalence of prenatal depression or anxiety in the general obstetric population.

Takotsubo Syndrome: An Epidemiologic Evaluation.

Takotsubo syndrome is characterized by regional wall motion abnormalities that reflect impairment of myocardial contractility in the absence of culprit epicardial coronary artery disease. The pathophysiologic mechanisms responsible for Takotsubo syndrome remain unknown and predominately occur in postmenopausal females suffering either a psychological or physical stressor. This study used the Hospital Corporation of America (HCA) Healthcare database evaluating demographic distribution of patients with Takotsubo syndrome to identify what comorbid conditions were most prevalent in patients found to have Takotsubo syndrome in the United States population and compare them to the traditional patient population with the condition. The patient population in the HCA Healthcare United States database was similar to prior known demographic factors including postmenopausal females and Caucasian ethnicity. Interestingly, in both the previously diagnosed group and diagnosed at the time of presentation with the Takotsubo syndrome group, there was a mismatch between the number of patients diagnosed with an underlying mood disorder and on psychiatric medication. This may provide further evidence of Takotsubo syndrome being a dramatic presentation of a mood disorder.

Biomarkers and treatments for mood disorders encompassing the neurosteroid and endocannabinoid systems.

Mood disorders, including major depressive disorder, postpartum depression, post-traumatic stress disorder and suicidality are highly prevalent, associated with a significant economic burden, and remain poorly diagnosed and poorly treated psychiatric conditions. In part, this may result from the lack of biomarkers that can guide precision medicine with individualized treatments for millions of individuals who suffer these debilitating conditions worldwide. While several biomarker candidates have been proposed for mood disorders, none has been implemented in clinical practice and the treatment still relies in the prescription of selective serotonin reuptake inhibitors that shows mixed efficacy and significant side effects. Both neurosteroid biosynthesis and the endocannabinoid system have recently provided evidence for pharmacological targets to improve mood symptoms and the neuroactive steroid allopregnanolone has recently been approved by the USA Food and Drug Administration for the treatment of post-partum depression. Clinical studies also show efficacy for the management of major depression and more studies are being conducted to study efficacy in post-traumatic stress disorder. Likewise, the endocannabinoid-like modulator, N-palmioyl ethanolamide (PEA) has shown efficacy in the treatment of major depression and bipolar disorder. While these new agents are coming forward in the field of neuropsychopharmacology as a new generation of fast-acting antidepressants, the hypothesis of whether their deficits underlying mood disorders could constitute valid predictive biomarkers to facilitate diagnosis and treatment of these conditions is under consideration.

Men's Depression, Externalizing, and DSM-5-TR: Primary Signs and Symptoms or Co-occurring Symptoms?

Men's Depression, Externalizing, and DSM-5-TR: Primary Signs and Symptoms or Co-occurring Symptoms?

Common and differential neural mechanisms underlying mood disorders.

Despite homogenous clinical presentations between bipolar and unipolar disorders, there are distinct neurobiological differences. Chronicity of illness may be a factor impacting and sustaining certain neural features. The goal of this study was to investigate common and shared neural mechanisms underlying mood disorders, and possible sustained neural changes relating to illness chronicity by investigating a cohort of euthymic patients with bipolar disorder (BD), unipolar depression who had responded to treatment (treatment-sensitive depression, TSD), and a chronically treatment-resistant depressed (TRD) group. One hundred and seventy-two participants (40 BD, 39 TSD, 40 TRD, and 53 age-gender-matched healthy controls) underwent resting-state fMRI scans. Seed-based and independent component analyses were performed to investigate group differences in resting-state connectivity between the four groups. All three clinical groups had significantly lower connectivity within the frontoparietal network (FPN) relative to controls. TRD and BD were significantly different from TSD (TRD, BD > TSD) but were not significantly different from each other. TRDs were also significantly different from both BD and TSD for salience network connectivity with the posterior cingulate (DMN) and the FPN with frontal pole (DMN). Additionally, the BD group exhibited greater DMN-FPN (sgACC-RDLPFC) connectivity relative to TRD, TSD, and controls, which was correlated with a previous number of depressive episodes, in the BD group only. BD demonstrated shared and differential connectivity features relative to symptomatic TRD and euthymic TSD groups. The increased sgACC-RDLPFC connectivity in BD and its correlation with a number of depressive episodes could be a neural feature associated with illness chronicity.

Pseudobulbar Affect Presenting as Aggressive Behavior

Pseudobulbar affect (PBA) is an affective disorder of emotional expression characterized by frequent uncontrollable outbursts of laughing or crying. It is usually associated with stroke, traumatic brain injury, and other neurological conditions. This disorder can present a challenge to clinicians to distinguish this from mood disorders or to diagnose this disorder in the context of underlying mood disorders. In addition, the delay in the diagnosis can impact patients' quality of life.We describe a 48-year-old man who presented with frequent episodes of sudden, frequent, uncontrollable laughing two years after his recurrent stroke. The patient initially had his first stroke about three years ago and had a recurrent stroke eight months after his first stroke. A few days after getting discharged after his second stroke, the patient was admitted to the psychiatric unit after his family members reported aggressive behavior. The patient also reported symptoms of depression and was discharged on escitalopram for mood and divalproex for his aggressive behavior. Unfortunately, the patient was not compliant with these medications with no resolution of his symptoms. The patient was then treated with dextromethorphan-quinidine, escitalopram, and divalproex, resulting in significant improvement in his mood and aggressive behavior with a resolution of uncontrollable laughing spells. Clinicians are encouraged to inquire about symptoms of pseudobulbar affect in the context of stroke or other neurological disorders. Appropriate management of this condition can help improve patients' symptoms and positively affect their wellbeing.

Pain experience and mood disorders during the lockdown of the COVID-19 pandemic in the United States: an opportunistic study.

The unknown and uncontrollable situation of the coronavirus disease 2019 (COVID-19) pandemic may have triggered changes in pain, anxiety, and depression along with a perception of nonspecific COVID-19 symptoms. We determined how anxiety, depression, and pain outcomes varied during the "Stay-at-Home" order compared with the prepandemic period and whether nonspecific COVID-19 symptoms would occur. We conducted an online survey to opportunistically reassess clinical anxiety, depression, pain intensity, and pain interference while controlling for somatic symptom severity during the prepandemic and Stay-at-Home order period. During the Stay-at-Home period, anxiety, depression, pain intensity, and pain interference were reassessed. Coping strategies were assessed as a critical factor influencing pain behaviors. In addition, we explored the occurrence of nonspecific COVID-19 symptoms with an ad hoc survey referencing the Centers for Disease Control and Prevention publicly available COVID-19 symptoms. We observed a significant increase in depression and anxiety levels during the Stay-at-Home period. Coping strategy changes (eg, increased exercise) were linked to lower pain severity and interference which improved overall. Participants who self-reported nonspecific COVID-19 symptoms had higher prepandemic depression. Among the 72 participants not diagnosed with COVID-19, 70.8% of the participants experienced symptoms resembling those associated with COVID-19. We suggest the parallel between pain outcome improvement and worsening anxiety and depression during the Stay-at-Home order might reflect a shift in symptoms, indicating that those patients with underlying mood disorders may require more help than they did before the pandemic.

Prenatal electrocardiogram testing and postpartum depression: A population-based cohort study.

BackgroundCardiovascular symptoms in pregnancy may be a clue to psychological distress. We examined whether electrocardiogram testing in pregnant women is associated with an increased risk of subsequent postpartum depression.MethodsWe conducted a population-based cohort study of pregnant women who delivered in Ontario, Canada comparing women who received a prenatal ECG to women who did not.ResultsIn total, 3,238,218 women gave birth during the 25-year study period of whom 157,352 (5%) received an electrocardiogram during prenatal care. Receiving an electrocardiogram test was associated with a one-third relative increase in the odds of postpartum depression (odds ratio 1.34; 95% confidence interval 1.29–1.39, p < 0.001).ConclusionThe association between prenatal electrocardiogram testing and postpartum depression suggests a possible link of organic disease with mental illness, and emphasizes that cardiovascular symptoms may be a clinical clue to the presence of an underlying mood disorder.

Untreated depressive symptoms significantly worsen quality of life in old age and may lead to the misdiagnosis of dementia: a cross-sectional study

BackgroundSeveral studies demonstrated the role of depressive mood and cognitive impairment in the background of elevated mortality and decreased Quality of Life (QoL) in old age. Our aim was to assess depressive and cognitive symptoms among older people in order to determine if those are recognized and treated or not, to elucidate the association between them and to investigate their impact on QoL.MethodsIn the framework of the ICT4Life project self-administered questionnaires and clinical screening tools were used to assess QoL, depressive symptoms and cognitive functions of 60 older persons over the age of 65.ResultsMales found to be depressed (53.8 vs. 40.4%) and cognitively declined (53.8 vs. 48.9%) more frequently; and had higher scores on the depression (6.85 vs. 5.32) and lower on the QoL (47.38 vs. 50.19) scales. Depressed older persons had lower cognitive levels (24.39 vs. 21.52) and their QoL was significantly poorer (53.97 vs. 43.85) than that of the non-depressed subjects. Depressive symptoms were detected in almost half of the older adults (43.9%), and the majority (80.77%) did not receive antidepressant medication.ConclusionsDepressive and cognitive symptoms found to be common among older people, but were not recognized and treated in most cases. Close correlation between depression and cognitive impairment was also confirmed, as well as the key role of depression in the background of pseudo-dementia and QoL decline. Early recognition of depressive symptoms is important not only to treat the underlying mood disorder, but also to improve QoL of older persons.

A possible mechanism underlying mood disorders associated with LUTS: Chronic bladder outlet obstruction causes NLRP3‐dependent inflammation in the hippocampus and depressive behavior in rats

Reports link urinary dysfunction and mood disorders, such as depression, but a causative mechanism has never been postulated. Contemporary discoveries demonstrate a local inflammatory response in peripheral organs can trigger inflammation in the brain, particularly the hippocampus, mediated through the NLRP3 inflammasome. Critically, central inflammation causes depressive behavior. Since bladder outlet obstruction (BOO) evokes a local inflammatory response in the bladder, we hypothesize it will induce NLRP3-dependent inflammation in the hippocampus and depressive behavior. There were four groups of rats: control, sham, BOO, or BOO + glyburide (an NLRP3 inhibitor). BOO was created by urethral ligation over a 1 mm catheter. Sham was tied loosely. Glyburide was provided by slow-release pellet (subcutaneous 50 mg, 21 day, replaced as needed). Rats were analyzed 12 weeks post-op for: hippocampal inflammation, microglial density, neurogenesis, and depression symptoms (open field and sucrose preference). BOO elicited hippocampal inflammation, accompanied by an increase in activated microglia (22%) and a decrease in neurogenesis (35%), which was blocked by glyburide. In addition, BOO rats displayed anxiety (57% decrease in exploratory behavior in the open field assay) and anhedonia (21% decrease in sucrose preference), two symptoms of depression. Like inflammation, these symptoms were diminished by glyburide to levels not statistically significantly different from controls. BOO, a bladder-localized event, stimulates NLRP3-dependent inflammation in the rat hippocampus after 12 weeks and this inflammation causes depressive behavior. This is the first mechanistic explanation of the link between BOO and depression and provides evidence for a distinct bladder-brain axis.

Association Between Antepartum Depression Score and Breastfeeding Outcomes [05O

INTRODUCTION: Despite abundant evidence supporting breastfeeding benefits, over 15% of women do not initiate breastfeeding and many stop earlier than recommended. Postpartum depression has a negative association with breastfeeding outcomes. Antepartum depression could have a similar effect. METHODS: Our retrospective chart review included all women from the University of Texas Physicians obstetrical practice who completed an Edinburgh Postnatal Depression Scale (EPDS) and delivered between January 2017 and February 2018. IRB approval was obtained. Of 988 potentially qualifying women, 176 were included [exclusions included no EPDS during pregnancy (809) or maternal breastfeeding contraindication (3)]. Dependent variables were breastfeeding initiation and duration through the postpartum visit. Antepartum depression was defined as a pregnancy EPDS greater than or equal to 13. Multivariable logistic regression was used to determine association between antepartum depression and breastfeeding outcomes. RESULTS: No significant association was found between antepartum depression scores and breastfeeding outcomes. Unadjusted OR 0.62 (95% CI 0.25–1.08); adjusted OR 1.08 (95% CI 0.39–3.03) for breastfeeding initiation. Unadjusted OR 0.80 (95% CI 0.36–1.78) adjusted OR 1.02 (95% CI 0.42–2.48). Women with antepartum underlying mood disorders did have significantly reduced odds of initiation and duration of breastfeeding [initiation adjusted OR 0.24 (95% CI 0.08–0.72), duration adjusted OR 0.25 (0.08–0.75)]. CONCLUSION: We found no association between antepartum depression scores and breastfeeding outcomes. Women with underlying mood disorders had significantly reduced odds of initiating and continuing breastfeeding at the postpartum visit. Addressing underlying mood disorders during pregnancy might be a novel strategy to increase breastfeeding rates.

Risk Factors and Outcomes of Opioid Users with and Without Concurrent Benzodiazepine Use in the North Carolina Medicaid Population.

Concurrent use of opioids and benzodiazepines is associated with increased risk of opioid overdose and death. Clinical guidelines recommend against this practice and quality measures incentivize plans to minimize concurrent use. To compare comorbidities, risky opioid-related behaviors such as high daily doses or multiple prescribers or pharmacies, and outcomes of users of opioids with and without benzodiazepine in the 2017-2018 North Carolina Medicaid population. This was a retrospective claims analysis that used 2017-2018 North Carolina Medicaid enrollment and administrative claims data to describe 3 populations: (1) opioid users who concurrently used benzodiazepine for at least 30 days, (2) opioid users who used some benzodiazepine for 0 to less than 30 overlapping days, and (3) opioid users who did not use benzodiazepines. From 2017 to 2018, 6% of opioid users concurrently used opioids and benzodiazepines for at least 30 days, and 14% used some benzodiazepine for less than 30 overlapping days. Persons filling prescriptions for opioids and benzodiazepines were more likely to have mood disorders and more likely to have depression than opioid users who did not use benzodiazepines. Compared with those not using benzodiazepines, opioid users using benzodiazepine were also more likely to have higher daily opioid doses (at least 90 morphine milligram equivalents), at least 3 prescribers, and at least 3 pharmacies for opioid prescriptions. Although enrollees with at least 30 days of overlapping benzodiazepines and opioids had a higher percentage diagnosed with opioid use disorder compared with those with less than 30 days (30% vs. 13%), a similar percentage received medication-assisted treatment continuously for 90 days (2.6% vs. 2.7%) during 2017-2018. Users of opioids and benzodiazepines, whether for at least 30 overlapping days or less, had higher 1-year cumulative incidences of all-cause outpatient emergency department visits (64% and 65% vs. 52%) and all-cause hospitalizations (25% and 21% vs. 14%) compared with opioid users without benzodiazepine use. Despite guidelines and quality measures, patients continue to use opioids and benzodiazepines concurrently. Addressing underlying mood disorders and depression, curbing risky opioid-related behaviors, and increasing access to medication-assisted treatment may benefit this population. This project was supported by Arnold Ventures (formerly Arnold Foundation). Hung reports personal fees from CVS Health and Blue Cross Blue Shield Association, unrelated to this work. Maciejewski reports Amgen stock ownership due to spouse employment, unrelated to this work. McKethan reports personal fees from North Carolina Department of Health and Human Services. All other authors have nothing to disclose. Part of this content was presented as a poster at AMCP Nexus 2019; October 29-November 1, 2019; National Harbor, MD.

Updates on Preclinical and Translational Neuroscience of Mood Disorders: A Brief Historical Focus on Ketamine for the Clinician.

The development of new-generation antidepressants comes at a time of great clinical need when the global burden of depression, suicide, and other psychiatric conditions continues to increase. Our current treatment armamentarium is limited by the time delay needed for antidepressant effects and the significant number of patients who do not show an adequate response to antidepressants. The past 2 decades of psychiatric research has revealed that ketamine, known to be used only as an anesthetic and drug of abuse and to produce experimental models of psychosis, is effective at subanesthetic doses to ameliorate clinical depression. We performed a systematic search of PubMed/MEDLINE indexed reports to identify clinical and translational research done with ketamine for purposes of treating depression. We will first present the rationale for investigating ketamine and other N-methyl-D-aspartate receptor antagonists as a novel class of glutamate system targeting antidepressants. We will summarize putative molecular pathways underlying mood disorders and outline a brief history of investigation into ketamine as a treatment for depression. Recent clinical/translational evidence of ketamine's rapid-acting antidepressant mechanism will be critically reviewed in detail. At the end of this review, we will opine on the role of ketamine and derivatives in clinical practice.