Current Major Depressive Episode Research Articles

The capacity of cognitive tests to detect generalized anxiety disorder (GAD): A pilot study

Cognitive impairment remains understudied in generalized anxiety disorder (GAD), despite the high prevalence and substantial burden associated with this disorder. We aimed to assess cognitive impairment in patients with GAD and evaluate the ability of cognitive tests to detect this disorder. Because of its high rate of comorbidity, we also examined how other anxiety disorders and current major depressive episodes affected our results. We tested 263 consecutive general practice outpatients. We used the GAD-7 and the Mini International Neuropsychiatric Interview (MINI) to detect anxiety and mood disorders. We assessed cognitive performance with the Stroop test, a facial emotion recognition test, and the trail-making test (TMT). Compared to patients without GAD, patients with GAD were significantly slower to complete the TMT(B-A) and faster to recognize emotions, especially negative ones such as disgust and anger. When controlling for other anxiety disorders and current major depressive episode, GAD retained a significant effect on the TMT(B-A), but not on the emotion recognition test. The TMT(B-A) could detect GAD with good accuracy (area under the curve (AUC) = 0.83, maximal Youden's index = 0.56), which was by no means comparable to the GAD-7 (AUC = 0.97, Youden's index = 0.81). While it is not efficient enough to replace the GAD-7 as a diagnostic tool, the capacity of the TMT(B-A) to detect GAD emphasizes the importance of cognitive flexibility impairment in GAD.

Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report

BackgroundRECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. ObjectiveTo describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine. MethodsMedical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE). ResultsUnipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least 1 INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials. ConclusionsRECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing 1 or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT. Trial registrationClinicalTrials.gov Identifier NCT03887715.

Sex differences in serum trace elements and minerals levels in unmedicated patients with major depressive episode: The role of suicidal ideation

BackgroundWe aimed to examine the influence of gender on serum trace elements and minerals levels in depression, as well as the impact of suicidal ideation (SI) on these gender dimorphisms. MethodsA total of 260 unmedicated patients with a current major depressive episode were enrolled. The Beck Scale for Suicide Ideation was utilized to evaluate SI. The serum levels of copper, zinc, iron, calcium, phosphorus, and magnesium were quantified. ResultsWithin the non-SI (NSI) group, females exhibited higher levels of copper (p = 0.001) and phosphorus (p = 0.008), and lower levels of zinc (p = 0.022) and calcium (p = 0.008) compared to males. Conversely, no discernible gender disparities were observed in the SI group (all p > 0.05). Also, no group differences in these trace elements/minerals were observed between the SI and NSI groups (all p > 0.05). Notably, serum iron levels exhibited a significant group-by-sex interaction effect (p = 0.024). Further analysis revealed that iron levels were higher in the SI group than in the NSI group among females (p = 0.048), but lower in females than in males within the NSI group (p < 0.001). Moreover, a positive association between the fourth quantile of serum iron and SI was detected in females (odds ratio [OR] = 2.88, 95 % confidence interval [CI]: 1.08–8.11). ConclusionsGender effects on serum trace element/mineral levels were different in depressed patients with and without SI. Female patients were susceptible to SI when serum iron was at the upper end of normal.

Computerized cognitive control training to reduce rumination in major depression: A randomized controlled trial

ObjectiveRumination is a major risk factor for the onset and recurrence of depressive episodes and has been associated with deficits in updating working memory content. This randomized controlled trial examines whether training updating-specific cognitive control processes reduces daily ruminative thoughts in clinically depressed individuals. MethodsSixty-five individuals with a current major depressive episode were randomized to 10 sessions of either cognitive control training (N = 31) or placebo training (N = 34). The frequency and negativity of individuals’ daily ruminative thoughts were assessed for seven days before training, after training, and at a 3-month follow-up using experience sampling methodology. Secondary outcomes were depressive symptoms, depressed mood, and level of disability. ResultsCognitive control training led to stronger improvements in the trained task than placebo training. However, cognitive control training did not lead to greater reductions in the frequency or negativity of daily ruminative thoughts than placebo training. There were no training-specific effects on participants' depressive symptoms or level of disability. ConclusionsThe robustness of the present null-findings, combined with the methodological strengths of the study, suggest that training currently depressed individuals to update emotional content in working memory does not affect the frequency or negativity of their daily ruminative thoughts.

A novel objective digital mental health platform based on machine learning for screening of current major depressive episode in sleep clinics

A novel objective digital mental health platform based on machine learning for screening of current major depressive episode in sleep clinics

Gender differences in prevalence and associations between cognitive symptoms and suicidal ideation in patients with recurrent major depressive disorder: findings from the Chinese NSSD study

BackgroundThis study aimed to explore gender differences in associations between cognitive symptoms and suicidal ideation (SI) among patients with recurrent major depressive disorder (MDD).MethodsWe recruited 1222 patients with recurrent MDD from the National Survey on Symptomatology of Depression (NSSD), a survey designed to investigate the symptoms experienced during current major depressive episodes in China. A four-point Likert questionnaire was used to assess the frequency of cognitive symptoms and SI in the past two weeks.ResultsGender differences in clinical features and cognitive symptoms of participants with recurrent MDD were found. Specifically, male patients had a higher prevalence of memory loss, decreased verbal output, indecisiveness, and impaired interpersonal relationships, while female patients exhibited a higher prevalence of impaired social and occupational functioning (all P < 0.05). No significant difference in SI prevalence was found between male and female patients. The logistic regression analysis revealed that in male patients, SI was associated with indecisiveness and impaired interpersonal relationships. In female patients, reduced verbal output and impaired social and professional functions were also associated with SI in addition to the above-mentioned variables.ConclusionThe findings of gender differences in associations between cognitive symptoms and SI highlight the need to carefully assess gender-specific cognitive predictors of SI in patients with recurrent MDD. This has further implications for more targeted prevention and treatment strategies for SI based on gender.

Self-Reported Mood and Lifestyle-Related Physical Activity of Young Adults With Major Depressive Disorder.

We investigated whether mood and lifestyle-related indicators of physical health are differentially expressed according to self-reported levels of depressive symptoms among young adults with a current episode of major depression. In a cross-sectional study, we recruited 94 young adults (females = 67, 71.3%; males = 27, 28.7%; aged 18-35years) with a current episode of major depression. We assessed their mood with the Profile of Mood States (POMS), and Beck Anxiety Inventory-(BAI), sleep with the Pittsburgh Sleep Quality Index (PSQI), physical activity with the Simple Physical Activity Questionnaire (SIMPAQ), and their cardiorespiratory fitness. Participants' depression levels were classified as follows using established cut-points: (a) Mild Depressive Symptoms (MIDS, BDI-II 14-19 points, n = 17), (b) Moderate Depressive Symptoms (MODS, BDI-II 20-28 points, n = 37) or (c) Severe Depressive Symptoms (SEDS, BDI-II 29-63 points, n = 40). As expected, we found that young adults with SEDS, when compared to those with MODS and MIDS, showed higher depressive mood on the POMS, and they exhibited greater anxiety symptoms, lower reported 'vigor' on physical activity measures, worse sleep quality as expressed by their global score sleep; daytime dysfunction; and sleep disturbance, and they showed lower cardiorespiratory fitness. Those with moderate depressive symptoms only differed from those with mild symptoms with respect to hostility, fatigue and mood disturbance. Although there was a gradient whereby worse mental and physical health indicators were more closely related to the SEDS depression categorization, while healthier indicators were associated with the MIDS category, some parameters were not different between the MDD severity groups, particularly when comparing MIDS and MODS. Clinicians treating patients with MDD should consider these factors when designing lifestyle-based interventions.

Functional neuroimaging biomarkers of anhedonia response to escitalopram plus adjunct aripiprazole treatment for major depressive disorder.

Identifying neuroimaging biomarkers of antidepressant response may help guide treatment decisions and advance precision medicine. To examine the relationship between anhedonia and functional neurocircuitry in key reward processing brain regions in people with major depressive disorder receiving aripiprazole adjunct therapy with escitalopram. Data were collected as part of the CAN-BIND-1 study. Participants experiencing a current major depressive episode received escitalopram for 8 weeks; escitalopram non-responders received adjunct aripiprazole for an additional 8 weeks. Functional magnetic resonance imaging (on weeks 0 and 8) and clinical assessment of anhedonia (on weeks 0, 8 and 16) were completed. Seed-based correlational analysis was employed to examine the relationship between baseline resting-state functional connectivity (rsFC), using the nucleus accumbens (NAc) and anterior cingulate cortex (ACC) as key regions of interest, and change in anhedonia severity after adjunct aripiprazole. Anhedonia severity significantly improved after treatment with adjunct aripiprazole.There was a positive correlation between anhedonia improvement and rsFC between the ACC and posterior cingulate cortex, ACC and posterior praecuneus, and NAc and posterior praecuneus. There was a negative correlation between anhedonia improvement and rsFC between the ACC and anterior praecuneus and NAc and anterior praecuneus. Eight weeks of aripiprazole, adjunct to escitalopram, was associated with improved anhedonia symptoms. Changes in functional connectivity between key reward regions were associated with anhedonia improvement, suggesting aripiprazole may be an effective treatment for individuals experiencing reward-related deficits. Future studies are required to replicate our findings and explore their generalisability, using other agents with partial dopamine (D2) agonism and/or serotonin (5-HT2A) antagonism.

Optimal risk and diagnosis assessment strategies in perinatal depression: A machine learning approach from the life-ON study cohort

This study aimed to assess the concordance of various psychometric scales in detecting Perinatal Depression (PND) risk and diagnosis. A cohort of 432 women was assessed at 10–15th and 23–25th gestational weeks, 33–40 days and 180–195 days after delivery using the Edinburgh Postnatal Depression Scale (EPDS), Visual Analogue Scale (VAS), Hamilton Depression Rating Scale (HDRS), Montgomery-Åsberg Depression Rating Scale (MADRS), and Mini International Neuropsychiatric Interview (MINI). Spearman's rank correlation coefficient was used to assess agreement across instruments, and multivariable classification models were developed to predict the values of a binary scale using the other scales. Moderate agreement was shown between the EPDS and VAS and between the HDRS and MADRS throughout the perinatal period. However, agreement between the EPDS and HDRS decreased postpartum. A well-performing model for the estimation of current depression risk (EPDS > 9) was obtained with the VAS and MADRS, and a less robust one for the estimation of current major depressive episode (MDE) diagnosis (MINI) with the VAS and HDRS. When the EPDS is not feasible, the VAS may be used for rapid and comprehensive postpartum screening with reliability. However, a thorough structured interview or clinical examination remains necessary to diagnose a MDE.

Depressive symptoms and anger and aggression in Russian adolescents

Research among adolescents exploring the association between depressive symptoms and aggression has produced inconsistent findings. This study investigated the prevalence of clinically significant (current major depressive episode) and subthreshold depressive symptoms in a general population sample of adolescents from Northern Russia and explored their association with aggression and anger, while controlling for comorbid mental health problems. The sample consisted of 2600 participants, aged 13–17 years (59.5% female; 95.7% ethnic Russian). Symptoms of a current major depressive episode, types of anger and aggression (anger rumination, trait anger, physical, verbal and social aggression) and comorbid problems (posttraumatic stress, alcohol use, anxiety, and hyperactivity/impulsivity) were assessed by means of self-reports. The prevalence of a clinically significant depressive episode in the past month was 3.5%, while for subthreshold depression it was 21.6%. All anger and aggression variables, as well as comorbid problems increased together with increasing levels of depression. The association between overt aggressive behavior and depression was primarily explained by comorbid mental health problems, whereas anger rumination and social aggression had more direct associations with depression, independent of comorbidity. Among adolescents with depression, boys reported higher levels of social and verbal aggression and of anger rumination than girls. The results of this study suggest that interventions aiming to reduce aggressive behavior in adolescents should consider depression and its comorbid conditions.

Screening for depression in the Serbian general population sample: an alternative to the traditional patient health questionnaire-9 cut-off score.

The Patient Health Questionnaire (PHQ-9) score≥10 balances best sensitivity and specificity when detecting probable depression in patients. In the general population, different cut-offs are suggested. European studies on general populations validating the PHQ-9 against a diagnostic interview to detect depression are rare. This was a cross-sectional observational epidemiological survey using multistage household probabilistic sampling to recruit a representative adult sample (N=1203; age=43.7±13.6; 48.7% male). Mental disorders including current major depressive episode (MDE) were observer-rated (Mini International Neuropsychiatric Interview). The PHQ-9, quality of life (QoL), and loneliness were self-assessed. We performed validity and reliability tests of the PHQ-9 and receiver operating curve (ROC) analysis. The Serbian PHQ-9 was internally consistent and correlated in the expected directions with QoL and loneliness. At the cut-off score≥8, sensitivity was .85 and specificity was .91. ROC analysis showed that the area under the curve was .95, indicating that the Serbian PHQ-9 can discriminate very well between persons with/without MDE. When the PHQ-9 is assessed against the structured diagnostic interview in the general population to detect depression, the cut-off of ≥8 balances best sensitivity and specificity.

50 Neuropsychological Functioning in Depression, Borderline Personality Disorder, and Suicidality

Objective:Depression and borderline personality disorder (BPD) are frequently comorbid psychiatric disorders that reliably share deficits in executive functioning (EF). In addition to EF, meta-analytic evidence indicates that processing speed and verbal memory are also affected in depression and BPD, but the impact of BPD further spans the domains of attention, nonverbal memory, and visuospatial abilities. Suicidality is a notable phenotypic commonality in depression and BPD. Neuropsychologically, there are consistent discrepancies between individuals who have and have not thought about suicide in global cognitive functioning, as well as between those who have attempted suicide and those who have just thought about suicide in EF. This study aims to replicate the effect size differences between these groups and explore whether neuropsychological functioning relates to dimensional measures of psychopathology.Participants and Methods:Right-handed women between the ages of 18 and 55 were recruited into one of three diagnostic groups: a) current major depressive episode (MDD; n=22); b) current major depressive episode with comorbid BPD (MDD+BPD; n=19); and c) absence of current major depressive episode and BPD (controls; n=20). Groups were also classified based on historical suicide attempt and on the presence or absence of historical suicidal ideation. Exclusions included bipolar disorder, neurodevelopmental disorder, moderate/severe brain injury, neurological illness, serious physical illness, eating disorder, and moderate/severe alcohol/substance use disorder. Participants were administered the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD), Beck Depression Inventory (BDI-II), Interpersonal Needs Questionnaire (INQ), UPPS-P Impulsive Behavior Scale, Everyday Memory Questionnaire, Brief Visuospatial Memory Test (BVMT), California Verbal Learning Test (CVLT), Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Test, D-KEFS Trail Making Test, D-KEFS Verbal Fluency, Wechsler Adult Intelligence Scale-IV Coding and Digit Span subtests, Wechsler Memory Scale-IV Logical Memory, and Wechsler Test of Adult Reading.Results:With one exception, analyses of raw scores indicated there were no significant neuropsychological differences between groups based on diagnosis, historical suicidal ideation, and suicide attempt (p&gt;.05). However, individuals with MDD+BPD, historical suicidal ideation, or suicide attempt endorsed more memory complaints than the other groups with large effect size differences. Differences in self-reported impulsivity indicated large effects between controls and MDD+BPD, moderate to large effects when comparing controls to MDD and MDD to MDD+BPD, and moderate effects among the suicidal ideation and suicide attempt groups. Impulsivity was rated highest in those with MDD+BPD, historical suicidal ideation, or suicide attempt. These analyses applied false-discovery rate correction and adjusted for age. Using ridge regressions to separately predict depressive symptoms, BPD symptoms, and suicide risk factors, neuropsychological indices were most associated with suicide risk factors and explained 22.8% of INQ variance. Conversely, these indices explained 9.6% of ZAN-BPD variance and 0.6% of BDI-II variance.Conclusions:The neuropsychological literature on BPD describes moderate crosscutting neuropsychological dysfunction, and clarifying the distinct cognitive alterations associated with comorbid psychiatric disorders and suicide phenomena offers novel avenues of research for investigating their mechanisms. While neuropsychological functioning may not strongly relate to psychiatric symptomatology, it may contribute to meaningful algorithms of suicide risk in individuals with depression and BPD.

Effect of next-step antidepressant treatment on suicidal ideation: findings from the VAST-D trial.

Major depressive disorder (MDD) contributes to suicide risk. Treating MDD effectively is considered a key suicide prevention intervention. Yet many patients with MDD do not respond to their initial medication and require a 'next-step'. The relationship between next-step treatments and suicidal thoughts and behaviors is uncharted. The VA Augmentation and Switching Treatments for Depression trial randomized 1522 participants to one of three next-step treatments: Switching to Bupropion, combining with Bupropion, and augmenting with Aripiprazole. In this secondary analysis, features associated with lifetime suicidal ideation (SI) and attempts (SA) at baseline and current SI during treatment were explored. Compared to those with SI only, those with lifetime SI + SA were more likely to be female, divorced, or separated, unemployed; and to have experienced more childhood adversity. They had a more severe depressive episode and were more likely to respond to 'next-step' treatment. The prevalence of SI decreased from 46.5% (694/1492) at baseline to 21.1% (315/1492) at end-of-treatment. SI during treatment was associated with baseline SI; low positive mental health, more anxiety, greater severity and longer duration of current MDD episode; being male and White; and treatment with S-BUP or C-BUP as compared to A-ARI. SI declines for most patients during next-step medication treatments. But about 1 in 5 experienced emergent or worsening SI during treatment, so vigilance for suicide risk through the entire 12-week acute treatment period is necessary. Treatment selection may affect the risk of SI.

Peripheral inflammatory markers in melancholic versus non-melancholic depression

BackgroundPeripheral inflammation has been associated with major depression, however there is a paucity of studies examining whether inflammatory profiles differ across depressive subtypes. The current study sought to compare peripheral inflammatory markers in patients with melancholic versus non-melancholic depression and with healthy controls. MethodEighty outpatients with a current major depressive episode (MDE) were assigned as having a melancholic or a non-melancholic depressive subtype based on clinician diagnosis and the Sydney Melancholic Prototypic Index (SMPI). Participants provided peripheral venous blood from which plasma levels of cytokines and other inflammatory markers (C-reactive protein (CRP), neutrophil/lymphocyte ratio, plasma cytokines) were compared across the two patient groups and also to a group of 81 age-matched healthy controls. ResultsPatients with melancholic and non-melancholic depression demonstrated increased CRP and decreased interferon-gamma (IFN-γ) levels compared to controls. Using clinician diagnosis of subtype, interleukin-12 (IL-12) and interleukin-10 (IL-10) levels were elevated in melancholic patients versus non-melancholic and control groups, with no differences found for the other measured markers of inflammation. ConclusionStudy findings demonstrate shared inflammatory changes across certain inflammatory markers (CRP and IFN-γ) and increases in IL-12 and IL-10 levels specific to melancholic depression. While generally supportive of previous work, our peripheral inflammation findings in melancholic depression are relatively novel and suggest this subgroup may benefit from anti-inflammatory therapies. Further studies are required to replicate these findings.

Routine treatment pathways in a cohort of patients with major depression and suicidality in Italy: the ARIANNA observational study

BackgroundMajor Depressive Disorder (MDD) with suicidal ideation, intent, or behavior is a psychiatric emergency with controversial care management. Our study describes the comprehensive treatment pathways of this population in Italian routine clinical practice. MethodsARIANNA [NCT 04463108] is an observational prospective and retrospective cohort study involving both primary data collection and secondary data extract. A total of 137 adult MDD patients with suicidality were enrolled from 24 Italian care sites and followed for 90 days. Other than the description of treatment patterns, the impact of treatment on depressive symptoms and suicidality, the burden on the patient's and caregiver's quality of life, healthcare resource utilization and costs were described. ResultsOf the 133 eligible patients, 68.4% were female, and the median age was 47. Approximately half of the study population had a current severe major depressive episode. Treatment strategies at the time of active suicidal ideation with intent definition/confirmation (t0) were heterogeneous, increasing in complexity during observation. According to the MADRS, patients with remission at t0+1 day were 2.6%, with the mean total score decreasing from 37.2 at t0 to 32.3. LimitationsThe study sites were not randomly selected. ConclusionsTo the best of our knowledge, this is the first cohort study that prospectively describes the characteristics of patients with MDD and suicide risk in Italy, and how they are treated in clinical practice. The study confirms this is a difficult-to-treat population. In addition, a lack of rapid, effective treatment for reducing depressive symptoms and suicidality is observed.

Anxious distress in people with major depressive episodes: a cross-sectional analysis of clinical correlates.

Most people with major depressive episodes meet the criteria for the anxious distress (AD) specifier defined by DSM-5 as the presence of symptoms such as feelings of tension, restlessness, difficulty concentrating, and fear that something awful may happen. This cross-sectional study was aimed at identifying clinical correlates of AD in people with unipolar or bipolar depression. Inpatients with a current major depressive episode were included. Data on socio-demographic and clinical variables were collected. The SCID-5 was used to diagnose depressive episodes and relevant specifiers. The Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were used to assess the severity of depressive and manic (mixed) symptoms, respectively. Multiple logistic regression analyses were carried out to identify clinical correlates of AD. We included 206 people (mean age: 48.4±18.6yrs.; males: 38.8%) admitted for a major depressive episode (155 with major depressive disorder and 51 with bipolar disorder). Around two-thirds of the sample (N=137; 66.5%) had AD. Multiple logistic regression models showed that AD was associated with mixed features, higher YMRS scores, psychotic features, and a diagnosis of major depressive disorder (p<0.05). Despite some limitations, including the cross-sectional design and the inpatient setting, our study shows that AD is likely to be associated with mixed and psychotic features, as well as with unipolar depression. The identification of these clinical domains may help clinicians to better contextualize AD in the context of major depressive episodes.

The kynurenine pathway in major depressive disorder under different disease states: A systematic review and meta-analysis

BackgroundA disruption of the kynurenine (KYN) pathway may exist in major depressive disorder (MDD). However, the changing pattern of the KYN pathway across the different disease states in MDD is unclear. Herein, we performed a meta-analysis to examine the differences in KYN metabolites between patients in the current episode of MDD (cMDD) and patients in remission (rMDD), as well as the changes after treatments. MethodsLiterature was systematically searched from electronic databases, from inception up to September 2022. Random-effect models were used to quantify the differences in KYN metabolites between patients with MDD across acute depressive episode and remission phases, as well as the changes after treatments. ResultsFifty-one studies involving 7056 participants were included. Tryptophan (TRP), KYN, kynurenic acid (KYNA), KYNA/quinolinic acid (QA), KYNA/3-hydroxykynurenine (3-HK), and KYNA/KYN were significantly lower, while KYN/TRP was significantly higher in patients with cMDD. Moreover, these effect sizes were generally larger in medication-free patients. No significant differences were found between patients with rMDD and HCs. Additionally, KYNA was found negatively correlated with depression severity and significantly increased after treatments, while the alteration was not found in QA. LimitationsThe number of included studies of patients with rMDD and longitudinal studies investigating the change of the KYN metabolites after treatment with antidepressants was limited. In addition, the heterogeneity across included studies was relatively high. ConclusionsThese findings showed a comprehensive image of the unique dysfunction pattern of the KYN pathway across different MDD states and highlighted KYNA as a potentially sensitive biomarker of MDD.

Gender Differences in the Psychopathology of Mixed Depression in Adolescents with a Major Depressive Episode.

Gender differences have been reported in the severity and psychopathological features of major depressive disorders among adults but are poorly reported in adolescent samples. This study aimed to examine gender differences in the psychopathology of mixed depression among adolescents. We analyzed 341 outpatients with the current major depressive episode (MDE) retrospectively to identify patients with DSM-5 MDE with mixed features. We compared examiner-rated depressive and (hypo)manic symptoms and self- and parent-reported symptoms between sexes. We identified 76 patients with an MDE with mixed features (67.1% females, 32.9% with bipolar disorder). Depression severity was significantly greater in females versus males (CDRS-R total score 56.2 vs. 48.2, p = 0.014). Depressive symptoms were significantly and independently found to be more severe among females in a logistic regression model, including excessive fatigue (OR 1.68; p = 0.025), low self-esteem (OR 1.67; p = 0.04), excessive weeping (OR 1.62; p = 0.021), and CBCL AAA index (OR 1.04; p = 0.015). None of the depressive symptoms scored greater in males. Males had higher levels of motor activity (2.12 vs. 1.69; p = 0.048) and pressured speech (1.80 vs. 1.24; p = 0.004). Self-rated anxiety (69.3 vs. 56.8, p = 0.047) and CBCL AAA index (207 vs. 189; p = 0.007) were higher in females. Adolescent depression with mixed features is more severe in women, with a higher expression of core affective symptoms and excessive fatigue. While in males, slightly higher levels of psychomotor activation are reported, in females, emotional dysregulation and excessive weeping may subtend a difference in a broader spectrum of mixed features.

Improvement in Anxiety Symptoms in Depressed Patients Treated With AXS-05 (DEXTROMETHORPHAN-BUPROPION): Results From the Evolve Open-Label, Long-Term Study

AbstractBackgroundInnovative therapies to treat individuals with MDD, especially those with comorbid anxiety, are urgently needed.AXS-05 (dextromethorphan HBr 45 mg-bupropion HCl 105 mg) is a novel, oral, investigational NMDA receptor antagonist with multimodal activity. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.ObjectiveTo evaluate the effects of AXS-05 on anxiety in MDD.MethodsEVOLVE was an open-label study, in which patients were treated with AXS-05 twice daily for up to 15 months. Subjects had either rolled in after a prior AXS-05 study or were directly enrolled and had a DSM-5 diagnosis of MDD, a MADRS score of ≥25, and had been treated with ≥ 1 antidepressant in the current major depressive episode. A total of 186 patients were enrolled. Efficacy endpoints included MADRS and HAM-A. Here we present the results for the directly enrolled patients (n =146).ResultsMean baseline HAM-A scores were 15.6. Reductions from baseline to Weeks 1, 2, and 6 were 3.4±5.34 (p&lt; 0.001), 5.5±5.81 (p&lt; 0.001), and 8.6±5.75 (p&lt; 0.001), respectively. Improvements on the HAM-A were durable through Month 12 (-10.2±6.33; p&lt; 0.001). Remission (HAM-A ≤7) rates on the HAM-A at Weeks 1, 2, and 6 were 19.9%, 36.0%, and 58.1%, respectively. Remission at Month 12 was 78.3%.Long-term treatment with AXS-05 was generally well tolerated. The most commonly reported adverse events were COVID-19 infection (8.9%), nausea (8.9%), headache (7.5%), dry mouth (6.2%), insomnia (5.5%), and dizziness (5.5%).ConclusionsThese data support the use of AXS-05 in patients with comorbid depression and anxiety.FundingAxsome Therapeutics

AXS-05 (DEXTROMETHORPHAN-BUPROPION) Improves Depressive Symptoms and Functioning in Patients With One Prior Treatment Failure: Results From the Evolve Long-Term, Open Label Study

AbstractBackgroundIn STAR*D, following non-remission with an SSRI, remission rates for second-line treatments were ~ 25%, regardless of the switch strategy employed. Antidepressants with novel mechanisms may improve outcomes in MDD. AXS-05 (dextromethorphan HBr 45 mg- bupropion HCl 105 mg) is a novel, oral, investigational, NMDA receptor antagonist with multimodal activity. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.MethodsEVOLVE was an open-label study, in which patients were treated with AXS-05 twice daily for up to 15 months. Subjects had either rolled in after a prior AXS-05 study or were directly enrolled and had a DSM-5 diagnosis of MDD, a MADRS score of ≥25, and had been treated with ≥1 antidepressant in the current major depressive episode (MDE). A total of 186 patients were enrolled. Here we present the results for the directly enrolled patients (n =146).ResultsMean change in MADRS total score from a baseline of 32.2 were -9.1±7.64, -13.3±8.58, and -20.4±7.79 points at Weeks 1, 2, and 6, respectively (p&lt; 0.001 for all). Remission (MADRS ≤10) was achieved by 5.7%, 16.2%, and 46.0% of patients at Weeks 1, 2, and 6, respectively. Improvement in functioning, measured by the SDS, was seen starting at Week 1 (p &lt; 0.001). Improvements in MADRS and SDS were sustained at Month 12.Long-term treatment with AXS-05 was generally well tolerated. The most commonly reported adverse events were COVID-19 infection (8.9%), nausea (8.9%), headache (7.5%), dry mouth (6.2%), insomnia (5.5%), and dizziness (5.5%).ConclusionsAXS-05 improved depression and functioning in patients who failed one prior antidepressant in the current MDE.FundingAxsome Therapeutics