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Abstract Background This study investigates the effects of accelerated high-frequency repetitive transcranial magnetic stimulation (aHF-rTMS), applied to the left dorsolateral prefrontal cortex (DLPFC), on locus coeruleus (LC) functional connectivity in the treatment of refractory medication-resistant major depression (MRD). Methods We studied 12 antidepressant-free refractory MRD patients, focusing on how aHF-rTMS affects the LC, a central component of the brain’s noradrenergic system and key to mood regulation and stress response. Results A stronger decrease in LC functional connectivity following aHF-rTMS treatment resulted in better clinical improvement. We observed such LC functional connectivity decreases with several brain regions, including the superior frontal gyrus, precentral gyrus, middle occipital gyrus, and cerebellum. Moreover, our exploratory analyses hint at a possible role for E-field modeling in forecasting clinical outcomes. Additional analyses suggest potential genetic and dopaminergic factors influencing changes in LC functional connectivity in relation to clinical response. Conclusions The findings of this study underscore the pivotal role of the LC in orchestrating higher cognitive functions through its extensive connections with the prefrontal cortices, facilitating decision-making, influencing attention, and addressing depressive rumination. Additionally, the observed enhancement in LC-(posterior) cerebellar connectivity not only highlights the cerebellum’s role in moderating clinical outcomes through noradrenergic system modulation but also suggests its potential as a predictive marker for aHF-rTMS efficacy. These results reveal new insights into the neural mechanisms of refractory depression and suggest therapeutic targets for enhancing noradrenergic activity, thereby addressing both cognitive and psychomotor symptoms associated with the disorder.

Abstract Background Stressors across the lifespan are associated with the onset of major depressive disorder (MDD) and increased severity of depressive symptoms. However, it is unclear how lifetime stressors are related to specific MDD subtypes. The present study aims to examine the relationships between MDD subtypes and stressors experienced across the lifespan while considering potential confounders. Methods Data analyzed were from the Zone d’Épidémiologie Psychiatrique du Sud-Ouest de Montréal (N = 1351). Lifetime stressors included childhood maltreatment, child–parent bonding, and stressful life events. Person-centered analyses were used to identify the clusters/profiles of the studied variables and multinomial logistic regression analyses were performed to examine the relationships between stressors and identified MDD subtypes. Intersectional analysis was applied to further examine how distal stressors interact with proximal stressors to impact the development of MDD subtypes. Results There was a significant association between proximal stressors and melancholic depression, whereas severe atypical depression and moderate depression were only associated with some domains of stressful life events. Additionally, those with severe atypical depression and melancholic depression were more likely to be exposed to distal stressors such as childhood maltreatment. The combinations of distal and proximal stressors predicted a greater risk of all MDD subtypes except for moderate atypical depression. Conclusions MDD was characterized into four subtypes based on depressive symptoms and severity. Different stressor profiles were linked with various MDD subtypes. More specific interventions and clinical management are called to provide precision treatment for MDD patients with unique stressor profiles and MDD subtypes.

Abstract Background Major depressive disorder (MDD) is a leading cause of disability and premature mortality. This study compared the overall survival (OS) between patients with MDD and non-MDD controls stratified by gender, age, and comorbidities. Methods This nationwide population-based cohort study utilized longitudinal patient data (01/01/2010 – 12/31/2020) from the Hungarian National Health Insurance Fund database, which contains healthcare service data for the Hungarian population. Patients with MDD were selected and matched 1:1 to those without MDD using exact matching. The rates of conversion from MDD to bipolar disorder (BD) or schizophrenia were also investigated. Results Overall, 471,773 patients were included in each of the matched MDD and non-MDD groups. Patients with MDD had significantly worse OS than non-MDD controls (hazard ratio [HR] = 1.50; 95% CI: 1.48−1.51; males HR = 1.69, 95% CI: 1.66–1.72; females HR = 1.40, 95% CI: 1.38–1.42). The estimated life expectancy of patients with MDD was 7.8 and 6.0 years less than that of controls aged 20 and 45 years, respectively. Adjusted analyses based on the presence of baseline comorbidities also showed that patients with MDD had worse survival than non-MDD controls (adjusted HR = 1.29, 95% CI: 1.28–1.31). After 11 years of follow-up, the cumulative conversions from MDD to BD and schizophrenia were 6.8 and 3.4%, respectively. Converted patients had significantly worse OS than non-converted patients. Conclusions Compared with the non-MDD controls, a higher mortality rate in patients with MDD, especially in those with comorbidities and/or who have converted to BD or schizophrenia, suggests that early detection and personalized treatment of MDD may reduce the mortality in patients diagnosed with MDD.

Abstract Background Major depressive disorder (MDD) is one of the most prevalent medical conditions worldwide. Different factors were found to play a role in its etiology, including environmental ones (e.g., air pollution). The aim of this study was to evaluate the association between air pollution exposure and MDD severity. Methods Four hundred sixteen MDD subjects were recruited. Severity of MDD and functioning were evaluated through five rating scales: Montgomery–Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAMD), Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), and Sheehan Disability Scale (SDS). Daily mean estimates of particulate matter with diameter ≤10 (PM10) and 2.5 μm (PM2.5), nitrogen dioxide (NO2), and apparent temperature (AT) were estimated based on subjects’ residential addresses. Daily estimates of the 2 weeks preceding recruitment were averaged to obtain cumulative exposure. Multivariate linear and ordinal regression models were applied to assess the associations between air pollutants and MDD severity, overall and stratifying by hypersusceptibility and AT. Results Two-thirds of subjects were women and one-third had a family history of depression. Most women had depression with symptoms of anxiety, while men had predominantly melancholic depression. NO2 exposure was associated with worsening of MDD severity (HAMD: β = 1.94, 95% confidence interval [CI], [0.41–3.47]; GAF: β = −1.93, 95% CI [−3.89 to 0.02]), especially when temperatures were low or among hypersusceptible subjects. PM exposure showed an association with MDD severity only in these subgroups. Conclusions Exposure to air pollution worsens MDD severity, with hypersusceptibility and lower temperatures being exacerbating factors.

Abstract Background Amygdala subregion-based network dysfunction has been determined to be centrally implicated in major depressive disorder (MDD). Little is known about whether ketamine modulates amygdala subarea-related networks. We aimed to investigate the relationships between changes in the resting-state functional connectivity (RSFC) of amygdala subregions and ketamine treatment and to identify important neuroimaging predictors of treatment outcomes. Methods Thirty-nine MDD patients received six doses of ketamine (0.5 mg/kg). Depressive symptoms were assessed, and magnetic resonance imaging (MRI) scans were performed before and after treatment. Forty-five healthy controls underwent one MRI scan. Seed-to-voxel RSFC analyses were performed on the amygdala subregions, including the centromedial amygdala (CMA), laterobasal amygdala (LBA), and superficial amygdala subregions. Results Abnormal RSFC between the left LBA and the left precuneus in MDD patients is related to the therapeutic efficacy of ketamine. There were significant differences in changes in bilateral CMA RSFC with the left orbital part superior frontal gyrus and in changes in the left LBA with the right middle frontal gyrus between responders and nonresponders following ketamine treatment. Moreover, there was a difference in the RSFC of left LBA and the right superior temporal gyrus/middle temporal gyrus (STG/MTG) between responders and nonresponders at baseline, which could predict the antidepressant effect of ketamine on Day 13. Conclusions The mechanism by which ketamine improves depressive symptoms may be related to its regulation of RSFC in the amygdala subregion. The RSFC between the left LBA and right STG/MTG may predict the response to the antidepressant effect of ketamine.

Abstract Background It is not clear if there is an interaction between psychotherapy and pharmacotherapy. First, there may be no interaction at all, meaning that the effects of both are independent of each other. Second, antidepressants may reduce the effects of psychotherapy, and third, antidepressants may increase the effects of psychotherapy. We examined which of the three is correct. Methods We conducted random effects meta-analyses of randomized trials comparing psychotherapies for adult depression with control conditions. The proportion of users of antidepressants was used as a predictor of the effect size in a series of meta-regression analyses, while adjusting for relevant moderators, such as type of control group and baseline severity. Results We included 300 randomized controlled trials (353 comparisons between treatment and control; 32,852 participants). The main effect size of psychotherapy was g = 0.71 (95% CI: 0.64; 0.79) with high heterogeneity (I2 = 82; 95% CI: 80; 84). We found no significant association between the proportion of antidepressants users and effect size (p = .07). We did find a significant association with some other predictors, including the type of control group and risk of bias. The use of antidepressants was associated with higher response rates within the control conditions, but not with the relative effects of the treatments compared to the control groups. Discussion We found support for the independent effects of psychotherapy and pharmacotherapy, which is good news from a clinical perspective. Apparently, patients can start with psychotherapy and do not have to be afraid that this will reduce the effects of the therapy.

Abstract Introduction Major depression episode (MDE) and postpartum depression (PPD) have the same diagnosis criteria, but dissimilarities may be present regarding the frequency and structure of depressive symptoms. Methods We used data from the IGEDEPP Cohort (France) to examine DSM-5 depressive symptoms in two groups of women: 486 with PPD and 871 with a history of non-perinatal MDE. We compare (i) the frequency of each depressive symptom adjusted for the severity of depression, (ii) the global structure of depressive symptom networks, and (iii) the centrality of each symptom in the two networks. Results Women with PPD were significantly more likely to have appetite disturbance, psychomotor symptoms, and fatigue than those with MDE, while sadness, anhedonia, sleep disturbance, and suicidal ideation were significantly less common. There were no significant differences in the global structure of depressive symptoms of MDE and PPD. However, the most central criterion of the MDE network was “Sadness” while it was “Suicidal ideations” for the PPD network. “Sleep” and “Suicidal ideations” criteria were more central for PPD network, whereas “Culpability” was more important for MDE network than for PPD network. Conclusion We found differences in depressive symptoms expression between PPD and MDE, which justify continuing to clinically distinguish PPD from MDE.

Abstract Background Major depressive disorder (MDD) is a leading cause of disability worldwide, and yet delivery of care for this illness is rife with gaps. The COVID-19 pandemic has had far reaching implications for every facet of healthcare, and MDD is no exception. This scoping review aimed to ascertain the impacts of COVID-19 on the delivery of MDD care in Europe, as well as to evaluate any novel MDD care strategies trialled in this period. Methods We searched the PubMed and PsycINFO databases up to January 2022 with a strategy centred around COVID-19 and MDD. Full texts of eligible studies examining working-age adults and conducted in Europe were evaluated against several criteria. All outcomes were then extracted and a narrative synthesis was constructed to summarise identified themes. Results Of 1,744 records identified in our search, 11 articles were eligible for inclusion in the review. In general, these studies reported a decrease in treatment rates, access to care, and perceived access to care during the COVID-19 pandemic. In addition, digital interventions trialled during the pandemic were broadly well-received by users, though their efficacy in improving MDD care was ambiguous. Conclusions Despite a limited number of pertinent studies, this scoping review identified a trend of exacerbated treatment gaps in MDD care during the pandemic. Several of our pre-specified gaps, including delays to detection or treatment of depression and rates of follow-up contacts, remained unexplored in the context of COVID-19. This highlights the need for further investigation to obtain a full understanding of the relationship between COVID-19 and MDD care in Europe.

Introduction Attachment style is defined by the American Psychological Association as “the characteristic way people relate to others in the context of intimate relationships”. Four attachment styles have been described: secure, fearful, preoccupied, and dismissing. While the effect of attachment style on psychotherapy was widely investigated, few studies have investigated its role in determining beliefs about medicines in patients with Major Depressive Disorder (MDD). Objectives This study aimed to investigate the relationship between preoccupied attachment style and beliefs about medicines in patients with MDD. Methods 27 patients admitted in the Psychiatric Unit of Careggi with diagnosis of MDD were enrolled. Working Alliance Inventory - patient version (WAI-P), Relationship Style Questionnaire (RSQ) and Beliefs about Medicines Questionnaire (BMQ) were administered. An ANCOVA model having BMQ total score as dependent variable and age, sex, RSQ preoccupied attachment subscale and WAI-P task subscale as predictors was considered. WAI-P task was intended to assess the role of agreement on therapeutic choices. Results The overall model was significant (F(4,22)=9,571, P

Introduction The only available genome-wide study (Minelli et al., 2018) indicated an association between the neglect CT and MED22, a transcriptional factor gene. Objectives To verify how the dysregulation of MED22 could be affected by environmental and genetic factors, we carried out an analysis on these components and a longitudinal study concerning the effect of trauma-focused psychotherapy in MDD patients that experienced CT. Methods On a large mRNA sequencing dataset including 368 MDD patients we computed the genetic (GReX) and the environmental (EReX) components affecting gene expression in relation to CT. Furthermore, we measured the expression of MED22 in 22 MDD patients treated with trauma-focused psychotherapy. Results The dissection of MED22 expression profiles revealed an association of neglect with environmental and genetic components (p=6x10-3 p=2.6x10-4). Furthermore, in an independent cohort of 177 controls, we also observed a significant association between cis-eSNPs of MED22 and higher neuroticism scores (best p-value: 0.00848) that are usually associated with a decreased amount of resilience to stress events. Finally, the results of psychotherapy revealed a reduction of depressive symptomatology (p

Introduction Early life stress (ELS) is a significant risk factor for major depressive disorder (MDD) in adults. Functional magnetic resonance imaging (fMRI) studies using face emotion processing paradigms have found altered blood-oxygen-level-dependent (BOLD) responses in the cortico-limbic network both in individuals exposed to ELS and in patients with MDD. Thus, early life stress may have a long-lasting impact on brain areas responsible for the processing of socio-affective cues. Objectives By applying a facial emotion recognition (FER) fMRI paradigm, we examined the long-term effect of childhood adversity on brain activity in MDD patients with and without ELS. Methods MDD patients without ELS (MDD, N=19), those with ELS (MDD+ELS, N=21), and healthy controls (HC, N=21) matched for age, sex, and intelligence quotient underwent fMRI scanning while performing a block design FER task with faces expressing negative emotions. The severity of ELS was assessed with the 28-item Childhood Trauma Questionnaire. Results Both MDD and MDD+ELS patients were slightly impaired in recognizing sad faces. Statistical analysis of brain activity found that MDD+ELS patients had significantly reduced negative BOLD responses in the right anterior paracingulate gyrus, subcallosal cortex accumbens compared to HCs. Moreover, the MDD+ELS group had a significantly increased negative BOLD signal in the right postcentral and precentral gyri relative to the HC group. MDD+ELS patients had reduced negative BOLD response in their anterior paracingulate gyrus compared to the MDD group. Conclusions Our results support that adult MDD patients with significant ELS are impaired in facial emotion recognition and they display functional alterations in the frontostriatal circuits. Disclosure This work was financially supported by the Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002)

Introduction Patients with major depressive disorder (MDD) with acute suicidal ideation or behavior (MDSI) require immediate intervention. Though oral antidepressants can be effective at reducing depressive symptoms, they can take 4–6 weeks to reach full effect. Objectives This study aimed to identify unmet needs in the treatment of patients with MDSI, specifically exploring the potential clinical benefits of rapid reduction of depressive symptoms. Methods A Delphi panel consisting of practicing psychiatrists (n=12) from the US, Canada and EU was conducted between December 2020–June 2021. Panelists were screened to ensure they had sufficient experience with managing patients with MDD and MDSI. Panelists completed two survey rounds, and a virtual consensus meeting. Results This research confirmed current unmet needs in the treatment of patients with MDSI. Hopelessness, functional impairment, worsening of MDD symptoms, recurrent hospitalization and higher risk of suicide attempt were considered as key consequences of the slow onset of action of oral antidepressants. Treatment with rapid acting antidepressant was anticipated by panelists to provide short-term benefit such as rapid reduction of core MDD symptoms which may contribute to shorter hospital stays and improved patient engagement/compliance, allowing for earlier interventions and improved patient outcomes. For long-term benefits, panelists agreed that improved daily functioning and increased trust/confidence in treatment options, constitute key benefits of rapid-acting treatments Conclusions There is need for rapid-acting treatments which may help address key unmet needs and provide clinically meaningful benefits driven by the rapid relief of depressive symptoms particularly in patients with MDSI. Disclosure SB, ED, KJ, MO’H, QZ, MM, MH, SR, JA and DZ are employees of Janssen and hold stock in Johnson & Johnson Inc. AN is currently employed by Neurocrine Biosciences Inc. RP is an employee of Adelphi Values PROVE hired by Janssen.

Introduction According to international studies, at least 70% of BPD in adolescence are comorbid with MDD. Objectives To determine the clinical and psychopathological markers of MDD in BPD in adolescence. Methods Clinical psychopathological interview, SCID-II, Hamilton Depression Rating Scale (HDRS). Sample: N=73 male and female, age: 18-25 with MDD and BPD. Results MDD comorbid with BPD in adolescence is characterized by polymorphism of its’ psychopathological manifestations due to the structure of BPD and the input of the age factor. In the studied sample 31 (42,5%) with both MDD and BPD also revealed addictions; 24 patients (32,9%) - anxiety and obsessive-compulsive (OCD) disorders, 18 patients (24,7%) had overvalued ideas. The high contingency of MDD with autoaggressive actions confirmed their high suicidal risk (53 patients). Among them - 31 patients (58,5%) - had non-suicidal self-harm (NSSI), 7 patients – (13,2%) had suicidal attempt (SA), and 15 patients (28,3%) had NSSI and suicidal attempts (NSSI+SA). The highest incidence of NSSI and NSSI+SA was noted in MDD with addictive disorders: NSSI – N=20 (80,00%), NSSI+SA - N=5 (20,00%), SA – N=0. MDD with BPD and anxiety disorders: NSSI – N=9 (56,25%), NSSI+SA – N= 6 (37,50%), SA–N=1 (6,25%). MDD with BPD and overvalued ideas: NSSI – N=2 (16,67%), NSSI +SA – N= 4 (33,33%), SA N=6 (50,0%), (results p

Introduction In major depressive disorder (MDD), reward-based decision-making (DM) is frequently impaired: e.g. patients don’t engage in pleasant activities as much as healthy subjects. Put differently, previous and expected future rewards have less reinforcing effects on DM. This study investigated two experimentally well-observable reward-based DM modes, namely model-based (based on cognitive models of the environment) and model-free (based on previous experience) DM. Objectives We hypothesized that model-based training can improve reward-based DM in patients with MDD. Answers to these questions could enhance the development of cognitive-behavioral therapeutic interventions. Methods 27 patients with MDD were recruited and assessed with psychometry. All patients performed the „two-step Markov decision-task“ (Daw, 2011), which allows the simultaneous investigation of model-based and model-free DM via computational modelling. All subjects performed the task 4 times: at the beginning and at the end of 2 assessment days (session-interval: 4 days). Subjects were randomly allocated to an intervention group, which performed model-based training, and a control group, which performed model-free training. The main outcomes of training effect were the influence of model-based reward expectations on decisions (quantified by computational modelling parameters) and overall monetary reward-success. Results In all patients, the influence of model-based reward expectations on decisions increased after training. However, there was no significant effect of group allocation. Furthermore, patients in the intervention group did not achieve significantly higher overall monetary reward. Conclusions Results suggest that in MDD, the influence of model-based reward expectations on decisions can be improved regardless of specific training type. Future studies should investigate the effects on everyday functioning. Disclosure No significant relationships.

Introduction The DiSCoVeR trial is a multi-site, double-blind, sham controlled, randomized controlled trial (RCT) investigating the feasibility and efficacy of an innovative, self-applied treatment approach for patients suffering from major depressive disorder (MDD). The treatment approach incorporates non-invasive brain stimulation, i.e. prefrontal transcranial direct current stimulation (tDCS), and a videogame designed to enhance emotional cognitive control. This treatment is aimed to be applied at home and monitored remotely. Objectives In this study we are looking at the first 10 single-site patients and comparing expected in person visits (according to the study protocol) versus actual in person visits as well as looking at the patients initial view of the therapy using the therapy evaluation form (CEQ) submitted after the 5th session. Methods Before continuing to self-administer the treatment at home patients undergo supervised training, during clinic visits, for up to 5 sessions. At the end of the 5th session, they are asked to fill out a therapy evaluation form (CEQ). Results Patients needed on average 2.3 in person training sessions before continuing the intervention remotely. Nine patients completed CEQ. Results show that on average patients thought that this course will be 4.78 (with probability 95% CI 4.74 to 4.82) points successful at raising their level of functioning and thought that their functioning will have increased on average by 37.8% (CI 37.2% to 38.4%) by the end of the study. Conclusions Patients needed less than half of planned in person training visits. Most patients felt like they will gain some improvement from this intervention. Disclosure No significant relationships.

Introduction Major depressive disorder is a prevalent disease, in which one third of sufferers do not respond to antidepressants. Disturbance in the equilibrium of the gut microbiota has been involved in the pathophysiology of depression. Probiotics have the potential to be well-tolerated and cost-efficient treatment options. However, there is not enough evidence of the impact of probiotics in patients suffering MDD. Objectives The main aim of this revision is to assess those clinical trials that evaluate the effects of probiotic treatment in patients with MDD. Methods A research on the database PubMed has been done with the terms “probiotics” AND “MDD” and then a systematic review has been performed between those articles meeting the inclusion criteria. Results Most of the articles show an improvement of the depressive symptoms in outpatients with mild to moderate TDM after 8 week treatment with probiotics added to the treatment as usual. Those articles assessing inpatients with severe MDD after four weeks of treatment with probiotics added to their usual treatment didn’t find statistical differences between treatment with probiotics from placebo. Conclusions Probiotics may be useful in mild to moderate symptoms of MDD after 8 weeks treatment added to usual treatment. Nevertheless, further investigation in larger samples during more time. Moreover, a new awareness is raised about gut- brain axis pathophysiology, that would lead the path to new investigations about this relation so as the difference in depressed patients microbiome, tryptophan metabolism and the pro- inflammatory compounds that reach the blood-brain barrier because of the “leaky-gut”. Disclosure No significant relationships.

Introduction Executive function organizes and directs behaviour but alterations in this cognitive domain can lead to inaccurate perception, interpretation and response to environmental information, which could be a risk factor for suicide. Objectives To explore executive function performance of depressed recent suicide attempters in comparison to depressed past suicide attempters, depressed non-attempters and healthy controls. Methods 96 participants from the Psychiatry Department of the Araba University Hospital-Santiago were recruited as follows: 20 patients with a recent suicide attempt (

Introduction Although numerous effective antidepressant (AD) strategies are available for the treatment of major depressive disorder (MDD), many patients do not achieve satisfactory treatment response. Objectives The aims of the present European, cross-sectional, multicenter, naturalistic study were (1) to determine the proportion of patients suffering from primary MDD who received additional psychotherapy to their ongoing psychopharmacotherapy and (2) to identify the associated socio-demographic and clinical patterns. Methods Patients receiving both treatments were compared to those lacking concomitant additional psychotherapy that was manual-driven psychotherapy (MDP) in all cases. Results While 68.8% of a total of 1279 MDD patients received exclusively psychopharmacotherapy, 31.2% underwent a psychopharmacotherapy-MDP combination. The latter patient population was rather younger, higher educated, employed, exhibited an earlier mean age of MDD onset, lower severity of current depressive symptoms with lower odds of suicidality and higher rates of melancholic features, and comorbid asthma and migraine, and was generally treated with lower daily doses of their first-line ADs. Whereas agomelatine was more commonly dispensed in these patients, selective serotonin reuptake inhibitors were more often prescribed in MDD patients lacking additional MDP. No significant between-group differences were detected in terms of treatment outcome. Conclusions The fact that the employment of additional MDP was not related to better treatment outcome in MDD represents our major and clinically most relevant finding. Generally, MDP was employed in a minority of our patients who experienced rather beneficial socio-demographic and clinical characteristics. This might reflect an inferior accessibility of these psychotherapeutic techniques for patients who are more severely ill and less socio-economically privileged. Disclosure References Bartova L, Fugger G, Dold M, Swoboda MMM, Zohar J, Mendlewicz J, Souery D, Montgomery S, Fabbri C, Serretti A, Kasper S. Combining psychopharmacotherapy and psychotherapy is not associated with better treatment outcome in major depressive disor

Introduction Major Depressive (MDD) and Bipolar Disorder (BD) are chronic relapsing condition in which mood episodes are interspersed with periods of euthymia. Impairments in Executive Attention (EA) are a trait characteristic of mood disorder that persists also during remission. Similarly prefrontal dysfunctions are crucial in the genesis and maintenance of Obsessive-Compulsive Symptoms (OCS), which are highly comorbid in both MDD and BD. Objectives The aim of this study is to test a model in which deficits in EA mediate the relationship between the OCS and the relapse in a cohort of patients with MDD and BD. Methods Sixty-four euthymic subjects with BD and MDD performed the Attentional Network Task Revised (ANT-R), that gauges EA in a standard conflict task. Here we adopted a drift diffusion model to measure the task efficiency as the drift rate in incongruent trials. Patients also completed at baseline the YBOCS, a questionnaire that evaluate the severity of OCS. All the participants have been followed-up for up to 5 years and relapses have been recorded. Results The association between OCS and time in euthymia was fully mediated by the EA so that greater OCS were associated with poorer executive functions (beta=-0.341; p=0.006) that in turn predicted a sooner relapse (beta=0.349; p=0.005). This held true even when controlling for classic predictors of recurrence such as previous episode distance, the duration of illness and medications. Conclusions Treatment targeting executive functions could hence be crucial in preventing relapses in subjects with mood disorders experiencing obsessive compulsive-symptoms. Disclosure No significant relationships.

Introduction Adolescents with major depressive disorder (MDD) often show reduced prefrontal functional connectivity with the subcortical regions than healthy controls (HC) (Tang et al., 2018). However, relatively little is known about longitudinal effects of antidepressant (AD) treatment on resting state functional connectivity (RSFC) in the prefrontal cortex (PFC). Objectives This study aimed to investigate abnormal PFC RSFC in MDD adolescents compared to HC and longitudinal effects of AD on PFC RSFC. Methods This study included 59 adolescents with MDD and 43 HC. MDD adolescents were treated with escitalopram in an 8 week, open-label trial. The treatment outcome was assessed by Children’s Depression Rating Scale (CDRS-R) and patients showing at least a 40% improvement in CDRS-R scores from baseline to week 8 were defined as “responders”. Functional and T1 images collected before and after treatment were processed using AFNI and Freesurfer. Our seed was the lateral PFC (LPFC, BA46). T-tests and repeated measures ANCOVAs, controlling for age and IQ, were conducted to examine abnormal PFC RSFC and longitudinal effects of AD on LPFC RSFC. Results Relative to HC, MDD showed increased LPFC RSFC with the posterior middle temporal gyrus (pMTG) and superior frontal cortex (SFG) involved in attentional networks. Responders showed greater changes in LPFC RSFC with the MTG and SFG after AD treatment compared to non-responders and HC (Figure 1). Conclusions Our finding suggests that reduced LPFC RSFC with the pMTG and SFG reflecting decreased attentional network connectivity may serve as a biomarker to predict AD treatment outcome in adolescents with MDD. Disclosure No significant relationships.

Introduction The challenge for primary care physicians (PCPs) is keeping up to date in managing major depressive disorder (MDD) and psychiatric emergencies. Objectives We evaluated whether an online educational video lecture directed at PCPs, could improve knowledge and confidence regarding management of psychiatric emergencies associated with MDD. Methods Educational effect was assessed using a 3-question repeated pairs, pre/post assessment survey. A paired-samples t-test was conducted to assess overall number correct and confidence change. A McNemar’s test was conducted to assess question-level significance. P values < 0.05 are statistically significant. Cohen’s d test was used to estimate the magnitude of effect of education. The activity launched on 8 April 2021, and preliminary data analysed as of 24 June 2021. Results 511 PCPs participated in the programme, of which 86 PCPs completed the pre- and post-assessment test. An average overall correct response rate of 28% pre- increased to 64% post- (129% relative increase, P

Introduction Childhood maltreatment (CM) contributes to negative mental and physical health outcomes including major depressive disorder (MDD), and an elevated risk for cardiovascular disease (CDV) in adults. Also, childhood maltreatment can be related to mentalizing deficits in MDD. Cardio-metabolic diseases often coincide with MDD and worsen its course and outcome. Little is known on the interplay of these factors. Objectives We examined MDD patients with and without CM to explore the effects of CM on serum lipid and lipoprotein levels and assessed their mentalizing abilities. Self-oriented mentalizing was operationalized as emotional self-awareness/alexithymia, other-oriented mentalizing was defined as theory of mind (ToM). Methods MDD patients (N=42) and healthy controls (n=20) matched in age, sex, and lifestyle were investigated. Total cholesterol, triglycerides, high- and low-density lipoproteins (HDL-C and LDL-C), body mass index, and exercise in a typical week were measured. Beck Depression Inventory, Childhood Trauma Questionnaire, Toronto Alexithymia scale, and the Reading the mind in the Eyes Test were used to assess clinical symptoms, mentalizing abilities and CM. Results After controlling for depressive symptom severity, demographic and lifestyle variables, CM was found to be a strong predictor of serum lipid alterations. Mentalizing deficits correlated with CM. Serum triglycerides, HDL-C were significant predictors of ToM performance (P

Introduction The challenge for psychiatrists is keeping up to date with the latest clinical trial data in managing major depressive disorder (MDD) and psychiatric emergencies. Objectives We evaluated whether an online educational video lecture directed at psychiatrists, could improve knowledge and confidence regarding management of psychiatric emergencies associated with MDD. Methods Educational effect was assessed using a 3-question repeated pairs, pre/post assessment survey. A paired-samples t-test was conducted to assess overall number correct and confidence change. A McNemar’s test was conducted to assess question-level significance. P values < 0.05 are statistically significant. Cohen’s d test was used to estimate the magnitude of effect of education. The activity launched on 8 April 2021, and preliminary data analysed as of 24 June 2021. Results 807 psychiatrists participated in the programme, of which 150 completed the pre- and post-assessment test. An average overall correct response rate of 44% pre- increased to 74% post- (67% relative increase, P

Introduction Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an exciting opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks. Objectives To describe the amount of data collected during a multimodal longitudinal RMT study, in an MDD population. Methods RADAR-MDD is a multi-centre, prospective observational cohort study. People with a history of MDD were provided with a wrist-worn wearable, and several apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks and cognitive assessments and followed-up for a maximum of 2 years. Results A total of 623 individuals with a history of MDD were enrolled in the study with 80% completion rates for primary outcome assessments across all timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. Data availability across all RMT data types varied depending on the source of data and the participant-burden for each data type. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. 110 participants had > 50% data available across all data types, and thus able to contribute to multiparametric analyses. Conclusions RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible. Disclosure No significant relationships.

Several data indicate that the success of pharmacological treatment in major depressive disorder (MDD) is still unsatisfactory. The determination of the optimal treatment generally requires multiple trials with different treatments, with the sobering observation that the more treatments tried without success, the less likely a successful outcome, with the result of a long unremitted disease, worse long term prognosis, increased rates of side effects, and important medical, social and economic burden. The reasons for the low response and remission rates are multiple and depend on environmental and biological factors intrinsic to the disease and drug treatments. Pharmacogenetic (PG) tests have the potential to increase efficacy predicting outcome and to reduce antidepressant discontinuation due to side effects. Several studies investigated the utility of PG tests for antidepressants in MDD with interesting but contrasting results. To date most of them are observational studies with no comparator group, and few are randomized controlled trials (RCTs). Several limitations concerning study design, generalization of results, duration of trials, patients group studied, and cost-effectiveness ratio were found, and a number of barriers have been noted in the adoption of PG tests into clinical practice. Despite some preliminary positive results, there is the need for larger and longer‐term RCT studies, with the goal to capture the real impact of PG tests, also with stratified analysis concerning MDD features in terms of severity and antidepressant treatment failures in different ethnicity cohorts.

Introduction Working Alliance is defined as the emotional bond and the agreement on therapeutic goals and tasks between patients and therapists. Despite the wide use of the construct of working alliance in research on psychotherapy, few studies have investigated the role of working alliance in influencing adherence to pharmacotherapy, and drug attitude. A deeper knowledge of the interplay between working alliance and drug attitude could help to challenge low adherence to psychopharmacological treatments in Major Depressive Disorder. Objectives This study aimed to investigate the relationship between working alliance and drug attitude in patients with Major Depressive Disorder. Methods 27 patients admitted in the Psychiatric Unit of Careggi with diagnosis of Major Depressive Disorders were enrolled. Working Alliance Inventory - patient version (WAI-P), Drug Attitude Inventory (DAI) and Beliefs about Medicines (BMQ) were administered. Pearson’s correlation was used to assess relationships between variables. Results A significant positive correlation was detected between BMQ total scores, DAI total scores and WAI-P task, bond, and goal subscales. Correlations between WAI-P subscales and BMQ and DAI total scores DAI total scores BMQ total scores r p r p WAI-P task 0.551 0.003 0.613 0.001 WAI-P bond 0.430 0.001 0.560 0.004 WAI-P goal 0.621 0.001 0.603 0.002 Conclusions Such preliminary data suggest a relationship between Working Alliance and drug attitude. This could contribute to provide tools to challenge low adherence to psychopharmacological treatments in patients with Major Depressive Disorder. Disclosure No significant relationships.

Introduction Identifying the optimal treatment for individuals with major depressive disorder (MDD) is often a long and complicated process. Functional magnetic resonance imaging (fMRI) studies have been used to help predict and explain differences in treatment response among individuals with MDD. Objectives We conducted a comprehensive meta-analysis of treatment prediction studies utilizing fMRI in patients with MDD to provide evidence that neural activity can be used to predict response to antidepressant treatment. Methods A multi-level kernel density analysis was applied to these primary fMRI studies, in which we analyzed brain activation patterns of depressed patients (N= 364) before receiving antidepressant treatment. Results The results of this analysis demonstrated that hyperactivity in six brain regions significantly predicted treatment response in patients with MDD: the right anterior cingulate, right cuneus, left fusiform gyrus, left middle frontal gyrus, right cingulate gyrus, and left superior frontal gyrus. Conclusions This study provides evidence that neural activity, as measured by standard fMRI paradigms, can be used to successfully predict response to antidepressant treatment. This may be used in the future clinically to improve decision-making processes and treatment outcomes for patients. Disclosure No significant relationships.

Introduction In vivo and in vitro studies suggest that inflammation and oxidative damage may contribute to the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). Imbalance between DNA damage and repair is an emerging research area examining pathophysiological mechanisms of these major mood disorders. Objectives This systematic review sought to examine current evidence on the association between mood disorders and deficits in base excision repair (BER), the primary repair mechanism for repair of oxidation-induced DNA lesions. Methods We conducted a comprehensive literature search of Ovid MEDLINE® Epub Ahead of Print, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Ovid MEDLINE® Daily, EMBASE (1947), and PsycINFO for studies investigating the alterations in base excision repair in patients with MDD or BD. Results A total of 1,364 records were identified. 1,352 records remained after duplicates were removed. 24 records were selected for full-text screening and a remaining 12 articles were included in the qualitative synthesis. SNPs (Single Nucleotide Polymorphisms) of several BER genes have been shown to be associated with MDD and BD. However, it was difficult to draw conclusions from BER gene expression studies due to conflicting findings and the small number of studies. Conclusions Future studies comparing DNA repair during the manic or depressive episode to remission will give us a better insight regarding the role of DNA repair in mood disorders. These alterations might be utilized as diagnostic and prognostic biomarkers as well as measuring treatment response. Disclosure No significant relationships.

Introduction Antidepressants that offer a rapid onset of action without requiring chronic use are greatly needed in both major depressive disorder (MDD) and postpartum depression (PPD). Zuranolone is an investigational, oral, neuroactive steroid and GABAA receptor positive allosteric modulator in clinical development as a 2-week treatment course for MDD and PPD. Objectives To present the efficacy and safety of zuranolone vs placebo in Phase 2 and 3 trials. Methods In the studies presented (Table 1), improvements in depressive symptoms were assessed by least-squares mean (LSM) using a mixed-effects model for repeated measures on the change from baseline (CFB) at Day 15 in the 17-item Hamilton Rating Scale for Depression total score (HAMD-17; primary endpoint for all trials) and the Montgomery–Åsberg Depression Rating Scale (MADRS; secondary endpoint) following a 14-day treatment course of once-daily zuranolone. Results Compared with placebo, zuranolone treatment led to rapid improvements in depressive symptoms across clinical trials, with significant improvements (LSM treatment difference [SE] in CFB) in HAMD-17 and MADRS scores at Day 15 in 3 of the 4 trials (Table 2). Common treatment-emergent adverse events (≥5% in zuranolone treatment arms) were headache, somnolence, dizziness, nausea, sedation, diarrhea, upper respiratory tract infection, and fatigue (Table 3). No incidences of loss of consciousness or excessive sedation were observed. Conclusions Across the completed studies in the zuranolone clinical trial program, patients receiving zuranolone consistently experienced improvement in depressive symptoms following a 2-week treatment course. Treatment with zuranolone was generally well tolerated with a consistent safety and tolerability profile. Disclosure The MDD-201B, MOUNTAIN, and ROBIN studies were sponsored by Sage Therapeutics, Inc; the WATERFALL study was sponsored by Sage Therapeutics, Inc, and Biogen. Medical writing and editorial support were provided by MediTech Media, Ltd, and funded by Biogen.

Introduction Major depressive disorder (MDD), especially in case of suicidal risk, is a psychiatric emergency, associated with high patient burden and healthcare resource utilization. Although active and urgent treatment is crucial, little is known on comprehensive care management of this condition in Italy. Objectives Here we report the ARIANNA study [NCT04463108] interim results to primarily describe the treatment utilization pathways of patients with MDD and active suicidal ideation with intent in the current clinical practice in Italy. Methods This observational prospective cohort study included adult patients with a moderate-to-severe major depressive episode (MDE) and active suicidality from 24 Italian sites. Real-world data on patient characteristics, treatments, clinical outcomes, and healthcare utilization were collected during a 90-day follow-up. Data collection is still ongoing. Results Sixty-four evaluable patients were considered for this interim analysis: 41 (64.1%) females, mean [SD] age 46.0 [15.4] years, a concomitant psychiatric diagnosis in 7 (10.9%), and other comorbidities in 26 (40.6%). The baseline mean [SD] MADRS total score was 37.5 [7.2], with severe MDE and prior suicidal behavior in 30 (46.9%) and 21 (32.8%) patients, respectively. Median [25th;75th percentiles] duration of current MDE was 1.1 [0.3;2.1] months. Acute inpatient hospitalization was provided for 43 (67.2%) patients. Antidepressant augmentation with mood stabilizers and/or antipsychotic drugs and optimization were the most frequent early standard-of-care treatment regimens in 32 (53.3%) and 24 (40.0%) patients with available data (N=60), respectively. Conclusions Our preliminary results suggest that initial treatment approaches in this critical population are mostly polypharmacological and delivered as inpatient care, with consequent intensive resource utilization. Disclosure The ARIANNA study was sponsored by Janssen-Cilag SpA, Italy. DD and MA are employees of Janssen-Cilag SpA. DA and BR are employees of MediNeos S.U.R.L., a company subject to the direction and coordination of IQVIA Solutions HQ Ltd.

Introduction Both Major Depressive and Alcohol Use Disorders are highly prevalent. They also are the major contributors to disability and decreased quality of life and, as they are often comorbid with each other, the diagnosis and treatment of concurrent depression and alcohol use disorder represents a challenging task with multiple clinical questions requiring evidence-based recommendations. Objectives The goal of this presentation is to review the optimal strategies to treat concurrent alcohol use and major depressive disorders in the context of current research findings and clinical practice. Methods Narrative review, knowledge synthesis. Results The most up-to-date research findings in the areas of epidemiology of concurrent depression and alcohol use disorder, their differential diagnosis, and treatment approaches will be reviewed. This review will include the current evidence of effectiveness of various antidepressants in treatment of depression concurrent with alcohol use disorder and antidipsotropic agents use for alcohol use disorder in the context of depressive symptoms, as well as their combinations. We will discuss the timeline of initiation of both antidepressants and antidipsotropic agents, non-pharmacological treatment modalities as well as the clinical tools that can be used to properly monitor patients’ progress and optimize the treatment process, and the integrative teamwork necessary to achieve optimal results. Conclusions Ultimately, the optimal diagnostic and treatment algorithm and the set of evidence-based treatment recommendations will be presented. Disclosure No significant relationships.

Background. Despite well-established guidelines for managing major depressive disorder, its extensive disability burden persists. This Value of Treatment mission from the European Brain Council aimed to elucidate the nature and extent of “gaps” between best-practice and current-practice care, specifically to: 1. Identify current treatment gaps along the care pathway and determine the extent of these gaps in comparison with the stepped-care model and 2. Recommend policies intending to better meet patient needs (i.e., minimize treatment gaps). Methods. After agreement upon a set of relevant treatment gaps, data pertaining to each gap were gathered and synthesized from several sources across six European countries. Subsequently, a modified Delphi approach was undertaken to attain consensus among an expert panel on proposed recommendations for minimizing treatment gaps. Results. Four recommendations were made to increase the depression diagnosis rate (from ~50% episodes), aiming to both increase the number of patients seeking help, and the likelihood of a practitioner to correctly detect depression. These should reduce time to treatment (from ~1 to ~8 years after illness onset) and increase rates of treatment; nine further recommendations aimed to increase rates of treatment (from ~25 to ~50% of patients currently treated), mainly focused on targeting the best treatment to each patient. To improve follow-up after treatment initiation (from ~30 to ~65% followed up within 3 months), seven recommendations focused on increasing continuity of care. For those not responding, 10 recommendations focused on ensuring access to more specialist care (currently at rates of ~5–25% of patients). Conclusions. The treatment gaps in depression care are substantial and concerning, from the proportion of people not entering care pathways to those stagnating in primary care with impairing and persistent illness. A wide range of recommendations can be made to enhance care throughout the pathway. [ABSTRACT FROM AUTHOR]

Background. There is increasing attention on the association of socioeconomic status and individual behaviors (SES/IB) with mental health. However, the impacts of SES/IB on mental disorders are still unclear. To provide evidence for establishing feasible strategies on disease screening and prevention, we implemented Mendelian randomization (MR) design to appraise causality between SES/IB and mental disorders. Methods. We conducted a two-sample MR study to assess the causal effects of SES and IB (dietary habits, habitual physical activity, smoking behaviors, drinking behaviors, sleeping behaviors, leisure sedentary behaviors, risky behaviors, and reproductive behaviors) on three mental disorders, including bipolar disorder, major depressive disorder and schizophrenia. A series of filtering steps were taken to select eligible genetic instruments robustly associated with each of the traits. Inverse variance weighted was used for primary analysis, with alternative MR methods including MR-Egger, weighted median, and weighted mode estimate. Complementary methods were further used to detect pleiotropic bias. Results. After Bonferroni correction and rigorous quality control, we identified that SES (educational attainment), smoking behaviors (smoking initiation, number of cigarettes per day), risky behaviors (adventurousness, number of sexual partners, automobile speeding pro)pensity) and reproductive behavior (age at first birth) were causally associated with at least one of the mental disorders. Conclusions. MR study provides robust evidence that SES/IB play broad impacts on mental disorders. [ABSTRACT FROM AUTHOR]

Background Major depressive disorder (MDD) is a polygenic disorder associated with brain alterations but until recently, there have been no brain-based metrics to quantify individual-level variation in brain morphology. Here, we evaluated and compared the performance of a new brain-based ‘Regional Vulnerability Index’ (RVI) with polygenic risk scores (PRS), in the context of MDD. We assessed associations with syndromal MDD in an adult sample (N = 702, age = 59 ± 10) and with subclinical depressive symptoms in a longitudinal adolescent sample (baseline N = 3,825, age = 10 ± 1; 2-year follow-up N = 2,081, age = 12 ± 1). Methods MDD-RVIs quantify the correlation of the individual’s corresponding brain metric with the expected pattern for MDD derived in an independent sample. Using the same methodology across samples, subject-specific MDD-PRS and six MDD-RVIs based on different brain modalities (subcortical volume, cortical thickness, cortical surface area, mean diffusivity, fractional anisotropy, and multimodal) were computed. Results In adults, MDD-RVIs (based on white matter and multimodal measures) were more strongly associated with MDD (β = 0.099–0.281, PFDR = 0.001–0.043) than MDD-PRS (β = 0.056–0.152, PFDR = 0.140–0.140). In adolescents, depressive symptoms were associated with MDD-PRS at baseline and follow-up (β = 0.084–0.086, p = 1.38 × 10−4−4.77 × 10−4) but not with any MDD-RVIs (β < 0.05, p > 0.05). Conclusions Our results potentially indicate the ability of brain-based risk scores to capture a broader range of risk exposures than genetic risk scores in adults and are also useful in helping us to understand the temporal origins of depression-related brain features. Longitudinal data, specific to the developmental period and on white matter measures, will be useful in informing risk for subsequent psychiatric illness. [ABSTRACT FROM AUTHOR]

Abstract Background Major depressive disorder (MDD) is a polygenic disorder associated with brain alterations but until recently, there have been no brain-based metrics to quantify individual-level variation in brain morphology. Here, we evaluated and compared the performance of a new brain-based ‘Regional Vulnerability Index’ (RVI) with polygenic risk scores (PRS), in the context of MDD. We assessed associations with syndromal MDD in an adult sample (N = 702, age = 59 ± 10) and with subclinical depressive symptoms in a longitudinal adolescent sample (baseline N = 3,825, age = 10 ± 1; 2-year follow-up N = 2,081, age = 12 ± 1). Methods MDD-RVIs quantify the correlation of the individual’s corresponding brain metric with the expected pattern for MDD derived in an independent sample. Using the same methodology across samples, subject-specific MDD-PRS and six MDD-RVIs based on different brain modalities (subcortical volume, cortical thickness, cortical surface area, mean diffusivity, fractional anisotropy, and multimodal) were computed. Results In adults, MDD-RVIs (based on white matter and multimodal measures) were more strongly associated with MDD (β = 0.099–0.281, PFDR = 0.001–0.043) than MDD-PRS (β = 0.056–0.152, PFDR = 0.140–0.140). In adolescents, depressive symptoms were associated with MDD-PRS at baseline and follow-up (β = 0.084–0.086, p = 1.38 × 10−4−4.77 × 10−4) but not with any MDD-RVIs (β 0.05). Conclusions Our results potentially indicate the ability of brain-based risk scores to capture a broader range of risk exposures than genetic risk scores in adults and are also useful in helping us to understand the temporal origins of depression-related brain features. Longitudinal data, specific to the developmental period and on white matter measures, will be useful in informing risk for subsequent psychiatric illness.

Abstract Background Despite well-established guidelines for managing major depressive disorder, its extensive disability burden persists. This Value of Treatment mission from the European Brain Council aimed to elucidate the nature and extent of “gaps” between best-practice and current-practice care, specifically to: 1. Identify current treatment gaps along the care pathway and determine the extent of these gaps in comparison with the stepped-care model and 2. Recommend policies intending to better meet patient needs (i.e., minimize treatment gaps). Methods After agreement upon a set of relevant treatment gaps, data pertaining to each gap were gathered and synthesized from several sources across six European countries. Subsequently, a modified Delphi approach was undertaken to attain consensus among an expert panel on proposed recommendations for minimizing treatment gaps. Results Four recommendations were made to increase the depression diagnosis rate (from ~50% episodes), aiming to both increase the number of patients seeking help, and the likelihood of a practitioner to correctly detect depression. These should reduce time to treatment (from ~1 to ~8 years after illness onset) and increase rates of treatment; nine further recommendations aimed to increase rates of treatment (from ~25 to ~50% of patients currently treated), mainly focused on targeting the best treatment to each patient. To improve follow-up after treatment initiation (from ~30 to ~65% followed up within 3 months), seven recommendations focused on increasing continuity of care. For those not responding, 10 recommendations focused on ensuring access to more specialist care (currently at rates of ~5–25% of patients). Conclusions The treatment gaps in depression care are substantial and concerning, from the proportion of people not entering care pathways to those stagnating in primary care with impairing and persistent illness. A wide range of recommendations can be made to enhance care throughout the pathway.

Introduction The relevance of inflammation to psychiatric disorders is well established. While inflammation was broadly investigated in mood disorders, obsessive-compulsive disorder (OCD) received little attention. C-reactive protein (CRP) is an inflammatory marker commonly assessed in clinical practice. Studies comparing CRP levels across mood disorders and OCD are lacking. Objectives We compared the prevalence of CRP-based low-grade inflammation (LGI) across major depressive disorder (MDD), bipolar disorder (BD) and OCD, taking into account multiple individual variables that may affect CRP levels. Methods Retrospective, observational cross-sectional study in a naturalistic sample of hospitalized patients with MDD or BD or OCD. Information was collected from electronic medical records. Based on serum CRP levels at admission, the following were defined: CRP: >3 mg/L and ≤10 mg/l, “yes” LGI; ≤3 mg/L, “no” LGI. Logistic regression models were applied. Results We included 156 patients with MDD, 135 with BD, and 97 with OCD. We found prevalence rates of CRP-LGI of 29.9%, 36.5%, and 47.4% in patients with OCD, MDD, and BD, respectively, without significant differences between groups. The entire set of individual variables considered (e.g., sex, body mass index, medication) explained only one-third of the observed variations in CRP-LGI. Conclusions CRP-LGI may be a transdiagnostic feature of a substantial portion of patients with MDD or BD or OCD, rather than being exclusive to a specific psychiatric disorder. The presence of LGI was not fully explained by individual confounding factors. Given the relevance of inflammation to psychiatric and medical outcome, routine measurements of CRP in psychiatric settings may be valuable. Disclosure No significant relationships.

Introduction Mindfulness-based cognitive therapy (MBCT) is a third wave cognitive-behavioral therapy (CBT) that incorporates meditation exercises in the classical, structured intervention. Mindfulness has been associated with psychological well-being, and certain symptoms that occur in major depressive disorder (MDD), e.g. worries, ruminations, ideas of incapacity or self-devaluation, are considered potential targets for MBCT. Objectives To evaluate the current level of evidence for the MCBT efficacy in MDD. Methods A literature serach was performed in the main electronic databases, targeting clinical trials that evaluated in a randomized manner the efficacy of MCBT versus active comparators or placebo in patients with MDD. Results MBCT was efficient in a 10-week randomized controlled trial (RCT) versus standard treatment, and it decreased ruminations, increased patients quality of life, mindfulness abilities, and self-compassion. In another randomized, 8-week RCT, MBCT prevented relapses in MDD, with similar rates when compared to psychoeducation and standard treatment. A 26-month follow-up study evidenced the persistence of symptoms improvement detected after 12 months of the trial, when compared to active control group and treatment as usual. MCBT was compared to cognitive therapy in a randomized 8-week trial, and both treatments had similar efficacy in MDD relapse prevention. Conclusions MCBT may be an useful adjuvant to the current treatment in acute MDD, but it may also decrease the risk of relapse after psychotherapy termination.

Introduction Major depressive disorder (MDD) is a severe, disabling condition with unknown etiology. Misdiagnosis is common when clinical symptomology criteria are used solely. Considerable evidence suggests that the upregulation of inflammatory factors and cortisol, and a decrease in neurotrophic factors, are involved in the pathogenesis of MDD. Objectives This study explored the application of platforms composed of these serum proteins in the objective diagnosis of MDD. Methods Serum samples from all participants including 30 MDD patients and 30 well-matched healthy controls were collected at enrollment, eight serum proteins selected initially according to previous studies were analyzed with ELISA. A logistic regression model with these proteins was built to construct the diagnostic platform for the MDD and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic potential of the model. Results Among the eight selected proteins, three (TNF-alpha, IL-6 and IL-1beta) were removed because the measurements in more than 1/3 participants were below the detectable limits of ELISA kits. Forward logistic stepwise regression analysis screened out three serum proteins including BDNF, cortisol and IFN-gamma to build the model. The regression equation was Z = 1/[1 + e−(1.438+0.005(BDNF)-0.049(cortisol)-0.007(IFN-gamma))], and the diagnostic efficacy of thees three proteins-combined achieved an area under the ROC curve of 0.884 with sensitivity of 86.7% and specificity of 83.3%. Conclusions The results of this study provided a more reliable method to diagnose MDD, and the combination of serum BDNF, cortisol and IFN-gamma may provide an objective diagnostic platform for MDD.

Introduction Psoriazis and major depressive disorder (MDD) have a high degree of overlap, and inflammatory citokines like tumor necrosis factor alpha, interleukins 1, 2, 6 and 10, and C-reactive protein have been involved in their common pathogenesis. The prevalence of MDD in patients with psoriazis has been reported to range between 28% to 67%. Objectives To monitor the core symptoms evolution in patients diagnosed with psoriazis and MDD during antidepressant treatment. Methods Four patients diagnosed with psoriazis and MDD (according to the DSM-5 criteria) were monitored during 6 months using Physician Static Global Assessment (PSGA), Hamilton Depression Rating Scale (HDRS)-17 items, and Global Assessment of Functioning (GAF). All patients underwent specific psoriazis and antidepressant treatment (with flexible dose of sertraline 100-200 mg daily, n=2, or escitalopram 10-20 mg/day, n=2). Results All patients significantly improved their depressive symptoms during sertraline or escitalopram treatment (-8.7 points on HAMD at week 24, p

Introduction Cognitive behavioral therapies (CBT) represent a heterogeneous group of psychotherapies in continuous development that share a directive, structured, collaborative approach. Due to a high degree of treatment-resistant cases of major depressive disorder (MDD), new augmentation therapies are urgently needed, in order to increase the chance of recovery in these patients. Objectives To analyze data that may support the indication of third wave CBT in patients with MDD. Methods A literature search was performed in the main electronic databases, and papers published between January 2000 and August 2020 were included. Results Acceptance and commitment therapy has been associated with positive results, but data are derived from low quality trials (n=2). Dialectical-behavioral therapy (DBT)-based skill group have been also associated with favorable outcome, in MDD patients (n=2). Mindfulness-based cognitive therapy (MBCT) was also proven effective in the treatment in MDD (n=4), treatment-resistant MDD included, but the difference between MBCT and active comparators was not always significant. Metacognitive therapy (MCT) has been evaluated in good quality clinical trials (n=4), and its efficacy was confirmed. Mild and moderate MDD patients may benefit from compassion-focused therapy (CFT) (n=1). Behavioral activation (BA) is dedicated to MDD patients and according to a meta-analysis (n=26 randomized controlled trials) BA is superior to other active comparators, although the quality of clinical trials was modest. Conclusions Third generation CBT could be useful in MDD patients as augmentative strategy, but more good-quality data are necessary before recommending them in an evidence-based treatment guideline as a distinctive intervention from classical CBT.

Introduction Previous study has identified increased antithrombin III (ATIII) in patients with major depressive disorder (MDD), supporting ATIII as a potential biomarker for depression diagnosis. Objectives This study aimed to reveal the alteration of ATIII after occipital repetitive transcranial magnetic stimulation (rTMS), and illuminate its power to evaluate and predict the curative effects in MDD treatment. Methods A total of 90 MDD patients were recruited and further intervened with rTMS in occipital for individualized, standard or sham treatment for five days. Those of 74 patients underwent entire detection, including clinical assessments, blood collection and protein measurement. Results After treatment, decreased ATIII were detected in both the individualized and the standard group (p=0.000 and 0.001, respectively) instead of the sham one. Especially, the reduction in ATIII in the individualized group was associated with improvements in several neuropsychological assessments. Besides, ATIII at baseline in the standard group and after the individualized rTMS showed high performance to evaluate or predict the response to the 5-day treatment (AUC=0.771, 95%CI, 0.571-0.971; AUC=0.875, 95%CI, 0.714-1.000, respectively) and the remission in follow-up (AUC=0.736, 95%CI, 0.529-0.943; AUC=0.828, 95%CI, 0.656-1.000, respectively). Furthermore, both baseline ATIII and change in ATIII involved in the prediction of 24-item Hamilton Depression Rating Scale in the follow-up study with significant predictive values (p=0.0240 and 0.0233, respectively). Conclusions This study detected a reduction in ATIII after occipital rTMS, further revealed the relationships between change in ATIII and therapeutic response, and ultimately provided evidence for the potential of ATIII as a biomarker for the evaluation and prediction of antidepressive effect. Disclosure No significant relationships.

Introduction Stressful life events (SLE) may influence the illness course and outcome. Objectives The present study aimed to characterize socio-demographic and clinical characteristics of euthymic major depressive disorder (MDD) outpatients with SLE relative to those without. Methods This sample included 628 (mean age=55.1 ± 16.1) currently euthymic MDD outpatients, among them 250 (39.8%) reported SLE and 378 (60.2%) did not. Results After univariate analyses, outpatients with SLE were most frequently widowed and lived predominantly with friends/others. Furthermore, compared to outpatients without SLE, those with SLE were more likely to have a family history of suicidal behavior, manifested melancholic characteristics and higher Coping Orientation to the Problems Experienced (COPE) positive reinterpretation/growth and less likely to manifest a comorbid panic disorder, residual interepisodic symptoms, have used psychiatric medications, and use current antidepressant medications. After regression analyses, having a family history of suicide (OR=9.697; p=≤.05), history of psychotropic medications use (OR=2.888; p=≤.05), and reduced use of antidepressants (OR=.321; p=.001) were significantly associated with SLE. Mediation analyses demonstrated that the association between current use of antidepressants and SLE was mediated by previous psychiatric medications. Conclusions Having a family history of suicide, history of psychotropic medications use, and reduced use of antidepressants may confer a specific “at risk” profile related to the enhanced vulnerability to experience SLE. Disclosure No significant relationships.

Introduction Cognitive function is impaired in depressive disorders. Among several factors implicated in regulation of the cognitive function, metabolic syndrome has been showed have a pivotal role cognitive functioning in healthy controls. However, the role of metabolic syndrome in regulating the cognitive functioning of subjects affected by depressive disorders is little studied. Objectives To investigate the effect of metabolic syndrome in regulation of cognition in unipolar and bipolar depression. Methods One-hundred-sixty-five people affected by a depressive disorder (unipolar depression, UP; bipolar depression, BP) were enrolled at the Psychiatric and Clinic Psychology Unit of the University of Rome Tor Vergata, Rome, Italy. A group of healthy controls (HC) matched for agender and age was enrolled. The cognitive functions were evaluated with a computerized tool, THINC-it. Results UP and BP had lower performances in THINC-it cognitive domains than HC. Metabolic syndrome is a negative, independent predictor of low performance in the THINC-it cognitive domains of people with depressive disorders. Conclusions Our findings confirm that metabolic syndrome has a prominent role in determining the cognitive efficiency in depressive disorders, independently by the presence of a unipolar or bipolar depressive disorder. Metabolic syndrome has to be considered a major factor that should be considered in the treatment strategies of cognitive functioning improvement of people affected by depressive disorders. Disclosure No significant relationships.

Introduction Suicide is a global health problem. The elderly is the range with the highest suicide rate and suicidal behaviors are more lethal, with greater planning and less possibility of rescue. In the elderly, Major Depressive Disorder is the diagnosis most frequently associated with suicidal behavior. 15% of the elderly with a depressive picture commit suicide. Loneliness, the main cause of suicides in the elderly population. Objectives The objective of the clinical case presented is to address the risk factors for suicide in the elderly. Methods 80-year-old patient, widower who makes a suicide attempt by ingesting glyphosate. Personal history: Acute myocardial infarction 1 month ago. Not mental illness. Family stressors: illness of his granddaughter, loss of his son’s job. Personal stressors: Loss of autonomy due to ischemic heart disease. The patient was admitted to the Intensive Care Unit with acute pulmonary edema secondary to the suicide attempt. Psychopathological exploration: Conscious, oriented and collaborative. Depressive mood in relation to the stressors presented. Makes partial criticism of the suicide attempt, recognizes its seriousness and planning. Results Diagnosis: Moderate depressive episode. SAD PERSONS scale: 9 High risk. Conclusions The risk factors for suicide in older people can be medical, psychiatric, psychological, family environment and social - environmental factors. There are hardly any specific action protocols that allow early intervention and suicide prevention in the elderly. As social health professionals, we must work on the elaboration and application of these, since consummated suicide represents a major public health problem throughout the world.

Introduction Associations between childhood trauma (CT), social support (SS), brain functions and major depressive disorder (MDD) is unknown. Objectives This study aimed to investigate whether brain functions mediated associations between CT, SS, and MDD. Methods 164 MDD and 98 healthy controls (HC) were recruited and measured by HAMD-24 and HAMA. Some completed CT questionnaire (CTQ) and social support rating scale (SSRS). We examined amplitude of low-frequency fluctuation (ALFF) between the two groups and correlations between HAMD-24, HAMA and ALFF in MDD. Then, the peak voxels of the ALFF changed regions were used as seeds to analyze whole-brain functional connectivity (FC). Next, correlations between FC and clinical variables of MDD were performed. Last, mediation analysis was used to further determine whether ALFF or FC could mediate the associations between CT, SS, and different clinical variables in MDD patients. Results Compared to HC, MDD showed decreased ALFF in right posterior cingulate (PCC_R), left postcentral gyrus, right precentral gyrus, and left thalamus (THA_L), but increased ALFF in right medial frontal gyrus, left subgenual anterior cingulate, and left middle occipital gyrus as well as decreased FC in bilateral PCC and THA_R. HAMD-24 had negative correlation with ALFF of THA_L, while positive with sexual abuse (SA) score in MDD. Mediation analysis revealed that FC of PCC_R mediated association between SA and baseline HAMD-24, and itself or together with SS mediated association between CT and onset age of MDD. Conclusions CT may influence the depression severity and onset age of MDD by moderating FC of PCC_R only or together with SS.

Introduction Electroconvulsive Therapy (ECT) is one of the most effective treatments for Depressive Disorder. Although its safety and tolerability have been throughout the years, it still holds common mild and rarely persistent side effects. Objectives The aim is to review some of the most recent data on the connection between inaugural seizures in psychiatric patients being submitted to ECT for treatment of Major Depressive Disorder, while also discussing the possible contribution of the concomitant use of clozapine and clomipramine. Methods The authors present a case report of an episode of an inaugural seizure in a patient submitted to ECT, with concomitant use of clozapine and clomipramine. A search on Pubmed and Clinicalkey was performed, from which the relevant publications were selected and reviewed. Results The authors present a 62 year old woman who developed an inaugural generalized tonic-clonic seizure after being submitted to ECT for treatment of Recurrent Major Depressive Disorder (RMDD), while also carrying out clozapine and clomipramine dosage reduction, with the purpose of discontinuation. The patient had no history of previous seizures, nor were there relevant findings in the patient’s neurological examination, blood work, brain CT or EEG. Conclusions There is a plethora of possible factors involved in the development of an inaugural seizure. Although, the risk of spontaneous seizure during ECT is low, it may be increased by the concomitant use of drugs which can lower the seizure threshold. In most cases, when ECT was resumed after removal of such triggers, there were no further complications.

The only available genome-wide study (Minelli et al., 2018) indicated an association between the neglect CT and MED22, a transcriptional factor gene. To verify how the dysregulation of MED22 could be affected by environmental and genetic factors, we carried out an analysis on these components and a longitudinal study concerning the effect of trauma-focused psychotherapy in MDD patients that experienced CT. On a large mRNA sequencing dataset including 368 MDD patients we computed the genetic (GReX) and the environmental (EReX) components affecting gene expression in relation to CT. Furthermore, we measured the expression of MED22 in 22 MDD patients treated with trauma-focused psychotherapy. The dissection of MED22 expression profiles revealed an association of neglect with environmental and genetic components (p=6x10-3 p=2.6x10-4). Furthermore, in an independent cohort of 177 controls, we also observed a significant association between cis-eSNPs of MED22 and higher neuroticism scores (best p-value: 0.00848) that are usually associated with a decreased amount of resilience to stress events. Finally, the results of psychotherapy revealed a reduction of depressive symptomatology (p

Introduction Chronic fatigue syndrome (CFS) is a complex condition, with an insufficiently known pathophysiology, that raises multiple challenges to the treating physicians. Due to its yet mostly unknown underlying mechanisms, there is no consensus treatment recommendation for CFS. The risk to associate major depression, anxiety disorders or substance use disorders is frequently reported, and this co-morbidity further complicates the evolution of CFS. Objectives To search the existing literature for pharmacological and psychotherapeutic recommendations in CFS. Methods A literature search was performed using the main electronic databases using the paradigm „chronic fatigue syndrome” AND „psychopharmacological treatment” OR „psychotherapy”. All papers published between January 2000 and August 2020 were included in the primary analysis. Results Anti-inflamatory drugs (corticosteroids and non-steroidal drugs), antidepressants, moodstabilizers, anxiolytics, immuno-modulatory drugs, and antivirals have been investigated for CFS, but the trials had low-quality designs, used various definition of CFS, and different criteria for monitoring the efficacy of treatment. Cognitive behavioral therapy (CBT) may be promising for decreasing the fatigue severity, but larger trials are needed. Graded exercise therapy (GET) also may be of some use for improving patients ability to engage in activities, but caution should be in order because of the risk of over-exercising that may exacerbate the core CFS symptoms. Conclusions Larger trials are needed in order to validate pharmacological and psychotherapeutic recommendations for CFS. No drug may be considered first line treatment for this indication, while CBT and GET may be useful, although they do not address all the central symptoms of CFS.

AbstractBackgroundRecent imaging studies of large datasets suggested that psychiatric disorders have common biological substrates. This study aimed to identify all the common neural substrates with connectomic abnormalities across four major psychiatric disorders by using the data-driven connectome-wide association method of multivariate distance matrix regression (MDMR).MethodsThis study analyzed a resting functional magnetic resonance imaging dataset of 100 patients with schizophrenia, 100 patients with bipolar I disorder, 100 patients with bipolar II disorder, 100 patients with major depressive disorder, and 100 healthy controls (HCs). We calculated a voxel-wise 4,330 × 4,330 matrix of whole-brain functional connectivity (FC) with 8-mm isotropic resolution for each participant and then performed MDMR to identify structures where the overall multivariate pattern of FC was significantly different between each patient group and the HC group. A conjunction analysis was performed to identify common neural regions with FC abnormalities across these four psychiatric disorders.ResultsThe conjunction of the MDMR maps revealed that the four groups of patients shared connectomic abnormalities in distributed cortical and subcortical structures, which included bilateral thalamus, cerebellum, frontal pole, supramarginal gyrus, postcentral gyrus, lingual gyrus, lateral occipital cortex, and parahippocampus. The follow-up analysis based on pair-wise FC of these regions demonstrated that these psychiatric disorders also shared similar patterns of FC abnormalities characterized by sensory/subcortical hyperconnectivity, association/subcortical hypoconnectivity, and sensory/association hyperconnectivity.ConclusionsThese findings suggest that major psychiatric disorders share common connectomic abnormalities in distributed cortical and subcortical regions and provide crucial support for the common network hypothesis of major psychiatric disorders.