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Depression is associated with general medical conditions (GMCs), but it is not known if treatment-resistant depression (TRD) affects GMC risk and vice versa. We estimated bidirec-tional associations between TRD and GMCs (prior and subsequent). All individuals aged 18-69 years, born and living in Denmark, with a first-time prescription for an antidepressant between 2005 and 2012 were identified in the Danish Prescription Registry ( N = 154,513). TRD was de -fined as at least two shifts in treatment regimes. For prior GMCs, we estimated odds ratios (ORs) using conditional logistic regression comparing TRD patients with matched non-TRD controls adjusted for other GMCs and number of other GMCs. For subsequent GMCs, we used Cox regression to calculate hazard ratios (HRs) in TRD vs. non-TRD patients adjusted for age at first prescription, calendar time, other GMCs and number of other GMCs. Patients with TRD had higher prevalence of prior GMCs related to the immune or neurological systems; musculoskeletal disorders (women aOR: 1.35, 95% CI: 1.26-1.46, men aOR: 1.30, 95% CI: 1.19-1.42) and migraine (women aOR: 1.22, 95% CI: 1.09-1.36, men aOR: 1.25, 95% CI: 1.00-1.56). Subsequent GMCs were related to a broader spectrum; cardiovascular (women aHR: 1.43, 95% CI: 1.32-1.54, men aHR: 1.31, 95% CI: 1.19-1.43), endocrine (women aHR: 1.52, 95% CI: 1.37-1.67, men aHR: 1.24, 95% CI: 1.07-1.44), and neurological disorders (women aHR: 1.24, 95% CI: 1.13-1.35, men aHR: 1.19, 95% CI: 1.07-1.34). Our study presents a broad overview of comorbid medical conditions in patients with TRD and further studies are needed to explore the associations in detail. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

The diagnosis and treatment of bipolar depression (BDep) poses complex clinical challenges for psychiatry. Proton magnetic resonance spectroscopy (1H-MRS) is a useful imaging tool for investigating in vivo levels of brain neuro-metabolites, critical to understanding the process of mood dysregulation in Bipolar Disorder. Few studies have evaluated longitudinal clinical outcomes in BDep associated with 1H-MRS metabolic changes. This study aimed to longitudinally assess brain 1H-MRS metabolites in the anterior cingulate cortex (ACC) correlated with improvement in depression (from BDep to euthymia) after lithium treatment in BDep patients versus matched healthy controls (HC). Twenty-eight medication-free BDep patients and 28 HC, matched for age and gender, were included in this study. All subjects were submitted to a 3-Tesla brain 1H-MRS scan in the ACC using a single-voxel (8cm3) PRESS sequence at baseline. At follow-up (6 weeks), 14 BDep patients repeated the exam in euthymia. Patients with current BDep had higher baseline Myo-inositol/Cr (mI/Cr) and Choline/Cr (Cho/Cr) compared to HC. After six weeks, mI/Cr or Cho/Cr levels in subjects that achieved euthymia no longer differed to levels in HC, while high Cho/Cr levels persisted in non-responders . Elevated ACC mI/Cr and Cho/Cr in BDep might indicate increased abnormal membrane phospholipid metabolism and phosphatidylinositol (PI) cycle activity. Return of mI/Cr and Cho/Cr to normal levels after lithium-induced euthymia suggests a critical regulatory effect of lithium targeting the PI cycle involved in mood regulation.

Using pre-treatment biomarkers to guide patients to the preferred antidepressant medication treatment could be a promising approach to enhance its current modest response and remission rates. This open-label prospective study assessed the feasibility of using such pre-treatment biomarkers, by using previously identified EEG features (paroxysmal activity; alpha peak frequency; frontal alpha asymmetry) to inform the clinician in selecting among three different antidepressants (ADs; escitalopram, sertraline, venlafaxine) as compared to Treatment As Usual (TAU). EEG data were obtained from 195 outpatients with major depressive disorder prior to eight weeks of AD treatment. Primary outcome measure was the percentage change between before and after treatment on the Beck Depression Inventory-II (BDI-II). We compared TAU and EEG-informed prescription through AN(C)OVAs. Recruitment started with patients receiving TAU to establish baseline effectiveness, after which we recruited patients receiving EEG-informed prescription. 108 patients received EEG-informed prescription and 87 patients received TAU. Clinicians and patients were satisfied with the protocol. Overall, 70 (65%) of the EEG-informed clinicians followed recommendations (compared to 52 (60%) following prescriptions in the TAU group), establishing feasibility. We here confirm that treatment allocation informed by EEG variables previously reported in correlational studies, was feasible.

Panic disorder (PD), a common anxiety disorder, is modestly heritable. The genetic basis of anxiety disorders overlaps with that of other psychiatric disorders and their intermediate phenotypes in individuals of European ancestry. Here, we investigated the transethnic polygenetic features shared between Japanese PD patients and European patients with psychiatric disorders and their intermediate phenotypes by conducting polygenic risk score (PRS) analyses. Large-scale European genome-wide association study (GWAS) datasets (n = 7,556–1,131,881) for ten psychiatric disorders and seven intermediate phenotypes were utilized as discovery samples. PRSs derived from these GWASs were calculated for Japanese target subjects [718 PD patients and 1,717 healthy controls (HCs)]. The effects of these PRSs from European GWASs on the risk of PD in Japanese patients were investigated. The PRSs from European studies of anxiety disorders were marginally higher in Japanese PD patients than in HCs (p = 0.013). Regarding other psychiatric disorders, the PRSs for depression in European patients were significantly higher in Japanese PD patients than in HCs (p = 2.31×10–4), while the PRSs for attention-deficit/hyperactivity disorder in European patients were nominally lower in Japanese PD patients than in HCs (p = 0.024). Regarding health-related, personality-based and cognitive intermediate phenotypes, the PRSs for loneliness (especially isolation) in European individuals were significantly higher in Japanese PD patients than in HCs (p = 9.02×10–4). Furthermore, Japanese PD patients scored nominally higher than HCs in PRSs for neuroticism in European people (p = 3.37×10–3), while Japanese PD patients scored nominally lower than HCs in PRSs for tiredness (p = 0.025), educational attainment (p = 0.035) and cognitive function (p = 9.63×10–3). Our findings suggest that PD shares transethnic genetic etiologies with other psychiatric disorders and related intermediate phenotypes.

Age and sex are critical factors for the diagnosis and treatment of major depression, since there is a well-known age-by-sex difference in the prevalence of major depression (being females the most vulnerable ones) and in antidepressant efficacy (being adolescence a less responsive period than adulthood). Although the induction of electroconvulsive seizures (ECS) is a very old technique in humans, there is not much evidence reporting sexand age-specific aspects of this treatment. The present study evaluated the antidepressantand neurogenic-like potential of repeated ECS across time in adolescent and adult rats (naive or in a model of early life stress capable of mimicking a pro-depressive phenotype), while including a sex perspective. The main results demonstrated ageand sex-specific differences in the antidepressant-like potential of repeated ECS, since it worked when administered during adolescence or adulthood in male rats (although with a shorter length in adolescence), while in females rendered deleterious during adolescence and ineffective in adulthood. Yet, repeated ECS increased cell proliferation and vastly boosted young neuronal survival in a time-dependent manner for both sexes and independently of age. Moreover, pharmacological inhibition of basal cell proliferation prevented the antidepressant-like effect induced by repeated ECS in male rats, but only partially blocked the very robust increase in the initial cell markers of hippocampal neurogenesis. Overall, the present results suggest that the induction of the early phases of neurogenesis by ECS, besides having a role in mediating its antidepressant-like effect, might participate in some other neuroplastic actions, opening the path for future studies. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/), Funding for this study was provided by Delegacion del Gobierno para el Plan Nacional sobre Drogas (grant 2016/002, MSSSI, Spain) and by Fundacion Alicia Koplowitz (Madrid, Spain) to MJG-F who is a member of RETICS-RTA (RD16/0017/0010; Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion FEDER); these entities had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The program TECH from project TALENT PLUS Construint Salut, Generant Valor (IdISBa, GOIB) supported CB-H's salary. Open Access was funded by the program Liberi from IdISBa (GOIB).

Major depressive disorder (MDD) is associated with alterations in circulatory cytokines, in adults as well as in children and adolescents. Administration of selective serotonin reuptake inhibitors (SSRIs) to MDD pediatric patients modifies cytokine levels. However, most studies only assessed changes over a short time period. In this study, we evaluated long-term effects of the SSRI fluoxetine (FLX) in children and adolescents treated for anxiety and/or MDD, including a high-risk group with pre-treatment suicidality. The study group included ninety-two patients (35 boys and 57 girls) with MDD and/or anxiety disorders, aged 13.90 ± 2.41 years. All patients were treated with FLX and followed for 6 months. The study group included children with pretreatment suicidality (high-risk group;N = 62) and without pretreatment suicidality (N = 30) according to the Columbia Suicide Severity Rating Scale. Plasma concentrations of TNFα, IL-6, and IL-1β were measured by enzyme linked immunosorbent assays before and after six months of treatment. IL-6 and IL-1β significantly increased as a factor of time after 6 months of treatment. The elevation was statistically significant confined to children with pretreatment suicidality. Within the children with pretreatment suicidality, IL-6 levels increased significantly after 6 months only in the children who developed SSRI-associated suicidality. To summarize, an increase in IL-6 levels after 6 months of treatment may be associated with SSRI-emergent suicidality in children with pretreatment suicidality. Further studies are needed to clarify the role and mechanism(s) of IL-6 in the pathogenesis of this life-threatening adverse event.

Negative symptoms are associated with poor clinical and psychosocial outcome in schizophrenia. Their prevalence and identification in first-episode patients remains controversial. In a large cohort of patients in the early stage of schizophrenia, schizophreniform or schizoaffective disorder, we investigated, over the different phases of the OPTiMiSE trial (baseline, 4, 10 and 22 weeks of treatment), the prevalence of negative symptoms of moderate severity, unconfounded by depression and extrapyramidal symptoms at baseline. Moreover, we assessed symptomatic remission, attrition rate and psychosocial functioning in subjects with short-term (4 weeks) persistent unconfounded negative symptoms (PNS) and in those with negative symptoms that did not persist at follow-up and/or were confounded at baseline (N-PNS). Negative symptoms of moderate severity were observed in 59% of subjects at baseline. They were associated with worse psychosocial functioning and longer duration of psychosis at intake in the study. Eleven percent of subjects had PNS unconfounded at baseline and 7.9% had PNS unconfounded at both baseline and end of 4-week treatment. Psychosocial functioning was comparable in PNS and N-PNS subjects at baseline but it was significantly worse in the former group after 4-weeks. PNS subjects showed lower remission and higher attrition rates at the end of all treatment phases. Fifty-six percent of subjects completing phase 3 (clozapine treatment) had PNS, and 60% of them were non-remitters at the end of this phase. The presence of short-term PNS during the first phases of psychosis was associated with poor clinical outcome and resistance to antipsychotic treatment, including clozapine.

The current study aimed to identify alterations in brain activation and connectivity related to nociceptive processing and pain sensitization in major depressive disorder (MDD), using repetitive heat pain stimulation during functional magnetic resonance imaging (fMRI) in 37 MDD patients and 33 healthy controls. Regional activation did not differ between groups, but functional connectivity was significantly decreased in MDD in a neural network connecting frontal, temporal and occipital areas (family-wise error-corrected pFWE = 0.045). Supporting analyses suggested a significant association between network connectivity and trait neuroticism (p = 0.007) but not with the clinical state or familiar risk of MDD (all p values > 0.13). Our data relate a network-based phenotype for altered pain processing and antinociceptive control to MDD and encourage future studies on the shared intermediate neural psychological risk architecture of MDD and chronic pain.

The objective of the present multicenter study was to elucidate relevant associations between major depressive disorder (MDD) and comorbid hypertension that are known for their frequent co-occurrence and interaction with regard to functional disability. Demographic and clinical information of altogether 1410 patients were retrieved cross-sectionally. Consecutively, a comparison of patient characteristics between MDD subjects with and without comorbid hypertension were conducted by descriptive statistics, analyses of covariance (ANCOVA) and binary logistic regression analyses. The point prevalence rate for comorbid hypertension was 18.9%. Patients with MDD+comorbid hypertension were significantly older, heavier, more likely to be in a relationship, inpatient and diagnosed with further comorbid chronic somatic diseases including heart disease, diabetes and thyroid dysfunction. In addition, individuals with MDD and comorbid hypertension exhibited a higher score at the Montgomery and Åsberg Depression Rating Scale (MADRS) at onset of the current depressive episode. Melancholic features of depression showed a higher probability. The first line antidepressant treatment did not differ significantly between MDD subjects with versus without comorbid hypertension. Augmentation with pregabalin and combination with one additional antidepressant, however, were more common in the MDD+hypertension group. In conclusion, high blood pressure may influence illness severity and is associated with a distinct psychopathology in MDD patients. Patients with MDD and comorbid hypertension, that seems to be underdiagnosed in MDD patients compared to the general population, are subject to additional somatic diseases in almost 100 percent of the cases and hence, need to be screened and treated accordingly.

Antidepressants must be taken for weeks before response can be assessed with many patients not responding to the first medication prescribed. This often results in long delays before effective treatment is started. Antidepressants induce changes in the processing of emotional stimuli early in the course of treatment. In the current study we assessed whether changes in emotional processing and subjective symptoms over the first week of antidepressant treatment predicted clinical response after 4-8 weeks of treatment. Such a predictive test may shorten the time taken to initiate effective treatment in depressed patients. Seventy-four depressed primary care patients completed measures of emotional bias and subjective symptoms before starting antidepressant treatment and then again 1 week later. Response to treatment was assessed after 4-6 weeks. The performance of classifiers based on these measures was assessed using a leave-one-out validation procedure with the best classifier then tested in an independent sample from a second study of 239 patients. The combination of a facial emotion recognition task and subjective symptoms predicted response with 77% accuracy in the training sample and 60% accuracy in the independent study, significantly better than possible using baseline response rates. The face based measure of emotional bias provided good quality data with high acceptability ratings. Changes in emotional processing can provide a sensitive early measure of antidepressant efficacy for individual patients. Early treatment induced changes in emotional processing may be used to guide antidepressant therapy and reduce the time taken for depressed patients to return to good mental health.

To critically examine the effectiveness of lithium in preventing depressive symptoms (mixed and depressive episodes) in real life settings, taking into account adherence to drug treatment and its implications for the clinical costs of the disease. Overall, 72 patients with bipolar disorder initially treated with lithium carbonate were included and followed-up for 10 years. Patients were assessed every 8 weeks for morbidity and alcohol/drug consumption. Patients with good adherence to lithium had fewer episodes with depressive features than poor adherers (B = 2.405, p = 0.046) and also fewer manic and hypomanic episodes (B = 2.572; p 0.001), after controlling for confounders. Time to relapse into a depressive or mixed episode and into a manic or hypomanic episode was shorter in patients with poor adherence. The costs of the 1.95 ± 2.38 (mean ± standard deviation) admissions of adherent patients through the 10 years of follow-up were €10,349, while the costs of the 6.25 ± 4.92 admissions of non-adherent patients were €44,547. In clinical practice settings, long-term lithium salts seem to have a preventive effect on depressive symptoms.

This cross-sectional European multicenter study with retrospective assessment of treatment response sought to determine variables associated with the administration of augmentation strategies with second-generation antipsychotics (SGAs) and lithium in the pharmacotherapy of major depressive disorder (MDD). In 349 DSM-IV-TR MDD patients, differences in socio-demographic, clinical, treatment, and pharmacological features between participants receiving add-on treatment of their antidepressants with either SGAs (n = 318) or lithium (n = 31) were investigated using analyses of covariance, chi-squared tests, and binary logistic regression analyses. As only significant between-group difference, we found SGA augmentation (compared with lithium augmentation) to be associated with high depressive symptom severity expressed by a higher mean Montgomery and Åsberg Depression Rating (MADRS) total score (27.19 ± 11.35 vs 18.87 ± 12.88, F = 14.82, p = .0001) and a higher mean 21-item Hamilton Rating Scale for Depression (HAM-D) total score (21.27 ± 9.30 vs 13.74 ± 9.11, F = 18.60, p = .0001). No significant differences for socio-demographic features, psychotic symptoms, suicidality, psychiatric and somatic comorbidities, antidepressant pharmacotherapy, and other add-on medications could be seen. Even if there was no significant superiority of one augmentation strategy with regard to treatment response pattern, a trend whereupon adjunctive SGAs were more likely dispensed in treatment-resistant and difficult-to-treat MDD conditions could be observed. In terms of the prescription pattern, we could demonstrate that lithium is less frequently used than SGAs in the clinical routine care which may reflect the need of continuous plasma level determinations and the anticipation of adverse effects.

Major depressive disorder (MDD) is the single largest contributor to global disability and up to 20–30% of patients do not respond to at least two antidepressants (treatment-resistant depression, TRD). This study leveraged imputed gene expression in TRD to perform a drug repurposing analysis. Among those with MDD, we defined TRD as having at least two antidepressant switches according to primary care records in UK Biobank (UKB). We performed a transcriptome-wide association study (TWAS) of TRD (n = 2165) vs healthy controls (n = 11,188) using FUSION and gene expression levels from 21 tissues. We identified compounds with opposite gene expression signatures (ConnectivityMap data) compared to our TWAS results using the Kolmogorov-Smirnov test, Spearman and Pearson correlation. As symptom patterns are routinely assessed in clinical practice and could be used to provide targeted treatments, we identified MDD subtypes associated with TRD in UKB and analysed them using the same pipeline described for TRD. Anxious MDD (n = 14,954) and MDD with weight gain (n = 4697) were associated with TRD. In the TWAS, two genes were significantly dysregulated (TMEM106B and ATP2A1 for anxious and weight gain MDD, respectively). A muscarinic receptor antagonist was identified as top candidate for repurposing in TRD; inhibition of heat shock protein 90 was the main mechanism of action identified for anxious MDD, while modulators of metabolism such as troglitazone showed promising results for MDD with weight gain. This was the first TWAS of TRD and associated MDD subtypes. Our results shed light on possible pharmacological approaches in individuals with difficult-to-treat depression.

Progress towards understanding the etiology of major depression (MD) is compromised by its clinical heterogeneity. The variety of contexts underlying the development of a major depressive episode may contribute to such heterogeneity. Here, we aimed to compare risk factor profiles of three subgroups of MD according to episode context.Using self-report questionnaires and administrative records from the UK Biobank, we characterised three contextual subgroups of MD: postpartum depression (3,581 cases), depression following diagnosis of a chronic disease (409 cases) and a more typical (named heterogeneous) MD phenotype excluding the two prior contexts (34,699 cases). Controls with the same exposure were also defined. We tested each subgroup for association with MD polygenic risk scores (PRS) and other risk factors previously associated with MD (bipolar disorder PRS, neuroticism, reported trauma in childhood and adulthood, socioeconomic status, family history of depression, education).MD polygenic risk scores were associated with all subgroups, however, postpartum depression cases had higher PRS than heterogeneous MD cases (OR = 1.06, 95% CI: 1.02 – 1.10). Relative to heterogeneous depression, postpartum depression was more weakly associated with adulthood trauma and neuroticism. Relative to heterogeneous depression, depression following diagnosis of a chronic disease did not have higher MD polygenic risk scores but had weaker associations with neuroticism and reported trauma in adulthood and childhood.The observed differences in risk factor profiles according to the context of a major depressive episode help provide insight into the heterogeneity of depression. Future studies dissecting such heterogeneity could help reveal more refined etiological insights.

Introduction: Acute stress reaction and Posttraumatic stress disorder (PTSD) are psychiatric disorders that develop in some people after traumatic events COVID-19 pandemic can be considered as a huge stress factor and a trigger for the occurrence of stress related disorders [1] Epidemiological studies of PTSD constantly indicate that the response of men and women to acute stress is significantly different - women have a higher risk of PTSD and greater severity of symptoms Aims: We aimed to systematically investigate gender specific stress-associated reactions (quality of life levels, PTSD symptoms, alexithymia rates, depression and anxiety levels) in patients who have experienced COVID-19 in Ukraine Methods: This abstract presents the results of a comparative analysis of questionnaires on post-stress reactions obtained from both women and men We created an online-based survey which contained a set of chosen questionnaires and participants were recruited via social media Survey was conducted by individuals diagnosed with COVID-19 within the first week after getting positive COVID-19 results We used Clinician-Administered PTSD Scale (CAPS-5), 36-Item Short Form Health Survey (SF-36), Toronto scale of alexithymia (TAS-20), Hospital Anxiety and Depression Scale (HADS) Sociodemographic indicators were age, gender, educational level, marital status The statistical packages IBM SPSS Statistics BASE v 22, EZR v 1 40 (Saitama Medical Center, Jichi Medical University) were used Results: Of the 141 participants who were invited, 117 participants were recruited into the study Participants were randomly chosen from the National Ukrainian registry of coronavirus cases The mean age of the respondents were 39,5±12,7 years (61% females) Such sociodemographic variables as age, level of education, marital status were not associated with the quality of life levels of patients Female respondents had worse quality of life levels in comparison with male respondents (women had significantly lower levels of emotional well-being and energy - 77 2 ±11vs 52 4±14, as well as lower levels of social functioning - 68,3±21 vs 59,1±17(p≥0 05) We noticed a correlation between the severity of post-traumatic stress symptomatology and the severity of COVID-19 symptoms (р=0,04) According to TAS-20, the average value in the sample was 63,4 ± 8,3 points (min - 49 points, max - 81 points) Statistical analysis of the data revealed a significant difference between the rates of alexithymia in men and women, in men the value on the TAS-20 scale was significantly higher (p ≤ 0 05) compared with women (67 ± 18 4 vs 51 ± 15) Levels of anxiety and depression were higher among female respondents (anxiety - 16,4±7,1, depression - 15,2±11,3) in comparison with men respondents (anxiety - 13,4±11,5, depression - 8,1±15,3) Conclusion: A small sample does not allow us to draw any conclusions concerning the intensity of stress response Nevertheless, there are a few differences between stress related reactions among gender groups Understanding the gender characteristics of the stress response can lead to more targeted and effective treatment and prevention of acute stress reactions and PTSD No conflict of interest

Introduction: The outbreak of COVID-19 highlighted the importance of psychological resilience and readiness to overcome the crisis Healthcare professionals report about anxiety, depression, and fear during COVID-19 related lockdown Resilience can be one of the mechanisms that reduce stress impact on the emotional state of healthcare professionals The aim: The aim was to assess the features and associations of resilience and emotional state in healthcare professionals during the COVID-19-related lockdown We hypothesized that: 1) effective resilience is associated with less fear of COVID-19 and symptoms of anxiety and depression;2) emotional state of healthcare professionals depends on age, gender, position, residence, and acquaintance with patients with COVID-19 Materials and methods: 101 healthcare professionals participated in the study Resilience was assessed with the Connor-Davidson Resilience 10-item scale (CD-RISC-10) Fear of COVID-19 Scale, PHQ-9, GAD-7 was used to assess emotional state Results: According to PHQ-9, 46 (45,54%) professionals had minimal or none symptoms of depression (0-4 score), 35 (34,65%) professionals had symptoms of mild depression (5-9 score), 14 (13,86%) had symptoms of moderate depression (10-14 score), and 6 (5,94%) had symptoms of moderately severe depression (20-27 score) According to GAD-7, 55 (54,46%) professionals had no symptoms of anxiety, 27 (26,73%) had symptoms of mild anxiety, 13 (12,57%) had symptoms of moderate anxiety, 6 (5,94%) had symptoms of severe anxiety The median and quartile range on CD-RISC was 30(25-33), on Fear of COVID-19 scale 16(15-22) Negative correlation between resilience and fear of COVID-19 (p≤0,01), anxiety (p≤0,01), and depression (p≤0,001) was found Positive correlations were found between depression, anxiety, and fear of COVID-19 (p≤0,001), between age and fear of COVID-19 (p≤0,05) No statistically significant association between age and depression, anxiety, or resilience was found The significant difference of COVID-19 fear depending on gender – female vs male (p≤0,05) was found No statistically significant difference in resilience and emotional state in healthcare professionals depending on the professional position, acquaintance with patients with COVID-19, and residence (city vs rural) was found Our first hypothesis that resilience is associated with less fear of COVID-19 and symptoms of anxiety and depression in healthcare professionals during the lockdown, was proved Our second hypothesis that emotional state depends on healthcare professionals‘ age, gender, position, residence, and acquaintance with patients with COVID-19 was partially proved Conclusions: Resilience is associated with a better emotional state in healthcare professionals during the quarantine Anxiety and depression are connected with the fear of COVID-19 and highly comorbid in healthcare professionals Among risk factors for a more deteriorated emotional state, there are elder age and female gender Fear of COVID-19, emotional state, and resilience are not dependent on position, acquaintance with patients with COVID-19, and residence Future research will be concentrated on studying resilience and psycho-emotional state of different groups of health care professionals – physicians involved in the treatment of patients with COVID-19, family doctors, doctors not involved in the treatment of patients with COVID-19 and further comparison of the groups [1–4] No conflict of interest

Introduction: The COVID-19 pandemic is a major health crisis, affecting several nations, including Portugal Such widespread outbreaks are associated with a significant mental health impact Isolation, uncertainty, and fear of contagion are some of the factors responsible for this outcome Aim: To survey the general public to better understand the level of psychological impact during the initial stage of COVID-19 outbreak Methods: From 11th March to 11th May 2020 we conducted a telephonic survey on patients diagnosed with COVID-19 (n= 120) and compared them with a contemporaneous control group (n=120) not diagnosed with COVID-19 These data were collected from a community-based population in the centre region of Portugal, using convenience sampling techniques Using a structured interview, we collected quantitative and qualitative information on demographic data, symptoms, psychological and social impact Psychological impact was also assessed using Brief Symptom Inventory (BSI-18), Beck Depression Inventory (BDI-II) and Quality of life scale (QOLS) Statistical analyses were performed using SPSS 26 0 Software Descriptive statistics and the appropriate parametric and non-parametric methods were used Summary: More than a half of the patients surveyed were in the age group between 31 and 50 years, with 79% being of female gender None of the patients diagnosed with COVID-19 needed treatment in hospital facilities and all of them spent 20-24h at home during the period surveyed The COVID-19 group showed a significant increase in the levels of anxiety and depressive symptoms when compared with the control group Most of the patients in the COVID-19 group reported feeling emotionally and physically exhausted (71%), fear of being infected (44,9%) and of infecting their family members (68,5%) during the period surveyed The impact of the quarantine, routine modification, social isolation and the stigma surrounding the COVID-19 infection were reported as contributing factors to this psychological impact More than a half of patients in the COVID-19 group showed high levels of “moderate to severe depression” in the BDI-II, with significant differences regarding the control group The BSI evidenced a higher level of symptoms reported when compared with the control group, namely anxiety, irritability, insomnia and tiredness An overall reduction in the quality of life was perceived in the COVID-19 group Conclusions: During the initial stage of COVID-19 pandemic in Portugal, more than a half of the responders in the COVID-19 group reported high levels of anxiety and depressive symptoms The emotional impact is associated with factors such as social isolation, uncertainty, lack of information, fear of infecting relatives and stigma These data reveal a major mental health impact during the initial stage of the COVID-19 outbreak All the patients surveyed will be evaluated in a posterior follow-up We're hopeful that these data can promote a shift to a greater concern with mental health in the future No conflict of interest

Introduction: After the outbreak of a new coronavirus subtype SARS-CoV-2 in China in late 2019, a global pandemic developed, generating a health, economic, and social emergency [1] In Spain, the COVID-19 pandemic crisis forced the government to declare a state of emergency on 14 March 2020 and to implement unprecedented lockdown restriction In this context, patients with severe mental disorders (SMD) may be particularly exposed to stress and social distancing measures [2, 3] and thus disproportionately vulnerable to public health interventions to fight the COVID-19 [4] However, the early psychological impact of the pandemic and the lockdown in this population is still mostly unknown Aims of the study: Here, we aim to compare the early psychological impact (depression, anxiety, and stress responses, intrusive and avoidant thoughts, and coping strategies) in a sample of people with SMD compared with two control groups: other mental disorders (OMD) and healthy controls (HC) Methods: An anonymous online questionnaire using a snowball sampling method was conducted from March 19-26, 2020 and included sociodemographic and clinical data along with the Spanish versions of the Depression, Anxiety, and Stress Scale (DASS-21) and the Impact of Event Scale (IES) A total of 21,279 people living in Spain answered the questionnaire, and 125 people with SMD were included in the analysis Subjects in each of the two control groups (OMD, n = 250;HC, n = 250) were matched (ratio 1:2) for sex and age (± 1 year) with the SMD group We performed descriptive and bivariate analyses and multinomial and linear regression models Results: People with SMD [mean age = 43 25 years (SD = 14 41);61 6% females] had statistically significantly higher scores on anxiety, stress, and depression subscales of the DASS-21 compared with the HC group, but lower scores than OMD in all domains (p < 0 05) Most people with SMD (87 2%) were able to enjoy free time, although control groups had higher percentages After controlling for confounding factors, anxiety was the only significant psychological domain with lower scores in HC than people with SMD (OR = 0 721;95% CI: 0 579 - 0 898) In the SMD group, the multiple linear regression model (R2 = 0 580, F = 41 027, p < 0 001) found that higher anxiety was associated with being single (ẞ = 0 144, t = 2 291, p = 0 024), having COVID-19 symptoms (ẞ = 0 146, t = 2 395, p = 0 018), and a higher score on the stress subscale (ẞ = 0 538, t = 7 635, p < 0 001);whereas being able to enjoy free time was a protective factor (ẞ = -0 244, t = -3 692, p < 0 001) Conclusions: Our results showed that patients with SMD reacted to the pandemic and the lockdown restrictions with higher anxiety levels than the general public, suggesting that this domain could be a criterion for early intervention strategies and closer follow-up No conflict of interest

Background: Previous studies have shown that epidemic outbreaks have significant effects on mental health and psychological wellbeing, increasing psychiatric morbidity among population [1] During the initial phase of the COVID-19 outbreak in China, more than half of the general population reported a strong psychological impact and approximately a third moderate to severe anxiety [2] Furthermore, there is evidence that the psychological effects of infection outbreaks can affect months or years later [3] A better understanding of the psychological impact of the COVID-19 outbreak is crucial to design coping programs that may mitigate these responses during such outbreaks Aim: The objective of this study is to determine the early impact of the COVID-19 on mental health among people with history of mental disorders (anxiety, depression and bipolar disorder) and the General Population and people in Spain Methods: In this study 252 people were included Sixty three people with a history of bipolar disorder (hBD) were matched by sex and gender with 63 people with a history of anxiety disorders (hAD), 63 people with a history of depression (hDD) and 63 healthy controls (HC) The assessment was made by an online survey during the first days of the national lockdown due to COVID-19 (from 19 March to 26 March 2020) in Spain Assessment: ad hoc sociodemographic, physical and clinical data questionnaire and the Spanish versions of the Depression, Anxiety and Stress Scale (DASS-21) and the Impact of Event Scale (IES) Results: Mean age was 45 (range 19-69, SD 14 8) years;69 8% were females for the total example and the four groups Regarding clinical symptoms, 61 9%hBD, 54 0% hAD, 54 0% hDD and 28 6% HC reported depressive symptoms (χ² =15 922, p

Introduction: The COVID-19 pandemic has impacted many spheres of society To control the dissemination of SARS-CoV-2, social isolation and closure of public spaces such as universities were implemented In Brazil it started in March 2020, one month after the beginning of the basic cycle year The quarantine situation added to daily stressing factors during the pandemic As a response to this abrupt transformation in ways of life, mental health may have been affected, and may have precipitated disorders such as depression differently amongst people Aims: We aim to compare the prevalence of depressive symptoms during the COVID-19 pandemic quarantine in Medical undergraduate University students in Brazil and to explore potential factors related to it Methods: All students from the first to the sixth year from Jundiai Medical School (Brazil) were invited to virtually respond the self-administered Hospital Anxiety and Depression Scale (HADS) from March to June of 2020 (during COVID quarantine) This study was based on the HADS subscale for depression (HADS-D), which ranges from 0 (absence) to 21 points The cut-off for screening clinically relevant depressive symptoms recommended [1] is 9 The study protocol was approved by the Ethics Committee For the statistical analysis Chi-Square Test was used for categorical data and Mann-Whitney test was used for comparisons of continuous variables Correlations were made using Sperman correlation test and binary logistic regression was used on the analysis of the influence of year class and where the students were during the quarantine Results: We had responses from 347 students (51% of the sample) The prevalence of HADS-D>8 (above cut-off) was 36% (n=125) First-year students had greater prevalence of HADS-D>8 (45 6%) as compared to the other years (32%) (p=0 015) An inverse correlation of year of class and depression (p=0 002;rho=-0 163) was found, with lower scores in internship;the average total scores of the HADS-D were greater in the first-year class (8 2±3 9) when compared to the other year classes (6 8±3 5) (p=0 001) When genders were compared women had higher prevalence of HADS-D>8 (40 2%) than man (27 4%) (p=0 019) Being with family during the quarantine was not a protective factor, even after logistic regression (p=0 900) for differences in year class Conclusion: High prevalence of depression during SARS-CoV-2 pandemic was found in Jundiai Medical School undergraduate medical students The negative consequences due to COVID-19 such as social isolation, lack of routine activities, fear of contagion and death and hopeless global scenario may have contributed to the development of depressive symptoms Students of the first year of college were the most affected in our sample It is expected a great exhilaration by freshmen when they entered the college and therefore, the impact of classes suspension and lockdown lead to a reduction of expectation, increasing risk factors for depression Medical students often have high prevalence of depression and future prospective studies could address if these depressive symptoms were higher during the quarantine No conflict of interest

Major Depressive Disorder (MDD) entails cognitive dysfunction in many cognitive domains, but it is still uncertain whether such deficits are present in the early stages. The purpose of the study is to determine the cognitive performance in first episode depression (FED) exploring the presence of different cognitive profiles, and the role of cognition in FED at baseline and long-term. Ninety subjects (18-50 years) were included, 50 patients with a FED and 40 healthy controls. Participants were assessed with a neuropsychological battery, covering language, attention, verbal memory, processing speed and executive domains. Neuropsychological group comparisons were performed with MANOVAs. A hierarchical cluster analysis was run to identify clusters of patients with similar neuropsychological performance. Two generalized linear models were built to predict baseline HDRS-17 and changes at 12 months. Patients performed significantly worse than healthy controls in language, attention/working memory, verbal memory, processing speed and executive functioning, with moderate to large effect sizes (0.5 - 1). Two clusters were found: cognitively preserved patients (n=37) and cognitively impaired patients (n=13). Large effect sizes of cognitive impairment in FED were observed between the two cognitive clusters (preserved and impaired). Depressive symptoms at baseline were predicted by verbal memory (p=0.003), while 12-month changes were predicted by executive function (p=0.041) and language (p=0.037). Cognitive performance predicted depressive symptoms at baseline and at follow-up, pointing to the usefulness of cognitive assessment even at the commencement of the illness. (C) 2018 Elsevier B.V. and ECNP. All rights reserved.

Although antidepressants (ADs) are widely used in bipolar depression, there is weak evidence for their effectiveness and safety in this condition. Furthermore, there is a paucity of studies on the risk-benefit ratio of AD maintenance treatment in bipolar disorder (BD). We compared rehospitalization rates of patients with BD-I depressive episode who were discharged with mood stabilizers (MSs) and/or atypical antipsychotics (AAPs) with or without adjunctive AD. Ninety-eight patients with BD-I who were hospitalized with a depressive episode between 2005 and 2013 were retrospectively followed for 6-months and 1-year rehospitalization rates, as well as time to rehospitalization, according to treatment at discharge: MSs and/or AAPs with or without AD. Multivariable survival models adjusted for covariates known to influence rehospitalization were conducted. Six-months and 1-year rehospitalization rates were significantly lower in the adjunctive-AD treatment group compared to the no-AD group (9.2% vs. 36.4%, P = .001, power = 0.87 and 12.3% vs. 42.4%, P = .001, power = 0.89, respectively). Time to rehospitalization within 6-months and 1-year was significantly longer in the adjunctive-AD treatment group (169.9 vs 141 days, P = .001 and 335.6 vs 252.3 days, P = .001, respectively). Adjunctive-AD treatment at discharge reduced significantly the adjusted risk of rehospitalization within 6-months (HR = 0.081, 95% CI: 0.016-0.412, P = 0.002) and 1-year (HR = 0.149, 95% CI: 0.041-0.536, P = 0.004). Moreover, adjunctive-AD treatment did not increase rehospitalization rates of manic episode. In conclusion, adjunctive-AD therapy to MS/AAP at discharge from BD-I depressive episode hospitalization is associated with a lower rate of and a longer time to rehospitalization during a 1-year follow up period.

Klotho is a humoral factor with pleiotropic effects. Most notably, Klotho deficiency is associated with a phenotype comprising organ manifestations accompanying aging including atherosclerosis and cognitive impairment. Research on the role of Klotho in affective disorder is scarce, which is surprising in light of the fact that depression is associated with accelerated cellular aging as well as aging-related phenotypes and comorbidity observed in Klotho deficiency. On these grounds we investigated Klotho levels in the cerebrospinal fluid (CSF) and serum of eight geriatric patients undergoing electroconvulsive therapy (ECT) for severe depression. We hypothesize that ECT as a highly effective antidepressant treatment leads enhances Klotho levels. We found a significant difference between pre- and post-ECT CSF Klotho (792.5pg/ml vs. 991.3pg/ml, p=0.0020), but no difference in serum Klotho (602.5 vs. 594.3, p=0.32). Moreover, CSF Klotho increase positively correlated with the number of single ECT sessions that were performed in each patient (F1, 6)=7.84, p=0.031). Conjointly, the results of our exploratory study with a small sample size suggest a central nervous system-specific impact of ECT on Klotho, which may in turn partake in mediating the antidepressant effect of ECT. We suggest the modulation of neuroinflammatory processes, which have been ascribed pathophysiological relevance within the conceptual framework of the neuroinflammation hypothesis of depression, through ECT as a potential mechanism by which Klotho is enhanced in response to treatment. Further preclinical and clinical investigation should aim for a precise identification of the role of Klotho in depressive disorder.

Relatives of people diagnosed with psychotic and affective disorders have a higher risk of developing psychiatric disorders compared to the general population. This study examined the risk of hospitalization for psychiatric disorders among siblings and parents of patients affected with major psychiatric disorders. In this large population-based case-control study, 17,895 siblings and parents of 7671 hospitalized subjects with a diagnosis of narrowly defined schizophrenia (SZ), broadly defined SZ, schizoaffective disorder (SAD), bipolar disorder (BD) or unipolar depression (UD) were identified from the Israeli Psychiatric Hospitalization Registry and compared to 71,580 age and gender-matched controls from the Israeli Population Registry. Results indicated that siblings of people diagnosed with broadly defined SZ had a significantly higher risk of hospitalization for broadly (OR=11.06, 95% CI=7.93-15.41) and narrowly defined SZ (OR=10.59, 95% CI=6.8-16.33), SAD (OR=9.69, 95% CI=4.76-19.73), BD (OR=7.46, 95% CI=21.8-25.52), UD (OR=2.84, 95% CI=1.01-8.00), and other psychiatric disorders (OR=1.85, 95% CI=1.16-2.93), compared to controls. Siblings of patients with BD had a significantly higher risk of hospitalization for broadly defined SZ (OR=2.92, 95% CI=1.11-7.71) and for other psychiatric disorders (OR=6.67, 95% CI=2.17-20.50), compared to controls. Parents of probands with SZ were at significantly increased risk for all disorders examined, except for UD and ¨other psychiatric disorders¨, which was not significant in parents of probands with BD. This large, population-based study provides evidence for common genetic risk across different psychiatric disorders.

Conventional rTMS in major depressive disorder (MDD) targets the dorsolateral prefrontal cortex (DLPFC). However, many patients do not respond to DLPFC-rTMS. Recent evidence suggests that the right lateral orbitofrontal cortex (OFC) plays a key role in 'non-reward' functions and shows hyperconnectivity in MDD. OFC-rTMS has been used successfully in obsessive-compulsive disorder, and achieved remission in an MDD case nonresponsive to DLPFC- and DMPFC-rTMS. Here, we assess the safety and tolerability of right OFC-rTMS, and examine the effectiveness of inhibitory right OFC-rTMS in MDD, particularly among patients with previous nonresponse to DMPFC-rTMS. We performed a chart review to retrieve data on clinical characteristics, stimulation parameters, adverse events, and clinical symptom outcomes for a series of 42 patients with medication-resistant and/or DMPFC-rTMS-nonresponsive MDD, who underwent 20-30 sessions of 1Hz right OFC-rTMS at a single Canadian clinic from 2015 to 2017. Over 882 sessions of treatment, there were no seizures, visual/ocular complications, or other serious or treatment-limiting adverse events. Pain ratings averaged 6-7/10 (10=maximum tolerable); no patient discontinued treatment prematurely due to pain. 15/42 patients (35.7%) achieved response (≥50% symptom reduction) and 10/42 (23.8%) achieved remission. Among the 30/42 patients who were previous nonresponders to DMPFC-rTMS, 9/30 (30.0%) achieved response and 7/30 (23.8%) achieved remission. Response distribution was sharply bimodal. 1Hz right OFC-rTMS appears safe and tolerable, and may achieve remission in MDD patients even when conventional rTMS has failed. Sham-controlled follow-up studies may be warranted.