Depressive Episode Research Articles

Anhedonia is associated with a specific depression profile and poor antidepressant response

Abstract Background Anhedonic features within major depressive disorder (MDD) have been associated with worse course and outcome and may predict non-response to treatment. However a detailed clinical profile of anhedonia in MDD is still lacking. Materials and Methods One thousand two hundred ninety-four patients with MDD were selected from the cross-sectional European multicenter Group for the Study of Resistant Depression (GSRD) study. Anhedonia was assessed through the Montgomery-Åsberg Depression Rating Scale anhedonia item “inability to feel”. Clinical and demographic features were then analyzed. Results The presence of anhedonia related to a distinct demographical (living alone) and clinical profile (thyroid diseases, diabetes, suicide risk, high number of previous depressive episodes, more severe MDD and more frequent inpatients status). Furthermore, anhedonia was associated with non-response to treatment and treatment resistance, even after adjusting for confounding variables. Conclusion Our findings support the role of anhedonia as a modulating feature of MDD, being associated with a more severe depression profile. Moreover, anhedonic features are independent predictors of poor treatment response.

Polygenic Risk Assessment for Schizophrenia in Patients with Nonpsychotic Disorders and Attenuated Symptoms of Psychosis: A Pilot Study

Background: significant contribution of genetic factors in the development of schizophrenia is a generally recognized fact. Polygenic risk index for schizophrenia turned out to be an effective tool allowing to draw a dividing line between schizophrenia and mentally healthy control in terms of genetics. Objective: to assess the predictive ability of the polygenic risk score for schizophrenia (SZ-PRS) in adolescent patients with a first depressive episode and attenuated psychotic symptoms (APS). Patients and Methods: sixty adolescent inpatient with a first depressive episode were examined. Based on the presence of APS at admission, patients were divided into two groups: a group with APS and a group without APS. Subgroups of patients in the first group were identified through follow-up observations: those with psychosis manifestation and/or low social functioning and those without manifestation and with high social functioning. Whole-genome genotyping was performed for all participants, and SZ-PRS were calculated. For comparison, a group of patients diagnosed with schizophrenia (n = 879) and a group of mentally healthy individuals (n = 759), who had previously undergone whole-genome genotyping and had their SZ-PRS calculated, were used. Results: SZ-PRS of the APS group occupy an intermediate position between the healthy control and schizophrenia patients, significantly differing from each of them. The group without APS did not differ from the control group, but compared to the group of schizophrenia patients, the SZ-PRS in this group was significantly lower. Comparing subgroups of patients showed that the SZ-PRS in the APS group without psychosis manifestation and social functioning impairment was significantly lower than in the group with schizophrenia manifestation. The APS subgroups with psychosis manifestation and with functioning impairment did not differ significantly from each other or from the schizophrenia group. Conclusion: the results obtained for the first time for the russian population showed that SZ-PRS can be considered as a tool for assessing the risk of developing psychosis or reduced social functioning in patients with APS.

Examining what works for whom and how in mindfulness-based cognitive therapy (MBCT) for recurrent depression: moderated-mediation analysis in the PREVENT trial

Background Personalised management of recurrent depression, considering individual patient characteristics, is crucial. Aims This study evaluates the potentially different mediating role of mindfulness skills in managing recurrent depression using mindfulness-based cognitive therapy (MBCT) among people with varying depression severity. Method Data from the Prevention of Depressive Relapse or Recurrence (PREVENT) trial, comparing MBCT (with antidepressant medication (ADM) tapering support, MBCT-tapering support) versus maintenance-ADM, were used. The study included pre, post, 9-, 12-, 18- and 24-month follow-ups. Adults with ≥3 previous major depressive episodes, in full/partial remission (below threshold for a current episode), on ADM, were assessed for eligibility in primary care practices in the UK. People were randomised (1:1) to MBCT-tapering support or maintenance-ADM. We used the Beck Depression Inventory-II to evaluate depressive symptom changes over the six time points. Pre-post treatment, we employed the Five Facets of Mindfulness Questionnaire to gauge mindfulness skills. Baseline symptom and history variables were used to identify individuals with varying severity profiles. We conducted Latent Profile Moderated-Mediation Growth Mixture Models. Results A total of 424 people (mean (s.d.) age = 49.44 (12.31) years; with 325 (76.7%) self-identified as female) were included. A mediating effect of mindfulness skills, between trial arm allocation and the linear rate of depressive symptoms change over 24 months, moderated by depression severity, was observed (moderated-mediation index = −0.27, 95% CI = −0.66, −0.03). Conditional indirect effects were −0.42 (95% CI = −0.78, −0.18) for higher severity (expected mean BDI-II reduction = 10 points), and −0.15 (95% CI = −0.35, −0.02) for lower severity (expected mean BDI-II reduction = 3.5 points). Conclusions Mindfulness skills constitute a unique mechanism driving change in MBCT (versus maintenance-ADM). Individuals with higher depression severity may benefit most from MBCT-tapering support for residual symptoms. It is unclear if these effects apply to those with a current depressive episode. Future research should investigate individuals who are not on medication. This study provides preliminary evidence for personalised management of recurrent depression. Trial Registration: ISRCTN26666654.

Responses to clinical treatment of bipolar versus unipolar depressive episodes in women versus men

Responses to clinical treatment of bipolar versus unipolar depressive episodes in women versus men

Addressing treatment hurdles in adults with late-onset attention-deficit/hyperactivity disorder: a detailed case report

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder in children, characterized by inattention, hyperactivity, and impulsivity. This neurobehavioral disorder often persists into adulthood, presenting significant challenges when undiagnosed and untreated, due to potential long-term implications and comorbidities, including anxiety, mood instability, and mixed symptoms along the bipolar spectrum.Case presentationA 49-year-old married male patient presented with anxiety and recurrent depressive episodes, initially diagnosed as major depressive disorder. His mood symptoms fluctuated between depressive lows, irritability, and impulsivity. His diagnosis was revised to ADHD with comorbid bipolar spectrum disorder. The patient exhibited lifelong ADHD symptoms affecting academic performance, relationships, and job responsibilities. Cognitive-behavioral therapy (CBT) was employed to manage symptoms and enhance coping strategies. Despite progress in controlling anger and impulsivity, challenges persisted in inhibitory control and negative triggers, causing impulsive decisions. The patient reported a restless mind, depressive mood, and a sense of inadequacy. Improvements were noted in anxiety regulation, concentration, and sleep quality, though deficits in cognitive and behavioral domains remained. The patient faced challenges in academic performance, information processing speed, attention, and executive functions.ConclusionThis case underscores the importance of accurately diagnosing ADHD and its comorbidities in adults to ensure effective treatment. Delayed diagnosis can have lasting impacts, emphasizing the need for further research and personalized therapeutic approaches. The insights from this case serve as a valuable resource for healthcare professionals enhancing their understanding of the diverse manifestations of ADHD, aiding in better diagnosis and management strategies.

Neurocognitive dysfunction in adolescents with recent onset major depressive disorder: a cross-sectional comparative study.

The aim of this study was to examine the neurocognitive deficits associated with the first episode of major depressive disorder (recent onset depression, ROD) in adolescents as compared to adult patients. Cross-sectional neurocognitive data from the baseline assessments of the PRONIA study with N = 650 (55.31% females) were analyzed. Based on a principal component analysis of eleven neurocognitive tests, we constructed an overall neurocognitive performance (NP) score. We examined mean score differences in NP between the groups of healthy controls (HC) and ROD and between adolescents (15-21years) and adults (22-40years) within a GLM approach. This accounts for unbalanced data with focus on interaction effects while controlling for effects of medication and educational years. Our results show lower NP for the ROD as compared to the HC group (d = -0.29, p = .046) and lower NP for the adolescent group as compared to the adult group (d = -0.29; p < .039). There was no interaction between these two group effects (F = 1.11; p = .29). Our findings suggest that the detrimental effect of ROD on neurocognitive functioning is comparable in adolescent and adult patients, since lower scores in adolescent patients are explained by effects of age and education. Neurocognitive impairment is an under addressed issue in clinical treatment guidelines for adolescent MDD. We suggest efficient monitoring in clinical practice by using an aggregate of the Digit Symbol Substitution Test and the Trail Making Test B, which highly correlated with the overall score of NP (r = 0.82).

Mixed Features and Nonfatal Suicide Attempt Among Individuals With Major Depressive Episode

Mixed Features and Nonfatal Suicide Attempt Among Individuals With Major Depressive Episode

The gut microbiota-brain connection: insights into major depressive disorder and bipolar disorder

Major depressive disorder (MDD) and bipolar disorder (BD) are two of the most prevalent mood disorders that seriously jeopardize both physical and mental health. The current diagnosis of MDD and BD relies primarily on clinical symptoms. However, correctly differentiating between MDD and BD during depressive episode states remains a substantial clinical challenge. The human gut hosts a large and diverse microbiota, which plays a pivotal role in various physiological processes. Emerging evidence suggests that the gut microbiota (GM) exerts beneficial effects on mental health disorders, including MDD, BD, and schizophrenia, through the microbe-gut-brain axis (MGBA). In recent years, the relationship between GM and mood disorders has garnered considerable attention, leading to intensive research in this area. The MGBA is a bidirectional communication system between the gut and the brain. Growing evidence indicates that the brain can influence the GM, which in turn may modulate the brain through this axis. This review aims to explore the changes in the GM of patients with MDD and BD and evaluate the effects of different treatments on their GM, including medication, probiotic, prebiotic and synbiotic interventions, and fecal microbiota transplantation (FMT). By doing so, we seek to identify potential disease-specific biomarkers, improve differential diagnosis, and offer novel therapeutic avenues for these disorders.

Prevalence of anxiety and depression disorders in patients with inflammatory bowel disease in a city in southern Brazil

Inflammatory bowel disease is a chronic disease with symptoms and possible complications that can bring disability to the patient and trigger impairment in mental health such as depression and anxiety disorder. Objective: To evaluate the prevalence of Anxiety and Depression Disorder in patients with IBD in the Inflammatory Bowel Disease outpatient clinic of UFPEL. Methodology: Applied socio-economic questionnaire, M.I.N.I. instrument and collection of data from the medical record during the medical consultation. In patients attending the FAMED-UFPEL outpatient clinic with a diagnosis of Inflammatory bowel disease and over 16 years of age in the period from 06/01/2021 to 02/28/2022. Results: During the exposed period, 59 patients diagnosed with IBD were evaluated, being 37 (62.7%) with Crohn's Disease and 22 (37.3%) with Ulcerative Colitis, the average age was 46 years. In the current study, disease activity was evaluated using the Mayo Score for patients with ulcerative colitis with a result with no statistical significance for depression (p:0,494) and anxiety disorder (p:0,484). The Harvey Bradshaw Score was used in patients with Crohn's Disease that also has no statistical relevance for depression (p:0.969) and anxiety disorder (p:0.380). In the present study, 29.4% of patients had Ulcerative Colitis and recurrent depressive episode and 54.2% of patients had generalized anxiety disorder. Conclusion: there is a high prevalence of mood disorders in the population studied, it is emphasized the need for the active search of these diagnoses in this population, offering adequate treatment of the pathologies found with a view to better quality of life.

Rosiridin Protects Against Aluminum Chloride-Induced Memory Impairment via Modulation of BDNF/NFκB/PI3K/Akt Pathway in Rats

Background and Objectives: Rosiridin is a monoterpene with outstanding monoamine inhibitory activity that is useful to treat depressive episodes and rapid-onset dementia. The current investigation aims to evaluate the neurologically protective impact of rosiridin, which opposes aluminum chloride (AlCl3) and causes memory dysfunction in rats. Materials and Methods: Memory impairment was developed in Wistar rats by administering AlCl3 (100 mg/kg p.o.) orally for 42 days and then supplemented with rosiridin at 10 and 20 mg/kg/p.o. Upon completion of the investigation, the behavior factor was performed utilizing the Y-maze, Morris Water Maze, and open field tests. Estimating numerous biological factors, such as nitric oxide (NO), oxidative stress (malondialdehyde MDA), acetylcholinesterase (AChE), butyrylcholinesterase levels (BuChE), antioxidants (glutathione GSH, catalase CAT, and superoxide dismutases SODs) and neurotransmitter (serotonin-5HT, dopamine-DA, acetylcholine-Ach) in the brain. Furthermore, interleukin-6 (IL-6), IL-1β, tumor necrosis factor (TNF-α), brain-derived neurotrophic factor (BNDF), nuclear factor kappa B (NFᴋB), phosphatidylinositol 3-kinase (PI3K), and pAkt were assessed in the diffused brain cells. Results: The rosiridin-treated group significantly improved in terms of behavioral parameters, including in the Y-maze, Morris Water Maze, and open field tests. Further, rosiridin restored biochemical parameters, including NO, oxidative stress AChE, BuChE, antioxidants, neurotransmitters, IL-6, IL-1β, TNF-α, BNDF, NFᴋB, PI3K, and pAkt compared to AlCl3. Conclusions: The current investigation reveals that rosiridin could ameliorate the impairment of memory that AlCl3 causes in rats via improvements in behavioral and restored biochemical parameters.

Effect of Depression in The Elderly on Glaucoma and Pharmacotherapy Options

Introduction: Depression in the elderly is often not detected because elderly people who are depressed show more somatic or cognitive complaints than affective complaints. The relationship between depression and the progression of glaucoma has been studied and taken into consideration in the selection of therapy to be given. Methods: This report is a case report from a patient who has been given an explanation and received consent regarding a psychiatric interview, physical examination and support, interventions, case discussion presentations, and the confidentiality of all patient personal information. Case: Education was carried out on a 72-year-old patient with a Major Depressive Episode without psychotic symptoms who also had glaucoma a few months after complaining of depression. The education provided includes knowledge about depression and its relationship to glaucoma, a management plan in the form of advice for hospitalization in a hospital that has a psychiatrist and an ophthalmologist. Conclusion: Depression in the elderly can affect the progression of glaucoma. The choice of psychopharmacological therapy needs to be adjusted by considering its side effects on the possibility of glaucoma or the risk of aggravating the progression of glaucoma.

Wide Range of First-Line Treatments for New Episode of Depression.

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Current Severe Depressive Episode in Bipolar II Disorder with Anxious Distress and Post-traumatic Stress-Disorder with Derealization: a Case Report

Introduction: Bipolar II disorder experiences more frequent episodes of depression and is sometimes comorbid with post-traumatic stress disorder (PTSD). However, there is no clear method to distinguish between depression induced by bipolar disorder and PTSD. Through this case, we aim to examine the features of the patient’s bipolar disorder and PTSD from the depressive episodes. Case: A 23-year-old Indonesian woman came with the chief complaint of unexplainable discomfort that had been experienced almost daily for the past two weeks. The patient also complained that she was often lonely. Patients did not get adequate parenting from her parents, so patients have unfavorable relationships with her family. In addition, patients previously experienced sexual harassment that caused severe trauma. She was diagnosed with a current severe depressive episode in bipolar II disorder with anxious distress and PTSD. Discussion: Bipolar disorder is frequently comorbid with PTSD. She was given Sertraline 25 mg once daily, Aripiprazole 5 mg twice a day, Clobazam 5 mg once a day at night, Folic acid 400 mcg once a day, and psychotherapy. After four weeks of treatment, there was an improvement in symptoms by a decrease in the HDRS and the HARS scores. Conclusion: In the case presented, bipolar patients have major complaints related to somatic symptoms accompanied by a history of experiencing severe traumatic events. Thus, bipolar patients do not always come with the chief complaint of mood swings. Furthermore, these complaints improved with the combination of anti-psychotic, anti-depressant, anti-anxiety, and psychotherapy.

Comparing the Neurocognitive Effects of Right-Unilateral Ultra-Brief Pulse Electroconvulsive Therapy and Magnetic Seizure Therapy for the Treatment of Major Depressive Episode

Comparing the Neurocognitive Effects of Right-Unilateral Ultra-Brief Pulse Electroconvulsive Therapy and Magnetic Seizure Therapy for the Treatment of Major Depressive Episode

Cariprazine in Bipolar Disorder and Substance Use: A Dual Approach to Treatment?

Bipolar disorder (BD) is characterized by recurrent episodes of mania, hypomania, and depression and is often complicated by comorbid substance use disorders (SUDs). Up to 60% of individuals with BD experience SUDs, which exacerbate mood instability and increase the risk of rapid cycling, suicide, and poor clinical outcomes. Current treatment strategies, including lithium and valproate, show limited efficacy in treating both BD and SUD. Psychotherapeutic approaches such as cognitive behavioral therapy (CBT) offer benefits but lack a specific focus on substances such as cannabis and cocaine. Since there is still debate on how to treat this comorbidity, there is a need to find new therapeutic options; this mini-review examines the pharmacological properties of cariprazine and its emerging role in the treatment of comorbid BD and SUD. Cariprazine, an atypical antipsychotic with partial agonism at dopamine D2 and D3 receptors, has shown promise in treating both mood symptoms and cognitive dysfunction in BD. Its unique affinity for D3 receptors, which are involved in motivation and reward processing, may offer advantages in reducing drug craving. Clinical trials indicate that cariprazine effectively treats manic, depressive, and mixed episodes in BD with a favorable side effect profile, particularly at lower doses. Preliminary results suggest its potential to reduce craving and substance use in individuals with co-occurring BD and SUD. Therefore, cariprazine, with its unique pharmacodynamic mechanism, could be further studied for the treatment of BD in comorbidity with SUD. However, evidence on the role of cariprazine in the treatment of SUDs remains limited, based primarily on case reports and animal studies. Further research, including large-scale clinical trials, is needed to determine its full efficacy in this dual diagnosis.

CYP2C19 Genetic Variants and Major Depressive Disorder: A Systematic Review

Major depressive disorder (MDD) affects over 300 million people globally and has a multifactorial etiology. The CYP2C19 enzyme, involved in metabolizing certain antidepressants, can influence treatment response. Following the PRISMA protocol and PECOS strategy, this systematic review assessed the variation in common CYP2C19 gene variants’ frequencies across populations with MDD, evaluating their impact on clinical characteristics and treatment response. We comprehensively searched five databases, identifying 240 articles, of which only nine within the last decade met our inclusion criteria. Except for one study that achieved 74.28% of STROPS items, the rest met at least 75% of GRIPS and STROPS guidelines for quality and bias risk assessment. The CYP2C19’s *1 allele, the *1/*1 genotype, and the NM phenotype, considered as references, were generally more frequent. Other CYP2C19 polymorphism frequencies exhibit significant variability across different populations. Some studies associated variants with MDD development, a more extended history of depression, prolonged depressive episodes, and symptom severity, while others reported no such association. Some studies confirmed variants’ effects on escitalopram and citalopram metabolism but not that of other drugs, such as sertraline, venlafaxine, and bupropion. Treatment tolerability and symptom improvement also varied between studies. Despite some common findings, inconsistencies highlight the need for further research to clarify the role of these polymorphisms in MDD and optimize treatment strategies.

Is alcohol use disorder associated with higher rates of depression and anxiety among people with new onset type 2 diabetes? A cohort study using linked primary care data in England

IntroductionDepression and alcohol use disorder (AUD) in people living with Type 2 diabetes mellitus (T2DM) are associated with worse health outcomes. AUD is strongly associated with depression and anxiety, but it is not known how these conditions cluster in people with T2DM. We investigated rates of new episodes of depression and anxiety following T2DM diagnosis in people with and without prior AUD among an English primary care population.MethodsThe study population was people diagnosed with T2DM between 2004 and 2019. We used the Clinical Practice Research Datalink (CPRD) Aurum database and linked Hospital Episode Statistics Admitted Patient Care (HES APC) and Office for National Statistics (ONS) mortality data. We examined incidence of new episodes of anxiety or depression in people with T2DM with and without AUD. AUD was defined as any of i) clinical diagnosis; ii) alcohol withdrawal; or iii) chronic alcohol-related harm (physical or mental) using SNOMED-CT or ICD-10 codes. People were excluded if they had codes for depression/anxiety 12 months prior to T2DM diagnosis. Poisson regression models were fitted adjusting sequentially for a) age, gender, calendar time; b) region, Index of Multiple Deprivation, ethnicity, body mass index, smoking status, Charlson co-morbidity index; and c) history of a mental health condition.ResultsOur study population was 479,447 people of whom 10,983 (2.3%) had an AUD code prior to T2DM diagnosis.After adjusting for all measured confounders except history of a mental health condition, IRR for depression was 2.00 (95% CI 1.93, 2.06) for people with AUD compared to without AUD. This reduced to 1.45 (95% CI 1.41, 1.50) after further adjustment for history of a mental health condition.Findings for anxiety were substantially similar to those for depression (adjusted for all measured confounders except history of a mental health condition, IRR 2.08 95% CI 1.99, 2.18 fully adjusted IRR 1.48 95% CI 1.41, 1.55).ConclusionsPeople with AUD have over double the rates of depression and anxiety following T2DM diagnosis than those without AUD. This was only partially explained by pre-existing diagnoses of mental health conditions. A holistic approach incorporating mental health support is needed to improve health outcomes for people with AUD who develop T2DM.Trial registrationNot applicable.

Plasma Brain-Derived Neurotrophic Factor (BDNF) Levels and BDNF Promoters’ DNA Methylation in Workers Exposed to Occupational Stress and Suffering from Psychiatric Disorders

Introduction: Decreased plasma BDNF (pBDNF) levels have been proposed as a biomarker in the illness phases of mood disorders. This cross-sectional study aimed to evaluate the pBDNF and BDNF promoters’ DNA methylation levels in workers exposed to occupational stress and suffering from work-related stress disorders. Methods: the pBDNF and BDNF exon I and IV promoters’ methylation levels were measured by specific immunoassays and methylation-sensitive high-resolution melting (MS-HRM) in 62 patients with adjustment disorders (AD), 79 patients with major depressive disorder (MDD) and 44 healthy controls. Occupational stress was evaluated in the patients and controls using the Job Content Questionnaire (JCQ). Results: the pBDNF levels were significantly higher in the MDD (p &lt; 0.001) and AD (p &lt; 0.0001) patients than in the controls. The MDD patients showed significantly lower pBDNF levels than the AD ones (p = 0.01). The BDNF exon I and IV promoters’ methylation levels were significantly higher in the MDD patients than in the AD ones (exon I promoter: p = 0.0001, exon IV promoter: p &lt; 0.0001) and controls (exon I promoter: p = 0.0001, exon IV promoter: p &lt; 0.0001). In the patients, but not in the controls, the BDNF promoters’ methylation levels showed significant negative correlations with occupational stress. Conclusions: BDNF could play a key role in the pathophysiology of stress-related disorders and the peripheral elevation of it observed in patients exposed to occupational stress could suggest a protective mechanism for neurons from stress-mediated damage. The elevation of the pBDNF levels, even in MDD, may characterize a “reactive” subtype of depressive episode, while the significant elevation of the BDNF promoters’ methylation levels in depressed patients could indicate a predisposition to more severe illness under stress. Further research is needed, focusing on biomarkers for stress-related disorders as a potential tool for the diagnosis and prevention of occupational diseases.

Adult mental health outcomes of adolescent depression and co-occurring alcohol use disorder: a longitudinal cohort study

AbstractDepression and alcohol use disorder (AUD) are frequently co-occurring in adolescence, which often goes undetected in routine care. While this may potentially compromise treatment effectiveness and lead to a less favourable long-term prognosis, few longitudinal studies have followed this group into adulthood. The aim of this study was to explore the risk for adult depression, anxiety disorders, suicidality, and AUD in adolescents with concurrent depression and AUD. The study was based on the Uppsala Longitudinal Adolescent Depression Study (ULADS), a Swedish prospective cohort study. Diagnostic interviews were conducted in adolescence (age 16-17) and adulthood (around age 30). Adolescents with concurrent depression and AUD (n = 38) were compared with peers having only depression (n = 189) or neither of the conditions (n = 144). Logistic regression was used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Adolescents with concurrent depression and AUD were more likely than their non-affected peers to experience adult depressive episodes (aOR, 5.33; 95% CI, 2.22–12.83), anxiety disorders (4.05; 1.77–9.27), suicidality (5.37; 2.28–12.66), and AUD (7.68; 2.59–22.81). Notably, 34% of adolescents with both depression and AUD subsequently experienced both these conditions as adults, compared to 7% of adolescents with only depression. Adolescents suffering only from depression were less likely than those with both conditions to experience suicidality (0.44; 0.21–0.95) and AUD in adulthood (0.18; 0.07–0.44). These findings underscore the clinical imperative to identify adolescents with this comorbidity. Recognition of the poor long-term prognosis can inform targeted interventions for this vulnerable group, ultimately improving health and well-being throughout the life course.

A prediction model for electroconvulsive therapy effectiveness in patients with major depressive disorder from the Dutch ECT Consortium (DEC).

Reliable predictors for electroconvulsive therapy (ECT) effectiveness would allow a more precise and personalized approach for the treatment of major depressive disorder (MDD). Prediction models were created using a priori selected clinical variables based on previous meta-analyses. Multivariable linear regression analysis was used, applying backwards selection to determine predictor variables while allowing non-linear relations, to develop a prediction model for depression outcome post-ECT (and logistic regression for remission and response as secondary outcome measures). Internal validation and internal-external cross-validation were used to examine overfitting and generalizability of the model's predictive performance. In total, 1892 adult patients with MDD were included from 22 clinical and research cohorts of the twelve sites within the Dutch ECT Consortium. The final primary prediction model showed several factors that significantly predicted a lower depression score post-ECT: higher age, shorter duration of the current depressive episode, severe MDD with psychotic features, lower level of previous antidepressant resistance in the current episode, higher pre-ECT global cognitive functioning, absence of a comorbid personality disorder, and a lower level of failed psychotherapy in the current episode. The optimism-adjusted R² of the final model was 19%. This prediction model based on readily available clinical information can reduce uncertainty of ECT outcomes and hereby inform clinical decision-making, as prompt referral for ECT may be particularly beneficial for individuals with the above-mentioned characteristics. However, despite including a large number of pretreatment factors, a large proportion of the variance in depression outcome post-ECT remained unpredictable.