Severe Major Depressive Episode Research Articles

Evaluating the influence of nonproblematic alcohol intake on the outcome of major depression.

The effect of light or moderate alcohol intake on the outcome of patients with major depression taking antidepressants is a question that remains unanswered. The main objective of this study was to assess the association between light or moderate alcohol consumption and the acute response (efficacy and tolerability) to pharmacological treatment in unipolar major depression. Efficacy and tolerability analyses compared 8-week outcomes between three subgroups, abstainers, light drinkers and moderate drinkers, of patients with major depression using a prospective naturalistic single-blind design. The treatment strategy was adapted from a local clinical guideline. Antidepressants prescribed were escitalopram, venlafaxine extended-release and imipramine; benzodiazepines and antipsychotics could be prescribed as needed. The final sample consisted of 614 severe unipolar major depressive inpatients and outpatients aged 18 years or older. Notably, no significant differences in efficacy or tolerability (including all subscores assessed) were found between the abstainer and nonproblematic drinker subgroups. Without ever forgetting the serious implicit risks associated with the inappropriate use of alcohol, in conclusion, our results suggest that nonproblematic alcohol consumption does not influence the outcome of patients diagnosed with an acute severe major depressive episode.

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

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

Depression in young women after hysterectomy: Emergency obstetric versus elective procedure – A comparative cross-sectional study

Emergency obstetric hysterectomy (EOH) is done during cesarean section or after normal vaginal delivery, or any time during puerperal period. Puerperal period is usually associated with anxiety and depression in most cases, having emergency hysterectomy can potentially trigger it more. Therefore, this study was conducted to compare emergency versus elective hysterectomy to determine the pattern of depression between two groups. During a period of four years (from 1st march 2019 to 28th February 2023), a total of 6658 patients were admitted in obstetrics & gynecology department and 31 underwent emergency obstetric hysterectomies and consented to be part of this study. These females were aged between 18 to 49 years. For comparison 31 married control females were randomly selected and interviewed 3 months after undergoing elective hysterectomy due to gynecological conditions. There was no past family history for any psychiatric illness in both groups. The studied groups were clinically evaluated for major depressive episode according to the American Psychiatric Association diagnostic and statistical Manual of mental disorders, 4th edition text revised (DSM-IV TR) criteria. Beck depression inventory (BDI)18 to assess the severity of major depressive episodes. Out of 31 patients 16 cases were performed after caesarean section, four during laparotomy for ruptured uterus and 11 for uterine atony after normal vaginal delivery. There was significantly higher rate of depression among patients undergoing emergency hysterectomy as compared to those with elective procedure. The frequency of complications was also observed to be higher in emergency cases. Our study concluded that the frequency of complications and severe depression was remarkably higher in the obstetric emergency hysterectomy group as compared to the elective hysterectomy group.

Stroke, depression, and self-harm in later life.

To examine recently published results of randomized placebo-controlled trials investigating the clinical effects of selective serotonin reuptake inhibitors on the prevalence of clinically significant symptoms of depression and suicidal ideation after an acute stroke. The prevalence of poststroke depression varies markedly according to the approach used to define depression, with recently published data suggesting that about one in every three stroke survivors will experience clinically significant symptoms of depression over a period of 12 months. The proportion of stroke survivors with clinically significant symptoms of depression decreases progressively with time, but in 30% of them symptoms persist or recur over 12 months. Routine daily treatment with 20 mg of fluoxetine for 6 months does not affect the prevalence of depression in this population, nor is it effective at treating or preventing poststroke depressive symptoms. Treatment discontinuation, gastrointestinal adverse effects, seizures and bone fractures are more frequent among stroke survivors treated with antidepressants than placebo. Moreover, current data show that thoughts about death or suicide are more frequent among adults who had a stroke than the general population, although recurring suicidal thoughts are uncommon. Routine daily treatment with 20 mg of fluoxetine for 6 months does not change the proportion of people who disclose suicidal thoughts over a period of 12 months after an acute stroke. Current evidence raises concerns about the efficacy and safety of antidepressants for the management and prevention of poststroke clinically significant symptoms of depression. It is unclear if these findings can be generalized to people with severe strokes or to stroke survivors with moderate to severe major depressive episodes.

Hyperthyroidism and depression: a clinical case of atypical thyrotoxicosis manifestation.

The relationship between psychiatric symptoms and thyroid function has been well known and studied since antiquity. The common view is that clinical hypothyroidism is associated with depressive symptoms, whereas the psychiatric manifestations of hyperthyroidism are agitation, emotional lability, hyperexcitability, occasionally accompanied by angry outbursts, and euphoria. The case here reported overturns this conventional medical knowledge. A 73-year-old Italian woman experienced a severe major depressive episode with psychotic and melancholic features during laboratory thyrotoxicosis. No classical clinical signs and symptoms of thyrotoxicosis were present. Psychiatric symptoms improved together with the resolution of the hyperthyroid state. Historically, different cases of so-called 'apathetic hyperthyroidism' have been described. Recent neuroimaging and animal studies provided possible neurobiological explanations, showing how the excess thyroid hormones could affect brain structures involved in the regulation of mood, leading to depression. A direct link between hyperthyroidism and depression seems to be likely. This insight may be relevant in facilitating early diagnosis of thyroid disease and the planning of therapeutic strategies.

Transcriptomic Studies of Antidepressant Action in Rodent Models of Depression: A First Meta-Analysis.

Antidepressants (ADs) are, for now, the best everyday treatment we have for moderate to severe major depressive episodes (MDEs). ADs are among the most prescribed drugs in the Western Hemisphere; however, the trial-and-error prescription strategy and side-effects leave a lot to be desired. More than 60% of patients suffering from major depression fail to respond to the first AD they are prescribed. For those who respond, full response is only observed after several weeks of treatment. In addition, there are no biomarkers that could help with therapeutic decisions; meanwhile, this is already true in cancer and other fields of medicine. For years, many investigators have been working to decipher the underlying mechanisms of AD response. Here, we provide the first systematic review of animal models. We thoroughly searched all the studies involving rodents, profiling transcriptomic alterations consecutive to AD treatment in naïve animals or in animals subjected to stress-induced models of depression. We have been confronted by an important heterogeneity regarding the drugs and the experimental settings. Thus, we perform a meta-analysis of the AD signature of fluoxetine (FLX) in the hippocampus, the most studied target. Among genes and pathways consistently modulated across species, we identify both old players of AD action and novel transcriptional biomarker candidates that warrant further investigation. We discuss the most prominent transcripts (immediate early genes and activity-dependent synaptic plasticity pathways). We also stress the need for systematic studies of AD action in animal models that span across sex, peripheral and central tissues, and pharmacological classes.

Race and ethnicity moderate the associations between lifetime psychedelic use (MDMA/ecstasy and psilocybin) and major depressive episodes.

Psychedelics are receiving renewed attention within Western medicine as they represent potential treatments for many difficult-to-treat mental health disorders. However, psychedelic science is limited in its focus and inclusion of racial and ethnic minorities. Hence, this study examines whether race and ethnicity moderate the associations that naturalistic 3,4-methylenedioxymethamphetamine (MDMA)/ecstasy use and psilocybin use share with major depressive episodes (MDEs). Data for this project are from The National Survey on Drug Use and Health (2005-2019). Participants were adults aged 18 years and older (unweighted N = 596,187). This study used multivariable logistic regression to test the interaction between race and ethnicity and MDMA/ecstasy use and psilocybin use for predicting lifetime, past year, and past year severe MDEs. Race and ethnicity significantly moderated the associations between MDMA/ecstasy use and psilocybin use and MDEs. For White participants, MDMA/ecstasy use and psilocybin use each were associated with lowered odds of all three MDE outcomes (adjusted odds ratio (aOR) range: 0.82-0.92). For Hispanic participants, MDMA/ecstasy use and psilocybin use each conferred lowered odds of only a past year MDE (MDMA/ecstasy aOR: 0.82; psilocybin aOR: 0.79). For Non-Hispanic Racial Minority participants, MDMA/ecstasy and psilocybin use did not confer lowered odds of any MDE outcomes. Race and ethnicity have an impact on the associations that psychedelics share with mental health outcomes. Future research should explore the impact of identity and discrimination on the effects of psychedelics and should explore whether these substances can serve as effective treatments for minorities when used in culturally informed contexts.

(PO-158) Case Report: Myxedema Coma, Scurvy, and Hospital-Acquired COVID-19 as Complications of Severe Major Depressive Episode in the Setting of a Global Pandemic

(PO-158) Case Report: Myxedema Coma, Scurvy, and Hospital-Acquired COVID-19 as Complications of Severe Major Depressive Episode in the Setting of a Global Pandemic

Interrogating Associations between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDE). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia, cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness.

Recurrent Catatonia Onset in an Octogenarian Woman Managed with Electroconvulsive Therapy

<h3>Introduction</h3> Catatonia is a neuropsychiatric syndrome of motor, affective and behavioral dysregulation, accompanied by potential systemic complications with significant morbidity and mortality¹^,². Multiple disorders have been associated with catatonia; these include structural and intrinsic brain diseases, systemic disorders, and psychiatric disorders³,⁴. In the elderly, the prevalence of catatonia fluctuates between 5.5%-11.22% depending on the clinical setting⁵^,⁶. Despite the significant prevalence, there is limited literature regarding the clinical characteristics of recurrent catatonia in the elderly. <h3>Methods</h3> We hereby describe a case of a 91-year-old woman with recurrent major depressive disorder, who presented with recurrent catatonia and comorbidities of atrial fibrillation on therapeutic anticoagulation, hypertension, mild cognitive impairment, and constipation. <h3>Results</h3> The patient's initial presentation occurred at the age of 87 years when she presented with symptoms of catatonia consisting of immobility, mutism, rigidity, negativism, and severe decline in oral intake as the initial manifestation of her first non-psychotic depressive episode. During her initial presentation, catatonia was treated with lorazepam with an adequate response but was transitioned to an acute course of bilateral electroconvulsive therapy (ECT) due to side effects with lorazepam. Her symptoms rapidly resolved after three ECT treatments, and she was on maintenance antidepressant therapy with venlafaxine extended-release 75 mg daily. Catatonia symptoms recurred after two years concomitantly with a depressive episode with psychotic features. The patient responded well once again to the acute course of bilateral ECT during her second episode of depression and required a prolonged course of maintenance ECT every one to three weeks with adequate tolerance. She had a recurrence of catatonia at the age of 91 years in the context of her husband's death. She was managed with an acute course of six ECT treatments and transitioned to weekly maintenance ECT. During all presentations, extensive medical workup was unremarkable for organic causes, and there was no evidence of cognitive decline. Her symptoms of catatonia remitted completely in between depressive episodes. <h3>Conclusions</h3> Catatonia can be a life-threatening emergency. Recurrent catatonia could be a precursor of severe major depressive episodes. This case highlights the importance of identifying catatonia in the elderly, brings awareness to the multiple etiologies to be considered when catatonia arises, including affective disorders, and the potential role of ECT in the management of recurrent catatonia. Further studies are needed regarding the prognosis of recurrent catatonia in the geriatric population. <h3>This research was funded by</h3> None

Special Report: Stress and Distress During Pregnancy—How to Protect Both Mother and Child

Special Report: Stress and Distress During Pregnancy—How to Protect Both Mother and Child

Esketamine nasal spray in patients with treatment-resistant depression: the real-world experience in the French cohort early-access programme

Objective To present the first real-world data of patients with treatment-resistant depression (TRD) treated with esketamine through a French cohort Temporary Authorisation for Use (ATUc) programme. Methods In 2019, the French Health Authorities exceptionally granted the first ATUc in psychiatry for TRD patients. Clinical characteristics, safety and efficacy data were reported by physicians. The ATUc ended ∼6 months after initiation. Results The cohort (n = 66; median age 53.0 years; 62.1% female; 78.8% with severe major depressive episodes; resistance to a mean of 4.2 previous antidepressants) received esketamine treatment for a median of 30 days. Among 46 analysed patients, 22 (47.8%) achieved response (Montgomery–Åsberg Depression Rating Scale [MADRS] total score reduction ≥50.0%) and 17 (37.0%) achieved remission (MADRS total score of ≤12) at least once at a median of 18.5 (2.0–77.0) and 21.0 (2.0–46.0) days after initiation, respectively. By Week 4, patients had a 31.6% probability of achieving remission (Kaplan–Meier method). Sedation, somnolence, dizziness, hypertension, anxiety and dissociation were the most frequently reported (>10.0%) adverse events. No new safety signals were identified. Conclusions Patient characteristics of this cohort demonstrate high-level treatment resistance. The safety and efficacy of esketamine in patients with TRD in real‐world clinical practice were consistent with Phase 3 trials. Key points Patients with treatment-resistant depression (TRD) exceptionally received esketamine nasal spray ahead of its launch through a French cohort Temporary Authorisation for Use (ATUc) programme. The clinical characteristics of 66 adult patients with TRD included in this cohort demonstrated a high-level of resistance to conventional treatments at the time of treatment request prior to esketamine initiation. No new safety signals were observed with esketamine initiation during the ATUc period compared with the Phase 3 clinical trials. The safety and efficacy of esketamine in the real world remain consistent with that established in Phase 3 clinical trials. The data collected during this ATUc also provide the first real-world data on the management and practical use of esketamine in a hospital setting in France.

Lifetime use of MDMA/ecstasy and psilocybin is associated with reduced odds of major depressive episodes.

Depression is a major mental health issue worldwide, with high rates of chronicity and non-recovery associated with the condition. Existing treatments such as antidepressant medication and psychological treatments have modest effectiveness, suggesting the need for alternative interventions. The aim of this study was to examine the relationships between MDMA (3,4-methylenedioxymethamphetamine)/ecstasy and psilocybin use and major depressive episodes (MDEs). This observational study used data from a large (N = 213,437) nationally representative sample of US adults to test the association of lifetime use of MDMA/ecstasy, psilocybin and other classic psychedelics (lysergic acid diethylamide (LSD), peyote, mescaline), other illegal substances (e.g. cocaine, phencyclidine (PCP)), and legal/medicinal substances of misuse (e.g. pain relievers, tranquilizers) with lifetime, past year, and past year severe MDEs. Results revealed that lifetime MDMA/ecstasy use was associated with significantly lowered odds of a lifetime MDE (adjusted odds ratio (aOR) = 0.84; p < 0.001), past year MDE (aOR = 0.84; p < 0.001), and past year severe MDE (aOR = 0.82; p < 0.001). Psilocybin was associated with significantly lowered odds of a past year MDE (aOR = 0.90; p < 0.05) and past year severe MDE (aOR = 0.87; p < 0.05). All other substances either shared no relationship with a MDE or conferred increased odds of an MDE. These results suggest that MDMA/ecstasy and psilocybin use is associated with lower risk of depression. Experimental studies are needed to test whether there is a causal association between use of these compounds and the alleviation of depressive symptoms.

Real-World Treatment Patterns, Outcomes, Resource Utilization and Costs in Treatment-Resistant Major Depressive Disorder: PATTERN, a Retrospective Cohort Study in Belgium.

ObjectiveTreatment-resistant depression (TRD), a subgroup of major depressive disorder (MDD) that does not adequately respond to treatment, has a substantial impact on the quality of life of patients and is associated with higher medical and mental health care costs. This study aimed to report real-world treatment patterns, outcomes, resource utilization, and costs in the management of TRD by psychiatrists in Belgium.MethodsWe conducted a retrospective, non-interventional cohort study of patients ≥ 18 years, with diagnosed MDD who are treatment-resistant, defined as not responding to two different antidepressant treatments in the current moderate to severe major depressive episode (MDE). Data obtained from medical records of patients included patient health state (MDE, response, remission, and recovery) and resource use (number of consultations and emergency room visits, non-drug and drug interventions, and hospitalizations).ResultsOne hundred and twenty-five patients were enrolled in nine sites, with an average observation period of 34 months. During the MDE, 89.7% of patients were treated with selective serotonin reuptake inhibitors, 63.2% with serotonin-norepinephrine reuptake inhibitors, and 60.8% with anti-psychotics. Twenty-four percent of patients did not respond to any treatment; 76% responded, of whom 61% experienced a relapse; 28% of patients reached recovery, of whom 31.4% experienced recurrence. The average yearly direct cost of a TRD patient is €9012, mainly driven by hospitalization in the MDE. The observed absenteeism relates to a high indirect cost, representing 70% of the total MDE cost.ConclusionTRD is associated with a high unmet need and economic burden for patients and society, with highest costs in the MDE health state driven by absenteeism.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-021-00306-2.

Clinical Features and Outcomes of 124 Italian Patients With Treatment Resistant Depression: A Real-World, Prospective Study

Introduction: Treatment-resistant depression (TRD) is a debilitating condition affecting 20–30% of patients with major depressive disorders (MDD). Currently, there is no established standard of care for TRD, and wide variation in the clinical approach for disease management has been documented. Real-world data could help describe TRD clinical features, disease burden, and treatment outcome and identify a potential unmet medical need.Methods: We analyzed the Italian data from a European, prospective, multicentric, observational cohort study of patients fulfilling TRD criteria by the European Medicine Agency, with moderate to severe major depressive episode, and starting a new antidepressant treatment according to routinary clinical practice. They were followed up for minimum 6 months. Treatments received throughout the study period, disease severity, health-related quality of life and functioning were prospectively recorded and analyzed.Results: The Italian subcohort included 124 TRD patients (30.2% of patients of the European cohort; mean age 53.2 [sd = 9.8], women: 82, 66.1%). At enrollement, the mean (SD) duration of MDD was 16 years (sd = 11.1) and the mean duration of the ongoing major depressive episode (MDE) was 97.5 weeks (sd = 143.5); low scores of quality of life and functioning were reported. The most frequently antidepressant classes started at baseline (data available for 98 subjects) were selective serotonin reuptake inhibitors (SSRI, 42 patients [42.9%]) and serotonin-norepinephrine reuptake inhibitors (SNRI, 32 patients [32.7%]). In terms of treatment strategies, 50 patients (51%) started augmentation therapies, 18 (18.4%) combination therapies and 24 (24.5%) monoterapies (6 patients [6%] started a non-antidepressant drug only). Fourteen patients (11.3%) were treated with a psychosocial approach, including psychotherapy. After 6 months of treatment, clinical assessments were collected for 89 patients: 64 (71.9%) showed no response, 9 (10.1%) response without remission and 16 (18.0%) were in remission; non-responder patients showed lower quality of life and higher disability scores than responder patients.Conclusions: In our sample of TRD patients, we documented substantial illness burden, low perceived quality of life and poor outcome, suggesting an unmet treatment need in TRD care in Italy.Registration Number: ClinicalTrials.gov, number: NCT03373253.

Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

BackgroundElectroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. MethodsA total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R2) at the optimal p-value threshold is reported. ResultsIn the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R2 = 8.18%, p = .0013), Belgium (R2 = 6.83%, p = .016), and the Netherlands (R2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R2 = 4.42%, p = .0024) and unipolar MDE only (R2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. ConclusionsA linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry.

Major Depressive Episode Severity Among Adults from Marginalized Racial and Ethnic Backgrounds in the US

Major Depressive Episode Severity Among Adults from Marginalized Racial and Ethnic Backgrounds in the US

A-84 Interdisciplinary Collaboration: Neuropsychology’s Role in Elucidating Neurocognitive Symptoms in a Patient with Arachnoid Cyst

Abstract Objective Arachnoid cysts (ACs) are typically cerebrospinal fluid-filled abnormalities that occur within the central nervous system. ACs are uncommon (prevalence rate of 1.2%), and typically occur within the left hemisphere middle cranial fossa or posterior fossa. Symptoms vary depending on location and size but often include headaches, weakness, cognitive changes, and hydrocephalus. We present an unusual case of a 68-year-old right-handed woman with 13 years of education who was admitted to the hospital following overdose. During a previous admission, Patient was found to have a large arachnoid cystic lesion and right-sided weakness, but was determined not to require acute intervention. Neuropsychology was consulted to assess current cognitive functioning. Method Patient was initially diagnosed with a severe major depressive episode with new-onset psychotic features following an overdose of baclofen and Tylenol. Suicide attempt was denied. Magnetic Resonance Imaging (MRI) confirmed previously identified arachnoid cystic lesion (Figure 1) causing mass effect. Patient’s MRI also revealed pituitary macroadenoma (Figure 2) that caused subtle distortion along the optic chiasm. Results The results (Table 1) suggested an abnormal cognitive profile characterized by deficits on measures of language, visuoperception, memory, and abstract reasoning in the context of relatively intact auditory attention and working memory. Conclusions The extent and severity of Patient’s deficits are likely attributable to the cystic lesion, with recent onset of visual hallucinations likely caused by location of pituitary macroadenoma. This case highlights the importance of having access to a neuropsychological inpatient consultation service to assist with clarification of symptom etiology and facilitation of appropriate diagnosis and intervention.

A positron emission tomography study of the serotonin1B receptor effect of electroconvulsive therapy for severe major depressive episodes

BackgroundElectroconvulsive therapy (ECT) is an effective treatment for depressive disorders, although its molecular mechanism of action is unknown. The serotonin 1B (5-HT1B) receptor is a potential target for treatment of depression and low 5-HT1B receptor binding in limbic regions has been reported in previous positron emission tomography (PET) studies of depression. MethodsThe objective of this longitudinal PET study was to examine the effect of ECT for depression on 5-HT1B receptor binding. Fifteen hospitalized patients with major depressive episodes were examined with PET and the 5-HT1B receptor selective radioligand [11C]AZ10419369, before and after ECT. Fifteen controls matched for age and sex were examined. Limbic regions with previously reported low 5-HT1B receptor binding in depression and a dorsal brain stem region were selected. ResultsThirteen patients completed the study according to protocol. Eleven out of thirteen patients responded to ECT. 5-HT1B receptor binding in hippocampus increased with 30 % after ECT (p=0.021). Using linear mixed effects modelling, we observed increases in 5-HT1B receptor binding following ECT with a moderate to large effect size, which did not differ significantly between regions. In an exploratory analysis, strong correlations between changes in 5-HT1B receptor binding and agitation scores on the Hamilton Depression Rating Scale after ECT were observed. LimitationsAlbeit representative of a PET study, the sample size is still small and there are potential confounding effects of medication. ConclusionsIncreased 5-HT1B receptor binding was observed following ECT for depression, corresponding to previous findings of increased 5-HT1B receptor binding in hippocampus after rapid acting ketamine for treatment resistant depression.

Genome-wide association study of patients with a severe major depressive episode treated with electroconvulsive therapy

Although large genome-wide association studies (GWAS) of major depressive disorder (MDD) have identified many significant loci, the SNP-based heritability remains notably low, which might be due to etiological heterogeneity in existing samples. Here, we test the utility of targeting the severe end of the MDD spectrum through genome-wide SNP genotyping of 2725 cases who received electroconvulsive therapy (ECT) for a major depressive episode (MDE) and 4035 controls. A subset of cases (n = 1796) met a narrow case definition (MDE occurring in the context of MDD). Standard GWAS quality control procedures and imputation were conducted. SNP heritability and genetic correlations with other traits were estimated using linkage disequilibrium score regression. Results were compared with MDD cases of mild-moderate severity receiving internet-based cognitive behavioral therapy (iCBT) and summary results from the Psychiatric Genomics Consortium (PGC). The SNP-based heritability was estimated at 29–34% (SE: 6%) for the narrow case definition, considerably higher than the 6.5–8.0% estimate in the most recent PGC MDD study. Our severe MDE cases had smaller genetic correlations with neurodevelopmental disorders and neuroticism than PGC MDD cases but higher genetic risk scores for bipolar disorder than iCBT MDD cases. One genome-wide significant locus was identified (rs114583506, P = 5e−8) in an intron of HLA-B in the major histocompatibility locus on chr6. These results indicate that individuals receiving ECT for an MDE have higher burden of common variant risk loci than individuals with mild-moderate MDD. Furthermore, severe MDE shows stronger relations with other severe adult-onset psychiatric disorders but weaker relations with personality and stress-related traits than mild-moderate MDD. These findings suggest a different genetic architecture at the severest end of the spectrum, and support further study of the severest MDD cases as an extreme phenotype approach to understand the etiology of MDD.