The cause of cognitive side effects after electroconvulsive therapy (ECT) is largely unknown. Alterations in the blood–brain barrier (BBB) have been considered in several recent ECT studies. We therefore found it worthwhile to perform a systematic review of the literature to examine if electrically induced seizures affect the permeability of the BBB.

PubMed/MEDLINE and Embase were searched 16 November 2022. Studies with a direct measurement of BBB permeability in animals treated with modified electroconvulsive stimulation (ECS) and in humans treated with ECT were included. Synthesis of results was narrative due to the low number of studies and differences in study designs.

Four animal and two human (31 participants) studies were included. In animals, two studies found increased BBB permeability to some smaller molecules after modified ECS, while the two other studies found marginally increased or unchanged permeability to albumin after treatment. In contrast, the human studies did not find increased BBB permeability to smaller molecules or albumin after ECT.

Animal but not human studies support increased BBB permeability to some smaller molecules after electrically induced seizures. However, this conclusion is confined by the low number of studies and the lack of studies applying state-of-the-art methods. More studies using modern approaches to measuring of BBB permeability are warranted.

The study was founded by Mental Health Services in the Capital Region of Denmark (grant number 61151-05) and was registered on PROSPERO before data extraction was initiated (CRD42022331385).

Previous research has suggested that some women are at increased risk of postpartum depression (PPD) because of an extra sensitivity to fluctuating hormones before and after parturition. This may particularly apply to women with endocrine disease, characterised by a less than optimal capability to self-regulate the hormonal feedback system.

To investigate if women with endocrine disease history are at increased risk of developing PPD.

Based on information from Danish national registers, this nationwide cohort study included 888 989 deliveries (1995–2018). Endocrine disease history was defined as thyroid disease, pre-pregnancy diabetes, polycystic ovary syndrome and/or previous gestational diabetes within 10 years before pregnancy start. PPD was defined as use of antidepressants and/or hospital contact for depression within 6 months after childbirth.

Among 888 989 deliveries, 4.1% had a history of endocrine disease and 0.5% had a PPD episode. Overall, women with an endocrine disease history had a 42% (risk ratio 1.42, 95% CI 1.24–1.62) higher risk of PPD when compared with women with no endocrine disease. However, we also found the reverse association, whereby women with a PPD history had a 50% (hazard ratio 1.5, 95% CI 1.4–1.6) higher risk of endocrine disease when compared with women with no PPD history.

Women with endocrine disease history had a 40% higher risk of PPD compared with women with no endocrine disease. More attention should be given to pregnant women with endocrine disease history to increase awareness of early signs of PPD. The bi-directionality of the association points to a common underlying factor.

The increasing global migration has made migrants’ health a pertinent topic. This article aimed to examine whether migrants were less likely than Danish-born residents to receive guideline recommended care when hospitalized for major depressive disorder (MDD) and potential differences in clinical outcomes, including all-cause mortality, suicidal behavior, and readmissions during 1-year follow-up after first-time admission.

A national cohort study was performed, including all adult MDD inpatients at mental care units in the period 2011–2017. Migrants and two migrant subgroups (non-Western and Western) were compared with Danish-born patients. Quality of care was examined using multivariable Poisson and linear regression models. Clinical outcomes were examined using Cox proportional hazards regression analysis.

Migrant-status was associated with a non-significantly lower chance of receiving high-quality care (relative risk [RR] = 0.93, confidence interval [CI] 0.86:1.01) and lower readmission rates for depression (hazard rate ratio [HR] = 0.93, CI 0.86:1.01), and significantly higher all-cause mortality (HR = 1.55, CI 1.19:2.01) and lower all-cause readmission rate (HR = 0.88, CI 0.83:0.94). No clear association was found regarding suicidal behavior. While associations were comparable for migrant subgroups regarding readmission, the associations with low quality of care and of all-cause mortality appeared strongest among Western migrants.

Among inpatients with MDD in a universal tax-financed healthcare system, being a migrant was associated with a potential lower quality of in-hospital care and worse clinical outcomes. These results warrant further investigation to clarify the underlying explanation for these inequalities and to develop and test interventions to ensure better quality of care and clinical outcomes for migrant patients.

S100B is a glial cell protein with bimodal function. In low concentrations, it exerts neurotrophic effects, but higher levels reflect neuronal distress. Recent research suggests that this molecule may be a biomarker of response to electroconvulsive therapy (ECT). We examined the effect of ECT on serum S100B and its utility as 1) a biomarker of a depressive state and 2) a predictor of ECT response. We also wanted to ensure that ECT does not cause a marked serum S100B elevation, indicating neural distress.

We measured serum S100B in 22 in-patients treated with ECT due to depression. Depression severity was assessed using 17-item Hamilton Rating Scale for Depression (HAMD-17). The data were collected before an ECT series, within 1 week after the series (post-ECT), and at a 6-month follow-up. Changes in serum S100B and clinical outcomes were tested using a linear mixed model. A relationship between serum S100B and the clinical outcomes was examined using Spearman’s and partial correlation.

Serum S100B did not change significantly immediately after an ECT series or 6 months later. The post-ECT serum S100B change was not associated with the clinical effect (rho = 0.14, n = 22, p = 0.54). The baseline serum S100B did not predict the clinical effect when controlling for age (r = 0.02, n = 22, df = 19, p = 0.92).

The study neither supports serum S100B as a state marker of depression nor a predictor of ECT response. No evidence for ECT-related neural distress was found.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has been shown to have a statistically and clinically significant anti-depressant effect. The present pilot study was carried out to investigate if right prefrontal low-frequency rTMS as an add-on to electroconvulsive therapy (ECT) accelerates the anti-depressant effect and reduces cognitive side effects.

In this randomised, controlled, double-blind study, thirty-five patients with major depression were allocated to ECT+placebo or ECT+low-frequency right prefrontal rTMS. The severity of depression was evaluated during the course using the Hamilton scale for depression (the 17-item as well as the 6-item scale) and the major depression inventory (MDI). Furthermore, neuropsychological assessment of cognitive function was carried out.

The study revealed no significant difference between the two groups for any of the outcomes, but with a visible trend to lower scores for MDI after treatment in the placebo group. The negative impact of ECT on neurocognitive functions was short-lived, and scores on logical memory were significantly improved compared to baseline 4 weeks after last treatment. The ECT-rTMS group revealed generally less impairment of cognitive functions than the ECT-placebo group.

The addition of low-frequency rTMS as an add-on to ECT treatment did not result in an accelerated response. On the contrary, the results suggest that low-frequency rTMS could inhibit the anti-depressant effect of ECT.

The efficacy of antidepressant treatment is fair, but the efficacy is considerably lower in patients failing two or more trials underscoring the need for new treatment options. Our study evaluated the augmenting antidepressant effect of 8-weeks transcranial pulsed electromagnetic field (T-PEMF) therapy in patients with treatment-resistant depression.

A multicenter 8-week single-arm cohort study conducted by the Danish University Antidepressant Group.

In total, 58 participants (20 men and 38 women) with a moderate to severe depression as part of a depressive disorder according to ICD-10 who fulfilled criteria for treatment resistance were included, with 19 participants being nonresponders to electroconvulsive therapy during the current depressive episode. Fifty-two participants completed the study period. Scores on the Hamilton Depression Scale 17-items version (HAM-D17) decreased significantly from baseline (mean = 20.6, SD 4.0) to endpoint (mean = 12.6, SD 7.1; N = 58). At endpoint, utilizing a Last Observation Carried Forward analysis, 49 and 28% of those participants with, respectively, a nonchronic current episode (≤2 years; N = 33) and a chronic current episode (>2 years; N = 25) were responders, that is, achieved a reduction of 50% or more on the HAM-D17 scale. At endpoint, respectively, 30 and 16% obtained remission, defined as HAM-D17 ≤ 7. On the Hamilton Scale 6-item version (HAM-D6), respectively, 51 and 16% obtained remission, defined as HAM-D6 ≤ 4.

The findings indicate a potential beneficial role of T-PEMF therapy as an augmentation treatment to ongoing pharmacotherapy in treatment-resistant depression.

Prior studies suggest that a dysregulation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is involved in the pathophysiology of major depression. We aimed to elucidate changes in cortical GABA content in relation to depression and electroconvulsive therapy (ECT) using magnetic resonance spectroscopy (MRS).

In total, 11 patients with major depression or depressive episode of bipolar disorder (mean pre-ECT Ham-17 of 26) and 11 healthy subjects were recruited. GABA was quantified using short-TE MRS in prefrontal and occipital cortex. Other neurometabolites such as glutathione (GSH), N-acetylaspartate (NAA) and glutamate (Glu) were secondary outcome measures.

No significant differences in GABA/Cr levels were observed between patients at baseline and healthy subjects in prefrontal cortex, t(20)=0.089, p=0.93 or occipital cortex t(21)=0.37, p=0.72. All patients improved on Ham-17 (mean post-ECT Ham-17 of 9). No significant difference was found in GABA, Glu, glutamine, choline or GSH between pre- and post-ECT values. However, we observed a significant decrease in NAA levels following ECT t(22)=3.89, p=0.0038, and a significant correlation between the NAA decline and the number of ECT sessions p=0.035.

Our study does not support prior studies arguing for GABA as a key factor in the treatment effect of ECT on major depression. The reduction in NAA levels following ECT could be due to neuronal loss or a transient dysfunction in prefrontal cortex. As no long-term follow-up scan was performed, it is unknown whether NAA levels will normalise over time.

The prognostic impact of previous depression on myocardial infarction survival remains poorly understood.

To examine the association between depression and all-cause mortality following myocardial infarction.

Using Danish medical registries, we conducted a nationwide population-based cohort study. We included all patients with first-time myocardial infarction (1995–2014) and identified previous depression as either a depression diagnosis or use of antidepressants. We used Cox regression to compute adjusted mortality rate ratios (aMRRs) with 95% confidence intervals.

We identified 170 771 patients with first-time myocardial infarction. Patients with myocardial infarction and a previous depression diagnosis had higher 19-year mortality risks (87% v. 78%). The overall aMRR was 1.11 (95% CI 1.07–1.15) increasing to 1.22 (95% CI 1.17–1.27) when including use of antidepressants in the depression definition.

A history of depression was associated with a moderately increased all-cause mortality following myocardial infarction.

Previous morphology and diffusion-imaging studies have suggested that structural changes in white matter is an important part of the pathophysiology of obsessive–compulsive disorder (OCD). However, different methodological approaches and the heterogeneity of patient samples question the validity of the findings.

In total, 30 patients were matched for age and sex with 30 healthy controls. All participants underwent T1-weighted magnetic resonance imaging, diffusion tensor imaging and T2 fluid-attenuated inversion recovery. Voxel-based morphometry and tract-based spatial statistics were used to compare white matter volumes and diffusion tensor imaging between groups. These data were analysed correcting for the effects of multiple comparisons, age, sex, severity and duration of illness as nuisance covariates. White matter hyperintensities were manually identified.

Increase in fractional anisotropy in cerebellum was the most prominent result. A decrease in fractional anisotrophy in patients comparable with previous studies was located in forceps minor. There were no differences in the white matter morphology or in the white matter hyperintensities between patients and healthy controls.

Decrease in fractional anisotrophy in forceps minor and increase in cerebellum were found, and they were not due to neither white matter hyperintensities nor morphology of the white matter. Cerebellar hyperconnectivity could be an important part of OCD pathophysiology.

The main aim of the present study was to replicate a previous finding in major depressive disorder (MDD) of association between reduced hippocampal volume and the long variant of the di- and triallelic serotonin transporter polymorphism in SLC6A4 on chromosome 17q11.2. Secondarily, we also hypothesised that 5-HTTLPR may be a risk factor for MDD.

Quantitative magnetic resonance imaging (MRI) of the hippocampus was studied in 23 inpatients suffering from MDD and in 33 healthy controls. Normalised volumetric MRI data of hippocampus were assessed with adjustment for total brain volume and tensor-based morphometry was used to elucidate structural brain differences. A triallelic genetic marker resulting from two SLC6A4 promoter region polymorphisms, 5-HTTLPR and rs25531, was analysed for association with MDD and quantitative traits.

Healthy controls had a smaller relative hippocampal volume (relative to brain size) but a larger total brain volume compared with patients with MDD. For patients compared with healthy controls, atrophy was found in the right temporal lobe and pons medulla. Allele and genotype frequencies were strikingly different from the previous study that we aimed to replicate, and no significant associations with the serotonin transporter polymorphism were found.

The present quantitative and morphometric MRI study was not able to replicate the previous finding of association between reduced hippocampal volume in depressed patients and the serotonin transporter polymorphism.

Studies investigating mortality secondary to electroconvulsive therapy (ECT) are few.

To assess the risk of mortality from natural and unnatural causes among ECT recipients compared with other psychiatric in-patients over a 25-year period.

Register-based cohort study of all in-patients admitted to a psychiatric hospital from 1976 to 2000. Cause-specific mortality was analysed using log–linear Poisson regression.

There were 783 deceased in-patients who had received ECT compared with 5781 who had not. Patients who had received ECT had a lower overall mortality rate from natural causes (RR=0.82,95% CI 0.74–0.90) but a slightly higher suicide rate (RR=1.20,95% CI 0.99–1.47), especially within the first 7 days after the last ECT treatment (RR=4.82,95% CI 2.12–10.95).

Further investigation of the effect of ECT on physical health and the observed increased suicide rate immediately following treatment are needed, although the last finding is likely to result from selection bias.