Differences in bacterial taxa between treatment-naive patients with major depressive disorder and non-affected controls may be related to a proinflammatory profile.

BACKGROUND: Major depressive disorder (MDD) is characterized by sadness and anhedonia, but also physical symptoms such as changes in appetite and weight. Gut microbiota has been hypothesized to be involved in MDD through gut-brain axis signaling. Moreover, antidepressants display antibacterial properties in the gastrointestinal tract. The aim of this study was to compare the gut microbiota and systemic inflammatory profile of young patients with MDD before and after initiation of antidepressant treatment and/or psychotherapy in comparison with a non-depressed control group (nonMDD). METHODS: Fecal and blood samples were collected at baseline and at follow-up after four and twelve weeks, respectively. Patients started treatment immediately after collection of the baseline samples. The gut microbiota was characterized by 16 S rRNA gene sequencing targeting the hypervariable V4 region. Plasma levels of 49 unique immune markers were assessed using Mesoscale. RESULTS: In total, 27 MDD patients and 32 nonMDD controls were included in the study. The gut microbiota in the baseline samples of MDD versus nonMDD participants did not differ regarding α- or ß-diversity. However, there was a higher relative abundance of the genera Ruminococcus gnavus group, and a lower relative abundance of the genera Desulfovibrio, Tyzzerella, Megamonas, Olsenella, Gordonibacter, Allisonella and Rothia in the MDD group compared to the nonMDD group. In the MDD group, there was an increase in the genera Rothia, Desulfovibrio, Gordinobacteer and Lactobacillus, while genera belonging to the Firmicutes phylum were found depleted at twelve weeks follow-up compared to baseline. In the MDD group, IL-7, IL-8 and IL-17b levels were elevated compared to the nonMDD group at baseline. Furthermore, MDI score in the MDD group was found to correlate with Bray-Curtis dissimilarity at baseline, and several inflammatory markers at both baseline and after initiation of antidepressant treatment. CONCLUSION: Several bacterial taxa differed between the MDD group and the nonMDD group at baseline and changed in relative abundance during antidepressant treatment and/or psychotherapy. The MDD group was furthermore found to have a pro-inflammatory profile compared to the nonMDD group at baseline. Further studies are required to investigate the gut microbiota and pro-inflammatory profile of patients with MDD.

Electroconvulsive Therapy and Risk of Road Traffic Accidents: A Danish Register-Based Cohort Study.

OBJECTIVE: The aim of the study is to examine whether electroconvulsive therapy (ECT) was associated with the subsequent risk of being involved in a road traffic accident. METHODS: A cohort of all 375,435 patients older than 18 years with their first psychiatric hospital contact between 2003 and 2017 in the Danish National Patient Registry was followed for road traffic accidents until December 2018. Associations between ECT and road traffic accidents were examined using Cox regression analyses with multiple adjustments and using propensity score matching on sociodemographic and clinical variables. RESULTS: A total of 8486 patients (0.2%) were treated with ECT. During the median follow-up of 5.9 years, 778 of these patients (12.5%) were involved in a road traffic accident and the unadjusted incidence of road traffic accidents was lower among these patients (incidence rate, 15.5 per 1000 patient-years; 95% confidence interval [CI], 14.5-16.7) compared with patients not treated with ECT (incidence rate, 20.0 per 1000 patient-years; 95% CI, 20.0-20.3). Electroconvulsive therapy was not associated with road traffic accidents in the Cox regression models after adjustment for all covariables (hazard ratio, 1.00; 95% CI, 0.92-1.08) or in the propensity score-matched sample (hazard ratio, 0.91; 95% CI, 0.83-1.08). The HRs did not vary materially with follow-up time or when analyses were stratified on sex, age, or type of hospital contact. CONCLUSIONS: The analysis of Danish National registry data indicates that ECT is not associated with the risk of being involved in major road traffic accidents.

The clinical use of electroencephalography in a general psychiatric setting.

OBJECTIVE: Electroencephalography (EEG) is used in psychiatric services, however, clinical guidelines do not clearly state when EEG is indicated, and its diagnostic value in psychiatric settings is unclear. We aimed to characterize the clinical use and diagnostic consequences of EEG in a general psychiatric setting to evaluate and optimize its use. METHODS: We performed a quality development project at the psychiatric services of the Central Denmark Region. We identified patients referred for EEG examination from psychiatric services between 1 September 2017 and 1 September 2022. We extracted data from electronic health records on patient characteristics, indications, EEG results, and treatment consequences and analyzed risk factors for abnormal EEGs. RESULTS: Among 57,031 persons seen in the psychiatric services in the study period, 219 (0.4%) were referred for EEG examination. Psychosis (n = 70, 32%) was the most common symptom and suspicion of epilepsy (n = 129, 59%) was the most common clinical suspicion leading to referral. Of the 219 patients, 53 (24%) had an abnormal EEG result including 17 (7.8%) with epileptiform changes. Abnormal EEGs led to treatment alterations in six patients (3%). Age, prior epilepsy, use of antiseizure medication, use of clozapine, and convulsions were associated with epileptiform changes in the EEG. CONCLUSION: EEG is rarely used in psychiatric settings and seldom has treatment consequences. However, in specific clinical settings, the EEG result leads to an alteration of clinical management and the findings, therefore, call for refinement of clinical guidelines to optimize the use of EEG.

Treatment of difficult-to-treat depression - clinical guideline for selected interventions.

BACKGROUND: Difficult-to-treat-depression (DTD) is a clinical challenge. The interventions that are well-established for DTD are not suitable or effective for all the patients. Therefore, more treatment options are highly warranted. We formulated an evidence-based guideline concerning six interventions not well-established for DTD in Denmark. METHODS: Selected review questions were formulated according to the PICO principle with specific definitions of the patient population (P), the intervention (I), the comparison (C), and the outcomes of interest (O), and systematic literature searches were performed stepwise for each review question to identify relevant systematic reviews/meta-analyses, and randomized controlled trials. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the methodological quality of the included studies. Clinical recommendations were formulated based on the evidence, the risk-benefit ratio, and perceived patient preferences. RESULTS: We found sufficient evidence for a weak recommendation of repetitive transcranial magnetic stimulation (rTMS) and cognitive behavioural analysis system of psychotherapy (CBASP). The use of bright light therapy in DTD was not sufficiently supported by the evidence, but should be considered as good clinical practice. The interventions should be considered in addition to ongoing antidepressant treatment. We did not find sufficient evidence to recommend intravenous ketamine/esketamine, rumination-focused psychotherapy, or cognitive remediation to patients with DTD. CONCLUSION: The evidence supported two of the six reviewed interventions, however it was generally weak which emphasizes the need for more good quality studies. This guideline does not cover all treatment options and should be regarded as a supplement to relevant DTD-guidelines.

Long-Term Risk of Developing Dementia After Electroconvulsive Therapy for Affective Disorders.

OBJECTIVES: Severe depression is associated with an increased risk of developing dementia, however, whether treatment with electroconvulsive therapy (ECT) modify this risk remains unknown. METHODS: In this matched cohort study, 1089 consecutive in-patients with affective disorders, receiving ECT during the period 1982 to 2000, were matched with 3011 in-patients with affective disorders not treated with ECT (non-ECT), and 108,867 individuals randomly selected from the background population. The comparison cohorts were matched on sex, age, and the non-ECT cohort was further matched according to diagnoses and admission period and hospital. Dementia diagnoses were retrieved from the national patient health registry. Analyses were adjusted for disease severity, somatic, and psychiatric comorbidities. RESULTS: The cumulative incidence of dementia was 13.45% (10.75-16.46%) in the ECT cohort after 34 years of follow-up, 10.53% (8.5-12.81%) in the non-ECT cohort, and 8.43% (8.17-8.7%) in the background cohort. Using the ECT cohort as reference and age as the underlying time scale, the adjusted hazard ratio of developing dementia was 0.73 (0.52-1.04) in the non-ECT cohort and 0.61 (0.49-0.76) in the background cohort. The stratified analysis based on age at index (<65 years; 65-80 years; >80 years) found no age-related difference in the risk of developing dementia between the ECT cohort and non-ECT cohort. CONCLUSIONS: The ECT treatment of affective disorders was not associated with an increased long-term risk of developing dementia compared with in-patients with affective disorders not treated with ECT.

Low-frequency rTMS inhibits the anti-depressive effect of ECT. A pilot study.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Electroconvulsive Therapy Practice in the Kingdom of Denmark: A Nationwide Register- and Questionnaire-Based Study.

OBJECTIVES: The aim of this study was to survey and describe the contemporary practice of electroconvulsive therapy (ECT) in the Kingdom of Denmark (Denmark, Greenland, and the Faroe Islands). METHODS: Data regarding number of ECTs and number of patients with different diagnoses treated with ECT were retrieved from the Danish National Patient Registry. In addition, a 45-item questionnaire was sent to all psychiatric departments practicing ECT in Denmark (n = 26), Greenland (n = 1), and the Faroe Islands (n = 1). RESULTS: According to the Danish National Patient Registry, a total of 21,730 ECTs were administered to 1891 unique patients in 2017. All departments responded to the survey. The psychiatric departments' attitude toward ECT was generally favorable and in accord with official guidelines. Maintenance ECT was used in all departments but one. Bilateral electrode placement was preferred. All departments used a preselected age-based dosing strategy. Involuntary ECT was performed in 96% of the psychiatric departments, but infrequently (3% of all treatments). All departments used a Thymatron (brief pulse) device, and in 71% of the departments, ECT was given in a specialized ECT unit and preanesthetic evaluation was carried out in all departments. The departments reported several different practices regarding documentation and monitoring of treatment effect, patient consent, screening for side effects (including cognitive side effects), and guidelines for the discharge of ECT patients. CONCLUSIONS: Electroconvulsive therapy is frequently used in Denmark, Greenland, and the Faroe Islands in a relatively uniform way in adherence with clinical guidelines.

Deep sequencing of hepatitis C virus reveals genetic compartmentalization in cerebrospinal fluid from cognitively impaired patients.

BACKGROUND & AIMS: Hepatitis C virus (HCV) causes neuropsychiatric impairment and fatigue with recent studies suggesting HCV invasion of the central nervous system (CNS). Our previous finding that endothelial cells from the blood-brain barrier support HCV infection warrants further investigation to elucidate whether the CNS can serve as a reservoir for independent HCV evolution. METHODS: Cerebrospinal fluid (CSF) and plasma from six HCV-infected patients without liver disease or co-morbidities together with plasma from six healthy subjects were profiled for markers of immune activation and viral quasispecies measured by deep sequencing. Unsupervised data analyses were used to identify any associations between cytokine activation markers and clinical outcomes. RESULTS: Four of six HCV-infected patients showed significant evidence of cognitive dysfunction and fatigue. Deep sequencing revealed independent viral evolution within the CNS of two cognitively impaired patients. Principal component analysis of peripheral cytokines demonstrated that individuals without cognitive impairment clustered together while a distinct cytokine pattern emerged with patients exhibiting cognitive dysfunction and fatigue. CONCLUSIONS: Deep sequencing demonstrated unique viral variants in the CSF of two cognitively impaired patients consistent with CNS replication or sequestration. Meanwhile, compartmentalization was absent in infected patients with no neurocognitive impairment. Examination of cytokine profiles in HCV-infected patients with cognitive dysfunction revealed elevated peripheral cytokine levels resulting in a distinct cytokine profile that may be related to cognitive impairment or viral penetration into the CNS. Further studies to determine the significance of unique HCV variants within the CNS are warranted.

Reduced cerebral cortical thickness in Non-cirrhotic patients with hepatitis C.

Hepatitis C virus (HCV) infection is associated with fatigue, depression, and cognitive impairment even in the absence of severe liver fibrosis or cirrhosis. HCV has been hypothesised to cause neurodegenerative changes through low-grade neuroinflammation. Our aim was to examine whether cortical thickness (CTh) differs between chronic HCV patients and healthy controls, suggestive of cortical atrophy. In this case-control study 43 HCV patients without severe liver fibrosis, substance abuse, or comorbid HIV or hepatitis B virus infection, and 43 age and sex matched controls underwent MRI. Cortical thickness was measured using a surface based approach. Participants underwent semi-structured psychiatric interview and fatigue was assessed using the fatigue severity scale. HCV was associated with higher fatigue scores, and 58 % of HCV patients suffered from significant fatigue (p < 0.0001). Depression was observed in 16 % of patients. Areas of significantly reduced CTh were found in both left and right occipital cortex and in the left frontal lobe after correction for multiple comparisons (p < 0.05). No association between fatigue, former substance abuse, or psychotropic medication and CTh was found. No overall difference in cerebral white and grey matter volume was found. The findings support the hypothesis that HCV is associated with neurodegenerative changes.

Depressive symptoms are frequent among drug users, but not associated with hepatitis C infection.

AIM: To compare the prevalence and severity of depressive symptoms among drug users with and without hepatitis C virus (HCV) infection. METHODS: This was a cross-sectional survey study carried out at the 2 major drug treatment centres on the island of Funen, Denmark. Participants were drug users presenting to the 2 treatment centres. Individuals with chronic hepatitis B virus or HIV infection were excluded. Participants completed the Major Depression Inventory (MDI) questionnaire when presenting at the centres. Patients with MDI scores indicating severe depression (total MDI score ≥ 35) were referred for treatment evaluation. Hepatitis C status was classified by the presence of anti-HCV as a marker of HCV exposure and HCV-RNA as a marker of ongoing infection. RESULTS: Two hundred and sixty-eight patients were included, of whom 235 (88%) had complete serological testing; 100 (43%, 95% confidence interval (CI) 36-49%) had chronic hepatitis C. The median MDI score was 22 (interquartile range 12-33); 32% (95% CI 26-39%) had a score compatible with depression and 14% (95% CI 10-19%) were rated as severe depression. Depression was not associated with hepatitis C (HCV-infected 29%, non-infected 35%; p = 0.25). Forty-one percent (11/27) of the evaluated participants started antidepressant treatment. CONCLUSIONS: Our study demonstrated a high prevalence of depressive symptoms among drug users, but this was not more frequent among HCV-infected patients. The high overall prevalence of depression underlines the relevance of screening for depression in patients who are drug users.

Adults with both bipolar disorder and ADHD.

ADHD and bipolar disorder (BP) commonly coexist, and both share key symptoms, depending on affective state and emotional dysregulation. The overlap poses diagnostic challenges and may lead to underdiagnoses. Comorbid cases exhibit worsened symptom burden, increased psychiatric morbidity, admissions, and suicide attempts. Treating BP before ADHD is recommended. Stimulant use combined with mood stabilisers may be effective and relatively safe; however, this review finds that well-designed randomised controlled studies in the area is warranted.

Organic delirious states and other psychiatric disorders: lessons for the hepatologists.

Hepatic encephalopathy (HE) is characterized by a wide variety of neuropsychiatric symptoms, and from a psychiatric perspective its nosological status calls for clarification. According to the ICD-10 classification, it can be classified as delirium due to overt HE's core symptom of clouding of consciousness in increasing degrees. Minimal/covert HE with impairment of neurocognitive function is more difficult to classify and could correspond to Mild Cognitive Impairment or mild degrees of dementia. However, the advantages of current psychiatric nosology is the possibility of thorough characterization of both dispositional and premorbid psychopathology as well as psychiatric morbidity induced by liverdiseases or even treatment. A future closer collaboration between hepatologists and psychiatrists is advocated.

Non-convulsive status epilepticus after electroconvulsive therapy.

Non-convulsive status epilepticus (NCSE) is a rare complication to electroconvulsive therapy (ECT). This case report presents a 28-year-old female with schizophrenia in clozapine treatment developing NCSE twice after two different series of ECT treatment. NCSE should be suspected in patients with impairment of consciousness after ECT and requires confirmation with electroencephalogram. Although NCSE is described after ECT, the diagnosis always necessitates thorough screening for other potential underlying causes.

Clinical decision-making style preferences of European psychiatrists: Results from the Ambassadors survey in 38 countries.

BACKGROUND: While shared clinical decision-making (SDM) is the preferred approach to decision-making in mental health care, its implementation in everyday clinical practice is still insufficient. The European Psychiatric Association undertook a study aiming to gather data on the clinical decision-making style preferences of psychiatrists working in Europe. METHODS: We conducted a cross-sectional online survey involving a sample of 751 psychiatrists and psychiatry specialist trainees from 38 European countries in 2021, using the Clinical Decision-Making Style - Staff questionnaire and a set of questions regarding clinicians' expertise, training, and practice. RESULTS: SDM was the preferred decision-making style across all European regions ([central and eastern Europe, CEE], northern and western Europe [NWE], and southern Europe [SE]), with an average of 73% of clinical decisions being rated as SDM. However, we found significant differences in non-SDM decision-making styles: participants working in NWE countries more often prefer shared and active decision-making styles rather than passive styles when compared to other European regions, especially to the CEE. Additionally, psychiatry specialist trainees (compared to psychiatrists), those working mainly with outpatients (compared to those working mainly with inpatients) and those working in community mental health services/public services (compared to mixed and private settings) have a significantly lower preference for passive decision-making style. CONCLUSIONS: The preferences for SDM styles among European psychiatrists are generally similar. However, the identified differences in the preferences for non-SDM styles across the regions call for more dialogue and educational efforts to harmonize practice across Europe.

Evaluation of depression as a risk factor for treatment failure in chronic hepatitis C.

UNLABELLED: The Major Depression Inventory (MDI) was used to estimate the value of routine medical interviews in diagnosing major depression among patients receiving peginterferon alfa-2a and ribavirin therapy for chronic hepatitis C virus (HCV) infection (n = 325). According to criteria from the MDI and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 19 patients (6%) had major depression at baseline. An additional 114 (37%) developed depression while on HCV combination therapy, with baseline MDI score and female sex independently predicting the emergence of major depression during treatment in a multivariate analysis. Only 36 (32%) of the 114 patients developing major depression according to MDI/DSM-IV criteria were correctly diagnosed during routine medical interviews. The emergence of major depression frequently led to premature discontinuation of peginterferon/ribavirin therapy, and an on-treatment MDI score increment exceeding 30 points (i.e., a validated marker of idiopathic DSM-IV major depression) was correlated with impaired outcome of HCV therapy (P = 0.02). This difference was even more pronounced among patients with an on-treatment increase in MDI score greater than 35 points (P = 0.003). CONCLUSION: We conclude that (1) depressive symptoms among patients undergoing HCV therapy are commonly overlooked by routine clinical interviews, (2) the emergence of depression compromises the outcome of HCV therapy, and (3) the MDI scale may be useful in identifying patients at risk for treatment-induced depression.

Gut microbiota variations in patients diagnosed with major depressive disorder-A systematic review.

OBJECTIVE: The etiology of major depressive disorder (MDD) is multi-factorial and has been associated with a perturbed gut microbiota. Thus, it is therefore of great importance to determine any variations in gut microbiota in patients with MDD. METHODS: A systematic literature search was conducted including original research articles based on gut microbiota studies performed in patients with MDD. Demographic and clinical characteristics, applied methodology and observed gut microbiota composition were compared between included studies. RESULTS: Seventeen studies were included with a total of 738 patients with MDD and 782 healthy controls using different DNA purification methods, sequencing platforms and data analysis models. Four studies found a reduced α-diversity in patients with MDD, while gut microbiota compositions clustered separately according to ß-diversity between patients and controls in twelve studies. Additionally, there was an increase in relative abundance of Eggerthella, Atopobium, and Bifidobacterium and a decreased relative abundance of Faecalibacterium in patients with MDD compared with healthy controls. CONCLUSION: Gut microbiota differs significantly when comparing patients with MDD and healthy controls, though inconsistently across studies. The heterogeneity in gut microbiota compositions between the studies may be explained by variations in study design.

Faecal microbiota transplantation from patients with depression or healthy individuals into rats modulates mood-related behaviour.

Differences in gut microbiota composition have been observed in patients with major depressive disorder (MDD) compared to healthy individuals. Here, we investigated if faecal microbiota transplantation (FMT) from patients with MDD into rats could induce a depressive-like phenotype. We performed FMT from patients with MDD (FMT-MDD) and healthy individuals (FMT-Healthy) into male Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats and assessed depressive-like behaviour. No behavioural differences were observed in the FSL rats. In FRL rats, the FMT-Healthy group displayed significantly less depressive-like behaviour than the FMT-MDD group. However, there was no difference in behaviour between FMT-MDD FRL rats and negative controls, indicating that FMT-Healthy FRL rats received beneficial bacteria. We additionally found different taxa between the FMT-MDD and the FMT-Healthy FRL rats, which could be traced to the donors. Four taxa, three belonging to the family Ruminococcaceae and the genus Lachnospira, were significantly elevated in relative abundance in FMT-MDD rats, while the genus Coprococcus was depleted. In this study, the FMT-MDD group was different from the FMT-Healthy group based on behaviour and intestinal taxa.

Long-term neuropsychiatric consequences of aseptic meningitis in adult patients.

Aseptic meningitis is considered a benign and self-limiting clinical condition. In contrast to viral encephalitis and bacterial meningitis, the prognosis is usually good. The existing literature is scarce on the potential long-term neuropsychiatric consequences of aseptic meningitis. Previous studies have primarily been retrospective and differences in methodologies make it difficult to draw conclusions regarding the prevalence and nature of neuropsychiatric manifestations. However, studies have reported decreased psychomotor speed and impaired executive and visuo-constructive functions following aseptic meningitis. Larger controlled prospective studies are urgently needed to elucidate the neuropsychiatric complications of aseptic meningitis.