Clinical ethics committees.

This review describes the clinical ethics committees in Denmark. The clinical ethics committee is an interdisciplinary committee at a hospital intended to analyse ethically challenging situations and burdensome choices in patient care. The work in Danish KEKs takes place without formal organisation, in contrast to several other countries, where clinical ethics is regulated by law as research ethics is in Denmark.

Effect of specialised versus generalised outpatient treatment for bipolar disorder: the CAG Bipolar trial - study protocol for a randomised controlled trial.

INTRODUCTION: Despite current available treatment patients with bipolar disorder often experience relapses and decreased overall functioning. Furthermore, patients with bipolar disorder are often not treated medically or psychologically according to guidelines and recommendations. A Clinical Academic Group is a new treatment initiative bringing together clinical services, research, education and training to offer care and treatment that is based on reliable evidence backed up by research. The present Clinical Academic Group for bipolar disorder (the CAG Bipolar) randomised controlled trial (RCT) aims for the first time to investigate whether specialised outpatient treatment in CAG Bipolar versus generalised community-based treatment improves patient outcomes and clinician's satisfaction with care in patients with bipolar disorder. METHODS AND ANALYSIS: The CAG Bipolar trial is a pragmatic randomised controlled parallel-group trial undertaken in the Capital Region of Denmark covering a catchment area of 1.85 million people. Patients with bipolar disorder are invited to participate as part of their outpatient treatment in the Mental Health Services. The included patients will be randomised to (1) specialised outpatient treatment in the CAG Bipolar (intervention group) or (2) generalised community-based outpatient treatment (control group). The trial started 13 January 2020 and has currently included more than 600 patients. The outcomes are (1) psychiatric hospitalisations and cumulated number and duration of psychiatric hospitalisations (primary), and (2) self-rated depressive symptoms, self-rated manic symptoms, quality of life, perceived stress, satisfaction with care, use of medication and the clinicians' satisfaction with their care (secondary). A total of 1000 patients with bipolar disorder will be included. ETHICS AND DISSEMINATION: The CAG Bipolar RCT is funded by the Capital Region of Denmark and ethical approval has been obtained from the Regional Ethical Committee in The Capital Region of Denmark (H-19067248). Results will be published in peer-reviewed academic journals, presented at scientific meetings and disseminated to patient organisations and media outlets. TRIAL REGISTRATION NUMBER: NCT04229875.

Cerebral hemodynamics and capillary dysfunction in late-onset major depressive disorder.

In major depressive disorder (MDD), perfusion changes in cortico-limbic pathways are interpreted as altered neuronal activity, but they could also signify changes in neurovascular coupling due to altered capillary function. To examine capillary function in late-onset MDD, 22 patients and 22 age- and gender-matched controls underwent perfusion MRI. We measured normalized cerebral blood flow (nCBF), cerebral blood volume (nCBV), and relative transit-time heterogeneity (RTH). Resulting brain oxygenation was estimated in terms of oxygen tension and normalized metabolic rate of oxygen (nCMRO2). Patients revealed signs of capillary dysfunction (elevated RTH) in the anterior prefrontal cortex and ventral anterior cingulate cortex bilaterally and in the left insulate cortex compared to controls, bilateral hypometabolism (parallel reductions of nCBV, nCBF, and CMRO2) but preserved capillary function in the subthalamic nucleus and globus pallidus bilaterally, and hyperactivity with preserved capillary function (increased nCBF) in the cerebellum and brainstem. Our data support that perfusion changes in deep nuclei and cerebellum reflect abnormally low and high activity, respectively, in MDD patients, but suggest that microvascular pathology affects neurovascular coupling in ventral circuits. We speculate that microvascular pathology is important for our understanding of etiology of late-onset MDD as well as infererences about resulting brain activity changes.

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.

Volume of hippocampal subregions and clinical improvement following electroconvulsive therapy in patients with depression.

It is thought that the hippocampal neurogenesis is an important mediator of the antidepressant effect of electroconvulsive therapy (ECT). However, most previous studies failed to demonstrate the relationship between the increase in the hippocampal volume and the antidepressant effect. We reinvestigated this relationship by looking at distinct hippocampal subregions and applying repeated measures correlation. Using a 3 Tesla MRI-scanner, we scanned 22 severely depressed in-patients at three time points: before the ECT series, after the series, and at six-month follow-up. The depression severity was assessed by the 17-item Hamilton Rating Scale for Depression (HAMD-17). The hippocampus was segmented into subregions using Freesurfer software. The dentate gyrus (DG) was the primary region of interest (ROI), due to the role of this region in neurogenesis. The other major hippocampal subregions were the secondary ROIs (n = 20). The general linear mixed model and the repeated measures correlation were used for statistical analyses. Immediately after the ECT series, a significant volume increase was present in the right DG (Cohen's d = 1.7) and the left DG (Cohen's d = 1.5), as well as 15 out of 20 secondary ROIs. The clinical improvement, i.e., the decrease in HAMD-17 score, was correlated to the increase in the right DG volume (rrm = -0.77, df = 20, p < .001), and the left DG volume (rrm = -0.75, df = 20, p < .001). Similar correlations were observed in 14 out of 20 secondary ROIs. Thus, ECT induces an increase not only in the volume of the DG, but also in the volume of other major hippocampal subregions. The volumetric increases may reflect a neurobiological process that may be related to the ECT's antidepressant effect. Further investigation of the relationship between hippocampal subregions and the antidepressant effect is warranted. A statistical approach taking the repeated measurements into account should be preferred in the analyses.

[Catatonia].

This review summarises the knowledge of catatonia, which is a neuropsychiatric syndrome with altered psychomotor and behavioural symptoms as well as autonomic dysfunction seen in a variety of psychiatric, neurologic and medical conditions. However, catatonia frequently remains unrecognised by clinicians. The classification of catatonia differs significantly in the international classifications, reflecting the controversy regarding the concept of catatonia and its complex symptomatology. Different rating scales are developed to diagnose catatonia in clinical practice. First-choice treatment is benzodiazepines and ECT regardless of underlying condition.

Hippocampal volume and cell number in depression, schizophrenia, and suicide subjects.

Many studies suggest that the hippocampus is involved in the pathophysiology of psychiatric disorders, especially major depressive disorder (MDD) and schizophrenia. Especially, in vivo imaging studies indicate that the volume of hippocampus may be reduced in both disorders. Moreover, suicide may have a unique neurobiology. The aim of the present study is to investigate if depression, schizophrenia or suicide is associated with reduced postmortem volume of the hippocampal formation and/or changes in the numbers of neurons and/or glial cells in the different subregions of the hippocampus. We studied postmortem brain samples from 10 subjects with schizophrenia, 8 subjects with major depression, 11 suicide subjects with a history of depressive disorder, and 10 control subjects with no history of psychiatric or neurological diseases. The total volume and numbers of neurons and glial cells were estimated for the main hippocampal subregions using design-unbiased stereological techniques. We found the total volume and total numbers of neurons and glial cells similarly reduced by approximately 20% to 35% in depression and schizophrenia subjects relative to control subjects across all hippocampal regions. In suicide subjects, we only found increased neuron number in CA2/3 subregion. The volume and number of cells are reduced in depression and schizophrenia subjects relative to control subjects across all hippocampal regions. Our findings imply that the hippocampus may be a common site of pathophysiology in depression and schizophrenia. Community living suicide subjects seem to differ in hippocampal neurobiology compared to hospitalized subjects dying with MDD without suicide.

Oxygenation differs among white matter hyperintensities, intersected fiber tracts and unaffected white matter.

White matter hyperintensities of presumed vascular origin are frequently observed on magnetic resonance imaging in normal aging. They are typically found in cerebral small vessel disease and suspected culprits in the etiology of complex age- and small vessel disease-related conditions, such as late-onset depression. White matter hyperintensities may interfere with surrounding white matter metabolic demands by disrupting fiber tract integrity. Meanwhile, risk factors for small vessel disease are thought to reduce tissue oxygenation, not only by reducing regional blood supply, but also by impairing capillary function. To address white matter oxygen supply-demand balance, we estimated voxel-wise capillary density as an index of resting white matter metabolism, and combined estimates of blood supply and capillary function to calculate white matter oxygen availability. We conducted a cross-sectional study with structural, perfusion- and diffusion-weighted magnetic resonance imaging in 21 patients with late-onset depression and 21 controls. We outlined white matter hyperintensities and used tractography to identify the tracts they intersect. Perfusion data comprised cerebral blood flow, blood volume, mean transit time and relative transit time heterogeneity-the latter a marker of capillary dysfunction. Based on these, white matter oxygenation was calculated as the steady state cerebral metabolic rate of oxygen under the assumption of normal tissue oxygen tension and vice versa. The number, volume and perfusion characteristics of white matter hyperintensities did not differ significantly between groups. Hemodynamic data showed white matter hyperintensities to have lower blood flow and blood volume, but higher relative transit time heterogeneity, than normal-appearing white matter, resulting in either reduced capillary metabolic rate of oxygen or oxygen tension. Intersected tracts showed significantly lower blood flow, blood volume and capillary metabolic rate of oxygen than normal-appearing white matter. Across groups, lower lesion oxygen tension was associated with higher lesion number and volume. Compared with normal-appearing white matter, tissue oxygenation is significantly reduced in white matter hyperintensities as well as the fiber tracts they intersect, independent of parallel late-onset depression. In white matter hyperintensities, reduced microvascular blood volume and concomitant capillary dysfunction indicate a severe oxygen supply-demand imbalance with hypoxic tissue injury. In intersected fiber tracts, parallel reductions in oxygenation and microvascular blood volume are consistent with adaptations to reduced metabolic demands. We speculate, that aging and vascular risk factors impair white matter hyperintensity perfusion and capillary function to create hypoxic tissue injury, which in turn affect the function and metabolic demands of the white matter tracts they disrupt.

[Hypochondriacal paranoia is a differential diagnostic challenge].

Patients with persistent complaints about somatic symptoms, which cannot be explained by somatic disease, constitute a major healthcare problem. Hypochondriacal paranoia is an important subset of paranoid conditions, which should not be overlooked in patients with persistent hypochondriacal complaints. It is rare, in contrast to illness anxiety disorder or body dysmorphic disorder optionally with insufficient insight. Recent research indicates, that hypochondriacal complaints present a spectrum of evident psychotic conditions over delusion-like complaints to excessive illness anxiety.

[Hypochondrical paranoia].

This is a case report of hypochondrical paranoia in a young man, who was convinced of a toxic infection by fungi following mold growth exposure. The patient was admitted to a psychiatric facility, severely pained by the delusional perception of his insides being eaten by fungus. He had undergone a thorough medical examination without the discovery of any somatic irregularities and had attempted to treat himself several times. After four months of hospital-ization and the prescription of antipsychotic treatment, he was in recovery. Mild delusions persisted but were no longer pathologically painful.