Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Depression: HELP
Articles by Maj Vinberg
Based on 58 articles published since 2010
(Why 58 articles?)
||||

Between 2010 and 2020, M. Vinberg wrote the following 58 articles about Depression.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial [Ketamine for treatment of depression?]. 2013

Vinberg, Maj. ·Region Hovedstadens Psykiatri, Psykiatrisk Center København, Kompetencecenter for Affektive Lidelser, Blegdamsvej 9, 2100 København Ø. maj.vinberg@regionh.dk. ·Ugeskr Laeger · Pubmed #24011202.

ABSTRACT: -- No abstract --

2 Review Does S100B have a potential role in affective disorders? A literature review. 2018

Kroksmark, Hilda / Vinberg, Maj. ·a Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen , Copenhagen , Denmark. ·Nord J Psychiatry · Pubmed #29764272.

ABSTRACT: BACKGROUND: S100B is a calcium-binding protein located in glial cells; it is regarded as a potential biomarker in affective disorders. AIM: To review the literature investigating the role of S100B in patients with affective disorders. METHOD: A systematic review of original English language studies investigating S100B in serum, cerebrospinal fluid, plasma and lymphocytes, in patients with affective disorders, was conducted. The literature search was conducted within the PubMed database. Effect sizes were calculated to adjust for systematic measurement effects. RESULTS: Twenty studies were included, with a total of 1292 participants. Of these, 398 patients had or have had depressive disorder, 301 patients had bipolar disorder and 593 were healthy controls. S100B levels in serum were consistently elevated in studies with statistically significant results which investigated acute affective episodes (comprising major depressive episode in major depressive disorder, and both manic and depressive episodes in patients with bipolar disorder), in comparison to healthy controls. There were few studies assessing S100B levels in cerebrospinal fluid, plasma or lymphocytes, and these had inconsistent results. CONCLUSION: The results indicated that elevated S100B levels might be associated with mood episodes in affective disorders. However, the role of S100B, and its possible impact in affective disorders, requires further investigation and at the present S100B does not have a role as clinically biomarker in affective disorder. Future longitudinal multicentre studies with larger transdiagnostic real life patient cohorts are warranted.

3 Review Risk of recurrence after a single manic or mixed episode - a systematic review and meta-analysis. 2018

Kessing, Lars Vedel / Andersen, Per Kragh / Vinberg, Maj. ·Department O, Psychiatric Center Copenhagen, Copenhagen, Denmark. · University of Copenhagen, Copenhagen, Denmark. · Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark. ·Bipolar Disord · Pubmed #29239075.

ABSTRACT: OBJECTIVES: For the first time to estimate the risk of recurrence among patients with a single manic/mixed episode by systematically reviewing prior studies on cohorts of adults, and cohorts of children and adolescents, respectively. METHODS: A systematic literature search up to August 2017 was carried out including studies in which < 25% of the participants were estimated to have had a mood episode that required pharmacological treatment prior to the index manic or mixed episode at inclusion. RESULTS: Three studies including a total of 293 adult patients with a single manic or mixed episode and three studies of children and adolescents including 126 patients were identified. In the adult studies, 31%, 40% and 42% experienced recurrence after recovery within 1 year, 59% after 2 years, and 58% after 4 years, respectively. In the studies on children and adolescents, 40% and 52% experienced recurrence after recovery within 1 year, 30% and 60% after 2 years and 64% and 67% after 4 to 5 years, respectively. Results from meta-analyses showed a 1-year rate of recurrence of 35% (95% confidence interval [CI]: 30-41%) in adults, and in adolescents/children, a 1-year rate of recurrence of 48% (95% CI: 38-58%), a 2-year rate of 46% (95% CI: 33-60%) and a 4-5-year rate of recurrence of 65% (95% CI: 52-77%; as data from different studies were included at 1, 2 and 5 years, rates of recurrence did not increase steadily with time). CONCLUSIONS: The rate of recurrence is high among adults as well as children and adolescents. It is important that clinicians and patients as well as relatives are well informed about these high risks when deciding to start maintenance treatment or not following onset of a single manic or mixed episode.

4 Review Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis. 2016

Rosenblat, Joshua D / Kakar, Ron / Berk, Michael / Kessing, Lars V / Vinberg, Maj / Baune, Bernhard T / Mansur, Rodrigo B / Brietzke, Elisa / Goldstein, Benjamin I / McIntyre, Roger S. ·Mood Disorders Psychopharmacology Unit, University Health Network, Department of Psychiatry and Pharmacology, University of Toronto, Toronto, Canada. · Department of Psychiatry, Western University, London and Windsor, ON, Canada. · IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Vic., Australia. · Department of Psychiatry, The Florey Institute of Neuroscience and Mental Health, and Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, University of Melbourne, Parkville, Vic., Australia. · Psychiatric Center Copenhagen, Faculty of Health and Medical Sciences and Department O, University of Copenhagen, Copenhagen, Denmark. · Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia. · Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Federal University of Sao Paulo, São Paulo, Brazil. · Program of Recognition and Intervention in Individuals in AT-Risk Mental States (PRISMA), Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil. · Departments of Psychiatry, Pharmacology, and Psychological Clinical Science, Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada. ·Bipolar Disord · Pubmed #26990051.

ABSTRACT: OBJECTIVE: Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti-inflammatory agents in the treatment of bipolar depression. METHODS: Completed and ongoing clinical trials of anti-inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, PsychINFO, and Clinicaltrials.gov databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti-inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone. RESULTS: Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti-inflammatory agents on depressive symptoms was -0.40 (95% confidence interval -0.14 to -0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low (I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment-emergent adverse events were reported. CONCLUSIONS: Overall, a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.

5 Review The prevalence, measurement, and treatment of the cognitive dimension/domain in major depressive disorder. 2015

McIntyre, Roger S / Xiao, Holly X / Syeda, Kahlood / Vinberg, Maj / Carvalho, Andre F / Mansur, Rodrigo B / Maruschak, Nadia / Cha, Danielle S. ·Department of Psychiatry, University of Toronto, Toronto, ON, Canada, roger.mcintyre@uhn.ca. ·CNS Drugs · Pubmed #26290264.

ABSTRACT: Insufficient outcomes amongst adults with major depressive disorder (MDD) provide the impetus to identify and refine therapeutic targets that are most critical to outcome from patient, provider, and societal perspectives. Towards this aim, a pivotal shift towards the transnosological domain, cognition, is occurring in the study of MDD and other brain disorders. This paper aims to provide a framework for conceptualizing and prioritizing cognitive function amongst adults with MDD with a particular view to provide a conceptual framework for research and clinical priorities. We also summarize extant data pertaining to psychotropic effects, notably antidepressants, on the cognitive dimension/domain. This narrative review was based on articles identified through a PubMed/MEDLINE search of all English-language articles published between January 1966 and October 2014. The search words were major depressive disorder, depression, unipolar depression, cognition, cognitive dysfunction, cognitive deficit, and cognitive function. The search was supplemented with a manual review of relevant references. The selection of articles for inclusion in this review was based on overall methodological quality as well as on their pertinence to informing the framework described herein. Cognitive dysfunction in MDD is a discrete domain subserved by discrete yet overlapping substrates. There is a need to provide a glossary of terms commonly employed in the cognition literature for consensus as to the appropriate screening, measurement, and monitoring tools. The guiding principle of measurement-based care should include systematic assessment and measurement of cognition in subpopulations with MDD, as a tactic to improve outcome. Relatively few treatment strategies have demonstrated efficacy specifically for the cognitive domain in MDD. The antidepressant vortioxetine has replicated evidence of specific pro-cognitive effects in adults with MDD across multiple subdomains of cognitive function. Vortioxetine is a novel antidepressant that is hypothesized to act through a combination of direct effects on receptor activity and serotonin receptor inhibition, as well as other systems. Pro-cognitive effects for other US FDA-approved agents are suggested, but pseudospecificity has not been excluded as a possible explanation of their beneficial effects on cognitive function. A disparate assortment of other agents are currently under investigation for possible benefit in mitigating cognitive deficits and improving cognitive performance (e.g., intranasal insulin, erythropoietin, anti-inflammatory agents). Non-pharmacological approaches including, but not limited to, cognitive remediation (CR), aerobic exercise, and neuromodulation are promising.

6 Review Psychostimulants in moderate to severe affective disorder: a systematic review of randomized controlled trials. 2013

Abbasowa, Leda / Kessing, Lars V / Vinberg, Maj. ·University of Copenhagen , Blegdamsvej 3, DK-2200 Copenhagen , Denmark. ·Nord J Psychiatry · Pubmed #23293898.

ABSTRACT: BACKGROUND: Despite antidepressant therapy of appropriate trial duration and dose optimization, 50-60% of depressed patients have an adequate treatment response, whereas only 35-40% achieve remission. Psychostimulants have been suggested as potential candidates to promote acceleration of response and to alleviate residual symptoms of depression. AIMS: In this review results from randomized clinical trials (RCTs) exploring the efficacy of psychostimulants in the treatment of major depressive disorder (MDD) were analyzed to clarify the current empirically founded evidence for clinical approaches involving psychostimulants. METHOD: Literature research via PubMed retrieved 846 articles. 18 RCTs reporting on the use of psychostimulants in the treatment of adult patient populations, suffering from moderate-severe depression and having no other concomitant medical illnesses, were included in this review. 14 articles provided results for unipolar depression, two for bipolar depression, whereas two articles presented mixed samples of unipolar and bipolar patients. RESULTS: Five different psychostimulants were evaluated: modafinil, methylphenidate, dexamphetamine, methylamphetamine and pemoline. Two studies examining modafinil demonstrated significant ameliorating characteristics pertaining to symptoms of depression. No clear evidence for the effectiveness of traditional psychostimulants in the therapeutic management of MDD was found. In general the quality of included trials was poor since the majority was of short-term duration, comprising relatively small sample sizes and some, especially older studies, were methodologically flawed. CONCLUSION: Clearly larger well designed placebo-controlled studies with longer follow-up accompanied by evaluations of tolerance/dependence are warranted before psychostimulants can be recommended in routine clinical practice for the treatment of MDD.

7 Review Erythropoietin: a candidate treatment for mood symptoms and memory dysfunction in depression. 2012

Miskowiak, Kamilla W / Vinberg, Maj / Harmer, Catherine J / Ehrenreich, Hannelore / Kessing, Lars V. ·Clinic for Affective Disorders, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet 6211, Blegdamsvej 9, 2100 Copenhagen, Denmark. kamilla@miskowiak.dk ·Psychopharmacology (Berl) · Pubmed #21947319.

ABSTRACT: OBJECTIVE: Current pharmacological treatments for depression have a significant treatment-onset-response delay, an insufficient efficacy for many patients and fail to reverse cognitive dysfunction. Erythropoietin (EPO) has neuroprotective and neurotrophic actions and improves cognitive function in animal models of acute and chronic neurodegenerative conditions and in patients with cognitive decline. METHODS: We systematically reviewed the published findings from animal and human studies exploring the potential of EPO to treat depression-related cognitive dysfunction and depression. RESULTS: We identified five animal studies (two in male rats, two in male mice and one in male rats and mice) and seven human proof-of-concept studies (five in healthy volunteers and two in depressed patients) that investigated the above. All of the reviewed animal studies but one and all human studies demonstrated beneficial effects of EPO on hippocampus-dependent memory and antidepressant-like effects. These effects appear to be mediated through direct neurobiological actions of EPO rather than upregulation of red cell mass. CONCLUSIONS: The reviewed studies demonstrate beneficial effects of EPO on hippocampus-dependent memory function and on depression-relevant behavior, thus highlighting EPO as a candidate agent for future management of cognitive dysfunction and mood symptoms in depression. Larger-scale clinical trials of EPO as a treatment for mood and neurocognitive symptoms in patients with mood disorder are therefore warranted.

8 Clinical Trial Effects of erythropoietin on memory-relevant neurocircuitry activity and recall in mood disorders. 2016

Miskowiak, K W / Macoveanu, J / Vinberg, M / Assentoft, E / Randers, L / Harmer, C J / Ehrenreich, H / Paulson, O B / Knudsen, G M / Siebner, H R / Kessing, L V. ·Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. · Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. · Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark. · Psychiatric Centre Copenhagen, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark. · Department of Psychiatry, University of Oxford, Oxford, UK. · Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany. · Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. · Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark. ·Acta Psychiatr Scand · Pubmed #27259062.

ABSTRACT: OBJECTIVE: Erythropoietin (EPO) improves verbal memory and reverses subfield hippocampal volume loss across depression and bipolar disorder (BD). This study aimed to investigate with functional magnetic resonance imaging (fMRI) whether these effects were accompanied by functional changes in memory-relevant neuro-circuits in this cohort. METHOD: Eighty-four patients with treatment-resistant unipolar depression who were moderately depressed or BD in remission were randomized to eight weekly EPO (40 000 IU) or saline infusions in a double-blind, parallel-group design. Participants underwent whole-brain fMRI at 3T, mood ratings, and blood tests at baseline and week 14. During fMRI, participants performed a picture encoding task followed by postscan recall. RESULTS: Sixty-two patients had complete data (EPO: N = 32, saline: N = 30). EPO improved picture recall and increased encoding-related activity in dorsolateral prefrontal cortex (dlPFC) and temporo-parietal regions, but not in hippocampus. Recall correlated with activity in the identified dlPFC and temporo-parietal regions at baseline, and change in recall correlated with activity change in these regions from baseline to follow-up across the entire cohort. The effects of EPO were not correlated with change in mood, red blood cells, blood pressure, or medication. CONCLUSION: The findings highlight enhanced encoding-related dlPFC and temporo-parietal activity as key neuronal underpinnings of EPO-associated memory improvement.

9 Clinical Trial Effects of Erythropoietin on Hippocampal Volume and Memory in Mood Disorders. 2015

Miskowiak, Kamilla W / Vinberg, Maj / Macoveanu, Julian / Ehrenreich, Hannelore / Køster, Nicolai / Inkster, Becky / Paulson, Olaf B / Kessing, Lars V / Skimminge, Arnold / Siebner, Hartwig R. ·Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: Kamilla@miskowiak.dk. · Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. · Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre. · Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany. · Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom. · Neurobiological Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. · Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre; Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark. ·Biol Psychiatry · Pubmed #25641635.

ABSTRACT: BACKGROUND: Persistent cognitive dysfunction in depression and bipolar disorder (BD) impedes patients' functional recovery. Erythropoietin (EPO) increases neuroplasticity and reduces cognitive difficulties in treatment-resistant depression (TRD) and remitted BD. This magnetic resonance imaging study assessed the neuroanatomical basis for these effects. METHODS: Patients with TRD who were moderately depressed or BD in partial remission were randomized to 8 weekly EPO (40,000 IU) or saline infusions in a double-blind, parallel-group design. Patients underwent magnetic resonance imaging, memory assessment with the Rey Auditory Verbal Learning Test, and mood ratings with the Beck Depression Inventory, Hamilton Depression Rating Scale, and Young Mania Rating Scale at baseline and week 14. Hippocampus segmentation and analysis of hippocampal volume, shape, and gray matter density were conducted with FMRIB Software Library tools. Memory change was analyzed with repeated-measures analysis of covariance adjusted for depression symptoms, diagnosis, age, and gender. RESULTS: Eighty-four patients were randomized; 1 patient withdrew and data collection was incomplete for 14 patients; data were thus analyzed for 69 patients (EPO: n = 35, saline: n = 34). Compared with saline, EPO was associated with mood-independent memory improvement and reversal of brain matter loss in the left hippocampal cornu ammonis 1 to cornu ammonis 3 and subiculum. Using the entire sample, memory improvement was associated with subfield hippocampal volume increase independent of mood change. CONCLUSIONS: EPO-associated memory improvement in TRD and BD may be mediated by reversal of brain matter loss in a subfield of the left hippocampus. EPO may provide a therapeutic option for patients with mood disorders who have impaired neuroplasticity and cognition.

10 Clinical Trial Recombinant human erythropoietin for treating treatment-resistant depression: a double-blind, randomized, placebo-controlled phase 2 trial. 2014

Miskowiak, Kamilla W / Vinberg, Maj / Christensen, Ellen M / Bukh, Jens D / Harmer, Catherine J / Ehrenreich, Hannelore / Kessing, Lars V. ·Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. · Department of Psychiatry, University of Oxford, Oxford, UK. · Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany. ·Neuropsychopharmacology · Pubmed #24322509.

ABSTRACT: Pharmacological treatments for depression have insufficient efficacy in 30-40% of patients and fail to reverse cognitive deficits. Erythropoietin (EPO) has neurotrophic actions and aids neurocognitive function. The aim of this exploratory study was to determine whether recombinant human EPO improves mood and memory in treatment-resistant depression. Forty treatment-resistant depressed unipolar patients with Hamilton Depression Rating Scale-17 (HDRS-17) score ≥ 17 were randomized to eight weekly EPO (Eprex; 40,000 IU) or saline infusions in a double-blind, placebo-controlled, parallel-group design. Patients were assessed at baseline and at weeks 5, 9, and 14. Primary outcome was reduction in HDRS-17 score. Global assessment of function (GAF) was reported in addition. Secondary outcome was remission rate, and tertiary outcomes were changes in Rey Auditory Verbal Learning Test (RAVLT), Beck Depression Inventory-21 (BDI-21), and World Health Organization Quality of life-BREF (WHOQOL-BREF). Exploratory outcomes were depression and cognition composite scores. HDRS-17, GAF, and remission rates showed no effects of EPO over saline at week 9 (P-value ≥ 0.09). However, EPO improved BDI (P=0.02) and WHOQOL-BREF (P=0.01), and this was maintained at follow-up week 14 (P-values ≤ 0.04). EPO enhanced verbal recall (P=0.02) and recognition (P=0.03), which was sustained at follow-up (P-values ≤ 0.04). Exploratory analysis in patients fulfilling depression severity criteria at trial start revealed ameliorated HDRS-17 in EPO (N=14) vs saline groups (N=17), which was sustained at week 14 (P-values ≤ 0.05). Exploratory analysis in the complete cohort showed that EPO reduced depression composite at weeks 9 and 14 (P-values=0.02). The findings of this exploratory study highlight EPO as an interesting compound for treatment-resistant depression, which deserves further investigation.

11 Article Emotional Mental Imagery Abnormalities in Monozygotic Twins With, at High-Risk of, and Without Affective Disorders: Present in Affected Twins in Remission but Absent in High-Risk Twins. 2019

Di Simplicio, Martina / Lau-Zhu, Alex / Meluken, Iselin / Taylor, Patrick / Kessing, Lars Vedel / Vinberg, Maj / Holmes, Emily Alexandra / Miskowiak, Kamilla Woznica. ·Division of Psychiatry, Department of Brain Sciences, Imperial College London, London, United Kingdom. · Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. · Medical Sciences Division, Oxford Institute of Clinical Psychology Training, University of Oxford, Oxford, United Kingdom. · Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. · Division of Psychology, Department for Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. · Department of Psychology, Uppsala University, Uppsala, Sweden. · Department of Psychology, University of Copenhagen, Copenhagen, Denmark. ·Front Psychiatry · Pubmed #31780967.

ABSTRACT:

12 Article Differences in mood instability in patients with bipolar disorder type I and II: a smartphone-based study. 2019

Faurholt-Jepsen, Maria / Frost, Mads / Busk, Jonas / Christensen, Ellen Margrethe / Bardram, Jakob E / Vinberg, Maj / Kessing, Lars Vedel. ·Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. maria@faurholt-jepsen.dk. · IT University of Copenhagen, Rued Langgaards Vej 7, 2300, Copenhagen, Denmark. · Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kongens Lyngby, Denmark. · Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. ·Int J Bipolar Disord · Pubmed #30706154.

ABSTRACT: BACKGROUND: Mood instability in bipolar disorder is associated with a risk of relapse. This study investigated differences in mood instability between patients with bipolar disorder type I and type II, which previously has been sparingly investigated. METHODS: Patients with bipolar disorder type I (n = 53) and type II (n = 31) used a daily smartphone-based self-monitoring system for 9 months. Data in the present reflect 15.975 observations of daily collected smartphone-based data on patient-evaluated mood. RESULTS: In models adjusted for age, gender, illness duration and psychopharmacological treatment, patients with bipolar disorder type II experienced more mood instability during depression compared with patients with bipolar disorder type I (B: 0.27, 95% CI 0.007; 0.53, p = 0.044), but lower intensity of manic symptoms. Patients with bipolar disorder type II did not experience lower mean mood or higher intensity of depressive symptoms compared with patients with bipolar disorder type I. CONCLUSIONS: Compared to bipolar disorder type I, patients with bipolar disorder type II had higher mood instability for depression. Clinically it is of importance to identify these inter-episodic symptoms. Future studies investigating the effect of treatment on mood instability measures are warranted. Trial registration NCT02221336.

13 Article Effects of recombinant human erythropoietin on cognition and neural activity in remitted patients with mood disorders and first-degree relatives of patients with psychiatric disorders: a study protocol for a randomized controlled trial. 2018

Petersen, Jeff Zarp / Schmidt, Lejla Sjanic / Vinberg, Maj / Jørgensen, Martin Balslev / Hageman, Ida / Ehrenreich, Hannelore / Knudsen, Gitte Moos / Kessing, Lars Vedel / Miskowiak, Kamilla Woznica. ·Neurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. · Department of Psychology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353, Copenhagen, Denmark. · Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany. · DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany. · Neurobiology Research Unit and Center for Integrated Molecular Imaging, Rigshospitalet, Copenhagen, Denmark. · Neurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. kamilla.woznica.miskowiak@regionh.dk. · Department of Psychology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353, Copenhagen, Denmark. kamilla.woznica.miskowiak@regionh.dk. ·Trials · Pubmed #30400939.

ABSTRACT: BACKGROUND: Bipolar disorder (BD) and unipolar disorder (UD) are associated with cognitive deficits and abnormal neural activity in a "cognitive control network." There is an increased prevalence of cognitive dysfunction in psychiatric patients' first-degree relatives, which constitutes a risk factor for psychiatric illness onset. However, there is no treatment with enduring pro-cognitive efficacy. We found preliminary evidence for beneficial effects of eight weekly doses of recombinant human erythropoietin (EPO) on cognition in BD in a recent randomized controlled trial (RCT). The present RCT consists of two sub-studies that extend our previous work by investigating important novel aspects: (1) the effects of 12 weekly doses of EPO on cognition in first-degree relatives of patients with BD, UD, or schizophrenia; and (2) the effects of extending the treatment schedule from 8 to 12 weeks in remitted patients with BD or UD; and (3) assessment of early treatment-associated neural activity changes that may predict cognitive improvement. METHODS: The trial comprises two parallel sub-studies with randomized, controlled, double-blinded, parallel group designs. First-degree relatives (sub-study 1; n = 52) and partially or fully remitted patients with BD or UD (sub-study 2; n = 52) with objectively verified cognitive dysfunction are randomized to receive weekly high-dose EPO (40,000 IU/mL) or placebo (saline) infusions for 12 weeks. Assessments of cognition and mood are conducted at baseline, after two weeks of treatment, after treatment completion, and at six-month follow-up. Functional magnetic resonance imaging (fMRI) is conducted at baseline and after two weeks of treatment. Psychosocial function is assessed at baseline, after treatment completion and six-month follow-up. The primary outcome is change in a cognitive composite score of attention, verbal memory, and executive functions. Statistical power of ≥ 80% is reached to detect a clinically relevant between-group difference by including 52 first-degree relatives and 52 patients with BD or UD, respectively. Behavioral data are analyzed with an intention-to-treat approach using mixed models. fMRI data are analyzed with the FMRIB Software Library. DISCUSSION: If this trial reveals pro-cognitive effects of EPO, this may influence future treatment of mood disorders and/or preventive strategies in at-risk populations. The fMRI analyses may unravel key neurobiological targets for pro-cognitive treatment. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03315897. Registered on 20 October 2017.

14 Article Effects of erythropoietin on body composition and fat-glucose metabolism in patients with affective disorders. 2018

Vinberg, Maj / Højman, Pernille / Pedersen, Bente Klarlund / Kessing, Lars Vedel / Miskowiak, Kamilla W. ·1Psychiatric Centre Copenhagen,Rigshospitalet,University Hospital of Copenhagen Blegdamsvej,Copenhagen,Denmark. · 2The Centre of Inflammation and Metabolism (CIM) and the Centre for Physical Activity Research (CFAS),Rigshospitalet,University Hospital of Copenhagen,Copenhagen,Denmark. ·Acta Neuropsychiatr · Pubmed #29880069.

ABSTRACT: BACKGROUND: Erythropoietin (EPO) has been suggested to improve metabolism and also cognition, but human studies are scarce. This randomised controlled trial aimed to investigate whether EPO treatment influences body composition and fat and glycated haemoglobin (HbA1c) and fasting glucose, and whether these changes would be associated with previous observed cognitive benefits of EPO. METHOD: In total, 84 non-obese patients with treatment-resistant unipolar depression or bipolar disorder in remission were randomised to 8 weekly EPO (40,000 IU) or saline (NaCl 0.9%) infusions in a double-blind, parallel-group design. Patients underwent dual X-ray absorptiometry scans at baseline and week 14 (6 weeks after treatment completion). Cognitive measures were assessed and fasting levels of cholesterol, lipoprotein fractions, triacylglycerides, glucose and HbA1c were obtained at baseline, week 9 and follow-up week 14. RESULTS: In total, 79 patients had complete pre- and post-treatment data (EPO: N=40, saline: N=39). EPO had no cumulative effect on body composition and markers of fat metabolism. The EPO-treated group exhibited significantly lower HbA1c levels after 8 weeks treatment [F(1, 80)=8.51, p=0.005], however, 6 weeks after treatment termination a significantly higher fasting glucose levels [F(1, 79)=5.85, p=0.02] and HbA1c levels [F(1, 79)=5.85, p=0.02] were seen. The latter increase in HbA1c was further significantly correlated with a better cognitive outcome on verbal memory (r=0.25, p=0.03). CONCLUSION: Repeated EPO infusions had no cumulative effect on body composition in this cohort of patients with affective disorders, however, EPO modulated HbA1c and fasting glucose and this was associated with patients' improvement of verbal memory.

15 Article Erythropoietin as an add-on treatment for cognitive side effects of electroconvulsive therapy: a study protocol for a randomized controlled trial. 2018

Schmidt, Lejla Sjanic / Petersen, Jeff Zarp / Vinberg, Maj / Hageman, Ida / Olsen, Niels Vidiendal / Kessing, Lars Vedel / Jørgensen, Martin Balslev / Miskowiak, Kamilla Woznica. ·Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. · Neurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Center, Psychiatric Center Copenhagen, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. · Department of Psychology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353, Copenhagen, Denmark. · Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. · Department of Neuroanaesthesia, The Neuroscience Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. · Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. kamilla.miskowiak@regionh.dk. · Department of Psychology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353, Copenhagen, Denmark. kamilla.miskowiak@regionh.dk. · Neurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Center, Psychiatric Center Copenhagen, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. kamilla.miskowiak@regionh.dk. ·Trials · Pubmed #29673379.

ABSTRACT: BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, but its use is impeded by its cognitive side effects. Novel treatments that can counteract these side effects may therefore improve current treatment strategies for depression. The present randomized trial investigates (1) whether short-term add-on treatment with erythropoietin (EPO) can reduce the cognitive side -effects of ECT and (2) whether such effects are long-lasting. Further, structural and functional magnetic resonance imaging (MRI) will be used to explore the neural underpinnings of such beneficial effects of EPO. Finally, the trial examines whether potential protective effects of EPO on cognition are accompanied by changes in markers of oxidative stress, inflammation, and neuroplasticity. METHODS/DESIGN: The trial has a double-blind, randomized, placebo-controlled, parallel group design. Patients with unipolar or bipolar disorder with current moderate to severe depression referred to ECT (N = 52) are randomized to receive four high-dose infusions of EPO (40,000 IU/ml) or placebo (saline). The first EPO/saline infusion is administered within 24 h before the first ECT. The following three infusions are administered at weekly intervals immediately after ECT sessions 1, 4, and 7. Cognition assessments are conducted at baseline, after the final EPO/saline infusion (3 days after eight ECT sessions), and at a 3 months follow-up after ECT treatment completion. The neuronal substrates for potential cognitive benefits of EPO are investigated with structural and functional MRI after the final EPO/saline infusion. The primary outcome is change from baseline to after EPO treatment (3 days after eight ECT sessions) in a cognitive composite score spanning attention, psychomotor speed, and executive functions. With a sample size of N = 52 (n = 26 per group), we have ≥ 80% power to detect a clinically relevant between-group difference in the primary outcome measure at an alpha level of 5% (two-sided test). Behavioral, mood, and blood-biomarker data will be analyzed using repeated measures analysis of covariance. Functional MRI data will be preprocessed and analyzed using the FMRIB Software Library. DISCUSSION: If EPO is found to reduce the cognitive side effects of ECT, this could have important implications for future treatment strategies for depression and for the scientific understanding of the neurobiological etiology of cognitive dysfunction in patients treated with ECT. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03339596 . Registered on 10 November 2017.

16 Article Increased sensitivity to positive social stimuli in monozygotic twins at risk of bipolar vs. unipolar disorder. 2018

Kærsgaard, S / Meluken, I / Kessing, L V / Vinberg, M / Miskowiak, K W. ·Copenhagen Affective Disorder Research Centre (CADIC); Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Psychology, University of Copenhagen, Denmark. Electronic address: signe.kaersgaard.mortensen@regionh.dk. · Copenhagen Affective Disorder Research Centre (CADIC); Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, University of Copenhagen, Denmark. Electronic address: iselin.meluken.01@regionh.dk. · Copenhagen Affective Disorder Research Centre (CADIC); Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, University of Copenhagen, Denmark. Electronic address: Lars.Vedel.Kessing@regionh.dk. · Copenhagen Affective Disorder Research Centre (CADIC); Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, University of Copenhagen, Denmark. Electronic address: maj.vinberg@regionh.dk. · Copenhagen Affective Disorder Research Centre (CADIC); Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Psychology, University of Copenhagen, Denmark. Electronic address: kamilla.miskowiak@regionh.dk. ·J Affect Disord · Pubmed #29499503.

ABSTRACT: BACKGROUND: Abnormalities in affective cognition are putative endophenotypes for bipolar and unipolar disorders but it is unclear whether some abnormalities are disorder-specific. We therefore investigated affective cognition in monozygotic twins at familial risk of bipolar disorder relative to those at risk of unipolar disorder and to low-risk twins. METHODS: Seventy monozygotic twins with a co-twin history of bipolar disorder (n = 11), of unipolar disorder (n = 38) or without co-twin history of affective disorder (n = 21) were included. Variables of interest were recognition of and vigilance to emotional faces, emotional reactivity and -regulation in social scenarios and non-affective cognition. RESULTS: Twins at familial risk of bipolar disorder showed increased recognition of low to moderate intensity of happy facial expressions relative to both unipolar disorder high-risk twins and low-risk twins. Bipolar disorder high-risk twins also displayed supraliminal attentional avoidance of happy faces compared with unipolar disorder high-risk twins and greater emotional reactivity in positive and neutral social scenarios and less reactivity in negative social scenarios than low-risk twins. In contrast with our hypothesis, there was no negative bias in unipolar disorder high-risk twins. There were no differences between the groups in demographic characteristics or non-affective cognition. LIMITATIONS: The modest sample size limited the statistical power of the study. CONCLUSIONS: Increased sensitivity and reactivity to positive social stimuli may be a neurocognitive endophenotype that is specific for bipolar disorder. If replicated in larger samples, this 'positive endophenotype' could potentially aid future diagnostic differentiation between unipolar and bipolar disorder.

17 Article Is negative self-referent bias an endophenotype for depression? An fMRI study of emotional self-referent words in twins at high vs. low risk of depression. 2018

Miskowiak, K W / Larsen, J E / Harmer, C J / Siebner, H R / Kessing, L V / Macoveanu, J / Vinberg, M. ·Mental Health Services - Capital Region of Denmark, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Denmark; Department of Psychology, University of Copenhagen, Denmark. Electronic address: Kamilla@miskowiak.dk. · Mental Health Services - Capital Region of Denmark, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Denmark. Electronic address: julia-evelyn@live.dk. · Department of Psychiatry, University of Oxford, United Kingdom. Electronic address: Catherine.harmer@psych.ox.ac.uk. · Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; Department of Neurology, Copenhagen University Hospital Bispebjerg, Denmark. Electronic address: hartwig.siebner@drcmr.dk. · Mental Health Services - Capital Region of Denmark, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Denmark. Electronic address: lars.vedel.kessing@regionh.dk. · Mental Health Services - Capital Region of Denmark, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Denmark. Electronic address: Julian.macoveanu@regionh.dk. · Mental Health Services - Capital Region of Denmark, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Denmark. Electronic address: maj.vinberg@regionh.dk. ·J Affect Disord · Pubmed #29020651.

ABSTRACT: BACKGROUND: Negative cognitive bias and aberrant neural processing of self-referent emotional words seem to be trait-marks of depression. However, it is unclear whether these neurocognitive changes are present in unaffected first-degree relatives and constitute an illness endophenotype. METHODS: Fifty-three healthy, never-depressed monozygotic or dizygotic twins with a co-twin history of depression (high-risk group: n = 26) or no first-degree family history of depression (low-risk group: n = 27) underwent neurocognitive testing and functional magnetic imaging (fMRI) as part of a follow-up cohort study. Participants performed a self-referent emotional word categorisation task and free word recall task followed by a recognition task during fMRI. Participants also completed questionnaires assessing mood, personality traits and coping strategies. RESULTS: High-risk and low-risk twins (age, mean ± SD: 40 ± 11) were well-balanced for demographic variables, mood, coping and neuroticism. High-risk twins showed lower accuracy during self-referent categorisation of emotional words independent of valence and more false recollections of negative words than low-risk twins during free recall. Functional MRI yielded no differences between high-risk and low-risk twins in retrieval-specific neural activity for positive or negative words or during the recognition of negative versus positive words within the hippocampus or prefrontal cortex. CONCLUSIONS: The subtle display of negative recall bias is consistent with the hypothesis that self-referent negative memory bias is an endophenotype for depression. High-risk twins' lower categorisation accuracy adds to the evidence for valence-independent cognitive deficits in individuals at familial risk for depression.

18 Article The Bipolar Illness Onset study: research protocol for the BIO cohort study. 2017

Kessing, Lars Vedel / Munkholm, Klaus / Faurholt-Jepsen, Maria / Miskowiak, Kamilla Woznica / Nielsen, Lars Bo / Frikke-Schmidt, Ruth / Ekstrøm, Claus / Winther, Ole / Pedersen, Bente Klarlund / Poulsen, Henrik Enghusen / McIntyre, Roger S / Kapczinski, Flavio / Gattaz, Wagner F / Bardram, Jakob / Frost, Mads / Mayora, Oscar / Knudsen, Gitte Moos / Phillips, Mary / Vinberg, Maj. ·Department of Psychiatry, Psychiatric Center Copenhagen, Copenhagen, Denmark. · Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. · Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark. · Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark. · Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kongens Lyngby, Denmark. · Gene Regulation Bioinformatics at the Bioinformatics Centre, Department of Biology/BRIC, University of Copenhagen, Copenhagen, Denmark. · The Centre of Inflammation and Metabolism at Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark. · Laboratory of Clinical Pharmacology, Rigshospitalet, Copenhagen, Denmark. · Department of Psychiatry and Pharmacology, University of Toronto, Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada. · McMaster University, Hamilton, Ontario, Canada. · Department and Institute of Psychiatry, and Laboratory of Neuroscience (LIM27), University of São Paulo Medical School, São Paulo, Brazil. · IT University Copenhagen, Copenhagen, Denmark. · Create-Net: Center for Research and Telecommunications Experimentation for Networked Communities, Trento, Italy. · Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark. · Department of Psychiatry, University of Pittsburgh, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA. ·BMJ Open · Pubmed #28645967.

ABSTRACT: INTRODUCTION: Bipolar disorder is an often disabling mental illness with a lifetime prevalence of 1%-2%, a high risk of recurrence of manic and depressive episodes, a lifelong elevated risk of suicide and a substantial heritability. The course of illness is frequently characterised by progressive shortening of interepisode intervals with each recurrence and increasing cognitive dysfunction in a subset of individuals with this condition. Clinically, diagnostic boundaries between bipolar disorder and other psychiatric disorders such as unipolar depression are unclear although pharmacological and psychological treatment strategies differ substantially. Patients with bipolar disorder are often misdiagnosed and the mean delay between onset and diagnosis is 5-10 years. Although the risk of relapse of depression and mania is high it is for most patients impossible to predict and consequently prevent upcoming episodes in an individual tailored way. The identification of objective biomarkers can both inform bipolar disorder diagnosis and provide biological targets for the development of new and personalised treatments. Accurate diagnosis of bipolar disorder in its early stages could help prevent the long-term detrimental effects of the illness.The present Bipolar Illness Onset study aims to identify (1) a composite blood-based biomarker, (2) a composite electronic smartphone-based biomarker and (3) a neurocognitive and neuroimaging-based signature for bipolar disorder. METHODS AND ANALYSIS: The study will include 300 patients with newly diagnosed/first-episode bipolar disorder, 200 of their healthy siblings or offspring and 100 healthy individuals without a family history of affective disorder. All participants will be followed longitudinally with repeated blood samples and other biological tissues, self-monitored and automatically generated smartphone data, neuropsychological tests and a subset of the cohort with neuroimaging during a 5 to 10-year study period. ETHICS AND DISSEMINATION: The study has been approved by the Local Ethical Committee (H-7-2014-007) and the data agency, Capital Region of Copenhagen (RHP-2015-023), and the findings will be widely disseminated at international conferences and meetings including conferences for the International Society for Bipolar Disorders and the World Federation of Societies for Biological Psychiatry and in scientific peer-reviewed papers. TRIAL REGISTRATION NUMBER: NCT02888262.

19 Article Increased blood BDNF in healthy individuals with a family history of depression. 2017

Knorr, Ulla / Søndergaard, Mia H Greisen / Koefoed, Pernille / Jørgensen, Anders / Faurholt-Jepsen, Maria / Vinberg, Maj / Kessing, Lars Vedel. ·Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen, Denmark. Electronic address: ulla.knorr@regionh.dk. · Laboratory of Neuropsychiatry, University Hospital of Copenhagen, Rigshospitalet and University of Copenhagen, Denmark. · Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen, Denmark; Laboratory of Neuropsychiatry, University Hospital of Copenhagen, Rigshospitalet and University of Copenhagen, Denmark. · Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen, Denmark. ·Psychiatry Res · Pubmed #28645077.

ABSTRACT: The brain-derive neurotrophic factor (BDNF) may play an important role in the course of depression. We aimed to study the associations between peripheral whole blood BDNF levels in healthy individuals with and without a family history of depression. BDNF levels were significantly increased in healthy individuals with (n = 76), compared with healthy individuals without (n = 39) a family history of depression and persisted after adjustment for age and gender differences. Higher BDNF levels were associated with increasing age and seasonality. A family history of depression may contribute to an elevation of peripheral BDNF levels in healthy individuals.

20 Article Differences in neural and cognitive response to emotional faces in middle-aged dizygotic twins at familial risk of depression. 2017

Miskowiak, K W / Svendsen, A M B / Harmer, C J / Elliott, R / Macoveanu, J / Siebner, H R / Kessing, L V / Vinberg, M. ·Copenhagen Affective Disorders Research Centre,Copenhagen Psychiatric Centre, Copenhagen University Hospital,Rigshospitalet,Denmark. · Department of Psychiatry,University of Oxford,UK. · Institute of Brain, Behaviour and Mental Health, University of Manchester,UK. · Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre,Denmark. ·Psychol Med · Pubmed #28397623.

ABSTRACT: BACKGROUND: Negative bias and aberrant neural processing of emotional faces are trait-marks of depression but findings in healthy high-risk groups are conflicting. METHODS: Healthy middle-aged dizygotic twins (N = 42) underwent functional magnetic resonance imaging (fMRI): 22 twins had a co-twin history of depression (high-risk) and 20 were without co-twin history of depression (low-risk). During fMRI, participants viewed fearful and happy faces while performing a gender discrimination task. After the scan, they were given a faces dot-probe task, a facial expression recognition task and questionnaires assessing mood, personality traits and coping. RESULTS: Unexpectedly, high-risk twins showed reduced fear vigilance and lower recognition of fear and happiness relative to low-risk twins. During face processing in the scanner, high-risk twins displayed distinct negative functional coupling between the amygdala and ventral prefrontal cortex and pregenual anterior cingulate. This was accompanied by greater fear-specific fronto-temporal response and reduced fronto-occipital response to all emotional faces relative to baseline. The risk groups showed no differences in mood, subjective state or coping. CONCLUSIONS: Less susceptibility to fearful faces and negative cortico-limbic coupling during emotional face processing may reflect neurocognitive compensatory mechanisms in middle-aged dizygotic twins who remain healthy despite their familial risk of depression.

21 Article Liraglutide promotes improvements in objective measures of cognitive dysfunction in individuals with mood disorders: A pilot, open-label study. 2017

Mansur, Rodrigo B / Ahmed, Juhie / Cha, Danielle S / Woldeyohannes, Hanna O / Subramaniapillai, Mehala / Lovshin, Julie / Lee, Jung G / Lee, Jae-Hon / Brietzke, Elisa / Reininghaus, Eva Z / Sim, Kang / Vinberg, Maj / Rasgon, Natalie / Hajek, Tomas / McIntyre, Roger S. ·Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada; Research Group in Molecular and Behavioral Neuroscience of Bipolar Disorder, Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Electronic address: rodrigomansur71@uol.com.br. · Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada. · Division of Endocrinology, Mount Sinai Hospital, University of Toronto, Toronto, Canada. · Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada; Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea. · Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada; Department of Psychiatry, Samsung Seoul Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea. · Research Group in Molecular and Behavioral Neuroscience of Bipolar Disorder, Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. · Medical University of Graz, Department of Psychiatry, Graz, Austria. · Research Division, Institute of Mental Health, Singapore. · Psychiatric Center Copenhagen, University of Copenhagen, Copenhagen, Denmark. · Department of Psychiatry, Stanford University, Palo Alto, CA, United States. · Department of Psychiatry, Dalhousie University, Halifax, Canada. ·J Affect Disord · Pubmed #27721184.

ABSTRACT: BACKGROUND: There is a paucity of treatments that are capable of reliably and robustly improving cognitive function in adults with mood disorders. Glucagon-like peptide-1 is synthesized centrally and its receptors are abundantly expressed in neural circuits subserving cognitive function. We aimed to determine the effects of liraglutide, a GLP-1 receptor (GLP-1R) agonist, on objective measures of cognition in adults with a depressive or bipolar disorder. METHODS: In this 4-week, pilot, open-label, domain-based study (e.g. cognition), we recruited 19 individuals with major depressive disorder (MDD) or bipolar disorder (BD) and an impairment in executive function, defined as a below-average performance in the Trail Making Test-B (TMTB). Liraglutide 1.8mg/day was added as an adjunct to existing pharmacotherapy. RESULTS: Participants had significant increases from baseline to week 4 in the TMTB standard score (age and education corrected) (Cohen's d=0.64, p=0.009) and in a composite Z-score comprising multiple cognitive tests (i.e. Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Stroop test) (Cohen's d=0.77, p<0.001). Neither changes in mood rating scales nor metabolic parameters were associated with changes in cognitive performance (all p>0.05); however baseline insulin resistance (IR) and body mass index (BMI) moderated the changes in the composite Z-score (p=0.021 and p=0.046, respectively), indicating larger responses in individuals with higher IR and BMI at baseline. There was a significant increase in lipase (p<0.001), but individual values were above the upper limit of normality. LIMITATIONS: Small sample size, open-label design, lack of a placebo group. CONCLUSIONS: Liraglutide was safe and well tolerated by a sample of non-diabetic individuals with mood disorders and had beneficial effects on objective measures of cognitive function. Larger studies with controlled trial designs are necessary to confirm and expand the results described herein.

22 Article Unaffected twins discordant for affective disorders show changes in anterior callosal white matter microstructure. 2016

Macoveanu, J / Vinberg, M / Madsen, K / Kessing, L V / Siebner, H R / Baaré, W. ·Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. julian.macoveanu@gmail.com. · Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. julian.macoveanu@gmail.com. · Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. · Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. · Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark. ·Acta Psychiatr Scand · Pubmed #27604681.

ABSTRACT: OBJECTIVE: The neurobiological mechanisms mediating an increased risk to develop affective disorders remain poorly understood. In a group of individuals with a family history of major depressive (MDD) or bipolar disorder (BD), we investigated the microstructural properties of white matter fiber tracts, that is, cingulum bundle, uncinate fasciculus, anterior limb of the internal capsule, and corpus callosum, that facilitate the communication between brain regions implicated in affective disorders. METHOD: Eighty-nine healthy mono- or dizygotic twins with a co-twin diagnosed with MDD or BD (high-risk) and 57 healthy twins with a co-twin with no familial history of affective disorders (low-risk) were included in a diffusion tensor imaging study. RESULT: The high-risk group showed decreased fractional anisotropy (FA), a measure of water diffusion directionality, and increased radial diffusivity in the anterior region of corpus callosum compared to the low-risk group. This abnormality was not associated with zygosity or type of depressive disorder of co-twin. CONCLUSION: The observed decreased anterior callosal fiber FA in the high-risk group may be indicative of a compromised interhemispheric communication between left and right frontal regions critically involved in mood regulation. Reduced anterior callosal FA may act as a vulnerability marker for affective disorders in individuals at familial risk.

23 Article Voice analysis as an objective state marker in bipolar disorder. 2016

Faurholt-Jepsen, M / Busk, J / Frost, M / Vinberg, M / Christensen, E M / Winther, O / Bardram, J E / Kessing, L V. ·Psychiatric Center Copenhagen, Rigshospitalet, Copenhagen, Denmark. · DTU Compute, Technical University of Denmark (DTU), Lyngby, Denmark. · The Pervasive Interaction Laboratory, IT University of Copenhagen, Copenhagen, Denmark. ·Transl Psychiatry · Pubmed #27434490.

ABSTRACT: Changes in speech have been suggested as sensitive and valid measures of depression and mania in bipolar disorder. The present study aimed at investigating (1) voice features collected during phone calls as objective markers of affective states in bipolar disorder and (2) if combining voice features with automatically generated objective smartphone data on behavioral activities (for example, number of text messages and phone calls per day) and electronic self-monitored data (mood) on illness activity would increase the accuracy as a marker of affective states. Using smartphones, voice features, automatically generated objective smartphone data on behavioral activities and electronic self-monitored data were collected from 28 outpatients with bipolar disorder in naturalistic settings on a daily basis during a period of 12 weeks. Depressive and manic symptoms were assessed using the Hamilton Depression Rating Scale 17-item and the Young Mania Rating Scale, respectively, by a researcher blinded to smartphone data. Data were analyzed using random forest algorithms. Affective states were classified using voice features extracted during everyday life phone calls. Voice features were found to be more accurate, sensitive and specific in the classification of manic or mixed states with an area under the curve (AUC)=0.89 compared with an AUC=0.78 for the classification of depressive states. Combining voice features with automatically generated objective smartphone data on behavioral activities and electronic self-monitored data increased the accuracy, sensitivity and specificity of classification of affective states slightly. Voice features collected in naturalistic settings using smartphones may be used as objective state markers in patients with bipolar disorder.

24 Article The effect of erythropoietin on cognition in affective disorders - Associations with baseline deficits and change in subjective cognitive complaints. 2016

Ott, Caroline Vintergaard / Vinberg, Maj / Kessing, Lars V / Miskowiak, Kamilla W. ·Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet Dep. 6233, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: caroline.vintergaard.ott@regionh.dk. · Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet Dep. 6233, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: maj.vinberg@regionh.dk. · Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet Dep. 6233, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: lars.vedel.kessing@regionh.dk. · Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet Dep. 6233, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: kamilla@miskowiak.dk. ·Eur Neuropsychopharmacol · Pubmed #27349944.

ABSTRACT: This is a secondary data analysis from our erythropoietin (EPO) trials. We examine (I) whether EPO improves speed of complex cognitive processing across bipolar and unipolar disorder, (II) if objective and subjective baseline cognitive impairment increases patients׳ chances of treatment-efficacy and (III) if cognitive improvement correlates with better subjective cognitive function, quality of life and socio-occupational capacity. Patients with unipolar or bipolar disorder were randomized to eight weekly EPO (N=40) or saline (N=39) infusions. Cognition, mood, quality of life and socio-occupational capacity were assessed at baseline (week 1), after treatment completion (week 9) and at follow-up (week 14). We used repeated measures analysis of covariance to investigate the effect of EPO on speed of complex cognitive processing. With logistic regression, we examined whether baseline cognitive impairment predicted treatment-efficacy. Pearson correlations were used to assess associations between objective and subjective cognition, quality of life and socio-occupational capacity. EPO improved speed of complex cognitive processing across affective disorders at weeks 9 and 14 (p≤0.05). In EPO-treated patients, baseline cognitive impairment increased the odds of treatment-efficacy on cognition at weeks 9 and 14 by a factor 9.7 (95% CI:1.2-81.1) and 9.9 (95% CI:1.1-88.4), respectively (p≤0.04). Subjective cognitive complaints did not affect chances of treatment-efficacy (p≥0.45). EPO-associated cognitive improvement correlated with reduced cognitive complaints but not with quality of life or socio-occupational function. As the analyses were performed post-hoc, findings are only hypothesis-generating. In conclusion, pro-cognitive effects of EPO occurred across affective disorders. Neuropsychological screening for cognitive dysfunction may be warranted in future cognition trials.

25 Article Effect of recombinant erythropoietin on inflammatory markers in patients with affective disorders: A randomised controlled study. 2016

Vinberg, Maj / Weikop, Pia / Olsen, Niels Vidiendal / Kessing, Lars Vedel / Miskowiak, Kamilla. ·Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: maj.vinberg@regionh.dk. · Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen, Denmark. Electronic address: pia.weikop@regionh.dk. · Department of Neuroanaesthesia, The Neuroscience Centre, University Hospital of Copenhagen (Rigshospitalet) and Department of Neuroscience and Pharmacology, The Health Faculty, University of Copenhagen, Denmark. Electronic address: nvolsen@sund.ku.dk. · Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: lars.vedel.kessing@regionh.dk. · Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: kamilla.miskowiak@regionh.dk. ·Brain Behav Immun · Pubmed #27181179.

ABSTRACT: AIM: This study investigated the effect of repeated infusions of recombinant human erythropoietin (EPO) on markers of inflammation in patients with affective disorders and whether any changes in inflammatory markers were associated with improvements on verbal memory. METHODS: In total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (sub-study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS)⩽14) (sub-study 2). In both sub-studies, patients were randomised in a double-blind, parallel-group design to receive eight weekly intravenous infusions of EPO (Eprex; 40,000IU/ml) or saline (0.9% NaCl). Plasma concentrations of interleukin 6 (IL-6), interleukin 18 (IL-18) and high sensitive c-reactive protein (hsCRP) were measured at week 1 (baseline) and weeks 5, 9 and 14. HDRS-17 and neuropsychological function was assessed at weeks 1, 9 and 14 using a test battery including the RAVLT Auditory Verbal Learning Test (primary depression and primary cognition outcomes in the original trial). RESULTS: EPO had no cumulative effect on plasma levels of IL-6 or IL-18 but increased hsCRP levels in patients with TRD (mean±SD change in ng/L: EPO: 0.43±1.64; Saline: -0.90±2.43; F(1,39)=4.78, p=0.04). EPO had no effects on inflammatory markers in BD. There was no correlation between change in inflammatory markers and change in verbal memory. CONCLUSIONS: Repeated EPO infusions had no effect on IL-6 and IL-18 levels but produced a modest increase in hsCRP levels in patients with TRD. Changes over time in inflammatory markers were not correlated with changes in cognition suggesting that modulation of the inflammatory pathway is not a putative mechanism of the EPO-associated improvement of cognition in affective disorders.

Next