Open and Calm–a randomized controlled trial evaluating a public stress reduction program in Denmark.

Open and Calm–a randomized controlled trial evaluating a public stress reduction program in Denmark.

BMC Public Health. 2015;15:1245 Dec.16-2015

Authors: Jensen CG, Lansner J, Petersen A, Vangkilde SA, Ringkøbing SP, Frokjaer VG, Adamsen D, Knudsen GM, Denninger JW, Hasselbalch SG

Abstract
BACKGROUND: Prolonged psychological stress is a risk factor for illness and constitutes an increasing public health challenge creating a need to develop public interventions specifically targeting stress and promoting mental health. The present randomized controlled trial evaluated health effects of a novel program: Relaxation-Response-based Mental Health Promotion (RR-MHP).
METHODS: The multimodal, meditation-based course was publicly entitled “Open and Calm” (OC) because it consistently trained relaxed and receptive (“Open”) attention, and consciously non-intervening (“Calm”) witnessing, in two standardized formats (individual or group) over nine weeks. Seventy-two participants who complained to their general practitioner about reduced daily functioning due to prolonged stress or who responded to an online health survey on stress were randomly assigned to OC formats or treatment as usual, involving e.g., unstandardized consultations with their general practitioner. Outcomes included perceived stress, depressive symptoms, quality of life, sleep disturbances, mental health, salivary cortisol, and visual perception. Control variables comprised a genetic stress-resiliency factor (serotonergic transporter genotype; 5-HTTLPR), demographics, personality, self-reported inattentiveness, and course format.
RESULTS: Intent-to-treat analyses showed significantly larger improvements in OC than in controls on all outcomes. Treatment effects on self-reported outcomes were sustained after 3 months and were not related to age, gender, education, or course format. The dropout rate was only 6 %.
CONCLUSIONS: The standardized OC program reduced stress and improved mental health for a period of 3 months. Further testing of the OC program for public mental health promotion and reduction of stress-related illnesses is therefore warranted. A larger implementation is in progress.
TRIAL REGISTRATION: ClinicalTrials.gov.: NCT02140307. Registered May 14 2014.

PMID: 26673225 [PubMed – in process]

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Evaluation of acute tryptophan depletion and sham depletion with a gelatin-based collagen peptide protein mixture.

Evaluation of acute tryptophan depletion and sham depletion with a gelatin-based collagen peptide protein mixture.

Eur Neuropsychopharmacol. 2015 Nov 26;

Authors: Stenbæk DS, Einarsdottir HS, Goregliad-Fjaellingsdal T, Knudsen GM, Frokjaer VG, Hasselbalch SG

Abstract
Acute Tryptophan Depletion (ATD) is a dietary method used to modulate central 5-HT to study the effects of temporarily reduced 5-HT synthesis. The aim of this study is to evaluate a novel method of ATD using a gelatin-based collagen peptide (CP) mixture. We administered CP-Trp or CP+Trp mixtures to 29 healthy volunteers; 13 from a randomized, double-blinded crossover study and sixteen from a randomized, double-blinded study run in our laboratory. Plasma amino acids, mood, side effects, cortisol concentrations, mean arterial blood pressure and heart rate were measured at multiple time-points. Repeated measures analysis of variance and Wilcoxon or Mann-Whitney U non-parametric tests were used to analyze the effects of intervention. Intake of the CP-Trp mixture efficiently reduced plasma Trp; however, the CP+Trp mixture induced a large significant increase in plasma Trp. No other significant effects of CP-Trp compared to CP+Trp were observed. The transient increase in plasma Trp after CP+Trp may impair comparison to the CP-Trp and we therefore recommend in future studies to use a smaller dose of Trp supplement to the CP mixture.

PMID: 26655163 [PubMed – as supplied by publisher]

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Development and psychometric validation of the verbal affective memory test.

Development and psychometric validation of the verbal affective memory test.

Memory. 2015 Sep 24;:1-16

Authors: Jensen CG, Hjordt LV, Stenbæk DS, Andersen E, Back SK, Lansner J, Hageman I, Dam H, Nielsen AP, Knudsen GM, Frokjaer VG, Hasselbalch SG

Abstract
We here present the development and validation of the Verbal Affective Memory Test-24 (VAMT-24). First, we ensured face validity by selecting 24 words reliably perceived as positive, negative or neutral, respectively, according to healthy Danish adults’ valence ratings of 210 common and non-taboo words. Second, we studied the test’s psychometric properties in healthy adults. Finally, we investigated whether individuals diagnosed with Seasonal Affective Disorder (SAD) differed from healthy controls on seasonal changes in affective recall. Recall rates were internally consistent and reliable and converged satisfactorily with established non-affective verbal tests. Immediate recall (IMR) for positive words exceeded IMR for negative words in the healthy sample. Relatedly, individuals with SAD showed a significantly larger decrease in positive recall from summer to winter than healthy controls. Furthermore, larger seasonal decreases in positive recall significantly predicted larger increases in depressive symptoms. Retest reliability was satisfactory, rs ≥ .77. In conclusion, VAMT-24 is more thoroughly developed and validated than existing verbal affective memory tests and showed satisfactory psychometric properties. VAMT-24 seems especially sensitive to measuring positive verbal recall bias, perhaps due to the application of common, non-taboo words. Based on the psychometric and clinical results, we recommend VAMT-24 for international translations and studies of affective memory.

PMID: 26401886 [PubMed – as supplied by publisher]

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Preserved consciousness in vegetative and minimal conscious states: systematic review and meta-analysis.

Preserved consciousness in vegetative and minimal conscious states: systematic review and meta-analysis.

J Neurol Neurosurg Psychiatry. 2015 Jul 2;

Authors: Kondziella D, Friberg CK, Frokjaer VG, Fabricius M, Møller K

Abstract
Active, passive and resting state paradigms using functional MRI (fMRI) or EEG may reveal consciousness in the vegetative (VS) and the minimal conscious state (MCS). A meta-analysis was performed to assess the prevalence of preserved consciousness in VS and MCS as revealed by fMRI and EEG, including command following (active paradigms), cortical functional connectivity elicited by external stimuli (passive paradigms) and default mode networks (resting state). Studies were selected from multiple indexing databases until February 2015 and evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. 37 studies were identified, including 1041 patients (mean age 43 years, range 16-89; male/female 2.1:1; 39.5% traumatic brain injuries). MCS patients were more likely than VS patients to follow commands during active paradigms (32% vs 14%; OR 2.85 (95% CI 1.90 to 4.27; p<0.0001)) and to show preserved functional cortical connectivity during passive paradigms (55% vs 26%; OR 3.53 (95% CI 2.49 to 4.99; p<0.0001)). Passive paradigms suggested preserved consciousness more often than active paradigms (38% vs 24%; OR 1.98 (95% CI 1.54 to 2.54; p<0.0001)). Data on resting state paradigms were insufficient for statistical evaluation. In conclusion, active paradigms may underestimate the degree of consciousness as compared to passive paradigms. While MCS patients show signs of preserved consciousness more frequently in both paradigms, roughly 15% of patients with a clinical diagnosis of VS are able to follow commands by modifying their brain activity. However, there remain important limitations at the single-subject level; for example, patients from both categories may show command following despite negative passive paradigms.

PMID: 26139551 [PubMed – as supplied by publisher]

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Hvordan spiller lys, genetik, stress og rusmidler ind på hjernens sundhed?

I anledningen af Forskningens Døgn inviterede Rigshospitalet københavnske gymnasieelever til en mini-konference under overskriften “Skarpe hjerner og kvikke midler”. Som noget helt nyt blev mini-konferencen livestreamet via Rigshospitalets LIVE Web-TV. Fik du ikke set oplæggene, har du nu mulighed for at se mit oplæg her:
Titel: “Hvordan spiller lys, genetik, stress og rusmidler ind på hjernens sundhed?”
v. læge, ph.d. Vibe Frøkjær, Neurobiologisk Forskningsenhed

 

Fluctuations in [¹¹C]SB207145 PET binding associated with change in threat-related amygdala reactivity in humans.

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Fluctuations in [¹¹C]SB207145 PET binding associated with change in threat-related amygdala reactivity in humans.

Neuropsychopharmacology. 2015 May;40(6):1510-8

Authors: Fisher PM, Haahr ME, Jensen CG, Frokjaer VG, Siebner HR, Knudsen GM

Abstract
Serotonin critically affects the neural processing of emotionally salient stimuli, including indices of threat; however, how alterations in serotonin signaling contribute to changes in brain function is not well understood. Recently, we showed in a placebo-controlled study of 32 healthy males that brain serotonin 4 receptor (5-HT4) binding, assessed with [(11)C]SB207145 PET, was sensitive to a 3-week intervention with the selective serotonin reuptake inhibitor fluoxetine, supporting it as an in vivo model for fluctuations in central serotonin levels. Participants also underwent functional magnetic resonance imaging while performing a gender discrimination task of fearful, angry, and neutral faces. This offered a unique opportunity to evaluate whether individual fluctuations in central serotonin levels, indexed by change in [(11)C]SB207145 binding, predicted changes in threat-related reactivity (ie, fear and angry vs neutral faces) within a corticolimbic circuit including the amygdala and medial prefrontal and anterior cingulate cortex. We observed a significant association such that decreased brain-wide [(11)C]SB207145 binding (ie, increased brain serotonin levels) was associated with lower threat-related amygdala reactivity, whereas intervention group status did not predict change in corticolimbic reactivity. This suggests that in the healthy brain, interindividual responses to pharmacologically induced and spontaneously occurring fluctuations in [(11)C]SB207145 binding, a putative marker of brain serotonin levels, affect amygdala reactivity to threat. Our finding also supports that change in brain [(11)C]SB207145 binding may be a relevant marker for evaluating neurobiological mechanisms underlying sensitivity to threat and serotonin signaling.

PMID: 25560201 [PubMed – in process]

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Role of emotional processing in depressive responses to sex-hormone manipulation: a pharmacological fMRI study.

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Role of emotional processing in depressive responses to sex-hormone manipulation: a pharmacological fMRI study.

Transl Psychiatry. 2015;5:e688

Authors: Henningsson S, Madsen KH, Pinborg A, Heede M, Knudsen GM, Siebner HR, Frokjaer VG

Abstract
Sex-hormone fluctuations may increase risk for developing depressive symptoms and alter emotional processing as supported by observations in menopausal and pre- to postpartum transition. In this double-blinded, placebo-controlled study, we used blood-oxygen level dependent functional magnetic resonance imaging (fMRI) to investigate if sex-steroid hormone manipulation with a gonadotropin-releasing hormone agonist (GnRHa) influences emotional processing. Fifty-six healthy women were investigated twice: at baseline (follicular phase of menstrual cycle) and 16 ± 3 days post intervention. At both sessions, fMRI-scans during exposure to faces expressing fear, anger, happiness or no emotion, depressive symptom scores and estradiol levels were acquired. The fMRI analyses focused on regions of interest for emotional processing. As expected, GnRHa initially increased and subsequently reduced estradiol to menopausal levels, which was accompanied by an increase in subclinical depressive symptoms relative to placebo. Women who displayed larger GnRHa-induced increase in depressive symptoms had a larger increase in both negative and positive emotion-elicited activity in the anterior insula. When considering the post-GnRHa scan only, depressive responses were associated with emotion-elicited activity in the anterior insula and amygdala. The effect on regional activity in anterior insula was not associated with the estradiol net decline, only by the GnRHa-induced changes in mood. Our data implicate enhanced insula recruitment during emotional processing in the emergence of depressive symptoms following sex-hormone fluctuations. This may correspond to the emotional hypersensitivity frequently experienced by women postpartum.

PMID: 26624927 [PubMed – in process]

Source: My publications feed from NCBI

Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation: A Positron Emission Tomography Study.

Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation: A Positron Emission Tomography Study.

Biol Psychiatry. 2015 Apr 27;

Authors: Frokjaer VG, Pinborg A, Holst KK, Overgaard A, Henningsson S, Heede M, Larsen EC, Jensen PS, Agn M, Nielsen AP, Stenbæk DS, da Cunha-Bang S, Lehel S, Siebner HR, Mikkelsen JD, Svarer C, Knudsen GM

Abstract
BACKGROUND: An adverse response to acute and pronounced changes in sex-hormone levels during, for example, the perimenopausal or postpartum period appears to heighten risk for major depression in women. The underlying risk mechanisms remain elusive but may include transiently compromised serotonergic brain signaling. Here, we modeled a biphasic ovarian sex hormone fluctuation using a gonadotropin-releasing hormone agonist (GnRHa) and evaluated if emergence of depressive symptoms was associated with change in cerebral serotonin transporter (SERT) binding following intervention.
METHODS: A double-blind, randomized, placebo-controlled study included 63 healthy female volunteers (mean age 24.3 ± 4.9 years) with regular menstrual cycles between 23 and 35 days. Participants were randomized to active (goserelin [GnRHa] 3.6 mg implant) or placebo intervention. Sixty women completed follow-up and entered the analyses. Primary outcome measures were changes from baseline in depressive symptoms assessed on the 17-item Hamilton Depression Rating Scale and SERT binding as imaged by [(11)C]DASB positron emission tomography. Outcome measures were acquired at baseline in the follicular phase (cycle day 6.6 ± 2.2) and at follow-up (16.2 ± 2.6 days after intervention start).
RESULTS: Sex hormone manipulation with GnRHa significantly triggered subclinical depressive symptoms within-group (p = .003) and relative to placebo (p = .02), which were positively associated with net decreases in estradiol levels (p = .02) from baseline within the GnRHa group. Depressive symptoms were associated with increases in neocortical SERT binding in the GnRHa group relative to placebo (p = .003).
CONCLUSIONS: Our data imply both serotonergic signaling and estradiol in the mechanisms by which sex-steroid hormone fluctuations provoke depressive symptoms and thus provide a rationale for future preventive strategies in high-risk groups.

PMID: 26004162 [PubMed – as supplied by publisher]

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Functional connectivity of the dorsal and median raphe nuclei at rest.

Functional connectivity of the dorsal and median raphe nuclei at rest.

Neuroimage. 2015 May 8;

Authors: Beliveau V, Svarer C, Frokjaer VG, Knudsen GM, Greve DN, Fisher PM

Abstract
Serotonin (5-HT) is a neurotransmitter critically involved in a broad range of brain functions and implicated in the pathophysiology of neuropsychiatric illnesses including major depression, anxiety and sleep disorders. Despite being widely distributed throughout the brain, there is limited knowledge on the contribution of 5-HT to intrinsic brain activity. The dorsal raphe (DR) and median raphe (MR) nuclei are the source of most serotonergic neurons projecting throughout the brain and thus provide a compelling target for a seed-based probe of resting-state activity related to 5-HT. Here we implemented a novel multimodal neuroimaging approach for investigating resting-state functional connectivity (FC) between DR and MR and cortical, subcortical and cerebellar target areas. Using [(11)C]DASB positron emission tomography (PET) images of the brain serotonin transporter (5-HTT) combined with structural MRI from 49 healthy volunteers, we delineated DR and MR and performed a seed-based resting-state FC analysis. The DR and MR seeds produced largely similar FC maps: significant positive FC with brain regions involved in cognitive and emotion processing including anterior cingulate, amygdala, insula, hippocampus, thalamus, basal ganglia and cerebellum. Significant negative FC was observed within pre- and postcentral gyri for the DR but not for the MR seed. We observed a significant association between DR and MR FC and regional 5-HTT binding. Our results provide evidence for a resting-state network related to DR and MR and comprising regions receiving serotonergic innervation and centrally involved in 5-HT related behaviors including emotion, cognition and reward processing. These findings provide a novel advance in estimating resting-state FC related to 5-HT signaling, which can benefit our understanding of its role in behavior and neuropsychiatric illnesses.

PMID: 25963733 [PubMed – as supplied by publisher]

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The Center for Integrated Molecular Brain Imaging (Cimbi) Database.

The Center for Integrated Molecular Brain Imaging (Cimbi) Database.

Neuroimage. 2015 Apr 16;

Authors: Knudsen GM, Jensen PS, Erritzoe D, Baaré WF, Ettrup A, Fisher PM, Gillings N, Hansen HD, Hansen LK, Hasselbalch SG, Henningsson S, Herth MM, Holst KK, Iversen P, Kessing LV, Macoveanu J, Madsen KS, Mortensen EL, Nielsen FÅ, Paulson OB, Siebner HR, Stenbæk DS, Svarer C, Jernigan TL, Strother SC, Frokjaer VG

Abstract
We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes. The Cimbi Database and Cimbi Biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies. The Cimbi database currently comprises a total of 1.100 PET and 1.000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank.

PMID: 25891375 [PubMed – as supplied by publisher]

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