ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Altres ajuts: Anxiety Disorders Research Network European College of Neuropsychopharmacology; Claude Leon Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 44541416-TRR58); EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant 'European and South African Research Network in Anxiety Disorders' (EUSARNAD); Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMw, 10-000-1002); Intramural Research Training Award (IRTA) program within the National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, MH002781); National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, ZIA-MH-002782); SA Medical Research Council; U.S. National Institutes of Health grants (P01 AG026572, P01 AG055367, P41 EB015922, R01 AG060610, R56 AG058854, RF1 AG051710, U54 EB020403).Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders

Cortical thickness and resting-state cardiac function across the lifespan: a cross-sectional pooled mega analysis

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS – or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between cortical thickness and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research

Hjärnan formas av psykologisk behandling

Social anxiety disorder (SAD) is a common psychiatric disorder associated with considerable suffering. Cognitive behaviour therapy (CBT) has been shown to be effective but a significant proportion does not respond or relapses, stressing the need of augmenting treatment. Using neuroimaging could elucidate the psychological and neurobiological interaction and may help to improve current therapeutics. To address this issue, functional and structural magnetic resonance imaging (MRI) were repeatedly conducted on individuals with SAD randomised to receive CBT or an active control condition. MRI was performed pre-, and post-treatment, as well as at one-year follow-up. Matched healthy controls were also scanned to be able to evaluate disorder-specific neural responsivity and structural morphology. This thesis aimed at answering three major questions. I) Does the brain’s fear circuitry (e.g., the amygdala) change, with regard to neural response and structural morphology, immediately after CBT? II) Are the immediate changes in the brain still present at long-term follow-up? III) Can neural responsivity in the fear circuitry predict long-term treatment outcome at the level of the individual? Thus, different analytic methods were performed. Firstly, multimodal neuroimaging addressed questions on concomitant changes in neural response and grey matter volume. Secondly, two different experimental functional MRI tasks captured both neural response to emotional faces and self-referential criticism. Thirdly, support vector machine learning (SVM) was used to evaluate neural predictors at the level of the individual. Amygdala responsivity to self-referential criticism was found to be elevated in individuals with SAD, as compared to matched healthy controls, and the neural response was attenuated after effective CBT. In individuals with SAD, amygdala grey matter volume was positively correlated with symptoms of anticipatory speech anxiety, and CBT-induced symptom reduction was associated with decreased grey matter volume of the amygdala. Also, CBT-induced reduction of amygdala grey matter volume was evident both at short- and long-term follow-up. In contrast, the amygdala neural response was weakened immediately after treatment, but not at one-year follow-up. In extension to treatment effects on the brain, pre-treatment connectivity between the amygdala and the dorsal anterior cingulate cortex (dACC) was stronger in long-term CBT non-responders, as compared to long-term CBT responders. Importantly, by use of an SVM algorithm, pre-treatment neural response to self-referential criticism in the dACC accurately predicted (&gt;90%) the clinical response to CBT. In conclusion, modifying the amygdala is a likely mechanism of action in CBT, underlying the anxiolytic effects of this treatment, and the brain’s neural activity during self-referential criticism may be an accurate and clinically relevant predictor of the long-term response to CBT. Along these lines, neuroimaging is a vital tool in clinical psychiatry that could potentially improve clinical decision-making based on an individual’s neural characteristics.Social ångest är en av de vanligaste psykiska sjukdomarna. Mer än en miljon svenskar bedöms lida av detta. Social ångest leder ofta till svåra konsekvenser för den som drabbas, men även ökade kostnader för samhället har noterats, t ex i form av ökad sjukfrånvaro. Även om många som drabbas inte söker hjälp så finns effektiva behandlingar för social ångest, både farmakologiska och psykologiska behandlingar rekommenderas av Socialstyrelsen. Kognitiv beteendeterapi (KBT) är en evidensbaserad och rekommenderad psykologisk behandling för social ångest. Trots att nuvarande interventioner är effektiva så är det fortfarande en andel individer som inte blir förbättrade. Det finns en stor andel studier som visar att individer med social ångest, i jämförelse med friska individer, karakteriseras av överdriven aktivitet i ett nätverk som har till uppgift att tolka och reagera på hotfull information. Denna aktivitet är lokaliserad i rädslonätverket där området amygdala spelar en central roll. Det finns ett behov att utveckla nuvarande behandlingar och denna avhandling syftar till att öka vår förståelse för en neurobiologisk verkningsmekanism bakom KBT för social ångest. I detta forskningsprojekt har magnetresonanstomografi (MRT) använts för att undersöka personer som lider av social ångest. Upprepade mätningar har genomförts, innan, efter, och vid uppföljning ett år efter ångestlindrande behandling. Utöver detta har individer som inte lider av social ångest undersökts för att förstå hur patienter skiljer sig från friska personer, men också för att undersöka om behandlingen normaliserar patientens hjärna. Under tiden som deltagarna undersöktes med MRT genomfördes två experiment för att ta reda på hur hjärnan reagerar på affektiv information. Deltagarna tittade på bilder med ansikten som uttrycker emotioner, t ex arga och rädda ansiktsuttryck, samt information som innehöll kritiska kommentarer riktade till personen själv eller någon annan, t ex ”ingen tycker om dig” eller ”hon är inkompetent”. Strukturella bilder på deltagarnas hjärnor har också samlats in vid varje mättillfälle. Utöver detta fick alla deltagare instruktioner om att de efter MRT skulle hålla en muntlig presentation inför en publik. Denna uppgift är oftast den värsta tänkbara för individer med social ångest, och syftet med uppgiften var att relatera hjärnans struktur och aktivitet till hur mycket ångest som individerna upplevde inför denna situation. I arbetet med denna avhandling har tre frågor ställts. a) Uppstår strukturella och funktionella förändringar i rädslonätverket direkt efter avslutad KBT (Studie I och II)? b) Är de tidiga förändringarna efter behandlingen även kvarstående ett år senare (Studie III)? c) Kan hjärnans reaktioner i rädslonätverket förutspå vilka individer som kommer att bli förbättrade av en ångestlindrande psykologisk behandling på lång sikt? Resultat från studierna i denna avhandling sammanfattas nedan: Reaktioner till självriktad kritik i amygdala är överdrivna hos individer med social ångest, i jämförelse med friska individer Reaktioner i amygdala minskar efter att individerna blivit behandlade med KBT och minskningarna korrelerar till minskade symptom av social ångest Den strukturella volymen av amygdala korrelerar positivt med hur mycket ångest individerna upplever inför en muntlig presentation, och minskningen av dessa symptom korrelerar även med hur mycket volymen av amygdala minskar efter KBT Minskningen av amygdalavolym och den samtidigt minskade reaktiviteten i amygdala till självriktad kritik är korrelerade. Medieringsanalyser antyder att det är den minskade volymen som driver förhållandet mellan minskad reaktivitet och minskad ångest inför att hålla en muntlig presentation Den strukturella minskningen av amygdala ses både direkt efter behandlingens avslut, men även vid uppföljning ett år senare. Hjärnans reaktivitet till självriktad kritik i amygdala minskar direkt efter behandling, men är inte kvarstående vid uppföljning ett år senare Kopplingen mellan hjärnans reaktivitet till självriktad kritik i amygdala och dorsala främre cingulum var starkare hos de som inte blev förbättrade (jämfört med de som blev bättre) av en ångestlindrande behandling på lång sikt Med hjälp av en stödvektormaskin (en. support vector machine learning) och ett mönster av hjärnaktivitet i dorsala främre cingulum innan behandling påbörjades, predicerades (med 92% träffsäkerhet) vilka individer som ett år senare var fortsatt förbättrade av en effektiv psykologisk behandling Utifrån dessa observationer är slutsatserna att strukturell och funktionell påverkan på amygdala är en möjlig neurobiologisk mekanism för minskad social ångest efter KBT, samt att reaktivitet i främre cingulum kan ge kliniskt relevant data om vem som kommer att bli förbättrad av en psykologisk behandling. Denna information kan potentiellt vara viktig i framtidens psykiatri för att utveckla existerande behandlingar, men även för att stödja klinikers beslutsfattande huruvida en viss individ bör erbjudas en specifik behandling eller ej.Illustration on the cover by Jan Lööf. Cover image printed with permission from Jan Lööf and Bonnier Carlsen Förlag. The cover was art directed by Staffan Lager.The thesis is reprinted and the previous ISBN was 9789176856888.</p

Neural respons till information i trevalenser för patienter med social ångest

Föreliggande studie har undersökt underliggande neurala regioner för informationsprocessning av lexikala stimuli hos patienter med socialt ångestsyndrom (SAD). Deltagarna bestod av 26 kvinnor och män i åldrarna nitton till femtiosju år (M = 32). Under mätning med funktionell magnetresonanstomografi (fMRI) fick forskningdeltagarna läsa olika påstående i tre valenser (positiva, neutrala och negativa). Dessa var i sin tur antingen riktade till personen själv, eller till någon annan. Resultaten visar att positiva stimuli, riktade till personen själv, aktiverar nätverk inom mediala prefrontalcortex (mPFC, BA 8 &amp; 10) och tenderade till lateralisering i höger hemisfär. Negativa stimuli, riktade till sig själv, antyder en mer lokal aktivering specifikt till BA 9, vänsterlateraliserat. Neutral valens gav aktivering i regioner associerade till tolkning och förståelse av språk. Neurala responser i amygdala har inte registrerats under någon av experimentets betingelser. Sammantaget visar studien aktivering av regioner som relateras till själv-hänvisande processning och hur semantiska och episodiska minnessystem (Cabeza &amp; Nyberg, 2000) potentiellt kan bidra till vidmakthållandet av social ångest

Internet treatment for social anxiety disorder in Romania: study protocol for a randomized controlled trial. Tulbure et al. Trials

Abstract Background: Social anxiety disorder (SAD) is one of the most common anxiety disorders and is associated with marked impairments. However, a small proportion of individuals with SAD seek and receive treatment. Internet-administrated cognitive behavior therapy (iCBT) has been found to be an effective treatment for SAD. This trial will be the first Internet-delivered guided self-help intervention for SAD in Romania

Enriching CBT by Neuroscience : Novel Avenues to Achieve Personalized Treatments

Although cognitive behavioral therapy (CBT) is an established and efficient treatment for a variety of common mental disorders, a considerable number of patients do not respond to treatment or relapse after successful CBT. Recent findings and approaches from neuroscience could pave the way for clinical developments to enhance the outcome of CBT. Herein, we will present how neuroscience can offer novel perspectives to better understand (a) the biological underpinnings of CBT, (b) how we can enrich CBT with neuroscience-informed techniques (augmentation of CBT), and (c) why some patients may respond better to CBT than others (predictors of therapy outcomes), thus paving the way for more personalized and effective treatments. We will introduce some key topics and describe a selection of findings from CBT-related research using tools from neuroscience, with the hope that this will provide clinicians and clinical researchers with a brief and comprehensible overview of the field

Internet treatment for social anxiety disorder in Romania : study protocol for a randomized controlled trial

BACKGROUND: Social anxiety disorder (SAD) is one of the most common anxiety disorders and is associated with marked impairments. However, a small proportion of individuals with SAD seek and receive treatment. Internet-administrated cognitive behavior therapy (iCBT) has been found to be an effective treatment for SAD. This trial will be the first Internet-delivered guided self-help intervention for SAD in Romania. METHODS: Participants with social anxiety disorder (N = 96) will be recruited via newspapers, online banners and Facebook. Participants will be randomized to either: a) an active treatment, or b) a waiting list control group.The treatment will have a guided iCBT format and will last for nine weeks. Self-report questionnaires on social phobia, anxiety, depression, treatment credibility and irrational thinking will be used. All assessments will be collected pre, post and at follow-up (six months after intervention). Liebowitz Social Anxiety Scale - Self-Report version (LSAS-SR) will be the primary outcome measure and will be administrated on a weekly basis in both conditions. DISCUSSION: The present randomized controlled trial investigates the efficacy of an Internet-administered intervention in reducing social anxiety symptoms in a culture where this form of treatment has not been tested. This trial will add to the body of knowledge on the efficacy of iCBT, and the results might lead to an increase of the accessibility of evidence-based psychological treatment in Romania. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01557894

Internet treatment for social anxiety disorder in Romania : study protocol for a randomized controlled trial

BACKGROUND: Social anxiety disorder (SAD) is one of the most common anxiety disorders and is associated with marked impairments. However, a small proportion of individuals with SAD seek and receive treatment. Internet-administrated cognitive behavior therapy (iCBT) has been found to be an effective treatment for SAD. This trial will be the first Internet-delivered guided self-help intervention for SAD in Romania. METHODS: Participants with social anxiety disorder (N = 96) will be recruited via newspapers, online banners and Facebook. Participants will be randomized to either: a) an active treatment, or b) a waiting list control group.The treatment will have a guided iCBT format and will last for nine weeks. Self-report questionnaires on social phobia, anxiety, depression, treatment credibility and irrational thinking will be used. All assessments will be collected pre, post and at follow-up (six months after intervention). Liebowitz Social Anxiety Scale - Self-Report version (LSAS-SR) will be the primary outcome measure and will be administrated on a weekly basis in both conditions. DISCUSSION: The present randomized controlled trial investigates the efficacy of an Internet-administered intervention in reducing social anxiety symptoms in a culture where this form of treatment has not been tested. This trial will add to the body of knowledge on the efficacy of iCBT, and the results might lead to an increase of the accessibility of evidence-based psychological treatment in Romania. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01557894

Internet treatment for social anxiety disorder in Romania: study protocol for a randomized controlled trial. Tulbure et al. Trials

Abstract Background: Social anxiety disorder (SAD) is one of the most common anxiety disorders and is associated with marked impairments. However, a small proportion of individuals with SAD seek and receive treatment. Internet-administrated cognitive behavior therapy (iCBT) has been found to be an effective treatment for SAD. This trial will be the first Internet-delivered guided self-help intervention for SAD in Romania

Leukocyte telomere length and hippocampus volume: a meta-analysis [version 1; referees: 2 approved]

Leukocyte telomere length has been shown to correlate to hippocampus volume, but effect estimates differ in magnitude and are not uniformly positive. This study aimed primarily to investigate the relationship between leukocyte telomere length and hippocampus gray matter volume by meta-analysis and secondarily to investigate possible effect moderators. Five studies were included with a total of 2107 participants, of which 1960 were contributed by one single influential study. A random-effects meta-analysis estimated the effect to r = 0.12 [95% CI -0.13, 0.37] in the presence of heterogeneity and a subjectively estimated moderate to high risk of bias. There was no evidence that apolipoprotein E (APOE) genotype was an effect moderator, nor that the ratio of leukocyte telomerase activity to telomere length was a better predictor than leukocyte telomere length for hippocampus volume. This meta-analysis, while not proving a positive relationship, also is not able to disprove the earlier finding of a positive correlation in the one large study included in analyses. We propose that a relationship between leukocyte telomere length and hippocamus volume may be mediated by transmigrating monocytes which differentiate into microglia in the brain parenchyma