Audrey Tyrka – The Psychiatric-Metabolic Syndrome

Stockholm Psychiatry Lectures 2019-11-04

Professor Tyrka is interested in the intersection of environment and biology, and how adverse experiences can affect the development of children. Early stress has been identified as a mechanism in both psychiatric and other medical conditions (such as metabolic syndrome and cardiovascular disease). It has also been associated with premature death, both due to natural and unnatural causes.

What are the mechanisms responsible for this relationship? One such mechanism is through the hypothalamic pituitary axis (HPA-axis) which activates the stress-response by releasing glucocorticoids, affecting many regulatory systems in the body. Another proposed mechanism is through the telomere/telomerase maintenance system. The telomeres are located at the end of chromosomes, and preserve the stability of replication in new cells. Their length is reduced over time, and older individuals have shorter telomeres than younger individuals. Telomere shortening is associated with a variety of negative health consequences, and recent research has found that psychosocial stress is associated with shorter telomeres. In Dr Tyrka’s own work, the findings point to an association between childhood maltreatment and shorter telomere length.

Mitochondria are present in virtually every cell, but are particularly common in structures with high energy demand such as the brain and heart. They are involved in energy production, stress response, immune function, and cell signalling. Furthermore, the mitochondrial DNA (mtDNA) also contains genes relevant for the regulation of glucocorticoids. Childhood maltreatment is in this case associated with higher numbers of copy numbers in the mtDNA, suggesting a compensatory mechanism.

In a recent, large scale study of maltreatment in children, Dr Tyrka’s group are studying children at 3-5 years of age. They are therefore able to compare children who have been maltreated within the last 6 months to children with no signs of maltreatment. This can overcome biases related to retrospective studies in adults. The number of traumatic life events and maltreatment were associated with telomere length and mtDNA copy numbers, but it should be noted that the maltreated children had longer telomeres than the control group! Internalising behaviours (depression and anxiety) were also associated with telomere length and mtDNA copy numbers. The same children are now being studied 6 years later, at age 9-11, and data collection is ongoing.

The effects of adverse childhood experiences are not limited to impact on biological systems, but also affect psychosocial and educational functioning. Executive functioning, attachment, self efficacy, attention, memory, and behavioral control are just a few examples where a large body of research has demonstrated detrimental effects. Having an even wider scope, there are also additional societal effects such as homelessness and crime.

You can read more about Professor Tyrka’s research at their lab website and Twitter account. A video of the lecture will appear on the Stockholm Psychiatry Lectures youtube channel.

New publication: Adapted CBT for individuals with OCD and ASD

We have just published an article in Autism, “Adapted cognitive behavior therapy for obsessive compulsive disorder with co-occurring autism spectrum disorder: A clinical effectiveness study”. The article is available for free for a limited amount of time!

Adults with autism spectrum disorder (ASD) often experience mental health problems such as obsessive compulsive disorder (OCD). However, individuals with ASD are typically excluded from research on the treatment of OCD. Previous research has also shown that individuals with ASD benefit less from standard cognitive behaviour therapy (CBT) compared to individuals without ASD. This means that little is known about how well CBT works for individuals with ASD and co-occurring OCD, and which adaptations are needed to improve the outcomes of CBT. Adapted CBT for individuals with OCD and ASD has been developed by researchers in the United Kingdom and has shown promising results in previous studies. In this study, 19 adults with OCD and ASD received adapted CBT at a specialist outpatient OCD clinic in Stockholm, Sweden. The treatment was partially effective: OCD symptoms decreased after treatment, but few participants were completely symptom free. The limitations of the study are, for example, that there was no measurement of therapist adherence to the treatment protocol, and that adapted CBT was not compared to another treatment. The need for further development and refinement of CBT for adults with OCD and ASD is discussed.

Figure-2-YBOCS

Full article citation: Flygare, O., Andersson, E., Ringberg, H., Hellstadius, A.-C., Edbacken, J., Enander, J., … Rück, C. (2019). Adapted cognitive behavior therapy for obsessive–compulsive disorder with co-occurring autism spectrum disorder: A clinical effectiveness study: Autism. https://doi.org/10.1177/1362361319856974

The future of psychiatry

Karolinska Institutet and Stockholm Psychiatry Lectures arranged the event The future of psychiatry yesterday, with lectures, discussions, and a poster session. A special guest at the event was Dr Joshua Gordon, the director of National Institute of Mental Health (NIMH) in the United States, which is the federal agency that funds research into mental health.

Ole Petter Ottersen – Sweden and Karolinska Institutet on the global arena

The first speaker was Ole Petter Ottersen, president of Karolinska Institutet. He mentioned how psychiatric disorders account for an increasing part of the global burden of disease. Sweden has a unique opportunity to advance research on psychiatric disorders, since the national registers and twin registry are well developed. He also pointed out that Karolinska Institutet needs a cohesive strategy for mental health across the university, as well as outreach to the public and important decision makers. Ottersen emphasised that Karolinska Institutet should strive to improve health not only in Sweden but also on a global level, because the challenge is global.

Nitya Jayaram-Lindström – Milestones achieved and future directions of CPF

Nitya Jayaram-Lindström is the head of Center for Psychiatry Research (CPF), the unit for clinical psychiatry research in Stockholm. She gave examples of the successful implementation of internet-delivered cognitive behavioural therapy, which is now offered both within child and adolescent psychiatry as well as adult psychiatry. Importantly, the interventions offered are evidence-based and have been evaluated in randomised controlled trials prior to implementation. Among the future directions for CPF and psychiatric research at large are efforts to prevent or intervene early, to broaden the scope of care (for example physical activity, adaptive treatment strategies in a stepped-care model), viewing psychiatric disorders through a life-span perspective, and combining research data with information on the lived experiences of individuals with mental illnesses.

Joshua Gordon – Challenges and opportunities in mental health research

Dr Joshua Gordon is the director of NIMH and was the keynote speaker of the event. He gave his view on the challenges and opportunities in mental health research.

Challenges

A longstanding challenge in psychiatry is the use of symptoms to classify mental illness. This means that overlap between diagnoses and high rates of comorbidity is the norm rather than the exception. Differences between conditions become vague and there is lots of variation within diagnoses as well.

Another issue is the lack of useful biomarkers in psychiatry. There are no biomarkers–a biological process that can be reliably observed and measured–that reliably give us prognostic, diagnostic, or predictive information for mental illnesses. There is a lot of research underway to try to identify biomarkers, but so far none have become useful in everyday clinical practice.

Dr Gordon also mentioned that our treatments fail to help a substantial minority of patients with mental illness. We have come a long way with psychological treatments such as cognitive behaviour therapy and pharmacological treatments such as antidepressant medications, but we still have a “one size fits all” approach that fails to help everyone.

Opportunities

Modern neuroscience has given us new tools to identify and control the neural circuits involved in mental illnesses, and Dr Gordon sees this as one of the major opportunities going forward. For example, we can use the new tools to find new clues about which processes in the brain are involved in mental illness. These processes are potential biomarkers and can be used to develop novel treatments.

The rapid development of research in psychiatric genetics also gives us pointers to brain regions and biological processes of interest.

Another opportunity comes from the field of computational psychiatry. The goal of computational psychiatry is to develop mathematical models of how the brain works. Using the increased computational power and new statistical techniques, we can make use of the information gained from brain scans and other assessments in new ways. For example, machine learning algorithms are able to detect patterns across many different types of data that would be hard or impossible for researchers to detect themselves.


After the presentations there was time for questions from the audience, as well as a poster session where members of CPF presented their research in three categories: clinical, translational, and epidemiology. There was also time to chat with friends and colleagues!

A visit to University of São Paulo, Brazil

Oskar and Christian in front of the Institute of Psychiatry

Christian and Oskar have just gotten back from a visit at University of São Paulo (USP) in Brazil. Our group is collaborating with researchers at USP to develop and test a Portuguese version of the OCD-NET internet-delivered cognitive behaviour therapy treatment.

Together with Professor Euripedes Constantino Miguel and Post-doc Alice de Mathis, we are working on a project to test OCD-NET in Brazil. The first step is to do a small feasibility study to see whether OCD-NET is a viable treatment option, and we have more projects planned together with the team at USP.

The University of São Paulo is the largest University in Brazil and enrolls over 90 000 students. The University also operates four hospitals in São Paulo, and we visited the department of psychiatry to work with Euripides and Alice, as well as meeting the rest of the flourishing OCD team.

Brazilians are known for their friendliness and hospitality, but we were still surprised of how welcoming our hosts were and how well they were taking care of us throughout the visit. We were shown some excellent restaurants and bars where we enjoyed the Brazilian cuisine, and found time to experience the pillars of Brazilian culture: Samba á la Carnaval and soccer! We are returning to Sweden with bags full of gifts, cameras full of pictures, and heads full of memories. Needless to say, we are looking forward to collaborate on the OCD-NET project and other research projects in the future.

Long-term outcomes after internet-delivered CBT for body dysmorphic disorder

Our lab has a new publication in BMJ Open where we look at two-year outcomes after internet-delivered CBT for body dysmorphic disorder (BDD-NET). The results were promising: we saw further improvements in BDD symptoms and 56% of participants no longer had BDD at the two-year follow-up.

A notable and perhaps surprising finding is that 29% of participants had a delayed response: they were not classified as treatment responders at post-treatment but were treatment responders at follow-up. We discuss this in the publication: “Perhaps participants continued to employ the techniques that they had acquired during the acute treatment phase in their daily lives, in part explaining the additional improvements seen in BDD symptoms during the follow-up.”

We conclude that BDD-NET is an effective treatment and that gains are sustained in the long term. However, since the follow-up was uncontrolled we cannot say that BDD-NET caused these improvements, and we also note that all participants were self-referred and motivated to do the treatment. The results are nonetheless encouraging and we will continue to evaluate BDD-NET as a treatment in different contexts.

Full citation: Enander, J., Ljótsson, B., Anderhell, L., Runeborg, M., Flygare, O., Cottman, O., … Rück, C. (2019). Long-term outcome of therapist-guided internet-based cognitive behavioural therapy for body dysmorphic disorder (BDD-NET): a naturalistic 2-year follow-up after a randomised controlled trial. BMJ Open9(1), e024307. https://doi.org/10.1136/bmjopen-2018-024307

Sudden gains in internet-delivered CBT for obsessive-compulsive disorder

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In our most recent paper, published in the Journal of Obsessive-Compulsive and Related Disorders, we investigate sudden gains in internet-based CBT for OCD. A sudden gain means a large improvement in symptoms between two therapy sessions (i.e. weeks in internet-based CBT), that is stable once the improvement has taken place. We used data from a previous trial where 128 participants received internet-based CBT.

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We found that 38% of the patients experienced a sudden gain. Sudden gainers showed significantly larger improvements on the clinician-administered Y-BOCS than non-sudden gainers at post-treatment (d = 1.11), as well as at 3-month (d = 1.06), 12-month (d = 0.88) and 24-month follow-up (d = 0.77). Sudden gainers also showed significantly less severe OCD symptoms than gradual gainers at post-treatment (d = 0.50), as well as 3-month (d = 0.55) and 12-month follow-up (d = 0.57). In addition, patients receiving DCS showed a significantly higher rate of sudden gains.

We conclude that sudden gains are common in ICBT for OCD and are associated with favourable short and long-term treatment outcomes. Sudden gains is something we will be investigating further in our other clinical trials for OCD and related disorders.

SweSRII 2018

 

Participants SweSRII 2018 Växjö Linnéuniversitetet
The participants of SweSRII 2018

The yearly conference for research on internet interventions took place in Växjö, att Linnaeus University, on 9th November. The meeting brought together researchers and practitioners from Sweden, Norway and Denmark to present and discuss recent developments and upcoming projects. The Rücklab team was represented by Oskar and Katja.

With a familial atmosphere and representation from both academia and health care, the conference provided a great opportunity to discuss common struggles and potential improvements of our treatment interventions. Some highlights of the programme include individually tailored treatments for patients with multiple psychiatric conditions, the use of emergent technologies like virtual reality to treat mental illness, and disseminating internet-delivered cognitive behavioural therapy in rural settings.

We had a great time and look forward to exchanging ideas and collaborating on project with our colleagues from all over Sweden and elsewhere. Next up is esrii 2019 in Copenhagen!

New study: Adapted CBT for adults with OCD and ASD

We have just released a pre-print1 where we describe an adapted cognitive behavior therapy for adults with obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD). You can find the full paper here.

OCD and ASD often co-occur but effective treatment options for this patient group are sorely lacking. We extended an adapted CBT protocol developed in the UK at our specialist clinic for OCD and related disorders (OCD-programmet).

Our results show that OCD-symptoms (both when rated by a clinician and by the participants themselves) decrease over the course of treatment, but that few participants were completely symptom free.

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Results on the main outcome: Yale-Brown Obsessive-compulsive Scale (YBOCS) rated by clinicians.

We discuss three ways to develop the treatment further: adding more support in between sessions to help participants do exposure exercises on their own, including interventions to help participants find meaningful daily activities, and intensifying the treatment over a shorter time span.

If you are interested in learning more, you can find the pre-print at the pre-print server PsyArXiv.


  1. A pre-print is a manuscript that has been read and approved by all authors but has not gone through peer-review yet. It’s a popular way to quickly disseminate results in fields like genetics, physics and mathematics. It is gaining popularity in other fields as well. Wikipedia article ↩︎

Internet-KBT för tvångssyndrom och dysmorfofobi i reguljär vård

Nu finns internet-KBT för tvångssyndrom (OCD) och dysmorfofobi (BDD) tillgängligt för vuxna personer i hela Sverige!

Vi har utvecklat och utvärderat dessa behandlingar i flera vetenskapliga studier sedan 2011 (OCD) respektive 2014 (BDD) och funnit att de fungerar bra vid båda tillstånden. Det slutgiltiga målet har alltid varit att fler patienter ska få tillgång till effektiv behandling och vi är stolta över att ha nått fram till den här punkten.

Lina Lundström är den person som varit projektledare för implementeringen i reguljär vård och det är tack vare hennes ihärdiga arbete som behandlingarna nu finns tillgängliga.

Instruktioner för egenanmälan till behandlingen

Boende i Stockholms län kan logga in via Vårdguidens e-tjänster för att anmäla sitt intresse för behandling.

World Congress of Psychiatry 2017

Lina, Diana, and Oskar traveled to Berlin for the World Congress of Psychiatry, arranged by the World Psychiatry Association. Lina presented the work we do in internet-delivered CBT treatments during a symposium on the frontiers of OCD research. We were also able to attend a multitude of presentations within the broad field of psychiatry.

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Some highlights from the conference:

  • Nasal oxytocin injections as a potential treatment for psychiatric problems
  • Genetic and epigenetic mechanisms underlying susceptibility to psychopathology (elegantly presented by Professor Michael Meaney of McGill University, Canada)
  • The future of cognitive behavioural therapies
  • Psychiatric needs of refugees
  • Using genetic data and artificial intelligence to predict treatment outcomes

Third wave of cognitive behavioural therapies

This symposium included short talks by Professor Emily Holmes, Professor Adrian Wells, Professor Paul Summergrad and Professor Fritz Hohagen.

A common theme in the discussion was to increase the theoretical rigor of our treatments by developing interventions that target specific mechanisms of change. Professor Holmes noted that there’s a wealth of research in basic science that can potentially inform what we do in the clinic. By identifying these mechanisms and translating them into clinical interventions, we will be able to improve our therapies and sharpen our clinical tools.

”Indeed, it’s a great challenge is to map therapeutic techniques to specific processes. First, we need to go back to models of causality of processes and mechanisms, and then devise therapeutic techniques to target specific processes.” – Adrian Wells

Mental health in Syrian refugees

The war and accompanying atrocities taking place in Syria has forced more than 5 million Syrians to flee the country. More than 600,000 of these refugees have ended up in Germany (150,000 in Sweden) so psychiatrists are now trying to understand the amount of psychological distress and the treatment options available.

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The experiences of war and oftentimes dangerous escape to Europe means these individuals are at increased risk of mental health problems. Stress, post-traumatic stress disorder, and depression are among the most common in a sample of 3000 refugees seen at a centre in Berlin.

However, the common theme of these presentations is resilience. Although Syrian refugees have witnessed and experienced things that are unimaginable to many Europeans, a majority of them recover and prosper without much psychiatric attention.