Mikael Landén research group

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Multidisciplinary clinical psychiatry

The S:t Göran project is a prospective study of patients with manic depressive illness and/or attention deficit disorder (ADD/ADHD). It studies the natural course of these disorders and how it relates to brain imaging, neurochemistry, blood chemistry, genetics, and neuropsychological testing. The goal is to identify predictive factors for long term outcome and thereby improve the prognosis for people with these disorders.

We are also interested in the role of sex hormones for psychiatric illness. Hence, we study psychiatric morbidity, personality, and cognitive function in women with polycystic ovaries (PCOS). PCOS serves as a model of increased levels of male sex hormones in women.

In another project we study the outcome after sex reassignment in transsexual people. We have found increased mortality and morbidity after sex reassignment which warrants improved follow-up after such surgery in order to improve the prognosis.

Finally, we are interested in psychiatric rating scales and have a project evaluating CGAS (Children’s global assessment scale). We have shown that the results in clinical trials (efficacy trials) differ from the results in the real world clinical settings (effectiveness trials).

Research group leader

Senior researcher

Mikael Landén

Phone: 08-524 860 56
Organizational unit: Department of Medical Epidemiology and Biostatistics (MEB), C8
E-mail: Mikael.Landen@ki.se

Research Projects

St. Göran project

An interdisciplinary prospective, longitudinal study of bipolar disorder and ADHD

Bipolar disorder (manic-depressive illness) and attention deficit disorders (ADD and ADHD) are psychiatric disorders that differ in both manifestation and prognosis. This makes it difficult to tailor treatment and rehabilitation and to identify the causes of the illness. Using several different assessment tools, patients in the St. Göran Project are comprehensively examined and then followed over time. This allows for the identification of clinically important subgroups and predictive factors, and it presents unique opportunities for illustrating underlying mechanisms leading to illness.

The short-term aim of this project is to study the pathophysiology of bipolar disorder and attention deficit disorders. The long-term goal is to identify influenceable predictive factors for relapses, treatment responses, side effects, cognitive and psychosocial function, as well as quality of life in these disorders. 

Flow chart life time

The figure above illustrates the flow of actions where patients with bipolar disorder undergo diagnostic, neuropsychological, and neuropsychiatric examinations as well as an MRI of the brain and analysis of cerebrospinal fluid. For genetic analyses, and to insure the future of the study, whole blood, serum, and cerebrospinal fluid are stored in the Karolinska Institutets biobank.

Download Flow chart life time bipolar 

This project includes patients who, after careful clinical diagnostics, are found to suffer from bipolar disorder or ADHD and who agree to participate. Today, patients are recruited from the Affective Center at Northern Stockholm Psychiatry and, as of the spring of 2009, from the Affective Unit in Mölndal. From the study's inception in October, 2005, we have included appr. 360 patients in the project. Age- and sex-matched controls are recruited from a random selection of a population-based cohort in the same catchment area.

Follow-up is carried out annually following the quality registry BipoläR (http://www.psykiatriregister.se/), yet with added outcome variables. At 7 and 12 years post baseline, the MRI and the neuropsychological testing are repeated. The goal is to follow the patient för life. 

If you have questions or would like to know more, please contact 

Johanna Olofsson, Research Nurse

Tel: 072-236 93 15

E-post: johanna.olofsson@sll.se

 Lena Lundberg, Research Nurse

Tel: 070- 73 74 006

E-post: lena.m.lundberg@sll.se 

 Haydeh Olofsson, PhD, Project Manager

Phone: +46-70 00 11 090

E-mail: haydeh.olofsson@sll.se 

 Professor Mikael Landén

E-mail: Mikael.Landen@ki.se


On the Children’s Global Assessment Scale (CGAS)

This project evaluates the usefulness of a widely used rating scale, the Children’s Global Assessment Scale (CGAS), which is designed to measure how a child functions in daily life.  Two training methods (seminar and CD-ROM) were developed and evaluated for usage of CGAS among clinicians in child psychiatry care.

We have also studied the effectiveness of child psychiatric outpatient treatment as measured by changes in CGAS ratings, and have identified predictive factors for CGAS change.

Our last study investigates if CGAS ratings adds useful prognostic information, and therefore has the potential to facilitate a more prudent use of healthcare resources, ultimately leading to prevention of later suffering and helping the most vulnerable.


The Significance of ADHD in Bipolar Disorder

We have found that individuals with bipolar disorder comorbid with attention-deficit hyperactivity disorder (ADHD) have a different life course than bipolar patients without ADHD. We have published these results in the article:

A history of childhood attention-deficit hyperactivity disorder (ADHD) impacts clinical outcome in adult bipolar patients regardless of current ADHD.
Rydén E, Thase M, Stråht D, Aberg-Wistedt A, Bejerot S, Landén M
Acta Psychiatr Scand 2009 Sep;120(3):239-46

We argue that this course is so different in individuals with comorbid ADHD that there is reason to speak of a distinct bipolar subgroup which might require another form of treatment than is usually offered for bipolar disorder. When we compare bipolar individuals with and without ADHD, we find that those with ADHD have lower levels of dopamine and serotonin metabolites in their cerebrospinal fluid. This provides biological support for bipolar disease with comorbid ADHD constituting a specific subgroup. These results have been published in the article:

Lower CSF HVA and 5-HIAA in bipolar disorder type 1 with a history of childhood ADHD.
Rydén E, Johansson C, Blennow K, Landén M
J Neural Transm (Vienna) 2009 Dec;116(12):1667-74

Eleonore Rydén has written a dissertation which summarizes studies covering the significance of ADHD in bipolar disorder.

Attention-deficit hyperactivity disorder in bipolar disorder

Scanning Electron Microscopy (SEM) of the Structures in Cerebrospinal Fluid (CSF) in Bipolar Disorder

We have found that many patients with bipolar disorder have microscopic structures in their cerebrospinal fluid (CSF). These structures in the CSF have not been previously described in bipolar disease. Hypothetically, the amount of SEM structures in the CSF can correlate to the degree of the ongoing disease process in the central nervous system in patients with bipolar disease.

Micrometer-sized thread-like and/or spherical particles in the first fraction of cerebrospinal fluid in patients with bipolar disorder.
Båve U, Nybom R, Landén M, Wetterberg L
Bipolar Disord 2010 May;12(3):298-305

The Immune System in Bipolar Disorder

In cooperation with the Department of pharmacology at Karolinska Institutet, Sara Olsson et al. found elevated levels of the neuroactive tryptophan metabolite KYNA and IL-1beta in the cerebrospinal fluid from bipolar patients, compared to controls.

Elevated levels of kynurenic acid in the cerebrospinal fluid of patients with bipolar disorder.
Olsson S, Samuelsson M, Saetre P, Lindström L, Jönsson E, Nordin C, et al
J Psychiatry Neurosci 2010 May;35(3):195-9

Elevation of cerebrospinal fluid interleukin-1ß in bipolar disorder.
Söderlund J, Olsson S, Samuelsson M, Walther-Jallow L, Johansson C, Erhardt S, et al
J Psychiatry Neurosci 2011 Mar;36(2):114-8

Using voxel-based morphometry to analyse images from magnetic resonance scans of the brain, we found that manic episodes are related to grey matter changes.

Manic episodes are associated with grey matter volume reduction - a voxel-based morphometry brain analysis.
Ekman C, Lind J, Rydén E, Ingvar M, Landén M
Acta Psychiatr Scand 2010 Dec;122(6):507-15

Sex steroids in Bipolar Disorder

Anette Johansson has in her thesis investigated the involvement of sex steroids in mediating risk to particular phenotypes of presentation of Bipolar disorder.

Sex Steroids and Gene Variants in Bipolar Disorder

Selected publications

An analysis of all applications for sex reassignment surgery in Sweden, 1960-2010: prevalence, incidence, and regrets.
Dhejne C, Öberg K, Arver S, Landén M
Arch Sex Behav 2014 Nov;43(8):1535-45

Elevated concentrations of neurofilament light chain in the cerebrospinal fluid of bipolar disorder patients.
Jakobsson J, Bjerke M, Ekman C, Sellgren C, Johansson A, Zetterberg H, et al
Neuropsychopharmacology 2014 Sep;39(10):2349-56

Subcortical morphometry and psychomotor function in euthymic bipolar disorder with a history of psychosis.
Liberg B, Ekman C, Sellgren C, Johansson A, Landén M
Brain Imaging Behav 2015 Jun;9(2):333-41

The societal cost of bipolar disorder in Sweden.
Ekman M, Granström O, Omérov S, Jacob J, Landén M
Soc Psychiatry Psychiatr Epidemiol 2013 Oct;48(10):1601-10

Manic episodes are associated with grey matter volume reduction - a voxel-based morphometry brain analysis.
Ekman C, Lind J, Rydén E, Ingvar M, Landén M
Acta Psychiatr Scand 2010 Dec;122(6):507-15

Group members

Anna Wistedt ÅbergAssociated
Bo JonssonAssociated
Cecilia Dhejne HelmyGraduate Student
Haydeh OlofssonAssociated
Lennart WetterbergAssociated
Mattias MånssonGraduate Student
Mikael LandénAssociated, Research team leader
Olle LidmanAssociated


Information regarding other projects within the research group is available at CIBRIS homepage.