Short project description

The project Brain connectivity in major depression’ in part of a larger project ‘Functional markers of cognitive disorders’ in which five Dutch University Medical Centers and Philips are involved.

The major research aim of the project is to investigate both functional (resting state fMRI) and structural connectivity (Diffusion Tensor Imaging (DTI)) in healthy volunteers (n=40), healthy volunteers with a family history of depression (n=40) and patients suffering from major depression (n=40). Additional research questions: 1) are low mood and impaired cognition related to brain connectivity in depressed patients, and 2) does brain connectivity change after successful treatment.

In order to qualify for a PhD position the candidate must have successfully completed a Master degree in Cognitive Neuroscience, Neuropsychology, Clinical Psychology or a related topic. Candidates should be interested in functional MRI research and psychiatric disorders. For this project it is important that the candidate has good social skills. The project is due to start on September 1, 2010.

Temporary employment for 4 years.

Your salary would be € 2.042,-- gross per month in the first year up to € 2.612,-- gross per month in the fourth year according to the PhD-student salary scale.
Each year an evaluation will take place.

The terms of employment of Maastricht University are set out in the Collective Labour Agreement of Dutch Universities (CAO). Furthermore, local UM provisions also apply. For more information look at the website http://www.maastrichtuniversity.nl/, A-Z Terms of Employment.

Maastricht University is renowned for its unique, innovative, problem-based learning system, which is characterized by a small-scale and student-oriented approach. Research at UM is characterized by a multidisciplinary and thematic approach, and is concentrated in research institutes and schools. Maastricht University has around 14,000 students and 3,500 employees. Reflecting the university's strong international profile, a fair amount of both students and staff are from abroad. The university hosts 6 faculties: Faculty of Health, Medicine and Life Sciences, Faculty of Law, School of Business and Economics, Faculty of Humanities and Sciences, Faculty of Arts and Social Sciences, Faculty of Psychology and Neuroscience.

Neuropsychology and Psychopharmacology

The department of Neuropsychology and Psychopharmacology (NP&PP) consists of two sections: Neuropsychology (NP) and Psychopharmacology (PP). Research and education in these sections is dedicated to the scientific investigation of brain-behaviour relationships. NP focuses on neurocognitive development, ageing and brain injury in a lifespan perspective as well as the underlying contributions of biological and psychosocial factors. PP assesses biological mechanisms that underlie cognitive, affective and behavioural functions by means of controlled pharmacological interventions.

The sections collaborate in many fields of research and education. For example, NP&PP runs three master's programmes (i.e. Neuropsychology, research master's Neuropsychology and research master's Fundamental Neuroscience) to which members of both sections equally contribute. In addition, research projects often integrate expertise from both sections in order to achieve maximal research quality. Staff members of NP&PP also participate in the European Graduate School of Neuroscience (EURON) to stimulate interfaculty research and education.

Additional information
For more information: dr. Lisbeth Evers, tel: +31-43-3884268, e-mail: lisbeth.evers@maastrichtuniversity.nl.

Brain connectivity in major depression

Research team
Dr. E.A.T. Evers, dr. P. Stiers, and prof. dr. J.G. Ramaekers
Department of Neuropsychology and Psychopharmacology,
Faculty of Psychology and Neuroscience (FPN), UM.

Prof. dr. M. Huibers
Department of Clinical Psychological Science
Faculty of Psychology and Neuroscience (FPN), UM.

Dr. F. Peeters MD,
Department of Psychiatry and Neuropsychology,
Faculty of Health, Medicine, and Life sciences (FHML), UM.

Introduction

Major depression is a life threatening psychiatric disease that has a high prevalence in western countries. It strongly reduces the quality of life of patients and their family members and places a high economic burden on society. To be able to identify individuals at risk for depression, to improve diagnosis and to increase to success rates of treatment, it is important to increase our knowledge about what goes wrong in the brain. The goal of the present study is to investigate abnormalities in brain connectivity in depressed patients in a state of resting.

            Major depression is characterized by persistent, pervasive feelings of sadness, guilt, and worthlessness. This baseline state has triggered a wealth of resting state studies. The majority of these studies have used positron emission tomography (PET) or single photon computed tomography (SPECT) to study brain functioning. It was shown that patients suffering from major depression show decreased brain activation in prefrontal cortex (PFC) regions, implicated in cognition, and increased activation in the regions involved in emotion processing (e.g. Mayberg et al. 2003; Drevets, 2000).

            The neuroimaging methods PET and SPECT have significant limitations, such as the use of radioactive tracers, which might be overcome by using non-invasive functional Magnetic Resonance Imaging (fMRI). Furthermore, since decreased or increased activation in a brain region could be the results of changes in neuronal input from other regions, it is important to investigate the connectivity between brain regions. Newly developed fMRI methods that assess low frequency fluctuations in the blood oxygen level dependent (BOLD) response allow the investigation of the functional connectivity between brain regions (Biswal et al. 1995).

            In the present study, 40 depressed patients and 40 age and gender matched healthy controls will participate. Resting state functional connectivity within the default mode and the central executive network and functional connectivity between regions with abnormal activation patterns and the rest of the brain will be studied. To detect changes in anatomical connectivity, we will use diffusion tensor imaging (DTI) to assess the integrity of white matter tracts.

             Interestingly, Anand et al. (2005) showed that antidepressant treatment did not normalize the decreased connectivity between limbic and cortical regions. It has therefore been suggested that the changes in brain functioning found in depressed patients are not merely structural correlate of depressive ‘state’, but of a depressive trait. This suggests that also people that have a genetic vulnerability to develop depression might have abnormal pattern of brain connectivity. To investigate this, a group of 40 healthy controls with a first degree relative with major depression will be added to the study.

 Research questions

1. What differences do exist in functional connectivity between patients with unipolar depression and healthy controls?
2. Can changes in functional connectivity be used as neurobiological marker for depression?
3. Do changes in anatomical connectivity underlie these changes in functional connectivity?
4. Is the severity of the depression and the amount of cognitive impairment related to changes in functional/anatomical connectivity?
5. Do healthy controls with an increased risk to develop depression, also show the changes in functional/anatomical connectivity that are found in depressed patients?
6. How does connectivity change after treatment?

 Study design

The research questions 1 till 5 will be answered with a between-subject design: functional and anatomical connectivity in three groups of participants: 1) depressed patients, 2) healthy volunteers with a genetic predisposition for depression, and 3) healthy controls. To answer research question 6 the group of depressed patients will be tested also after treatment (within-subject design). Their first test session will take place in the week before they start treatment and the second test session will be planned 9 months later.

A test session will consist of 1) MRI scanning, including preparatory localizer scans, a standard structural T1-weighted gradient echo scan, cognitive fMRI task, DTI scans, and resting state scans, 2) performing behavioral tasks outside the scanner and 3) completing mood questionnaires.

Relevant literature

Anand A, Li Y, Wang Y, Wu J, Gao S, Bukhari L, Mathews VP, Kalnin A, Lowe MJ. (2005). Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study. Neuropsychopharmacology. 30(7):1334-44.

Anand A, Li Y, Wang Y, Wu J, Gao S, Bukhari L, Mathews VP, Kalnin A, Lowe MJ. (2005). Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study. Biol Psychiatry. 57(10):1079-88.

Biswal B, Yetkin FZ, Haughton VM, Hyde JS. (1995). Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 34(4):537-41.

Drevets WC (2000). Neuroimaging studies of mood disorders. Biol Psychiatry 48: 813–829.

Greicius MD, Flores BH, Menon V, Glover GH, Solvason HB, Kenna H, Reiss AL, Schatzberg AF. (2007). Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry. 62(5):429-37.

Mayberg HS (2003). Positron emission tomography imaging in depression: a neural systems perspective.Neuroimaging Clin N Am, 13(4):805-15. Review.

Damoiseaux JS, Rombouts SA, Barkhof F, Scheltens P, Stam CJ, Smith SM, Beckmann CF. (2006). Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci U S A. 103(37):13848-53.