Fluitman S

PhD Student
Section Psychopathology of developmental disorders
Department of Psychiatry

email s.fluitman@umcutrecht.nl

Supervisors
W.A.Nolen, C.Heijnen, C.C. Gispen-de Wied

Research area
The psychoneuroimmunology of depression

Project
Studying immunological and (neuro)endocrine parameters, in depressive patient, in relation to clinical response to treatment with antidepressants or placebo.

Summary
Different regulatory systems in the human body apear to play a role in the pathophysiology of depression, for example the neurotransmitter systems (i.e. the serotonergic and noradrenergic) and the neuroendocriene systems (especially the hypothalamus-pituitary-adrenal system).
Over the past 20 years more evidence is found linking the immune system to the pathophysiology of depression; signs of activation and inhibiton are found during depression.
In a placebo controlled pharmocological trial we are researching the following questions:

Are changes in severity of depression (i.e. changes in HDRS) over time (8 weeks) related to changes in basal HPA axis parameters (e.g. cortisol, CRH, ACTH and vasopressin levels in plasma) and/or changes in immune parameters (e.g. cytokines, cell activity and cell-numbers)?
What is the effect of the antidepressants mirtazapine and sertraline on these changes?
Are changes in severity of depression over time (8 weeks) related to changes in functional HPA-axis and/or immune parameters, as assessed by a psychological challenge test?
What is the effect of the antidepressants mirtazapine and sertraline on these changes?
Are the changes in HPA axis and immune parameters related to each other?

Inclusion criteria

• Male and female
• Age between 18 and 60 years, preferably <45
• Diagnosis: Major Depression, single or recurrent episode according to DSM IV criteria (296.2/296.3)
• Depression severity: Hamilton Depression Rating Scale (17 items) score of 16 or higher

Exclusion criteria

• Primary psychotic disorders (e.g. schizophrenia), Cluster A or B personality disorders, obsessive-compulsive disorders
• Suicide risk (i.e. Hamilton Depression Rating Scale item 3: ( 3 or earlier severe suicide attempts)
• Psychotic features
• Severe depression in need of immediate treatment up to the discretion of the clinician
• Pregnancy / not using adequate contraceptive measures or breast-feeding
• Acute or chronic infectious disease
• Autoimmune, neoplastic, or endocrine disease
• Myocardial infarction, or other major cardiovascular disorders in the last 6 months
• Use of immune system or HPA axis modulating medication in the last three months.(All used medications will be checked before inclusion whether they have immune system or HPA axis modulating effects, if so the patient will not be included in the study; for example corticosteroids, antihistaminics, oral contraceptives and immunosuppressants)
• Recent (within the last three months) surgery
• Known hypersensitivity to used antidepressant(s)
• Alcohol or drug abuse (within the last three months) according to DSM-IV criteria
• Alcohol or drug dependency (within the last six months) according to DSM-IV criteria
• Prior treatment with either mirtazapine 45 mg/d or sertraline 150 mg/d, in the current episode, for at least 4 weeks