Effects of ECT on Monoamine Oxidase A in Depression Investigated With PET
Condition: Major Depression
MeSH terms: Depression; Depressive Disorder
Study type: Observational

Summary: 
      This study aims at evaluating the effect of electroconvulsive therapy in treatment-resistant
      depressed patients on the major serotonin degrading enzyme in the human brain using
      neuroimaging methods, the monoamine oxidase A. Electroconvulsive therapy is an effective
      treatment option in severe cases of depression. However, the mechanisms underlying its effect
      remain uncertain, though variations within the serotonergic neurotransmitter system seem to
      be crucially involved.
    

Detailed description: 
      In treatment-resistant depression, electroconvulsive therapy (ECT) has been shown to
      effectively reduce depressive symptoms; however, the underlying neurobiological mechanisms
      remain to be fully understood. Recent neuroimaging findings underline the involvement of the
      serotonergic system in the mechanism of action of ECT, but studies in this context mainly
      focused on serotonin receptor and the serotonin transporter. Here, the aim of the study is to
      assess the effects ECT on monoamine oxidase A (MAO-A), the main serotonin degrading enzyme
      which is known to be involved in antidepressant action, in humans using positron emission
      tomography (PET) and the radiotracer [11C]harmine. Moreover, as the antidepressant effects of
      electroconvulsive stimulations were shown to be partly mediated via changes in
      neuroplasticity, a secondary aim of the present study is to assess structural alterations
      caused by ECT using magnetic resonance imaging (sMRI).

      Based on the literature, the investigators expect higher baseline MAO-A distribution volumes
      (DVs) in depressed patients than compared to healthy subjects.Moreover, the investigators
      expect overall MAO-A distribution volume (DVs) changes in the brain of depressed patients
      following ECT according to the individual treatment-response. Similarly, the investigators
      assume that depressed patients will exhibit structural changes of grey matter volume
      following ECT.

      The investigation is designed as a longitudinal mono-centre study over a duration of 36
      months. 18 subjects with therapy-resistant, severe unipolar depression, aged between 18-60
      years and 18 age- and sex-matched healthy subjects will be included in the study. Patients
      will be recruited at the Department of Psychiatry and Psychotherapy, Medical University of
      Vienna, and will be offered inpatient care. Psychotropic medication (except for drugs
      directly binding MAO-A, e.g. moclobemid) of the patients is allowed if steady state has been
      reached > 10 days prior to inclusion. Healthy subject will be recruited using announcements
      of poster boards at the General Hospital of Vienna. Each patient will be measured three times
      using a GE Advance PET scanner and the radioligand [11C]harmine. The first and second
      measurements determine baseline changes in the MAO-A DVs while the third scan is used to
      quantify changes induced by ECT. Healthy subjects will be measured with PET only once.
      Similarly, patients will undergo three structural (T1-weighted) MRI sessions temporally
      coordinated to the PET scans. Healthy subjects will be measured with MRI only once.

      Each patient will be treated in 6 to 14 ECT sessions within a time interval of 2 to 5 weeks.
      A brief pulse ECT machine (Thymatron System IVTM) will be used three times per week to
      administer treatments either unilaterally over the right hemisphere or, if required,
      bilaterally.

      The MAO-A DVs will be determined using a region of interest and a whole brain voxel-wise
      approach. A repeated-measures analysis of variance (ANOVA) will compare the change in the
      MAO-A DVs before and after ECT (PET2-PET3) with the change between the baseline PET scans
      (PET1-PET2). Secondly, MAO-A DVs from PET1 will be compared to the scans of healthy subjects
      (cross-sectional part). Additionally, the correlation between treatment effects reflected in
      HAM-D score and changes in MAO-A DVs will be computed. Similar statistical analyses will be
      done with sMRI data.

      This study would be the first to demonstrate an effect of ECT on MAO-A DVs in humans in vivo.
      Given the involvement of the MAO-A in the pathophysiology of mood disorders, the present
      study would be an important step towards a better understanding of antidepressant treatment
      and treatment response. By comparing treatment effects and the underlying biological
      mechanism, the study might help to identify biomarkers that distinguish patients who are
      likely to benefit from ECT from patients who will rather be non-responders. Finally, by
      investigating the role of the MAO-A DVs in ECT, its highly discussed relevance for
      antidepressant action will be further elucidated and might prepare the ground for new
      therapeutic strategies. Additionally, this study might contribute in substantiating potential
      effects of ECT on brain structure.
    

Intervention name(s): Electroconvulsive therapy; Positron emission tomography of the brain using [11C]harmine; Structural magnetic resonance imaging
Intervention type(s): Device; Other; Other
Intervention MeSH terms: Harmine
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        18 patients with severe unipolar depression determined by a structured clinical interview
        for DSM-IV (SCID) and the 17-item Hamilton Rating Scale for Depression (HAM-D score ≥ 23)
        who did not respond to conventional pharmacological antidepressant treatment (at least two
        adequate trials with antidepressants of different pharmacological classes over a minimum
        period of one month, equivalent to 150mg of tricyclic antidepressants) will be recruited at
        the Department of Psychiatry and Psychotherapy at the General Hospital of Vienna.
        Additionally, 18 healthy age- and sex-matched controls will participate in this
        longitudinal study.