Effect of Quetiapine on Brain Activity Patterns in Patients With Heightened Risk of Bipolar Disorder

Cognitive Control and Functional Connectivity During Resting State in Patients With Heightened Risk of Bipolar Disorder - a Quetiapine Challenge

Bipolar disorder (BPD) is often misdiagnosed as unipolar depression. This leads to inadequate treatment and can have negative impact on the course of the disease. There is now preliminary evidence that patients with unipolar and bipolar depression as well as healthy individuals with a heightened risk of BPD can be distinguished from each other based on their brain activity patterns and functional connectivity during resting state.

However, the impact of pharmacological treatment on these functional brain measures have not yet been clarified. For common antidepressants it has been shown that they seem to normalise aberrant brain activity patterns and functional connectivity. The problem is that some antidepressants can induce mania or accelerate pathological cycling in depressive patients with unrecognised BPD. Therefore, pharmacological drugs with mood-stabilising properties such as quetiapine are more and more prescribed. Although the effectiveness and tolerability have been proven, the neuronal effects of these adjunctive treatments are not clear. The aim of the study is thus to investigate the impact of quetiapine on measures of brain activity in depressive patients with a heightened risk of BPD. Moreover, the investigators want to examine whether the investigators can distinguish depressive patients with a heightened risk of BPD from depressive patients without a heightened risk of BPD using neuroimaging techniques, and whether these measures can predict the course of the disease.

Inclusion Criteria:

• diagnosis of depressive episode (F32.X, F33.X) with duration less than < 6 months

• max. three previous episodes of illness

• no manic or hypomanic episodes in the past

• current treatment with one antidepressant

• MRI-compatibility

• unequivocal understanding of study information and autonomous consent

• for women: negative pregnancy test

• for risk-group:

  • 14 or more points on hypomania checklist (HCL-32)

  • additionally at least one of the following four risk factors:

    1. positive family history (i.e. first or second order relatives with BPD, schizoaffective or schizophrenic psychosis, mania or suicide attempt)
    2. initial manifestation before 30 years of age
    3. initial manifestation after childbirth
    4. suicide attempt in the past

Exclusion Criteria:

• additional diagnoses of psychiatric disorders (Organic, including symptomatic, mental disorders [F0X.X]; mental and behavioural disorders due to psychoactive substance use [F1X.X]; schizophrenia, schizotypal and delusional disorders [F2X.X]; mental retardation [F7X.X])

• chronic or acute physical disease

• individuals who are in a dependence- or work-relation with the sponsor

• limited or annulled legal capacity

• court or administrative order for hospitalisation

• for women: pregnancy, nursing period or unsafe contraceptive methods

• for the risk group:

  • clinical relevant changes in clinical chemistry, hematology, EEG or EKG
  • known contraindication for quetiapine (e.g. hypersensitivity to [active] ingredient[s], HIV-protease inhibitors, antimycotics, antibiotics)