Wednesday, June 12, 2013

Brain Imaging for Diagnosis of Mood Disorders

Brain imaging holds promise for improving the accuracy of diagnosis in brain disorders falling under the psychiatric domain.

No reliable and valid brain imaging techniques currently exist for the diagnosis of depression or bipolar disorder.  However, research progress has been rapid.

Jonathan Savitz from the Laureate Institute for Brain Research and colleagues at Harvard University and Johnson and Johnson Research and Development recently summarized the current state of knowledge in brain imaging for the diagnosis of mood disorders.

Savitz participated in an American Psychiatric Association Consensus group that worked on a consensus document on this topic.  The current paper addresses some of the elements of this effort.

Following an introduction the topic, the manuscript reviews the importance of biomarker definition, validation and qualification of this topic.  Key points in this area include:

  • NIH definition of a biomarker: "A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic response to a therapeutic intervention".
  • US FDA and European Medicines Agency definition of types of biomarkers that can be applied to drug development: prognostic biomarkers, predictive biomarkers, pharmacodynamic biomarkers and surrogate end point biomarkers
  • It is important to distinguish between the validation and qualification in determining the utility of a biomarker
  • Validation refers to the reliability, sensitivity and specificity of a measurement in the targeted biological construct
  • Qualification refers to the approval of  a biomarker that "refers to the establishment of a credibility of a biomarker in its application to questions specifically relevant to drug development".
Savitz summarizes some of what is known about brain imaging research in mood disorders that may be promising targets for biomarkers, diagnostic assessment and response to treatment:
  • Brain gray matter volume reductions: major depression and risk for major depression appear to be linked to gray matter reductions in multiple brain regions including the hippocampus, anterior cingulate cortex, prefrontal cortex, hypothalamus, pallidum and habenula
  • Brain white matter abnormalities: late onset depression appears linked to white matter hyperintensities suggesting a vascular pathology, both major depression and bipolar disorder subjects show white matter diffusion tensor imaging changes suggestive of structure integrity pathology
  • In vivo neuroreceptor abnormalities: Positron imaging technology (PET) imaging studies show reduction in postsynaptic serotonin 1A receptor function in the temporal cortex of both major depression and bipolar depression subjects
  • Functional MRI response to tasks: A study of fMRI hemodynamic response to sad faces produced a test with 82% sensitivity and 89% specificity to classify subjects as depressed or non-depressed
  • Response to pharmacological treatment: A study using machine learning techniques and voxel-based morphology was able to predict response to fluoxetine in depression with a sensitivity of 89% and a specificity of 89%

In the conclusion section of the manuscript, the authors note using brain imaging in the diagnosis of mood disorders may be hampered by the limitations of the current classification approach.  They note, research advances in this area may be quickened through use of the NIMH Research Domain.  This effort seeks to improve the future of neuroscience nosology (classification) using constructs (such as response to reward attainment)  known to be linked to underlying neurobiology.

Despite significant challenges, I see significant progress in biomarker research in the mood disorders.  I think the current approach will ultimately lead to useful clinical tools in diagnosis, treatment selection and treatment research.  Dr. Savitz and colleagues have done an excellent job in summarizing the current state of knowledge on this topic and interested readers are directed to the free full-text manuscript that can be accessed by clicking on the link below.

Disclosure:  I have been employed as a research psychiatrist at the Laureate Institute for Brain Research.

Photo of naso tang is from the author's files and was taken at the Oklahoma Aquarium.

Savitz JB, Rauch SL, & Drevets WC (2013). Clinical application of brain imaging for the diagnosis of mood disorders: the current state of play. Molecular psychiatry, 18 (5), 528-39 PMID: 23546169

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