Wednesday, June 10, 2015

Brain Default Network in Psychotic Bipolar Disorder

BrainPosts: In a previous post I reviewed a summary of research related to genetics and improved diagnosis in bipolar disorder. One key point in this review was a highlight of the promise for integrating genetic with imaging research in bipolar disorder and other neuropsychiatric disorders. An example of this type of integrated research has been recently published in PNAS by a group of Yale University, the University of New Mexico and the University of Texas Southwestern Medical Center. This study used functional magnetic resonance imaging (fMRI) default mode network (DMN) across a group of subjects with psychotic bipolar disorder, schizophrenia and healthy controls. Additionally, study included imaging a group of unaffected relatives of the psychotic bipolar subjects and schizophrenia.

Subjects also had genetic analyses available for comparison with any imaging results that would emerge in the study.
The research team identified three circuit components in the DMN. The included the networks below (also identified by color as highlighted in group name): Anterior DMN--Medial prefrontal cortex-anterior cingulate caudate DMN Inferior posterior DMN--posterior cingulate caudate, inferior parietal lobule, middle temporal gyrus, cuneus/pre-cuneus Superior posterior DMN--cuneus/pre-cuneus, inferior parietal lobule, cingulate
The key findings from the study include the following:

  • Measures of hypoconnectivity in all three networks were identified in the psychotic bipolar and schizophrenia groups compared to controls.
  • Unaffected psychotic bipolar disorder relatives had normal DMN measures in the three networks while the unaffected schizophrenic relatives showed hypoconnectivity in on one of the three networks.
  • Genetic analysis revealed five genetic links to a brain connectivity sub-DMNs.
  • Genes identified in this brain mapping linkage had previously been linked to psychosis and mood disorders

The five genetic clusters identified in this study were related to specific brain developmental and neuronal processes:

  • NMDA long-term potentiation
  • Protein kinase A regulation
  • Immune response signaling
  • Guidance of axonal development
  • Synaptogenesis

The authors note an important advance in their study is the ability to

"dissect the underlying biological/molecular pathways and processes that might mediate genetic risk of psychosis via a valuable, noninvasive imaging marker."
Default mode network imaging and analysis is advancing as a promising research and clinical tool. It holds the promise of improving diagnostic accuracy and potentially improvement in targeting best treatment interventions for many brain disorders.

Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link below.

Image of the cingulate fiber connectivity anatomy is an iPad screen shot from the app Brain Tutor.