Deep-down diagnosis

The facts of the (grey) matter

First up was Altered insular-prefrontal network in bipolar disorder¹ from the Karolina Institut and Gothenburg University in Sweden. This study delved into the underlying neuropathology of affective regulation in bipolar disorder, a subject which the authors hope will shed some light on the apparently-multifactorial causes of this episodic condition.

Prompted by a lack of single-centre large-scale trials, Ekman et al. have conducted what they believe to be the largest MRI-study of meticulously phenotyped patients with bipolar disorder to be conducted at one site. MRI-scans of 219 patients with confirmed bipolar disorder and 102 healthy controls were analysed for differentiation in relative volume of regions of affective regulation.

Compared to healthy controls, patients with bipolar disorder were found to have significantly smaller volumes of gray matter in the anterior insulae, right medial prefrontal cortex, left ventrolateral prefrontal cortex and posterior cingulate cortex. These are all areas implicated in either interception or emotional regulation, painting a picture of an individual with an unfortunate mix of dysfunctions. On the one hand, their ability to connect with their feelings could be reduced, leading to a muted anhedonia-like state. However, when these feelings reached a certain level of intensity they would also be unable to restrain them, flipping their state into one of overstimulation. Work of this type, linking the physical systems of the brain to their behavioural outcomes is not only extremely insightful; if corroborated, it could represent another tool for early identification of bipolar disorder.

Bipolar spectrometry

Early identification was also the theme of my second poster Identification and semi-quantification of potential biomarkers for bipolar disorder with a novel mass spectrometric methodology², also from Gothenburg University. Though constituted of a much smaller patient population than the first Gothenburg University poster, what this study lacked in numbers, it more than made up for in scope.

Author Jessica Holmén Larsson and colleagues used an innovative technique combining high-resolution liquid chromatography-mass spectrometry (LC-MS) with Tandem Mass Tag (TMT) labeling to conduct a differential analysis of the proteins present in the CSF of 15 bipolar patients vs. 15 healthy controls.

From this small population, the group identified a list of 37 proteins, implicated in functions from cell-cell adhesion to lipid transport, which are present in significantly different concentrations in bipolar patients vs. healthy individuals

A few notable proteins, less present in bipolar patients, included cadherin 13, neuronal pentraxin receptor, voltage-dependent calcium channel subunit alpha-2/delta-1, SLIT- and NTRK-like protein 1, ly-6/neurotoxin-like protein and chromogranin A. These proteins, previously implicated in neuropsychiatric disorders were, said Dr Holmén Larsson, promising targets for further investigation into their viability as biomarkers for bipolar disorder.

She said she hoped this kind of wide-scale proteomic analysis, common in many other conditions such as cancers or Alzheimers disease, would enable a bigger-picture view of bipolar disorder. Dr Holmén Larsson added that, having proved the new technique within the current study, she was looking forward to large-scale trials aimed at forming a more focussed list of marker proteins.

In summary, two different avenues to early identification of bipolar disorder which, together or separately, offer this correspondent great hope for the future treatment of this condition. Not a bad way to end my ECNP 2014 experience.

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