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24-05-2012 | Mental health | Article

Research supports nitrergic dysregulation in bipolar disorder


Free abstract

MedWire News: Results from a German study provide further evidence to suggest that nitric oxide (NO) signaling is impaired in patients with bipolar disorder.

Writing in Brain Research, Hendrik Bielau (University of Magdeburg) and colleagues explain that NO plays an important role in brain signaling and influences the balance of monoaminergic and glutamatergic neurotransmission.

They add: "The locus coeruleus (LC) comprises the largest group of norepinephrine-containing neurons in the mammalian brain [and] these norepinephrinergic LC neurons are able to generate NO."

However, they add that although alterations in NO signaling are thought to play a role in the pathophysiology of mood disorders, "to date, there has been no postmortem investigation of neuronal nitric oxide synthase (nNOS)-immunoreactive (ir) neurons in the LC in bipolar disorder."

To address this, the team studied postmortem LC samples collected from 10 patients with bipolar I disorder, eight with major depressive disorder (MDD), and 16 mentally healthy individuals.

Levels of nNOS-ir neurons were compared among the groups using immunohistochemical staining.

Analysis revealed nNOS-ir neuron numbers in bipolar disorder patients were reduced by a significant 34% and 17% in left and right LC hemispheres, respectively, compared with controls.

In MDD patients, there was a nonsignificant 20% reduction in nNOS-ir neuron numbers in the left hemisphere compared with controls.

Although no significant differences in nNOS-ir neuron density was detected among the groups, a trend toward lower density in bipolar disorder patients compared with controls was observed in the left LC.

There was a significant negative correlation between nNOS-ir neuron numbers and illness duration in both groups of mood disorder patients, but there was no correlation with medication use, age, gender, brain weight, or postmortem delay.

Bielau et al conclude: "These data provide further evidence for the dysregulation of the nitrergic system in mood disorders."

They add: "Future studies may clarify the potential role of glial cells in the context of the described nNOS deficit."

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

By Mark Cowen

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