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J Affect Disord. 2013 Oct;151(1):405-8. doi: 10.1016/j.jad.2013.06.042. Epub 2013 Jul 12.

Minor hemoglobins HbA2 and HbF associate with disease severity in bipolar disorder with a likely protective role of HbA2 against post-partum episodes.

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  • 1Department of Psychiatry, Sanliurfa Research and Training Hospital Sanliurfa, Turkey.



There exist studies indicating that bipolar disorder (BD) associates with changes in brain blood flow. Human brain with its high demand to oxygen constitutes 2% of the total body weight, while it receives 20% of cardiac output. α and β globin chains of hemoglobin were recently found in neural tissues, yet no study has questioned blood hemoglobins in BD.


A total of 120 euthymic BD patients (40 males and 80 females) were analyzed via high performance liquid chromatography (HPLC) to measure minor hemoglobin levels, which were statistically compared with disease characteristics.


Minor hemoglobins HbA2 and HbF associated positively with episode density as a measure of disease severity in BD. An increased level of HbA2 meant significantly less postpartum episodes in child bearing women. HbF levels were higher in patients with a positive family history of any psychotic disorder. Sum of HbA2 and HbF correlated with episode density with a stronger significance (p<0.001) supporting intermittent hypoxia hypothesis in BD.


The study was conducted only on euthymic patients to avoid likely bigger exogenous effects such as electro-convulsive therapy and diverse drug regimes, yet larger comparative studies are needed to support our current findings.


Higher HbA2 and HbF in more severe bipolar disorder may be compensations against intermittent hypoxias in BD. HbA2 increases following myocardial angina and in mountain dwellers, which may indicate protective roles in extreme conditions. HbF increase may act more as a maladaptation or emerge via haplotypal associations of BD genes and gamma-globin locus at 11p15.5.

© 2013 Elsevier B.V. All rights reserved.


Bipolar disorder; Episode density; Fetal hemoglobin; Hemoglobin A2; Intermittent hypoxia; Postpartum episode

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