Microcytic Anaemia as Susceptibility Factors in Bipolar Spectrum Disorders: Review of the Literature, Replication Survey, and Co-Segregation within Families

Alberto Bocchetta1, 2, *, Caterina Chillotti2, Raffaella Ardau2, Maria Carla Sollaino3
1 Department of Biomedical Sciences, Section of Clinical Pharmacology, University of Cagliari, Via Ospedale 46, 09124 Cagliari, Italy
2 Unit of Clinical Pharmacology, Cagliari University Hospital, Cagliari, Italy
3 Ospedale Microcitemico “Antonio Cao” –Azienda di Rilievo Nazionale ed Alta Specializzazione”GiuseppeBrotzu”, Cagliari, Italy

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© 2021 Bocchetta et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: ( This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Biomedical Sciences, Section of Clinical Pharmacology, University of Cagliari, Via Ospedale 46, 09124 Cagliari, Italy; Tel: +39 070 6092321; E-mail:



Potential interactions between mood disorders and microcytic anaemias have been suggested by case reports, surveys of haematological parameters in psychiatric populations, and surveys of psychiatric morbidity in thalassaemic carriers.


a) To review published studies.

b) To study the prevalence of microcytic anaemia in a sample of Sardinian outpatients with recurrent mood disorders.

c) To check whether mood disorders and microcytic anaemia co-segregate within families.


We extracted data on blood count and serum iron concentrations from the records of patients admitted between January 1st, 2001 and December 31st, 2016, to our clinic for mood disorders. Moreover, we studied siblings of subjects with both major mood disorders (according to Research Diagnostic Criteria) and heterozygous thalassaemia (according to Mean Corpuscular Volume, serum iron, and haemoglobin A2 concentrations). Siblings affected with a major mood disorder were examined for haematological concordance with the proband (reduced MCV and/or increased HbA2 in case of heterozygous β-thalassaemia, or presence of gene deletions in case of α-thalassaemia).


Microcytic anaemia was highly prevalent (81/337 = 24.0%) among outpatients with mood disorders. Starting from 30 probands with heterozygous ß-thalassaemia, concordance for reduced MCV and/or increased HbA2 was found in 78% (35/45) of affected siblings. Starting from 3 probands with heterozygous α-thalassaemia, only one of the 5 affected siblings carried four α-globin functional genes.


Based on the review of the literature, the high prevalence of microcytic anaemia in outpatients, and the concordance between affected siblings, we can conclude that a role of heterozygous thalassaemias is highly probable. Future studies are required to establish the relevance of heterozygous thalassaemias and evaluate the magnitude of the effect, possibly using a molecular diagnosis also in the case of heterozygous β-thalassaemia.

Keywords: Alpha-thalassemia, Anemia, Beta-thalassemia, Blood cell count, Erythrocyte indices, Hemoglobin A2, Mood disorders.