Cytokine polymorphisms in the pathophysiology of mood disorders.
BACKGROUND
An increasing amount of data suggests that dysregulation of the immune system, including the cytokine network, is associated with the etiology and pathophysiology of mood disorders. Genes encoding cytokines are highly polymorphic and single nucleotide polymorphisms, associated with increased or reduced cytokine production, have been described. The aim of this study was to define the genetic immunologic scenario associated with major depressive disorder (MDD) and bipolar disorder.


METHODS
Eighty-four Italian outpatients affected by bipolar disorder type I, bipolar disorder type II, or MDD, and 363 healthy controls were enrolled into the study. We analyzed allele and genotype distribution of -308 (G/A) tumor necrosis factor-a (TNF-a), +874 (T/A) interferon-g (IFN-g), -174 (G/C) interleukin (IL)-6, and -1082 (G/A) IL-10 promoter polymorphisms by Polymerase Chain Reaction Sequence Specific Primers technique.


RESULTS
We observed different genotype and allele distributions of TNF-a, IFN-g, and IL-10 polymorphisms in the three groups of patients analyzed. In particular, bipolar II patients were characterized by an absence of adenine (A) high producer allele of TNF-a (P<.001) and a lower percentage of TT high producer genotype of IFN-g (P<.001); bipolar I individuals showed reduced percentage of AA low producer genotype of IL-10 (P<.001). Both bipolar I and bipolar II patients not carrying guanine (G) high producer IL-6 allele showed a lower mean age at onset (P=.048).


CONCLUSIONS
These data support the existence of a genetic profile related to pro-inflammatory cytokines in patients affected by mood disorders. The differences observed across the three clinical phenotypes suggest the presence of different pathogenetic mechanisms involved in the susceptibility of phenotypically different mood disorders.
Clerici
Mario
M
Department of Biomedical Sciences and Technologies, University of Milan, Italy.
Arosio
Beatrice
B
Mundo
Emanuela
E
Cattaneo
Elisabetta
E
Pozzoli
Sara
S
Dell'osso
Bernardo
B
Vergani
Carlo
C
Trabattoni
Daria
D
Altamura
A Carlo
AC
D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D016207:Cytokines / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha