Polymorphisms in the galanin gene are associated with symptom-severity in female patients suffering from panic disorder.
BACKGROUND
Galanin (GAL) is a neuropeptide, which is expressed primarily in limbic nuclei in the brain and mediates miscellaneous physiological processes and behaviors. In animal studies, both the application of GAL and antagonism of its receptors have been shown to affect anxiety-like and depression-related behavior. In humans, intravenous administration of the neuropeptide galanin has been reported to have fast antidepressant efficacy. Furthermore, GAL is involved in hypothalamic-hypophysiotropic signalling and cosecreted with luteinizing hormone-releasing hormone (LHRH), possibly acting as a mediator of estrogen action.


METHODS
In this study six single nucleotide polymorphisms (SNPs) within the gene coding for GAL were analyzed for possible associations with diagnosis and severity of symptoms in 121 male and female patients suffering from panic disorder (PD).


RESULTS
Our results suggest an association between genetic variations in the GAL-gene and severity of PD-symptoms in female patients. The most pronounced effects could be observed for two haplotypes containing the closely linked, non-protein-coding SNPs rs948854 and rs4432027. Both polymorphisms are located within CpG-dinucleotides in the promoter region of GAL and thus might be involved in epigenetic regulation of the GAL-gene.


CONCLUSIONS
A relatively small patient sample was analyzed in this study, the herein presented results need to be validated in independent studies.


CONCLUSIONS
The results of this study underline the potential of further genetic research concerning GAL and a possible role of this neuropeptide in the pathogenesis of female PD. In this regard, GAL and its receptors appear to be a promising target for pharmacological therapy of anxiety and affective disorders.
Unschuld
Paul G
PG
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 München, Germany. unschuld@mpipsykl.mpg.de
Ising
Marcus
M
Erhardt
Angelika
A
Lucae
Susanne
S
Kohli
Martin
M
Kloiber
Stefan
S
Salyakina
Daria
D
Thoeringer
Christoph K
CK
Kern
Nikola
N
Lieb
Roselind
R
Uhr
Manfred
M
Binder
Elisabeth B
EB
Müller-Myhsok
Bertram
B
Holsboer
Florian
F
Keck
Martin E
ME
D000328:Adult; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D019004:Galanin / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000502:physiology
C056567:GAL protein, human; D007987:Gonadotropin-Releasing Hormone; D019004:Galanin