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Natural polyamines (putrescine, spermidine and spermine) are low molecular weight highly protonated aliphatic molecules that physiologically modulate NMDA, AMPA/kainate glutamatergic receptors and limbic dopaminergic neurotransmission. Previous studies had demonstrated that polyamine metabolism might be disrupted in schizophrenia, what could potentially be linked to glutamatergic dysfunction. In particular, polyamine levels in blood and fibroblast cultures from patients with schizophrenia had previously been found to be higher than in healthy controls. Indeed, a significant positive correlation between blood polyamine levels and severity of illness may exist.
In order to test potential differences in blood polyamine levels between drug-free schizophrenia in-patients (n = 12), and healthy controls (n = 26, blood donors), spermidine (spd), spermine (spm), and spermidine/spermine index (spd/spm) were determined using HPLC after dansylation.
No significant differences were found between groups (t = 0,974; df = 36; P = 0,337 for spd, t = l0, 52; df = 36; P = 0,959 for Spm, and, t = 0, 662; df = 36; P = 0,512 for spd/spm).
Though we couldn’t replicate previous findings suggesting disturbances in blood polyamine levels in schizophrenia, this issue may be a promising target. Future research should take into account possible factors such as sex, nutritional state, and stress.
A growing interest in the potential role of polyamines in stress, mood disorders and suicidal behavior has recently emerged. In particular, the expression of polyamine's rate-limiting catabolic enzyme (SAT-1, Spermidine/spermine N1-acetyltransferase-1) may be reduced in ventral prefrontal cortex and posterior cyngulate gyrus of patients who committed suicide. However, there is some controversy regarding the involvement of potential cis-acting loci controlling SAT-1 gene expression (rs6526342 or rs17286006) in suicidal behavior. Moreover, a significant association between SAT-1 rs1960264 SNP and anxiety disorders has been found in a male caucasian spanish sample.
In order to test the potential association of SAT-1 -1415T/C SNP (rs1960264) with suicidal behavior, genotype frequencies for that SNP were compared between 193 suicidal attempters (126 female and 67 male) and 650 non-suicidal patients (314 female and 336 male) from an in-patient sample.
We could not find a significant difference in the distribution of the genotypes for rs1960264 SNP between suicide attempters versus non-suicidal individuals (Linear-by-Linear association X2 = 0,203; df = 1; P = 0,652, females; Linear-by-Linear association X2 = 0,000; df = 1; P = 0,990, males). Neither could we demonstrate a relationship between rs1960264 genotype and past history of suicidal attempts (Linear-by-Linear association X2 = 2,966 ; df = 1; P = 0,085, females; Linear-by-Linear association X2 = 1,171; df = 1; P = 0,279, males).
Although we did not find a link between rs1960264 genotype and suicidal behavior, SAT-1 may be an interesting target to investigate the biology of this phenotype. Future studies should take into account other genetic polymorphisms at SAT-1, and definitively evaluate whether or not rs6526342 and rs1960264 have any functional implications.
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