Association of Serotonin Transporter Promoter Gene Polymorphism (5-HTTLPR) With Depression in Costa Rican Schizophrenic Patients

Abstract

Depression and suicidal behavior are frequently observed in patients with schizophrenia. The serotonin transporter protein regulates serotonergic signaling at synapses and is encoded by a single gene (SLC6A4; Locus Link ID: 6532), located at 17q11.1-q12 with two polymorphic variants (the short and the long allele). The short allele of serotonin transporter gene has been associated with depression and suicidality in individuals who suffered negative life events and with depression in individuals with chronic psychosis.. Subjects were recruited from a genetic study of schizophrenia conducted in Costa Rica. The authors replicated their previous research, using a more narrow phenotype (only schizophrenic subjects) and a more ethnically homogenous sample (only Costa Rican schizophrenic individuals who were not included in the previous study). The authors hypothesized that subjects with at least one copy of the serotonin transporter promoter gene polymorphism (5-HTTLPR) "s" allele would have a greater history of lifetime depression and suicidability rate than those who had an "l/l" genotype. The authors analyzed 155 subjects with a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosis of schizophrenia (73% male, age at interview 38.3, SD = 11.23). The genotype distribution was "ss" 58 (37%), "sl" 69 (45%), and "ll" 28 (18%). In the secondary analysis, the authors explored association of the "s" allele with lifetime history of suicide behavior in 173 subjects (18 more subjects than primary analysis because schizophrenic individuals were included regardless of history of depression). The authors found that subjects carrying at least one short allele had a significant increased lifetime risk for depressive syndromes (chi(2) = 5.4, df = 1, P = 0.02; odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.15-6.3). No association was found for suicidal behavior in the same sample (chi(2) = 0.928, P = 0.629). In conclusion, the genotype at the 5-HTTLPR promoter polymorphic locus increases the risk of developing major depression but not suicidal behavior during the course of the schizophrenia in these patients. Due to the small sample size, these results should be followed by definitive replication.

Association of antibody titers and 5-HTTLPR gene polymorphisms in pediatric autoimmune neuropsychiatric disorder associated with streptococci

“…Since OCD is a heterogeneous disorder, its etiology could not be explained by a single gene but rather by a polygenic basis, as well as environmental factors as child abuse and daily life stress in which the 5-HTTLPR genotype could act as a moderator in the development of a psychiatric disease (Caspi et al, 2003;Caspi et al, 2008). It is proposed that the S allele moderates the influence of life stressing events in the onset of depressive symptoms and suicide risk when compared with homozygous carriers of the allele L (Caspi et al, 2003;Contreras et al, 2010), for which our study found an associated increase in autoantibody titers.…”

Genetic variability of serotonin pathway associated with schizophrenia onset, progression, and treatment

“…The short and long allele differentially affects expression (Dolzan et al, ; Han, Park, Na, Kee, & Lee, ; Heils et al, ). This leads to changes in 5‐HT concentration in the synaptic cleft, amygdala volume, and subsequent behavioral characteristics, such as aggression, stress, depression, and suicide in SZ patients (Contreras et al, ; Hung et al, ; Kobiella et al, ). However, the long alleles differ in expression, as the expression of G allele is similar to that of the short allele (Hung et al, ).…”

Ancestry Informative Markers Clarify the Regional Admixture Variation in the Costa Rican Population

“…Furthermore, understanding admixture in this population is essential for disease susceptibility mapping studies, and Costa Rica's population has been extensively studied for psychiatric diseases (Contreras et al 2010;Escamilla et al 2009;Escamilla et al 2007; Walss- Bass et al 2006;Walss-Bass et al 2009), longevity (Castri et al 2011;Castri et al 2009) and other disease studies (Leon et al 1992). …”