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 (χ2 = 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 (χ2 = 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.
To test whether lipoprotein lipase or hepatic lipase activities are associated with lipoprotein subclasses, and to assess the effects of dietary manipulations on these associations, enzyme activities were measured in postheparin plasma (75 U heparidkg) from 43 healthy men who were randomly allocated to a low-fat (24% fat, 60% carbohydrate) and a high-fat (46% fat, 38% carbohydrate) diet for 6 weeks each in a cross-over design. The high-fat diet significantly increased both lipoprotein lipase (+20%, P = 0.02) and hepatic lipase (+8%, P = 0.007) activities. On both diets, hepatic lipase activity was significantly positively correlated (P < 0.01) with plasma apolipoprotein (apo)B concentrations, and with levels of small dense low density lipoprotein (LDL) 111, measured by analytic ultracentrifugation as mass of lipoproteins of flotation rate (Si') 3-5, while lipoprotein lipase activity was inversely associated with levels of LDL 111 (P < 0.05). Despite the cross-sectional correlations, increased hepatic lipase activity was not significantly correlated with the reduction in LDL I11 mass observed on the high-fat diet. Rather, changes in hepatic lipase were correlated inversely with changes in small very low density lipoproteins (VLDL) of Sg 20-40, and small intermediate density lipoproteins (IDL) of Sp 10-16. Moreover, changes in lipoprotein lipase activity were not significantly correlated with changes in small LDL, but were positively associated with changes in small IDL of Sp 10-14, and large LDL I of Sp 7-10. Thus, while increased levels of small dense LDL are associated with a metabolic state characterized by relatively increased hepatic lipase and decreased lipoprotein lipase activity, changes in these enzymes do not appear to be primary determinants of diet-induced changes in levels of this LDL subfraction. On the other hand, increased lipoprotein lipase activity induced by high-fat feeding may contribute to the accumulation in plasma of both large LDL I and small IDL, whereas increased hepatic lipase may promote catabolism or clearance of triglyceride-rich lipoprotein remnants.
