Association of polymorphisms of the serotonergic pathways with clinical traits of impulsive-aggression and suicidality in adolescents: a multi-center study.

OBJECTIVES: Suicidal behaviour runs in families. This study evaluated association between common polymorphisms in the serotonergic and adrenergic candidate genes (HTR2A, 5HTTLPR, and MAOA) and suicidality, psychopathology and aggression in adolescents. METHODS: Four groups of adolescents were included: Suicidal (N=35) and non-suicidal (N=30) psychiatric inpatients, suicide attempters admitted to three psychiatric emergency rooms (N=51) and a community-based control group (N=95). All were genotyped and underwent psychological assessment for relevant endophenotypes and plasma serotonin content (p5HT) was measured. RESULTS: Homozygosity for the T allele of the HTR2A 102T/C polymorphism was associated with lower impulsivity (P=0.03) and aggression (P=0.01) compared to TC carriers. Low activity MAOA genotypes were associated with suicidality (P=0.04). No association was found between p5HT level and the examined polymorphisms. CONCLUSIONS: Our findings are in line with the associations described in adult suicidal population. Further studies are needed to evaluate the gene ? environmental interactions in larger samples in an attempt to clarify the possible role of genetic factors in pediatric suicidal and impulsive-aggressive behaviour.

Effect of exposure to selective serotonin reuptake inhibitors in utero on fetal growth: potential role for the IGF-I and HPA axes.

To investigate the possible effect of fetal exposure to selective serotonin reuptake inhibitors (SSRIs) on somatic growth and on hormones of the hypothalamic-pituitary-adrenal (HPA) and insulin-like growth factor (IGF)-I axes, we compared the anthropometric parameters and hormonal profile of 21 SSRI-exposed infants and 20 matched controls. The SSRI group was characterized by lower crown-heel length (p < 0.01), smaller head circumference (p = 0.08), and higher percentage of infants with birth weight, birth length, and head circumference below the 10th percentile (p < 0.045, p = 0.08, p < 0.04, respectively), in addition to a significantly lower cord blood level of cortisol (p < 0.03) and higher level of thyroid-stimulating hormone (TSH) (p < 0.004). Infants exposed to citalopram had a lower cord blood IGF-I level than infants exposed to paroxetine (p < 0.001) and controls (p < 0.003). Placental IGF-I receptor (IGF-IR) expression was significantly higher in the SSRI group than in controls (p < 0.01). Urine 5-hydroxyindoleacetic acid (5-HIAA) level was negatively correlated with birth weight (r = -0.71, p < 0.025) and with dehydroepiandrosterone (DHEA) level (r = -0.71, p < 0.025). The Finnegan score was correlated with dehydroepiandrosterone sulfate (DHEAS) (r = 0.8, p < 0.005) and cortisol (r = 0.62, p = 0.05). Fetal exposure to SSRIs causes impaired intrauterine growth accompanied by alterations in the IGF-I and HPA axes. The findings may raise concern regarding maternal use of SSRIs during pregnancy.

Plasma serotonin levels and suicidal behavior in adolescents.

To evaluate the relationship between plasma serotonin (p5-HT) levels and psychometric measures in suicidal adolescents vs. controls, 211 adolescents from three sites in Israel were divided into four groups: suicidal psychiatric inpatients (n=35); non-suicidal psychiatric inpatients (n=30); adolescents referred to the emergency room (ER) due to a suicide attempt (n=51); and a community-based control group from 4 high schools in the same catchment areas (n=95). All were interviewed and assessed for violence, aggression, depression, impulsivity, anger, anxiety, and p5-HT. p5-HT levels were significantly lower in the control group compared to all other groups. A significant negative correlation was found between p5-HT level and suicidal behavior severity among the suicidal inpatients. p5-HT did not discriminate between the psychiatric diagnostic categories and was significantly lower in ER violent compared to non-violent subjects. Gender, depression, and anger were associated with suicidal behavior in all four groups. Beck Depression Inventory (BDI) scores together with p5-HT levels discriminated between healthy controls and other groups. p5-HT level in combination with some of the psychometric scales may serve as a safe and inexpensive peripheral marker of psychopathology, and may help to differentiate between sub-populations of suicidal adolescents. The biological mechanism behind the serotonin dysregulation in suicidal adolescents requires further investigation.

Serum NT-proBNP concentrations in the early phase do not predict the severity of systolic or diastolic left ventricular dysfunction among patients with ST-elevation acute myocardial infarction.

The cohort included 55 consecutive patients with first ST elevation acute myocardial infarction (STEAMI) who underwent reperfusion. Blood samples were drawn for N-terminal pro B-type natriuretic peptide (NT-proBNP), highly-sensitive C-reactive protein (hs-CRP), creatinine kinase (CK), cardiac troponin l (cTnl), and white blood cell (WBC) count within 24 hours of admission. Transthoracic echocardiography, performed within the same time frame, assessed left ventricular (LV) systolic function, as well as diastolic function. Variables significantly associated with poor systolic LV dysfunction were hs-CRP, peak CK, cTnl, and WBC. There was no significant correlation between NT-proBNP and systolic function early after STEAMI (p=0.49). Among patients with diastolic dysfunction, there was no significant correlation between NT-proBNP levels and peak mitral E-wave velocity to peak initial A-wave velocity (E/A ratio) (r =0.19, p=0.18) or E-wave deceleration time (r =0.22, p=0.15). Thus, NT-proBNP levels in the early phase after STEAMI were not indicative of systolic or diastolic function.

Family history, plasma homocysteine, and age at onset of symptoms of myocardial ischemia in patients with different methylenetetrahydrofolate reductase genotypes.

A high plasma homocysteine level is associated with early onset of coronary artery disease (CAD), particularly in homozygotes for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Family history is a predictor of increased plasma homocysteine and may be involved in early-onset CAD. This study examined the relations among family history, plasma homocysteine, and age at onset of CAD, and the role of the MTHFR genotype in this context. We screened 284 patients who developed first symptoms of CAD at < or =65 years of age for fasting plasma homocysteine and the C677T mutation. On multiple regression analysis, homocysteine, family history, male gender, and smoking were independently associated with age at onset of CAD. However, separate analysis of patients who had the MTHFR 677 T/T genotype (n = 57) and those who did not (n = 209) showed that plasma homocysteine and family history were associated with earlier onset of CAD only in T/T homozygotes and that family history in patients who had this genotype was also associated with higher plasma homocysteine levels and a stronger association between plasma homocysteine and age at onset of CAD. In patients who had other genotypes, these associations were not observed, and earlier onset of CAD was associated only with male gender and smoking. Thus, the MTHFR genotype modifies the effects of family history and other risk factors on age at onset of CAD. In T/T homozygotes, family history is associated with earlier onset of CAD, higher plasma homocysteine levels, and a stronger association between plasma homocysteine and age at onset of CAD.

Body temperature - a marker of infarct size in the era of early reperfusion.

We measured body temperature in 40 consecutive patients treated for a first ST elevation acute myocardial infarction (AMI) with primary percutaneous coronary interventions. Left ventricular function was assessed by echocardiography, and blood samples were drawn for highly sensitive C-reactive protein (hs-CRP), white blood cell (WBC) count, fibrinogen, creatine kinase (CK), and cardiac troponin I levels (cTnI). The median (25th, 75th quartiles) peak 24-hour temperature was 37.4 degrees C (36.9 degrees C, 37.6 degrees C). Variables significantly associated with peak 24-hour temperature were CK (p = 0.01, r = 0.42), wall motion index (p = 0.01, r = 0.41), hs-CRP (p = 0.01, r = 0.41), and cTnI (p = 0.03, r = 0.35). There was no significant correlation between peak 24-hour temperature and WBC count (p = 0.39, r = 0.14) and fibrinogen (p = 0.12, r = 0.21). Thus, peak 24-hour body temperature after ST elevation AMI probably reflects infarct size rather than a nonspecific inflammatory response.

Association of CagA+ Helicobacter pylori infection with aortic atheroma.

BACKGROUND: To investigate possible association between infection with CagA(+) strains of Helicobacter pylori and aortic atheroma diagnosed by transesophageal echocardiography. METHODS AND RESULTS: One hundred and eighty-eight consecutive subjects prospectively examined for presence of aortic atheroma (localized intimal thickening of >/=3mm) by transesophageal echocardiography were tested for serum IgG antibodies against H. pylori (enzyme-linked immunosorbent assay) and CagA protein (Western blot assay). The association between infection with H. pylori, CagA status of the infecting H. pylori strains, and aortic atherosclerosis was evaluated after adjusting for coronary artery disease risk factors. There was a linear trend for presence of atheroma in subjects with CagA-positive H. pylori infection (51/81, 63%) compared to subjects with CagA-negative H. pylori infection (21/45, 46.7%) and uninfected subjects (18/62, 29%) (p=0.003). H. pylori seropositivity was not associated with aortic atheroma (OR 2.9; 95% CI, 0.8-10.3; p=0.11) when CagA status is not taken into account. On multivariate analysis, parameters associated with risk of aortic atheroma were CagA-positive H. pylori seropositivity (OR 4.4; 95% CI, 1.4-14.7; p=0.01), older age (OR 1.2; 95% CI, 0.9-14.7; p=0.01), having ever smoked cigarettes (OR 3.6; 95% CI, 1.3-10.0; p<0.001), and elevated serum triglyceride level (OR 3.4; 95% CI, 1.3-9.4; p=0.02). CONCLUSIONS: After controlling for H. pylori infection and coronary artery disease risk factors, infection with a CagA-positive strain of H. pylori was independently associated with aortic atherosclerosis. This study suggests a gradient of atherosclerosis between uninfected individuals and patients with CagA-positive H. pylori infection and should prompt research into the role of CagA-positive H. pylori infection in the inflammatory atherosclerotic process.

Effect of different LDL-apheresis methods on parameters involved in atherosclerosis.

LDL-apheresis lowers the LDL level in patients with severe hypercholesterolemia. The present study compared three apheresis methods--DSA, DALI, and plasma exchange--for effectiveness in removal of LDL and effect on various blood parameters involved in atherogenesis. The study group included 6 patients with primary hypercholesterolemia unresponsive to maximal drug therapy. All were treated first with 4 consecutive plasma exchange sessions followed by 4 DSA sessions; in four out of six, an additional 4 sessions of DALI were then performed. Levels of lipoproteins, apoproteins, CRP, homocysteine, fibrinogen, and blood count were determined before and after each session. All 3 procedures yielded a significant reduction in total cholesterol and ApoB-containing lipoproteins, with DALI being the most effective. Also, a significant reduction in triglycerides, HDL, and ApoA1 was observed with all the methods. The reduction in HDL-C with DSA and DALI was greater than previously reported. The LDL/HDL-cholesterol ratio decreased significantly with DSA and DALI and increased with plasma exchange. There was a significant decrease in CRP, fibrinogen, and platelets with all three methods, and a significant decrease in homocysteine only with DSA and DALI. All three procedures effectively reduced the concentration of various compounds involved in atherosclerosis. Plasma exchange is nonselective and cannot be recommended as the procedure of choice.

Plasma levels of vitamin E in pregnant women prior to the development of preeclampsia and other hypertensive complications.

Our aim was to investigate whether decreased levels of vitamin E can be measured during the early stages of pregnancy in women at risk of developing preeclampsia or other associated complications before the onset of the clinical syndrome. We prospectively measured the plasma concentrations of vitamin E in 62 pregnant women at 7-32 weeks of gestation who were at risk of developing preeclampsia and other complications, before the appearance of clinical signs. The results were compared with those of 16 healthy controls. Of the 62 study patients, 8 (13%) developed preeclampsia, and 18 (29%) had other complications, such as intrauterine growth restriction (n = 8), fetal or neonatal loss (n = 9), and preterm delivery (< or = 30 weeks of gestation; n = 7). Both gestational age at delivery and birth weight were significantly lower in the patients with complications than in the healthy controls. However, there were no significant differences in vitamin E levels between women who developed preeclampsia or other complications and those who did not. There was no significant correlation between plasma vitamin E and creatinine concentrations. A significant positive correlation was found in both the complicated and normal pregnancies between plasma vitamin E concentration and gestational week of blood collection (R = 0.485, p < 0.001, and R = 0.718, p = 0.004, respectively). We conclude that the vitamin E concentrations are not decreased prior to the development of preeclampsia or other complications in women at risk.

The elevated plasma lipoprotein(a) concentrations in preeclampsia do not precede the development of the disorder.

We sought to determine whether maternal plasma lipoprotein(a) [Lp(a)] levels are elevated in the second trimester, before the development of preeclampsia and other obstetrical complications, in women at risk. In the first part of the study (cross-sectional), plasma concentrations of Lp(a) were compared among 16 women with preeclampsia, 35 normotensive pregnant women and 18 healthy nonpregnant women. In the second part (nested case-control), blood samples were collected prospectively from 82 women at risk of preeclampsia, at 14-24 weeks of gestation, and Lp(a) levels were compared between those in whom preeclampsia or other obstetrical complications developed and those in whom they did not. In the cross-sectional study, plasma concentrations of Lp(a) were significantly higher in women with preeclampsia than in normotensive pregnant and healthy nonpregnant women (41 +/- 31 vs. 24 +/- 16 and 15 +/- 10 mg/dl, respectively; P=.001). Of the 82 women in the second part of the study, 9 (11%) developed preeclampsia and 19 (23%) had complications such as intrauterine growth restriction, preterm delivery and fetal or neonatal loss. There were no differences in plasma Lp(a) concentrations between the women with preeclampsia and those without complications, though Lp(a) levels were significantly higher in women with other complications than in those with either preeclampsia or uncomplicated pregnancies (40 +/- 29 vs. 17 +/- 13 or 28 +/- 18 mg/dl, respectively; P=.05). In conclusion, elevated plasma levels of Lp(a), associated with clinically established preeclampsia, are not detected before the appearance of the disorder in pregnant women at risk.