The role of personality dimensions, depressive symptoms and other psychosocial variables in predicting postpartum suicidal ideation: a cohort study.

Suicidability has been associated with neuroticism and psychoticism, but its role during perinatal period has not been analyzed. We explore the association between personality dimensions, depressive symptoms, and other psychosocial variables in postpartum suicidal ideation. A cohort of 1795 healthy Spanish women from the general population was assessed for suicidal ideation (EPDS-Item10) in early postpartum, 8 and 32 weeks postpartum. Sociodemographic, obstetric, and reproductive variables, psychiatric history, social support, stressful life-events during pregnancy, depressive symptoms (EPDS), and the Eysenck's personality dimensions (EPQ-RS) were also assessed at baseline. A major depressive episode (DSM-IV) was confirmed in women with EPDS>10 at follow-up assessments. Descriptive, bivariate, and multivariate analyses were conducted. Adjusted logistic regression analysis was reported as odds ratio (ORs) with 95% confidence intervals (CIs). Seven percent of mothers reported suicidal ideation during the first 8 months postpartum. Sixty-two percent of women with suicidal ideation had a major depressive episode at 8 weeks, and 70% at 32 weeks postpartum. Neuroticism and psychoticism predicted suicidal ideation throughout the first 2 weeks after delivery (OR, 1.03; 95%CI 1.01-1.06; and OR, 1.03; 95%CI 1.01-1.05 respectively). Early postpartum depressive symptoms (OR 1.2; 95%CI 1.11-1.26), personal psychiatric history (OR 2.1; 95%CI 1.33-3.27), and stressful life events during pregnancy (OR 1.88; 95%CI 1.12-3.16) also emerged as predictors of postpartum suicidal ideation. Analysis of women for postpartum suicidal ideation should include not only psychiatric symptoms but also psychosocial assessment (i.e., covering psychiatric history, stressful events, or long-standing personality vulnerabilities) in order to identify those in need of early psychosocial or psychiatric care.

Coping strategies and postpartum depressive symptoms: A structural equation modelling approach.

BACKGROUND: Variables such as the mother's personality, social support, coping strategies and stressful events have been described as risk factors for postpartum depression. Structural Equation Modelling (SEM) analysis was used to examine whether neuroticism, perceived social support, perceived life events, and coping strategies are associated with postpartum depressive symptoms at the 8th and 32nd weeks. METHODS: A total of 1626 pregnant women participated in a longitudinal study. Different evaluations were performed 8 and 32weeks after delivery. Several measures were used: the Edinburgh Postnatal Depression Scale (EPDS), the Diagnostic Interview for Genetic Studies (DIGS), the Eysenck Personality Questionnaire (EPQ-RS), the St. Paul Ramsey life events scale and the Duke-UNC Functional Social Support Questionnaire. The brief COPE scale was used to measure coping strategies. SEM analysis was conducted for all women and in those women with a clinical diagnosis of postpartum depression. RESULTS: Passive coping strategies were associated with postpartum depressive symptoms at both visits (8th and 32nd weeks). Neuroticism was associated with more passive coping strategies and less active coping strategies. Neuroticism and life stress were positively correlated, and social support was negatively correlated with life stress and neuroticism. CONCLUSIONS: Early identification of potential risk for symptomatology of depression postpartum should include assessment of neuroticism, life events, social support and coping strategies.

Association of common copy number variants at the glutathione S-transferase genes and rare novel genomic changes with schizophrenia.

Copy number variants (CNVs) are a substantial source of human genetic diversity, influencing the variable susceptibility to multifactorial disorders. Schizophrenia is a complex illness thought to be caused by a number of genetic and environmental effects, few of which have been clearly defined. Recent reports have found several low prevalent CNVs associated with the disease. We have used a multiplex ligation-dependent probe amplification-based (MLPA) method to target 140 previously reported and putatively relevant gene-containing CNV regions in 654 schizophrenic patients and 604 controls for association studies. Most genotyped CNVs (95%) showed very low (<1%) population frequency. A few novel rare variants were only present in patients suggesting a possible pathogenic involvement, including 1.39 Mb overlapping duplications at 22q11.23 found in two unrelated patients, and duplications of the somatostatin receptor 5 gene (SSTR5) at 16p13.3 in three unrelated patients. Furthermore, among the few relatively common CNVs observed in patients and controls, the combined analysis of gene copy number genotypes at two glutathione S-transferase (GST) genes, GSTM1 (glutathione S-transferase mu 1) (1p13.3) and GSTT2 (glutathione S-transferase theta 2) (22q11.23), showed a statistically significant association of non-null genotypes at both loci with an additive effect for increased vulnerability to schizophrenia (odds ratio of 1.92; P=0.0008). Our data provide complementary evidences for low prevalent, but highly penetrant chromosomal variants associated with schizophrenia, as well as for common CNVs that may act as susceptibility factors by disturbing glutathione metabolism.

Mood changes after delivery: role of the serotonin transporter gene.

BACKGROUND: Polymorphic variations in the serotonin transporter gene (5-HTT) moderate the depressogenic effects of tryptophan depletion. After childbirth there is a sharp reduction in brain tryptophan availability, thus polymorphic variations in 5-HTT may play a similar role in the post-partum period. AIMS: To study the role of 5-HTT polymorphic variations in mood changes after delivery. METHOD: One thousand, eight hundred and four depression-free Spanish women were studied post-partum. We evaluated depressive symptoms at 2-3 days, 8 weeks and 32 weeks post-partum. We used diagnostic interview to confirm major depression for all probable cases. Based on two polymorphisms of 5-HTT (5-HTTLPR and STin2 VNTR), three genotype combinations were created to reflect different levels of 5-HTT expression. RESULTS: One hundred and seventy-three women (12.7%) experienced major depression during the 32-week post-partum period. Depressive symptoms were associated with the high-expression 5-HTT genotypes in a dose-response fashion at 8 weeks post-partum, but not at 32 weeks. CONCLUSIONS: High-expression 5-HTT genotypes may render women more vulnerable to depressive symptoms after childbirth.

Subjective quality of life in schizophrenic outpatients in a Catalan urban site.

The aim of this cross-sectional study was to assess the subjective quality of life of chronic schizophrenic outpatients living in an urban site in Catalonia (Spain) during a stable phase of the illness. We included 44 patients with a DSM-IV diagnosis of psychotic disorder. Sociodemographic, clinical, and treatment variables were obtained and compared with the subjective quality of life as assessed by the Lehman Quality of Life Interview-short version. The descriptive analysis of the subjective quality of life profile obtained in our sample shows moderate levels of satisfaction in most subscales. Results regarding comparisons showed that sociodemographic, clinical, premorbid adjustment and treatment variables were only related to subjective quality of life in particular life domains and in a nonconclusive way. The need to include other relevant variables such as insight or psychological traits in the study of the quality of life phenomenon in schizophrenia is highlighted.

Increased morbid risk for schizophrenia in families of in-patients with bipolar illness.

BACKGROUND: It has been reported that relatives of probands with severe, psychotic forms of bipolar illness have increased rates of schizophrenia but not the relatives of individuals with milder, non-psychotic forms of disorder. In this study, we examined the prevalence of psychiatric disorders in the first degree relatives of a sample of 103 inpatients with bipolar disorder and in a matched control sample of 84 healthy individuals. METHOD: Relatives of cases and controls were interviewed using the FH-RDC to determine familial morbid risk for schizophrenia and bipolar disorder. Age- and sex-adjusted morbidity risks were calculated in both samples according to the method of Strömgren. RESULTS: The morbid risks for both bipolar disorder (4.9%) and schizophrenia (2.8%) were higher in relatives of patients than in relatives of controls (0.3% and 0.6% respectively). The relative risks were 14.2 [95% confidence interval (CI)=3.1-64.2] for bipolar disorder and 4.9 (95% CI=1.3-18.8) for schizophrenia. Relatives of women with early onset of bipolar illness had the highest morbid risks for both bipolar illness and schizophrenia. The presence of more than one patient with bipolar disorder in a family increased the risk for schizophrenia nearly fourfold (RR=3.5, 95% CI=1.2-10.2). There was no additional effect of presence of psychotic features. CONCLUSION: Our results suggest that the transmission of psychosis is not disorder-specific. Bipolar illness characterised by a high familial loading is associated with increased risk of schizophrenia in the relatives.

Congenital dermatoglyphic malformations in severe bipolar disorder.

Dermatoglyphic alterations may be the result of early prenatal disturbances thought to be implicated in the aetiology of psychiatric illness. In order to test this hypothesis in the particular case of bipolar disorder, we assessed two congenital dermatoglyphic malformations (ridge dissociation (RD) and abnormal features (AF)) and two metric dermatoglyphic traits (total finger ridge count (TFRC) and total a-b ridge count (TABRC)) in a sample of 118 patients with chronic DSM-III-R bipolar illness, and 216 healthy controls. Bipolar cases showed a significant excess of RD and AF (OR = 2.80; 95% CI: 2.31-3.38) when compared with controls. In the cases, the presence of anomalies was associated with earlier age of onset. No differences were found for TFRC and TABRC. No associations were found with sex or familial morbid risk of psychiatric disorders. Our findings add further weight to the suggestion that early developmental disruption is a risk factor for later bipolar disorder.

Serotonin transporter gene and risk for bipolar affective disorder: an association study in Spanish population.

BACKGROUND: The serotonin transporter (5-HTT) is an important candidate gene for the genetic transmission of manic depressive illness. Many studies of patients with affective disorders have found abnormalities in serotonin metabolism and dysregulation of the transporter itself. In the present study, we hypothesize that genetic variation in the 5-HTT gene (17q11.1-17q12) may have an effect in the etiology of manic depression. METHODS: To test this hypothesis, we analyzed allele, genotype, and haplotype frequencies of two polymorphisms recently described in the 5-HTT gene (a variable number of tandem repeats in intron 2 and a deletion/insertion polymorphism in the transcriptional control region) in a sample of 88 patients with manic-depressive illness and 113 controls. Cases and controls were matched for ethnic and geographic origin. RESULTS: No associations were found between any of these polymorphisms, tested individually or as haplotypes, and manic depression. Moreover, the genetic analysis by sex, presence/absence of psychiatric family history, and age of onset did not reveal significant differences in allele or genotype distributions. CONCLUSIONS: Our results suggest that the genetic variability of the 5-HTT gene is not a major risk factor for manic depression.

Genetic variation of the 5-HT2A receptor gene and bipolar affective disorder.

Abnormalities of the serotonergic system have classically been associated with the origin of affective disorders through the biochemical action of therapeutic agents and their role in affective and perceptual states. In the present study, we hypothesized that genetic variation in the 5-hydroxytryptamine (serotonin) type 2A (5-HT2A) receptor gene (HTR2A) might have an effect on the aetiology of bipolar affective disorder. Four different polymorphisms in the HTR2A gene were studied in 88 patients with bipolar affective disorder and 113 healthy controls, all of Spanish origin. No significant association was observed between any of the four polymorphisms at the HTR2A locus, whether tested individually or as haplotypes, and bipolar affective disorder. The lack of association suggests that HTR2A is not a major risk factor for bipolar affective disorder.

Haptoglobin phenotypes and gene frequencies in bipolar disorder: an association study in family-history subgroups.

Several studies have shown that major depression is accompanied by significantly increased plasma levels of positive acute-phase proteins such as haptoglobin (Hp). A significant higher frequency of the HP*1 allele has recently been detected in patients with unipolar major depression. Pursuing the hypothesis that certain unipolar and bipolar disorders may be genetically related, this study analyzed Hp genotype and allele frequencies in bipolar patients, taking into account their family history of major affective disorders. An increase of HP*1 allele frequency was found in the subgroup of patients with family history of exclusively unipolar disorder (70% in patients vs. 38% in controls, chi2 = 8.34, p = 0.004). The relative risk for the HP*1 carriers in this subgroup was 3.8 (chi2 = 7.29, p = 0.007). These results suggest a genetic and etiological heterogeneity in the bipolar disorder.

Association analysis of the catechol O-methyltransferase gene and bipolar affective disorder.

OBJECTIVE: Catechol O-methyltransferase (COMT) is an enzyme that inactivates catecholamines. Two common COMT alleles determine high and low activity of the enzyme. Previous studies using biochemical methods found lower enzyme activity in patients with major depression and bipolar disorder in comparison with control values, suggesting that a dysfunction in catecholamine metabolism may be related to the etiology of depression. METHOD: The authors studied two recently described DNA polymorphisms at the COMT gene (a silent C256G mutation and a structural mutation, Val-108-Met) in 88 patients with bipolar disorder and in 113 healthy comparison subjects, all of Spanish origin. RESULTS: The frequency of the C256 allele was 0.58 in the patients and 0.54 in the comparison subjects. The frequency of the Val108 variant was 0.57 for both the patients and the comparison subjects. No allelic or genotypic associations were observed. CONCLUSIONS: The lack of association suggests that the COMT gene is not a major risk factor for bipolar disorder.

Allelic association analysis of the 5-HT2C receptor gene in bipolar affective disorder.

We have examined a structural variant of the 5-HT2C receptor (Cys23Ser) for allelic association with bipolar affective disorder in 88 cases and 113 controls. Overall, there was no significant difference in allele frequencies between the two groups, indicating that the 5-HT2C gene is not a major risk factor for bipolar affective disorder. However, when the subjects were analysed according to sex, there was a small excess of the serine ser23 allele in female cases (P = 0.04) and this effect was also seen if the ser23 allele was considered recessive (P = 0.03). A small increase in significance was found if only female cases with a known family history were included (P = 0.01). These results suggest that the ser23 allele may increase susceptibility to bipolar affective disorder in women.

Urinary phenylacetic acid excretion in depressive patients.

Phenylacetic acid (PAA), a metabolite of phenylethylamine, has been found in the urine of depressed patients at lower levels than in control subjects. It has been suggested that the determination of PAA in urine could be used as a biological marker of the depressive condition. In this study the levels of PAA in urine were investigated by gas-liquid chromatography in 39 patients diagnosed as having major depression according to DSM-III criteria, and in 32 healthy subjects. The values found in the patients were markedly lower than in controls. No relationship was found between the decrease of PAA excretion and weight loss. Using a discriminant equation, a value of 69% was obtained for both sensitivity and specificity. The results suggest that the determination of urine PAA could be a biological parameter comparable to the dexamethasone suppression test.