Substance use during pregnancy and personality dimensions. / Consumo de substancias durante el embarazo y dimensiones de personalidad.

Our aim was to assess personality traits associated with substance use during pregnancy in a population-based, multicentre study of 1804 pregnant women. On day 2-3 postpartum, participants completed a semi-structured interview, including self-reported drug use (alcohol, tobacco, caffeine, cannabis, cocaine, opioids) during pregnancy, and socio-demographic, reproductive and obstetric variables, personal and family psychiatric history, social support, and the Eysenck personality questionnaire, short version (EPQ-RS). Logistic regression models were conducted. Fifty per cent of women reported substance use during pregnancy: 40% caffeine, 21% tobacco, 3.5% alcohol, and 0.3 % cannabis. Mean T-scores (SD) for personality dimensions were 51.1 (9.6) for extraversion, 48 (8.9) for psychoticism, and 43.6 (8.5) for neuroticism. Extroversion (p = .029) and psychoticism (p = .009) were identified as risk factors after adjustment by age, level of education, employment status during pregnancy, low social support, and previous psychiatric history. For each increment of 10 units in their scores, the odds of substance use increased by 12% and 16% respectively. Low education, being on leave during pregnancy, and previous psychiatric history were independent factors (p < .05) associated with substance use during pregnancy. Primiparity was a protective factor (p = .001). The final models showed a good fit (p = .26). The screening of substance use during pregnancy should include personality dimensions apart from psychosocial variables and history of psychiatric disorders. It is important to identify the associated risk factors for substance use during pregnancy to prevent and improve foetal/neonatal and maternal health during perinatal period.

Este estudio evalúa los patrones de consumo de substancias durante el embarazo y las dimensiones de personalidad asociadas, en una muestra multicéntrica de 1804 mujeres de población general. En el 2-3 día posparto, completaron una entrevista auto-administrada sobre el consumo de alcohol, tabaco, cafeína, cannabis, cocaína, opiáceos, drogas de diseño, además de variables socio-demográficas, obstétricas/reproductivas, historia psiquiátrica previa, apoyo social durante el embarazo y el cuestionario de personalidad de Eysenck (EPQ-RS). Se generaron modelos de regresión logística múltiple. La prevalencia del consumo fue del 50% (N=909): 40% cafeína, 21% tabaco, 3,5% alcohol, y 0,3 cannabis. Las puntuaciones T medias (DE) de personalidad fueron: extraversión 51,1 (9,6), psicoticismo 48 (8,9) y neuroticismo 43,6 (8,5). Las dimensiones de extraversión (p=0,029) y psicoticismo (p=0,009), fueron identificadas como factores de riesgo tras ajustar por edad, nivel educación, estatus laboral durante el embarazo, bajo apoyo social, e historia psiquiátrica previa. Para cada incremento de 10 unidades en sus puntuaciones, el odds de consumo de substancias durante el embarazo se incrementó un 12% y un 16% respectivamente. Menor educación, estar de baja, y antecedentes psiquiátricos fueron también factores independientes (p<0,05) asociados al consumo. Ser primípara fue factor protector (p=0,001). El modelo final mostró un ajuste satisfactorio (p=0,26). El cribaje de las mujeres con riesgo de consumo de substancias durante el embarazo debería incluir la personalidad además de variables psicosociales y antecedentes psiquiátricos. Identificar los factores de riesgo asociados es importante para prevenir y mejorar la salud materna y fetal/neonatal durante el embarazo y posparto.

Factor Structure of the Spanish Version of the Edinburgh Postnatal Depression Scale.

INTRODUCTION: The Edinburgh Postnatal Depression Scale (EPDS) is considered the gold standard in screening for postpartum depression. Although the Spanish version has been widely used, its factorial structure has not yet been studied . METHODS: A total of 1,204 women completed the EPDS 32 weeks after delivery. To avoid multiple testing, we split the sample into two halves, randomly drawing two subsamples of 602 participants each. We conducted exploratory factor analysis (EFA), followed by an oblimin rotation with the first sub-sample. Confirmatory factor analysis (CFA) was conducted using a Weighted Least Squares Means and Variance (WLSMV) estimation of the data. We explored different solutions between two and four factors. We compared the factors between two groups with depression and non-depression (evaluated with the Diagnostic Interview for Genetic Studies (DIGS) for the DSM-IV). RESULTS: The EFA indicated a three-factor model consisting of anxiety, depression and anhedonia. The results of the CFA confirmed the three-factor model (χ2=99.203, p<0.001; RMSEA=0.06, 90% CI=0.04/0.07, CFI=0.87 and TLI=0.82). Women with depression in the first 32 weeks obtained higher scores for anxiety, depression and anhedonia dimensions (p<0.001). CONCLUSIONS: This is the first study of confirmatory analysis with the Spanish version of EPDS in a large sample of women without psychiatric care during pregnancy. A three-factor model consisting of anxiety, depression and anhedonia was used. Women with depression had a higher score in the three dimensions of the EPDS.

Sudden gains in exposure-focused cognitive-behavioral group therapy for panic disorder.

In the context of psychological treatment, a sudden gain is a large and enduring improvement in symptom severity that occurs between two single therapy sessions. The influence of sudden gains on long-term outcomes and functional impairment in anxiety disorders is not well understood, and little is known with regard to panic disorder in particular. In addition, previous research on patients with anxiety disorders has produced inconsistent results regarding the relationship between sudden gains and cognitive change. We examined the incidence of sudden gains in a large sample (n = 116) of panic disorder patients undergoing exposure-focused cognitive-behavioral group therapy, and compared panic severity, functional impairment, and cognitive change in patients with and without sudden gains at posttreatment and 6-month follow-up. Participants who experienced sudden gains displayed lower levels of panic severity and functional impairment at posttreatment and 6-month follow-up than those who did not experience sudden gains. However, we observed no difference in cognitive changes between groups, either at posttreatment or at follow-up. Our results demonstrate that the beneficial effects of sudden gains on therapeutic outcomes not only extend to long-term and functional outcome measures but are also evident in less cognitive (i.e., exposure-focused) forms of psychological treatment. KEY PRACTITIONER MESSAGE: Sudden gains are common in panic disorder patients undergoing exposure-based cognitive-behavioral group therapy. Sudden gains during exposure-focused therapy are linked to greater improvement in panic disorder severity and functional impairment. The positive impact of sudden gains on panic disorder severity and functional impairment is maintained in the long term.

Correction: Predicting Response Trajectories during Cognitive-Behavioural Therapy for Panic Disorder: No Association with the BDNF Gene or Childhood Maltreatment.

[This corrects the article DOI: 10.1371/journal.pone.0158224.].

Predicting Response Trajectories during Cognitive-Behavioural Therapy for Panic Disorder: No Association with the BDNF Gene or Childhood Maltreatment.

BACKGROUND: Anxiety disorders are highly prevalent and result in low quality of life and a high social and economic cost. The efficacy of cognitive-behavioural therapy (CBT) for anxiety disorders is well established, but a substantial proportion of patients do not respond to this treatment. Understanding which genetic and environmental factors are responsible for this differential response to treatment is a key step towards "personalized medicine". Based on previous research, our objective was to test whether the BDNF Val66Met polymorphism and/or childhood maltreatment are associated with response trajectories during exposure-based CBT for panic disorder (PD). METHOD: We used Growth Mixture Modeling to identify latent classes of change (response trajectories) in patients with PD (N = 97) who underwent group manualized exposure-based CBT. We conducted logistic regression to investigate the effect on these trajectories of the BDNF Val66Met polymorphism and two different types of childhood maltreatment, abuse and neglect. RESULTS: We identified two response trajectories ("high response" and "low response"), and found that they were not significantly associated with either the genetic (BDNF Val66Met polymorphism) or childhood trauma-related variables of interest, nor with an interaction between these variables. CONCLUSIONS: We found no evidence to support an effect of the BDNF gene or childhood trauma-related variables on CBT outcome in PD. Future studies in this field may benefit from looking at other genotypes or using different (e.g. whole-genome) approaches.

Coping strategies for postpartum depression: a multi-centric study of 1626 women.

The transition to motherhood is stressful as it requires several important changes in family dynamics, finances, and working life, along with physical and psychological adjustments. This study aimed at determining whether some forms of coping might predict postpartum depressive symptomatology. A total of 1626 pregnant women participated in a multi-centric longitudinal study. Different evaluations were performed 8 and 32 weeks after delivery. Depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS) and the structured Diagnostic Interview for Genetic Studies (DIGS). The brief Coping Orientation for Problem Experiences (COPE) scale was used to measure coping strategies 2-3 days postpartum. Some coping strategies differentiate between women with and without postpartum depression. A logistic regression analysis was used to explore the relationships between the predictors of coping strategies and major depression (according to DSM-IV criteria). In this model, the predictor variables during the first 32 weeks were self-distraction (OR 1.18, 95 % CI 1.04-1.33), substance use (OR 0.58, 95 % CI 0.35-0.97), and self-blame (OR 1.18, 95 % CI 1.04-1.34). In healthy women with no psychiatric history, some passive coping strategies, both cognitive and behavioral, are predictors of depressive symptoms and postpartum depression and help differentiate between patients with and without depression.

Psychometric properties of the Spanish self-report version of the panic disorder severity scale.

OBJECTIVE: The goal of the study was to assess the psychometric properties and the factor structure of the Spanish self-report version of the Panic Disorder Severity Scale (PDSS-SR). METHOD: One hundred and twenty four patients meeting DSM-IV criteria for panic disorder were assessed with the Spanish PDSS-SR, the Anxiety Sensitivity Index-3 (ASI-3), the Sheehan Disability Inventory (SDI) and the Beck Depression Inventory-II (BDI-II). Cronbach's alpha was used to evaluate internal consistency. Pearson correlations were used to evaluate test-retest reliability, convergent and divergent validity. Sensitivity to change data was obtained for 91 patients that had completed a cognitive behavioural therapy. The factor structure was analysed using a confirmatory factor analysis (CFA). RESULTS: The Spanish PDSS-SR showed excellent internal consistency, good test-retest reliability and adequate convergent validity. Regarding divergent validity, the correlation with the BDI-II was larger than expected. The Spanish PDSS-SR was sensitive to change. Our CFA suggested a two-factor model for the scale. CONCLUSIONS: The Spanish PDSS-SR has similar psychometric properties as the previous versions of the PDSS-SR and it can become a useful instrument to assess panic symptoms in clinical and research settings in Spanish-speaking countries.

An association between plasma ferritin concentrations measured 48 h after delivery and postpartum depression.

CONTEXT: Iron deficiency is the most common nutritional problem experienced by childbearing women, and postpartum depression (PPD) is the most common psychiatric disorder seen during the first year after delivery. The possible link between iron deficiency and PPD is not clear. OBJECTIVE: To evaluate whether iron status 48 h after delivery was associated with PPD. Our hypothesis was that iron deficiency would be associated with PPD. DESIGN: This was a prospective cohort study of depression-free women studied in the postpartum period. SETTING: Women who give birth at obstetric units in several general hospitals in Spain. PARTICIPANTS: A subsample of 729 women was included in the present study after exclusion of women with high C-reactive protein (CRP) and other diseases known to interfere with iron metabolism. MAIN OUTCOME MEASURES: We evaluated depressive symptoms at 48 h, 8 weeks and 32 weeks postpartum and used a diagnostic interview to confirm the diagnosis of major depression. A blood sample obtained 48 h after delivery was used to measure the following iron storage parameters: ferritin, transferrin (Tf), free iron and transferrin saturation (TfS) and the inflammatory marker CCRP. RESULTS: Overall, the women in the study had low iron concentrations (8.8 ± 6.9 µmol/L) and low TfS (12.6 ± 9.6%) but normal ferritin and Tf concentrations. A total of 65 women (9%) developed PPD during the 32 week postpartum period; these women also had a lower ferritin concentration (15.4 ± 12.7 µg/L vs. 21.6 ± 13.5 µg/L, P = 0.002). A strong association between ferritin and PPD was observed (odds ratio = 3.73, 95% CI: 1.84-7.56; P = 0.0001 for ferritin cutoff value of 7.26 µg/L). In our study, ferritin concentrations have a high specificity but low sensitivity in predicting PPD. CONCLUSIONS: These findings support the role of iron in the etiology of PPD and the use of ferritin as a marker of iron deficiency in the postpartum period. We believe that this topic deserves further investigation.

Association study of 44 candidate genes with depressive and anxiety symptoms in post-partum women.

The post-partum period is a time of extreme vulnerability for a whole spectrum of psychiatric disorders. Delivery may be considered an important risk factor in genetically susceptible women. Five hundred and eight SNPs in 44 genes at candidate pathways putatively related to mood changes after delivery were genotyped in a multicenter cohort of 1804 women from Spain. Participants completed two scales at 2-3 days, 8 weeks, and 32 weeks post-partum, the Edinburgh Post-partum Depression Scale (EPDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Those women who scored 9 or more on EPDS were evaluated for major depression using the Diagnostic Interview for Genetics Studies (DIGS) adapted for post-partum depression. Association with major depression was assessed using likelihood ratio tests under a codominant genotype model. Association with scale scores was tested using linear mixed models to take into account repeated measures over time. Two intronic SNPs, one at the serotonin transporter gene (SLC6A4) and another at dopa decarboxylase (DDC), were significantly associated to STAI anxiety scores after multiple testing correction (nominal P=0.0000513 and 0.000097, respectively). In addition, post hoc analysis at the unphased haplotype level using nominal significant SNPs revealed an association with a combination of three SNPs at protein kinase C, beta (PRKCB) with major depression, significant after multiple testing correction (nominal global P=0.0001596). In conclusion, we detected a role of SLC6A4 in mood changes after stressful events, and revealed new putative associations involving DDC and PRKCB. Therefore, these genes deserve further investigation to confirm these results.

Thyroid function 48h after delivery as a marker for subsequent postpartum depression.

Physiological changes during gestation and after delivery are associated with postpartum thyroid dysfunction, which is due to thyroid autoimmunity in some cases. Postpartum thyroid dysfunction, in turn, has been associated with postpartum depression (PPD). The aim of the present study was to evaluate whether thyroid function immediately after delivery can predict postpartum depression at 8 weeks and 32 weeks after delivery. This study examined 1053 postpartum Spanish women without a previous history of depression. We evaluated depressive symptoms at 48h, 8 weeks and 32 weeks postpartum and used a diagnostic interview to confirm major depression for all probable cases. Free thyroxin (fT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb) and C-reactive protein (CRP) were assayed at 48h postpartum. Binary and multivariate logistic regression analyses were performed to determine independent risk factors for PPD. Although 152 women (14.4%) had high TPOAb (>27IU/mL) and slightly elevated TSH concentrations with normal fT4, we did not find any association between thyroid function and PPD. This thyroid dysfunction was not associated with CRP concentrations that were outside of the normal range (>3mg/L). We conclude that thyroid function at 48h after delivery does not predict PPD susceptibility.

Prediction of postpartum depression using multilayer perceptrons and pruning.

OBJECTIVE: The main goal of this paper is to obtain a classification model based on feed-forward multilayer perceptrons in order to improve postpartum depression prediction during the 32 weeks after childbirth with a high sensitivity and specificity and to develop a tool to be integrated in a decision support system for clinicians. MATERIALS AND METHODS: Multilayer perceptrons were trained on data from 1397 women who had just given birth, from seven Spanish general hospitals, including clinical, environmental and genetic variables. A prospective cohort study was made just after delivery, at 8 weeks and at 32 weeks after delivery. The models were evaluated with the geometric mean of accuracies using a hold-out strategy. RESULTS: Multilayer perceptrons showed good performance (high sensitivity and specificity) as predictive models for postpartum depression. CONCLUSIONS: The use of these models in a decision support system can be clinically evaluated in future work. The analysis of the models by pruning leads to a qualitative interpretation of the influence of each variable in the interest of clinical protocols.

Failure to detect the 22q11.2 duplication syndrome rearrangement among patients with schizophrenia.

Chromosome aberrations have long been studied in an effort to identify susceptibility genes for schizophrenia. Chromosome 22q11.2 microdeletion is associated with DiGeorge and Velocardiofacial syndromes (DG/VCF) and provides the most convincing evidence of an association between molecular cytogenetic abnormality and schizophrenia. In addition, this region is one of the best replicated linkage findings for schizophrenia. Recently, the reciprocal microduplication on 22q11.2 has been reported as a new syndrome. Preliminary data indicates that individuals with these duplications also suffer from neuropsychiatric disorders. In this study we have investigated the appropriateness of testing schizophrenia patients for the 22q11.2 microduplication. We used multiplex ligation-dependent probe amplification (MLPA) to measure copy number changes on the 22q11.2 region in a sample of 190 patients with schizophrenia. Our results corroborate the prevalence of the 22q11.2 microdeletion in patients with schizophrenia and clinical features of DG/VCFS and do not suggest an association between 22q11.2 microduplication and schizophrenia.

Analyses of variants located in estrogen metabolism genes (ESR1, ESR2, COMT and APOE) and schizophrenia.

Relationships between gender, age-of-onset of schizophrenia and reproductive age strongly suggest a key role for gonadal hormones, and more specifically for estrogens, in the etiology of the illness. Also, estrogens act as neural growth and trophic factors influencing neuron and glial cells in many areas of the central nervous system. Therefore, we investigated the association between schizophrenia and 4 genes related to estrogen metabolism. These genes are ESR1 (estrogen receptor 1), ESR2 (estrogen receptor 2), APOE (apolipoprotein E) and COMT (catechol-O-methyltransferase). The expression of APOE and COMT, which contain estrogen response elements, have been demonstrated to be regulated by the estrogen receptors. In this current association study, we examined 59 single nucleotide polymorphisms (SNPs) located in the ESR1 (26), ESR2 (14), APOE (7) and COMT (12) loci. Allele frequencies were evaluated in the schizophrenia (n=585)-control (n=615) sample and no association was found with any of the four genes. In conclusion, our data suggest that the four analyzed genes do not play an important role in susceptibility to schizophrenia.

Association of schizophrenia with DTNBP1 but not with DAO, DAOA, NRG1 and RGS4 nor their genetic interaction.

Recent reports indicate that DAO, DAOA, DTNBP1, NRG1 and RGS4 are some of the most-replicated genes implicated in susceptibility to schizophrenia. Also, the functions of these genes could converge in a common pathway of glutamate metabolism. The aim of this study was to evaluate if each of these genes, or their interaction, was associated with schizophrenia. A case-control study was conducted in 589 Spanish patients having a diagnosis of schizophrenia, and compared with 617 equivalent control subjects. Several single nucleotide polymorphisms (SNPs) in each gene were determined in all individuals. SNP and haplotype frequencies were compared between cases and controls. The interaction between different SNPs at the same, or at different gene, loci was analyzed by the multifactor dimensionality reduction (MDR) method. We found a new schizophrenia risk and protective haplotypes in intron VII of DTNBP1; one of the most important candidate genes for this disorder, to-date. However, no association was found between DAO, DAOA, NRG1 and RGS4 and schizophrenia. The hypothesis that gene-gene interaction in these five genes could increase the risk for the disorder was not confirmed in the present study. In summary, these results may provide further support for an association between the dysbindin gene (DTNBP1) and schizophrenia, but not between the disease and DAO, DAOA, NRG1 and RGS4 or with the interaction of these genes. In the light of recent data, these results need to be interpreted with caution and future analyses with dense genetic maps are awaited.