Mutational landscape of risk variants in comorbid depression and obesity: a next-generation sequencing approach.

Major depression (MD) and obesity are complex genetic disorders that are frequently comorbid. However, the study of both diseases concurrently remains poorly addressed and therefore the underlying genetic mechanisms involved in this comorbidity remain largely unknown. Here we examine the contribution of common and rare variants to this comorbidity through a next-generation sequencing (NGS) approach. Specific genomic regions of interest in MD and obesity were sequenced in a group of 654 individuals from the PISMA-ep epidemiological study. We obtained variants across the entire frequency spectrum and assessed their association with comorbid MD and obesity, both at variant and gene levels. We identified 55 independent common variants and a burden of rare variants in 4 genes (PARK2, FGF21, HIST1H3D and RSRC1) associated with the comorbid phenotype. Follow-up analyses revealed significantly enriched gene-sets associated with biological processes and pathways involved in metabolic dysregulation, hormone signaling and cell cycle regulation. Our results suggest that, while risk variants specific to the comorbid phenotype have been identified, the genes functionally impacted by the risk variants share cell biological processes and signaling pathways with MD and obesity phenotypes separately. To the best of our knowledge, this is the first study involving a targeted sequencing approach toward the study of the comorbid MD and obesity. The framework presented here allowed a deep characterization of the genetics of the co-occurring MD and obesity, revealing insights into the mutational and functional profile that underlies this comorbidity and contributing to a better understanding of the relationship between these two disabling disorders.

Identification of differentially expressed miRNA in the rat hippocampus during adolescence through an epigenome-wide analysis.

INTRODUCTION: Epigenetic mechanisms involving microRNAs (miRNAs) play a fundamental role in many biological processes, particularly during prenatal and early postnatal development. Their role in adolescent brain development, however, has been poorly described. The present study aims to explore miRNA expression in the hippocampus during adolescence compared to adulthood in rats. METHOD: The brains of female and male Wistar rats were extracted and the hippocampus was freshly dissected at postnatal day 41 (adolescence) and postnatal day 98 (adulthood). An epigenome-wide analysis was conducted to identify the miRNAs significantly expressed in adolescence compared to adulthood. Additionally, target genes of such miRNAs were considered to perform an exploratory gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. RESULTS: We identified 16 differentially expressed miRNAs in adolescent male rats compared with adult male rats, and 4 differentially expressed miRNAs in adolescent females compared with adult females. Enrichment analysis reinforced that the target genes found are related to neurodevelopmental processes such as cell proliferation, cell migration and nervous system development. CONCLUSION: Our findings suggest a complex pattern of miRNA expression during adolescence, which differs from that in adulthood. The differential expression of miRNA in the hippocampus during adolescence may be associated with the late developmental changes occurring in this brain region. Furthermore, the observed sex differences in miRNA expression patterns indicate potential sexual differentiation in hippocampal development. Further comprehensive investigations are needed to elucidate the roles of miRNA in normal brain development.

A Cross-Sectional Study on the Prevalence and Risk Correlates of Mental Disorders: The GRANADΣP Study.

This is a cross-sectional study of participants from a population census living in the province of Granada (Spain). A total of 1176 persons were contacted, 367 (31%) refused and 54 (6.7%) needed substitution. A final sample of 809 participants (response rate, 69.3%) were screened for mental disorder (MD) using the MINI International Neuropsychiatric Interview, a comprehensive interview validated to generate diagnoses compatible with ICD-10/DSM-4 criteria. Current (1-month) prevalence for any MD was 11.3% (95% confidence interval [CI], 9.7%-13.4%; affective 8.2%, anxiety 9.6%, psychotic 2.1%, addiction 1.8%, personality disorder 3.6%). Lifetime MD prevalence was 24.6% (95% CI, 21.6-27.6; affective 14.9%, anxiety 15.5%, psychotic 3.4%, addiction 4.4%, personality disorder 3.6%). Female sex was associated with MD, but this appeared partially due to higher levels of neuroticism among women. MD also correlated significantly with cannabis use, family history of MD, higher social adversity, higher suicide risk, poorer physical health, poorer cognitive performance, and personality problems.

Neural substrates of cognitive flexibility in cocaine and gambling addictions.

BACKGROUND: Individuals with cocaine and gambling addictions exhibit cognitive flexibility deficits that may underlie persistence of harmful behaviours. AIMS: We investigated the neural substrates of cognitive inflexibility in cocaine users v. pathological gamblers, aiming to disambiguate common mechanisms v. cocaine effects. METHOD: Eighteen cocaine users, 18 pathological gamblers and 18 controls performed a probabilistic reversal learning task during functional magnetic resonance imaging, and were genotyped for the DRD2/ANKK Taq1A polymorphism. RESULTS: Cocaine users and pathological gamblers exhibited reduced ventrolateral prefrontal cortex (PFC) signal during reversal shifting. Cocaine users further showed increased dorsomedial PFC (dmPFC) activation relative to pathological gamblers during perseveration, and decreased dorsolateral PFC activation relative to pathological gamblers and controls during shifting. Preliminary genetic findings indicated that cocaine users carrying the DRD2/ANKK Taq1A1+ genotype may derive unique stimulatory effects on shifting-related ventrolateral PFC signal. CONCLUSIONS: Reduced ventrolateral PFC activation during shifting may constitute a common neural marker across gambling and cocaine addictions. Additional cocaine-related effects relate to a wider pattern of task-related dysregulation, reflected in signal abnormalities in dorsolateral and dmPFC.

The risk for major depression conferred by childhood maltreatment is multiplied by BDNF and SERT genetic vulnerability: a replication study.

BACKGROUND: There is limited evidence for a moderating role of both serotonin transporter (SERT) and brain-derived neurotrophic factor (BDNF) genes on the risk for major depression (MD) developing after childhood maltreatment. However, research on this topic remains inconclusive, and there is a lack of data from longitudinal studies with large and representative population samples. Our study aimed to clarify whether, in the presence of previous childhood maltreatment, individuals carrying low functional alleles for both SERT 5-HTTLPR and BDNF Val66Met polymorphisms had a higher risk for MD. METHODS: We explored 2- and 3-way gene (SERT and BDNF) × environment (childhood maltreatment) interactions in a large sample of Spanish adults who were followed up over a 3-year period and assessed in person for both DSM-IV MD and exposure to childhood maltreatment. RESULTS: Our study included 2679 participants. Those with both the 5-HTTLPR s allele and the BDNF Met allele showed the highest risk of MD if they had previously experienced emotional (z = 2.08, p = 0.037), sexual (z = 2.19, p = 0.029) or any kind of childhood abuse (z = 2.37, p = 0.018). These 3-way interactions remained significant regardless of whether the 5-HTTLPR triallelic or the 5-HTTLPR biallelic polymorphisms were included in the analyses. LIMITATIONS: Retrospective assessment of childhood maltreatment may have resulted in a moderate degree of recall bias. CONCLUSION: Our results confirm that the risk of depression conferred by childhood maltreatment is modified by variation at both SERT and BDNF genes.

Epidemiology of social phobia in Andalusia.

INTRODUCTION: Population studies on social anxiety disorder (SAD) are relatively scarce and there is no previous reported evidence on prevalence or correlates of SAD in an Andalusian general population sample. MATERIAL AND METHODS: We used a random representative sample previously identified via standard stratification procedures. Thus, a final sample of 4507 participants were included (response rate 83.7%). Interviewees were thoroughly assessed on sociodemographic, clinical and psychosocial factors, including: exposures to threatening life events (TLEs), childhood abuse, personality disorder and traits (neuroticism, impulsivity, paranoia), global functioning, physical health and toxics consumption. SAD diagnosis was ascertained using the Mini International Neuropsychiatric Interview. Both, pooled prevalences (with 95% confidence intervals) and risk correlates for SAD were estimated using binary logistic regression. RESULTS: Estimated prevalence for SAD was 1.1% (95% CI=0.8-1.4). Having a SAD diagnosis was independently and significantly associated with younger age, poorer global functioning, higher neuroticism and paranoia personality traits, having suffered childhood abuse and exposure to previous TLEs. Furthermore, SAD was significantly associated with comorbid personality disorder, major depression, panic disorder and alcohol abuse. CONCLUSIONS: Among this large Andalusian population sample, the prevalence of SAD and its associated factors are relatively similar to previously reported international studies, although no population study had previously reported such a strong association with paranoia.

An epidemiological survey on personality disorder in Andalusia (the PISMA-ep PD study).

BACKGROUND: Despite a significant clinical and social burden, there is a relative scarcity of epidemiological studies on Personality Disorder (PD). AIM: To determine the current prevalence of PD and the psychosocial correlates associated with this in the Andalusian population. METHOD: We carried out a cross-sectional population mental-health survey in Andalusia, southern Spain. Thus, 4,518 randomly selected participants were interviewed following sampling using different standard stratification levels. We used the Spanish version of the SAPAS to estimate PD prevalence. In addition, a full battery of other instruments was utilized to explore global functionality, childhood abuse, maltreatment, threatening life events, personality traits (neuroticism, impulsivity and paranoia), medical and psychiatric comorbidities, family history of psychological problems and other potential risk factors for PD. RESULTS: PD prevalence (10.8%; 95% CI [9.8, 11.7]) and ran two different multivariate models for PD. We obtained the highest PD prevalence in those affected by any mental disorder plus those reporting having suffered childhood abuse, particularly sexual abuse. Additional potential risk factors or correlates of PD identified were: younger age, lower levels of functioning, less social support, poorer general health, having suffered maltreatment, threatening life events, higher suicidal risk scores and higher levels of both neuroticism and impulsivity. CONCLUSIONS: This study reports PD prevalence and risk correlates in consonance with similar findings reported in other Western populations. However, longitudinal studies are needed to elicit a more thorough group of prospective determinants of PD.

Psychotic symptoms associate inversely with social support, social autonomy and psychosocial functioning: A community-based study.

BACKGROUND: Population-based studies exploring psychotic symptoms (PS) show that their prevalence in the community is higher than previously thought. Psychosocial functioning and social support are poorer among people presenting clinical and subclinical PS. AIMS: We aimed to estimate the prevalence rate of PS in Andalusia and to explore the association between PS and psychosocial functioning, social support and social autonomy in a Southern European population. MATERIAL AND METHODS: This is a cross-sectional study. We undertook multi-stage sampling using different standard stratification techniques. Out of 5496 households approached, we interviewed 4507 (83.7%) randomly selected participants living in the autonomous region of Andalusia (Southern Spain). The Spanish version of the MINI International Neuropsychiatric Interview was used to elicit PS. We also gathered information on socio-demographic factors, suicidality risk, psychosocial functioning, social support and social autonomy. RESULTS: The overall prevalence of PS was 6.7% (95% CI: 5.99-6.45). PS were associated with lower age (OR 0.975; 95% CI (0.967-0.983); p < .0001), female gender (OR = 1.346; 95% CI (1.05-1.07) p = .018), not living in a rural area (OR = 0.677; 95% CI (0.50-0.90) p = 0.009), lower social support (OR = 0.898; 95% CI (0.85-0.94) p < .0001), lower scores on social autonomy (OR = 0.889; 95% CI (0.79-1.00) p = .050), having an increased suicidality risk score (OR = 1.038; 95% CI (1.005-1.07); p = .023) and having lower scores on psychosocial functioning (OR = 0.956; 95% CI (0.95-0.96); p < 0.0001). CONCLUSIONS: Social outcomes seem to be strongly inversely associated with PS in spite of presumed higher levels of social support among Southern European cultures.

Paranoia and Suicidality: A Cross-Sectional Study in the General Population.

Paranoia and suicidality seem to be common traits expressing in the general population to varying degrees. This study aims to explore the association between both and to identify determinants of comorbidity. We interviewed a representative sample of the population in Andalusia (n = 4507) and assessed paranoia and suicidality utilizing the Spanish Green's Paranoid Thoughts Scale (S-GPTS) and the suicidality section of the MINI Neuropsychiatric Interview, respectively. We gathered data on socio-demographics, personality, substance abuse, social support, and environmental distress. We found that paranoia and suicidality were rather common with 6.4% (95% CI: 5.7-7.12) of the sample admitting to some (vs. none) level of suicidality. We also found a robust association between paranoia and suicidality, independent of age and sex (F:298.2; p =.0001; Eta2: .065); 0.5% (95% CI: 0.32-0.76) of the sample (n = 21) presented combinedly high levels of paranoia and some suicidality risk and were considered as having paranoia-suicidality comorbidity (PSC). We identified factors associating with PSC, including poor social support, childhood maltreatment, threatening life-events and increasing personality disorder, and nicotine dependence scores. Paranoia and suicidality are common traits in the general population and their comorbidity seems to associate with low social support, environmental adversity and disordered personality. Suicidality and paranoia are common traits present dimensionally in a representative nonclinical sample. Paranoia strongly and independently associates with suicidality risk in a large population-based study. Paranoia and suicidality comorbidity may be commonly determined by poor social support, disordered personality, previous childhood maltreatment, and exposure to threatening life-events.

Interaction Effect between Physical Activity and the BDNF Val66Met Polymorphism on Depression in Women from the PISMA-ep Study.

The relationship between depression and the Val66Met polymorphism at the brain-derived neurotrophic factor gene (BDNF), has been largely studied. It has also been related to physical activity, although the results remain inconclusive. The aim of this study is to investigate the relationship between this polymorphism, depression and physical activity in a thoroughly characterised sample of community-based individuals from the PISMA-ep study. A total of 3123 participants from the PISMA-ep study were genotyped for the BDNF Val66Met polymorphism, of which 209 had depression. Our results are in line with previous studies reporting a protective effect of physical activity on depression, specifically in light intensity. Interestingly, we report a gene-environment interaction effect in which Met allele carriers of the BDNF Val66Met polymorphism who reported more hours of physical activity showed a decreased prevalence of depression. This effect was observed in the total sample (OR = 0.95, 95%CI = 0.90-0.99, p = 0.027) and was strengthened in women (OR = 0.93, 95%CI = 0.87-0.98, p = 0.019). These results highlight the potential role of physical activity as a promising therapeutic strategy for preventing and adjuvant treatment of depression and suggest molecular and genetic particularities of depression between sexes.

Toxoplasma gondii Seropositivity Interacts with Catechol-O-methyltransferase Val105/158Met Variation Increasing the Risk of Schizophrenia.

Schizophrenia is a heterogeneous and severe psychotic disorder. Epidemiological findings have suggested that the exposure to infectious agents such as Toxoplasma gondii (T. gondii) is associated with an increased risk for schizophrenia. On the other hand, there is evidence involving the catechol-O-methyltransferase (COMT) Val105/158Met polymorphism in the aetiology of schizophrenia since it alters the dopamine metabolism. A case−control study of 141 patients and 142 controls was conducted to analyse the polymorphism, the prevalence of anti-T. gondii IgG, and their interaction on the risk for schizophrenia. IgG were detected by ELISA, and genotyping was performed with TaqMan Real-Time PCR. Although no association was found between any COMT genotype and schizophrenia, we found a significant association between T. gondii seropositivity and the disorder (χ2 = 11.71; p-value < 0.001). Furthermore, the risk for schizophrenia conferred by T. gondii was modified by the COMT genotype, with those who had been exposed to the infection showing a different risk compared to that of nonexposed ones depending on the COMT genotype (χ2 for the interaction = 7.28, p-value = 0.007). This study provides evidence that the COMT genotype modifies the risk for schizophrenia conferred by T. gondii infection, with it being higher in those individuals with the Met/Met phenotype, intermediate in heterozygous, and lower in those with the Val/Val phenotype.

Body mass index interacts with a genetic-risk score for depression increasing the risk of the disease in high-susceptibility individuals.

Depression is strongly associated with obesity among other chronic physical diseases. The latest mega- and meta-analysis of genome-wide association studies have identified multiple risk loci robustly associated with depression. In this study, we aimed to investigate whether a genetic-risk score (GRS) combining multiple depression risk single nucleotide polymorphisms (SNPs) might have utility in the prediction of this disorder in individuals with obesity. A total of 30 depression-associated SNPs were included in a GRS to predict the risk of depression in a large case-control sample from the Spanish PredictD-CCRT study, a national multicentre, randomized controlled trial, which included 104 cases of depression and 1546 controls. An unweighted GRS was calculated as a summation of the number of risk alleles for depression and incorporated into several logistic regression models with depression status as the main outcome. Constructed models were trained and evaluated in the whole recruited sample. Non-genetic-risk factors were combined with the GRS in several ways across the five predictive models in order to improve predictive ability. An enrichment functional analysis was finally conducted with the aim of providing a general understanding of the biological pathways mapped by analyzed SNPs. We found that an unweighted GRS based on 30 risk loci was significantly associated with a higher risk of depression. Although the GRS itself explained a small amount of variance of depression, we found a significant improvement in the prediction of depression after including some non-genetic-risk factors into the models. The highest predictive ability for depression was achieved when the model included an interaction term between the GRS and the body mass index (BMI), apart from the inclusion of classical demographic information as marginal terms (AUC = 0.71, 95% CI = [0.65, 0.76]). Functional analyses on the 30 SNPs composing the GRS revealed an over-representation of the mapped genes in signaling pathways involved in processes such as extracellular remodeling, proinflammatory regulatory mechanisms, and circadian rhythm alterations. Although the GRS on its own explained a small amount of variance of depression, a significant novel feature of this study is that including non-genetic-risk factors such as BMI together with a GRS came close to the conventional threshold for clinical utility used in ROC analysis and improves the prediction of depression. In this study, the highest predictive ability was achieved by the model combining the GRS and the BMI under an interaction term. Particularly, BMI was identified as a trigger-like risk factor for depression acting in a concerted way with the GRS component. This is an interesting finding since it suggests the existence of a risk overlap between both diseases, and the need for individual depression genetics-risk evaluation in subjects with obesity. This research has therefore potential clinical implications and set the basis for future research directions in exploring the link between depression and obesity-associated disorders. While it is likely that future genome-wide studies with large samples will detect novel genetic variants associated with depression, it seems clear that a combination of genetics and non-genetic information (such is the case of obesity status and other depression comorbidities) will still be needed for the optimization prediction of depression in high-susceptibility individuals.

Type 2 Diabetes-Related Variants Influence the Risk of Developing Prostate Cancer: A Population-Based Case-Control Study and Meta-Analysis.

In this study, we have evaluated whether 57 genome-wide association studies (GWAS)-identified common variants for type 2 diabetes (T2D) influence the risk of developing prostate cancer (PCa) in a population of 304 Caucasian PCa patients and 686 controls. The association of selected single nucleotide polymorphisms (SNPs) with the risk of PCa was validated through meta-analysis of our data with those from the UKBiobank and FinnGen cohorts, but also previously published genetic studies. We also evaluated whether T2D SNPs associated with PCa risk could influence host immune responses by analysing their correlation with absolute numbers of 91 blood-derived cell populations and circulating levels of 103 immunological proteins and 7 steroid hormones. We also investigated the correlation of the most interesting SNPs with cytokine levels after in vitro stimulation of whole blood, peripheral mononuclear cells (PBMCs), and monocyte-derived macrophages with LPS, PHA, Pam3Cys, and Staphylococcus Aureus. The meta-analysis of our data with those from six large cohorts confirmed that each copy of the FTOrs9939609A, HNF1Brs7501939T, HNF1Brs757210T, HNF1Brs4430796G, and JAZF1rs10486567A alleles significantly decreased risk of developing PCa (p = 3.70 × 10-5, p = 9.39 × 10-54, p = 5.04 × 10-54, p = 1.19 × 10-71, and p = 1.66 × 10-18, respectively). Although it was not statistically significant after correction for multiple testing, we also found that the NOTCH2rs10923931T and RBMS1rs7593730 SNPs associated with the risk of developing PCa (p = 8.49 × 10-4 and 0.004). Interestingly, we found that the protective effect attributed to the HFN1B locus could be mediated by the SULT1A1 protein (p = 0.00030), an arylsulfotransferase that catalyzes the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. In addition to these results, eQTL analysis revealed that the HNF1Brs7501939, HNF1Brs757210, HNF1Brs4430796, NOTCH2rs10923931, and RBMS1rs7593730 SNPs influence the risk of PCa through the modulation of mRNA levels of their respective genes in whole blood and/or liver. These results confirm that functional TD2-related variants influence the risk of developing PCa, but also highlight the need of additional experiments to validate our functional results in a tumoral tissue context.

[The health system of El Salvador]. / Sistema de salud de El Salvador.

This paper describes the health conditions in El Salvador and the main característics of the Salvadoran health system, including its structure and coverage, its financial sources, the physical, material and human resources available, the stewardship functions developed by the Ministry of Public Health, and the participation of health care users in the evaluation of the system. It also discusses the most recent policy innovations including the approval of the Law for the Creation of the National Health System, which intends to expand coverage, reduce health inequalities and improve the coordination of public health institutions.

A population-based cross-sectional study of cognitive deficits in paranoia.

This study sought to investigate the association between paranoia and performance in a range of neurocognitive domains using a large community sample. We conducted a cross-sectional survey of 4507 individuals within the PISMA-ep Study. We used a large community sample selected after multistage sampling using standard stratification techniques. Socio-demographic variables such as age, gender, educational level, urbanicity, and geographical region were recorded. The Spanish version of the Green Paranoid Thought Scale (S-GPTS) was used to assess paranoid thoughts. The Screening for Cognitive Impairment in Psychiatry (SCIP) was used to assess neurocognitive performance both globally and by domains (i.e., immediate and delayed verbal learning, working memory, verbal fluency and processing speed). Individuals with high S-GPTS paranoia scores showed significantly lower performance on global cognitive function and also on immediate (but not delayed) verbal learning, working memory, verbal fluency and processing speed. These results held statistical significance even after controlling for the effects of education and estimated IQ. We propose that cognitive deficits may be mediators of paranoid thinking formation and need to be considered when assessing patients with high levels of paranoia.

Prevalence and correlates of suicidality in Andalusia (Spain): Results of the epidemiological study PISMA-ep.

BACKGROUND: Suicidality is an important public health problem. Hence, the aims of this study are to report prevalence rates and correlates of suicidality in Andalusia (Southern Spain). METHODS: This is a cross-sectional household survey conducted on a representative sample of adults living in Andalusia. 4507 subjects were interviewed using the Mini International Neuropsychiatric Interview (MINI) to assess suicidality and standardized instruments were employed to evaluate associated variables. A multivariate logistic regression analysis was used to explore independent associations with suicidality. RESULTS: Current prevalence of suicidality was 6.4%, 4.4% showed death wish, 1.4% had ideas of self-harm, 2.4% had suicidal thoughts, 1.1% had a suicidal plan, 0.6% had attempted suicide during the month prior to the interview, and, lastly, 2.6% reported to have had any sort of suicide attempt during his/her previous life. Independent factors associated with suicidality were being female, older age, not having a stable couple, lower levels of social support, having had physical childhood abuse experience, having experienced an increasing number of stressful life events, higher neuroticism scores, having a family history of mental disorder and nicotine or drugs dependence. LIMITATIONS: The instrument employed to measure suicidality is a screening tool rather than a more in-depth diagnostic measure. We have not included all potential correlates of suicidality. This is a cross-sectional study which cannot establish causal relationships between exposures and outcomes. CONCLUSIONS: This is the first epidemiological study in Andalusia on suicidality offering important results of clinical interest for suicide prevention.

Fewer neurological soft signs among first episode psychosis patients with heavy cannabis use.

BACKGROUND: Although neurological soft signs (NSS) have been consistently associated with schizophrenia and a variety of risk factors, few studies have focused on the association between NSS and environmental factors such as cannabis use, particularly in patients with first episode psychosis. METHODS: We administered the Neurological Evaluation Scale (NES) to 92 patients during their first episode of functional psychosis. Psychopathology was assessed with the Positive And Negative Syndrome Scale (PANSS) and the family history of psychotic disorder was established on the basis of the Family Interview for Genetic Studies (FIGS). We also assessed lifetime cannabis and cocaine use utilizing that specific section of the Composite International Diagnostic Interview. The outcome variable was the presence of high NSS, defined by a score above the median split of the NES score (>21). RESULTS: Most patients (80/92, 87%) presented a non-affective psychosis. The presence of high NSS showed a significant independent association with not having been a heavy cannabis user (OR=8.3; 95% CI, 2.4-33.3), family history of psychosis (OR=4.3; 95% CI, 1.2-14.9), male sex (OR=4.0; 95% CI, 1.2-14.0), lower score in verbal fluency and higher score in negative symptoms (both p<0.01). CONCLUSION: Our cross-sectional results support the hypothesis that potentially different pathways associated with the emergence of first episode psychosis may exist, including neurological premorbid alteration and environmental cannabis abuse.

High-activity variants of the uMAOA polymorphism increase the risk for depression in a large primary care sample.

Studies on the association between the functional uMAOA polymorphism and depression have yielded non-conclusive results up till now. One thousand two hundred twenty eight consecutive Spanish primary care attendees, participating in the PREDICT study, agreed to take part in this genetic PREDICT-Gene study. We explored the association between depression and either high-activity uMAOA alleles or genotypes. Depression was diagnosed using the Composite International Diagnostic Interview (CIDI) to establish three different depressive outcomes (ICD-10 Depressive Episode (DE), ICD-10 Severe Depressive Episode (SDE) and DSM-IV Major Depression (MD)). uMAOA genetic variation was determined by PCR amplification and subsequent electrophoresis. Crude and adjusted (gender and/or age) odds ratios, with 95% confidence intervals, were calculated for the associations between allele or genotype frequencies and all three depressive outcomes. We found associations between all three depressive phenotypes and either high-activity alleles or high-activity genotypes in both sexes. The associations were statistically significant for females but not for males. Testing the same associations on the entire sample (males and females) also yielded significant associations between depression and either high-activity alleles or high-activity genotype distribution that were independent of age and/or gender (ICD-10 DE: OR = 1.98; 95% CI: 1.42-1.77; P = 0.00002; ICD-10-SDE: OR = 2.05; 95% CI: 1.38-3.05; P = 0.0002; DSM-IV MD: OR = 1.91; 95% CI: (1.26-2.91); P = 0.0014). Our results provide fairly consistent evidence that high-activity variants of the MAOA promoter polymorphism confer a modestly higher risk for depression.

Associations of major depressive disorder with chronic physical conditions, obesity and medication use: Results from the PISMA-ep study.

BACKGROUND: Life expectancy of people with depression is on average 15 years less than that of the general population. This excess of mortality is largely attributed to a deteriorated physical health. Evidence about the association between major depressive disorder (MDD) and physical health is still lacking in some areas. The aim of this study was to explore the association between MDD and physical health-related variables in southern Spain. METHODS: The PISMA-ep is a cross-sectional study based on community-dwelling adult population. Our main outcome was current prevalence of MDD. Independent variables explored were: lifetime prevalence of twenty-one chronic physical conditions (CPCs), anthropometric measures (height, weight, body max index, and hip and waist circumferences), general health status, and medication use. RESULTS: MDD was significantly associated with any CPC (OR = 2.60; 95% CI: 2.01-3.35; p < 0.001). Increases in BMI were associated with MDD in women (OR=1.08; 95% CI: 1.05-1.11; p < 0.001), but not in men (OR=0.99; 95% CI: 0.95-1.05; p = 0.916). Variables associated with MDD in the multivariate model were: female gender, obesity, general health status, cancer, peptic ulcer, tinnitus and vertigo. 21.4% of participants with MDD received antidepressant treatment. CONCLUSIONS: MDD is associated with CPCs, obesity, and increased use of medication. The high rates of comorbidity between MDD and CPCs call for a more holistic management of patients in the clinical practice. The low rate of antidepressant use may be indicating underdiagnosis. Anthropometric variables were differently associated with MDD depending on gender, suggesting a strong influence of psychosocial factors.