Parent psychopathology and offspring mental disorders: results from the WHO World Mental Health Surveys

Background Associations between specific parent and offspring mental disorders are likely to have been overestimated in studies that have failed to control for parent comorbidity. Aims To examine the associations of parent with respondent disorders. Method Data come from the World Health Organization (WHO) World Mental Health Surveys (n = 51 507). Respondent disorders were assessed with the Composite International Diagnostic Interview and parent disorders with informant-based Family History Research Diagnostic Criteria interviews. Results Although virtually all parent disorders examined (major depressive, generalised anxiety, panic, substance and antisocial behaviour disorders and suicidality) were significantly associated with offspring disorders in multivariate analyses, little specificity was found. Comorbid parent disorders had significant sub-additive associations with offspring disorders. Population-attributable risk proportions for parent disorders were 12.4% across all offspring disorders, generally higher in high- and upper-middle-than low-/lower-middle-income countries, and consistently higher for behaviour (11.0-19.9%) than other (7.1-14.0%) disorders. Conclusions Parent psychopathology is a robust non-specific predictor associated with a substantial proportion of offspring disorders.

Psychiatric comorbidities in temporal lobe epilepsy: Possible relationships between psychotic disorders and involvement of limbic circuits

Objective: Mounting evidence suggests that the limbic system is pathologically involved in cases of psychiatric comorbidities in temporal lobe epilepsy (TLE) patients. Our objective was to develop a conceptual framework describing how neuropathological and connectivity changes might contribute to the development of psychosis and to the potential neurobiological mechanisms that cause schizophrenia-like psychosis in TLE patients. Methods: In this review, clinical and neuropathological findings, especially brain circuitry of the limbic system, were examined together to enhance our understanding of the association between TLE and psychosis. Finally, the importance of animal models in epilepsy and psychiatric disorders was discussed. Conclusions: TLE and psychiatric symptoms coexist more frequently than chance would predict. Damage and deregulation among critical anatomical regions, such as the hippocampus, amygdala, thalamus, and the temporal, frontal and cingulate cortices, might predispose TLE brains to psychosis. Studies of the effects of kindling and injection of neuroactive substances on behavior and electrophysiological patterns may offer a model of how limbic seizures in humans increase the vulnerability of TLE patients to psychiatric symptoms.

Sleep disorders in climacteric women

Introduction: This paper examines the various factors that contribute to the occurrence of sleep alterations during peri and post climacteric and thus produce significant imperil to women's quality of life. Among the probable causes of insomnia or sleep disorders associated to climacteric stand out the occurrence of vasomotor symptoms, depressive state and respiratory distress during sleep, such as sleep apnea, along with chronic pain, although psychosocial factors related to the climacteric bear major influence on such clinical status. Method: The bibliographic analysis was carried out using several electronic data base namely: Cochrane, Medline, Embase, Bni Plus, Biological Abstracts, Psycinfo, Web Of Science, Sigle, Dissertation Abstracts and ZETOC published in English, Spanish and Poruguese. The key terms used were: sleep, REM sleep, slow wave sleep polysomnography; electroencephalogram; sleep disturbances; disturbances of sleep onset and maintenance; excessive somnolence disturbances; climacteric; menopause; depression; neurobiology; biologic models; circadian rhythm; mental health and epidemiology. Case studies and letters to the editor were excluded. The summaries of the identified studies found in the data base were analyzed and assessed, and the data analyzed separately according to the subjective or objective criteria for data collection. Results: The climacteric transition constitutes a period of major risk for the development of depressive, vasomotor and insomnia symptoms although not caused solely by hypoestrogenism. The diagnostic methods used in the study of sleep disorders range from subjective assessment by means of response to specific questionnaires to the objective analysis of actigraphic or polissonographic daytime and nocturnal reports. Polissonographic studies of the whole night, performed at the laboratory, are the golden method of choice for diagnostic of sleep disorders. Studies point to the high prevalence of sleep disorders in the climacteric, especially insomnia, apnea and periodic movement of legs and also to the fact that this phase of life presents decrease in the quality of sleep. Women in peri and post climacteric show higher sleep latency and difficulty in its maintenance and refer being less satisfied with its quality even when compared to those who are not climacteric. Exception made to the vasomotor symptomatology, the other climacteric complaints such as mood disturbances, libido alterations, cognitive deficit, articular pain and sleep disorders are markedly associated to psychosocial factors, lifestyle and especially to women's perception of what the climacteric means to their lives. Conclusion: The analysis of the available studies revealed a proneness to deterioration of quality of life of climacteric women markedly in the sleep disturbances, depressed mood and anxiety domains and should not to be basically attributed to the climacteric. It is necessary that the professionals consider the need of assessment of such pathologies as complex phenomena and the literature lacks studies contemplating such dimensions.

Matrix metalloproteinase-9 polymorphisms affect plasma MMP-9 levels and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy

Abnormal matrix metalloproteinase (MMP)-9 levels may have a role in hypertensive disorders of pregnancy. We examined whether MMP-9 genetic polymorphisms (g.-1562C>T and g.-90(CA)(13-25)) modify plasma MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels and the responses to antihypertensive therapy in 214 patients with preeclampsia (PE), 185 patients with gestational hypertension (GH) and a control group of 214 healthy pregnant (HP). Alleles for the g.-90(CA)(13-25) polymorphism were grouped L (low) (<21 CA repeats) or H (high) (>= 21 CA repeats). Plasma MMP-9 and TIMP-1 concentrations were measured by enzyme-linked immunosorbent assay. Plasma MMP-9 concentrations were not affected by genotypes or haplotypes in HP and PE groups, except for the g.-90(CA)(13-25) polymorphism: GH patients with the LH genotype for this polymorphism have higher MMP-9 levels than those with other genotypes. The T allele for the g.-1562C>T polymorphism and the H4 haplotype (combining T and H alleles) are associated with GH and lack of responsiveness to antihypertensive therapy in GH. The H2 haplotype (combining C and H alleles) was associated with lack of responsiveness to antihypertensive therapy in PE, but not in GH. In conclusion, our results show that MMP-9 genetic variants are associated with GH and suggest that MMP-9 haplotypes affect the responsiveness to antihypertensive therapy in hypertensive disorders of pregnancy. The Pharmacogenomics Journal (2012) 12, 489-498; doi: 10.1038/tpj.2011.31; published online 19 July 2011

Pathophysiology of mood disorders in temporal lobe epilepsy

Objective: There is accumulating evidence that the limbic system is pathologically involved in cases of psychiatric comorbidities in temporal lobe epilepsy (TLE) patients. Our objective was to develop a conceptual framework describing how neuropathological, neurochemical and electrophysiological aspects might contribute to the development of psychiatric symptoms in TLE and the putative neurobiological mechanisms that cause mood disorders in this patient subgroup. Methods: In this review, clinical, experimental and neuropathological findings, as well as neurochemical features of the limbic system were examined together to enhance our understanding of the association between TLE and psychiatric comorbidities. Finally, the value of animal models in epilepsy and mood disorders was discussed. Conclusions: TLE and psychiatric symptoms coexist more frequently than chance would predict. Alterations and neurotransmission disturbance among critical anatomical networks, and impaired or aberrant plastic changes might predispose patients with TLE to mood disorders. Clinical and experimental studies of the effects of seizures on behavior and electrophysiological patterns may offer a model of how limbic seizures increase the vulnerability of TLE patients to precipitants of psychiatric symptoms.

Vitamin D receptor polymorphisms in hypertensive disorders of pregnancy

Hypertension is the most common medical disorder in pregnancy, and a leading cause of maternal and neonatal morbidity and mortality. Vitamin D endocrine system has important influence on immune modulation and endothelial function, which play a role in preeclampsia (PE) and gestational hypertension (GH). Vitamin D receptor (VDR) is present in a large variety of cell types, including placental cells. We examined whether there is an association between VDR polymorphisms (FokI, ApaI and BsmI) with PE or with GH. Restriction fragment length polymorphism techniques were used to genotype 529 pregnant (154 with GH, 162 with PE, and 213 healthy pregnant-HP). VDR haplotype frequencies were inferred using the PHASE 2.1 program. We found similar genotype distributions for the three VDR polymorphisms in both PE and GH groups compared with the HP group (all P > 0.05). In parallel with these findings, the VDR haplotype frequency distribution was similar in both PE and GH groups compared with the HP group (all P > 0.05). Our results showing no significant association between VDR polymorphisms or haplotypes with PE or GH suggest that genetic variations in VDR do not predispose to hypertensive disorders of pregnancy.

Epistasis among eNOS, MMP-9 and VEGF maternal genotypes in hypertensive disorders of pregnancy

Polymorphisms of the endothelial nitric oxide synthase (eNOS), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) genes were shown to be associated with hypertensive disorders of pregnancy. However, epistasis is suggested to be an important component of the genetic susceptibility to preeclampsia (PE). The aim of this study was to characterize the interactions among these genes in PE and gestational hypertension (GH). Seven clinically relevant polymorphisms of eNOS (T-786C, rs2070744, a variable number of tandem repeats in intron 4 and Glu298Asp, rs1799983), MMP-9 (C-1562T, rs3918242 and -90(CA)(13-25), rs2234681) and VEGF (C-2578A, rs699947 and G-634C, rs2010963) were genotyped by TaqMan allelic discrimination assays or PCR and fragment separation by electrophoresis in 122 patients with PE, 107 patients with GH and a control group of 102 normotensive pregnant (NP) women. A robust multifactor dimensionality reduction analysis was used to characterize gene-gene interactions. Although no significant genotype combinations were observed for the comparison between the GH and NP groups (P>0.05), the combination of MMP-9-1562CC with VEGF-634GG was more frequent in NP women than in women with PE (P<0.05). Moreover, the combination of MMP-9-1562CC with VEGF-634CC or MMP-9-1562CT with VEGF-634CC or-634GG was more frequent in women with PE than in NP women (P<0.05). These results are obscured when single polymorphisms in these genes are considered and suggest that specific genotype combinations of MMP-9 and VEGF contribute to PE susceptibility. Hypertension Research (2012) 35, 917-921; doi:10.1038/hr.2012.60; published online 10 May 2012

Social Skills and Psychological Disorders: Converging and Criterion-Related Validity for YSR and IHSA-Del-Prette in Adolescents at Risk

This study evaluated indexes of converging and criterion-related validity for the Social Skills Inventory for Adolescents (IHSA-Del-Prette) and the Youth Self-Report (YSR) in two samples: one referring to clinical service (CLIN), with 28 adolescents (64.3% boys), 11 through 17 years old (M = 13.75; SD = 1.74), and the other referring to a psycho-educational program (PME = 46.2%), mainly composed of boys (91.7%) aged 13 through 17 (M = 15.33; SD = 1.47). Both samples completed the two inventories. Results showed a high incidence of psychological disorders in both samples (between 4% and 79% in the borderline or clinical range on YSR scales) and accentuated deficits in the general and subscale scores of IHSA-Del-Prette, especially on the frequency scale (25% to 58%). The correlations between the instruments in the two groups supported criterion-related and converging validity. Some issues concerning the differences between the samples and about the construct of social competence, underlying these inventories, are discussed. Key words authors:

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

We examined whether two functional polymorphisms (g.-1306 C> T and g.-735 C>T) in matrix metalloproteinase (MMP)-2 gene are associated with preeclampsia (PE) or gestational hypertension (GH), and whether they modify MMP-2 or tissue inhibitor of metalloproteinase (TIMP)-2 plasma concentrations in these hypertensive disorders of pregnancy. We studied 130 healthy pregnant (HP), 130 pregnant with GH, and 133 pregnant with PE. Genomic DNA was extracted from whole blood and genotypes for g.-1306 C>T and g.-735 C>T polymorphisms were determined by Real Time-PCR, using Taqman allele discrimination assays. Haplotypes were inferred using the PHASE program. Plasma MMP-2 and TIMP-2 concentrations were measured by ELISA. The main findings were that pregnant with PE have higher plasma MMP-2 and TIMP-2 concentrations than HP (P<0.05), although the MMP-2/TIMP-2 ratios were similar (P>0.05). Moreover, pregnant with GH have elevated plasma MMP-2 levels and MMP-2/TIMP-2 ratios compared to HP (P<0.05). While MMP-2 genotypes and haplotypes are not linked with hypertensive disorders of pregnancy, MMP-2 genotypes and haplotypes are associated with significant alterations in plasma MMP-2 and TIMP-2 concentrations in preeclampsia (P<0.05). Our findings may help to understand the relevance of MMP-2 and its genetic polymorphisms to the pathophysiology of hypertensive disorders of pregnancy. It is possible that patients with PE and the MMP-2 haplotype combining the C and T alleles for the g.-1306 C>T and g.-735 C>T polymorphisms may benefit from the use of MMPs inhibitors such as doxycycline. However, this possibility remains to be determined. (C) 2012 Elsevier Inc. All rights reserved.

Mental Disorders in Megacities: Findings from the Sao Paulo Megacity Mental Health Survey, Brazil

Background: World population growth is projected to be concentrated in megacities, with increases in social inequality and urbanization-associated stress. Sao Paulo Metropolitan Area (SPMA) provides a forewarning of the burden of mental disorders in urban settings in developing world. The aim of this study is to estimate prevalence, severity, and treatment of recently active DSM-IV mental disorders. We examined socio-demographic correlates, aspects of urban living such as internal migration, exposure to violence, and neighborhood-level social deprivation with 12-month mental disorders. Methods and Results: A representative cross-sectional household sample of 5,037 adults was interviewed face-to-face using the WHO Composite International Diagnostic Interview (CIDI), to generate diagnoses of DSM-IV mental disorders within 12 months of interview, disorder severity, and treatment. Administrative data on neighborhood social deprivation were gathered. Multiple logistic regression was used to evaluate individual and contextual correlates of disorders, severity, and treatment. Around thirty percent of respondents reported a 12-month disorder, with an even distribution across severity levels. Anxiety disorders were the most common disorders (affecting 19.9%), followed by mood (11%), impulse-control (4.3%), and substance use (3.6%) disorders. Exposure to crime was associated with all four types of disorder. Migrants had low prevalence of all four types compared to stable residents. High urbanicity was associated with impulse-control disorders and high social deprivation with substance use disorders. Vulnerable subgroups were observed: women and migrant men living in most deprived areas. Only one-third of serious cases had received treatment in the previous year. Discussion: Adults living in Sao Paulo megacity had prevalence of mental disorders at greater levels than similar surveys conducted in other areas of the world. Integration of mental health promotion and care into the rapidly expanding Brazilian primary health system should be strengthened. This strategy might become a model for poorly resourced and highly populated developing countries.

Teachers' sick leave due to mental and behavioral disorders and return to work

This manuscript presents a review of the literature about medical leaves due to mental and behavioral disorders and return to work of teachers. There are scarce published manuscripts. Most articles relate with prevalence of mental disorders and factors associated with the work organization, and did not mention intervention proposals and or changes in the work organization and teaching work. Proposed actions are discussed.

Lifetime Prevalence, Age and Gender Distribution and Age-of-Onset of Psychiatric Disorders in the Sao Paulo Metropolitan Area, Brazil: Results from the Sao Paulo Megacity Mental Health Survey

Objectives: To estimate prevalence, age-of-onset, gender distribution and identify correlates of lifetime psychiatric disorders in the Sao Paulo Metropolitan Area (SPMA). Methods: The Sao Paulo Megacity Mental Health Survey assessed psychiatric disorders on a probabilistic sample of 5,037 adult residents in the SPMA, using the World Mental Health Survey Version of the Composite International Diagnostic Interview. Response rate was 81.3%. Results: Lifetime prevalence for any disorder was 44.8%; estimated risk at age 75 was 57.7%; comorbidity was frequent. Major depression, specific phobias and alcohol abuse were the most prevalent across disorders; anxiety disorders were the most frequent class. Early age-of-onset for phobic and impulse-control disorders and later age-of-onset for mood disorders were observed. Women were more likely to have anxiety and mood disorders, whereas men, substance use disorders. Apart from conduct disorders, more frequent in men, there were no gender differences in impulse-control disorders. There was a consistent trend of higher prevalence in the youngest cohorts. Low education level was associated to substance use disorders. Conclusions: Psychiatric disorders are highly prevalent among the general adult population in the SPMA, with frequent comorbidity, early age-of-onset for most disorders, and younger cohorts presenting higher rates of morbidity. Such scenario calls for vigorous public health action.

Maternal iNOS genetic polymorphisms and hypertensive disorders of pregnancy

Increased expression and activity of inducible nitric oxide synthase (iNOS) may contribute to the pathogenesis of pre-eclampsia (PE) and gestational hypertension (GH). However, no previous study has examined whether genetic polymorphisms in the iNOS gene are associated with PE or GH. We examined whether two functional, clinically relevant iNOS genetic polymorphisms (the C(-1026)A polymorphism, rs2779249, in the promoter region, and the G2087A polymorphism, rs2297518, in exon 16) are associated with GH or with PE. We studied 565 pregnant women: 212 healthy pregnant (HP), 166 pregnant with GH and 187 pregnant with PE. Genotypes were determined by real-time PCR, using the Taqman allele discrimination assay. The PHASE 2.1 program was used to estimate haplotype distributions in the three study groups. We found no significant association between the C(-1026)A polymorphism and PE or GH (P>0.05). However, we found the GA genotype and the A allele for the G2087A polymorphism at higher frequency in PE, but not in GH, compared with HP (P<0.05). The haplotype analysis showed no significant intergroup differences (P>0.05). These findings suggest that iNOS genetic variants may affect the susceptibility to PE, but not to GH. Journal of Human Hypertension (2012) 26, 547-552; doi:10.1038/jhh.2011.65; published online 30 June 2011

Speech perception and cortical auditory evoked potentials in cochlear implant users with auditory neuropathy spectrum disorders

Objective: To characterize the PI component of long latency auditory evoked potentials (LLAEPs) in cochlear implant users with auditory neuropathy spectrum disorder (ANSD) and determine firstly whether they correlate with speech perception performance and secondly whether they correlate with other variables related to cochlear implant use. Methods: This study was conducted at the Center for Audiological Research at the University of Sao Paulo. The sample included 14 pediatric (4-11 years of age) cochlear implant users with ANSD, of both sexes, with profound prelingual hearing loss. Patients with hypoplasia or agenesis of the auditory nerve were excluded from the study. LLAEPs produced in response to speech stimuli were recorded using a Smart EP USB Jr. system. The subjects' speech perception was evaluated using tests 5 and 6 of the Glendonald Auditory Screening Procedure (GASP). Results: The P-1 component was detected in 12/14 (85.7%) children with ANSD. Latency of the P-1 component correlated with duration of sensorial hearing deprivation (*p = 0.007, r = 0.7278), but not with duration of cochlear implant use. An analysis of groups assigned according to GASP performance (k-means clustering) revealed that aspects of prior central auditory system development reflected in the P-1 component are related to behavioral auditory skills. Conclusions: In children with ANSD using cochlear implants, the P-1 component can serve as a marker of central auditory cortical development and a predictor of the implanted child's speech perception performance. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

Voice disorders in children and its relationship with auditory, acoustic and vocal behavior parameters

Objective: Parameters to distinguish normal from deviant voices in early childhood have not been established. The current study sought to auditorily and acoustically characterize voices of children, and to study the relationship between vocal behavior reported by teachers and the presence of vocal aberrations. Methods: One hundred children between four and 6 years and 11 months, who attended early childhood educational institutions, were included. The sample comprised 50 children with normal voices (NVG) and 50 with deviant voices (DVG) matched by gender and age. All participants were submitted to auditory and acoustic analysis of vocal quality and had their vocal behaviors assessed by teachers through a specific protocol. Results: DVG had a higher incidence of breathiness (p < 0.001) and roughness (p < 0.001), but not vocal strain (p = 0.546), which was similar in both groups. The average F-0 was lower in the DVG and a higher noise component was observed in this group as well. Regarding the protocol used "Aspects Related to Phonotrauma - Children's Protocol", higher means were observed for children from DVG in all analyzed aspects and also on the overall means (DVG = 2.15; NVG = 1.12, p < 0.001). In NVG, a higher incidence of vocal behavior without alterations or with discrete alterations was observed, whereas a higher incidence of moderate, severe or extreme alterations of vocal behavior was observed in DVG. Conclusions: Perceptual assessment of voice, vocal acoustic parameters (F-0, noise and GNE), and aspects related to vocal trauma and vocal behavior differentiated the groups of children with normal voice and deviant voice. (C) 2012 Elsevier Ireland Ltd. All rights reserved.