The specificity of the familial aggregation of early-onset bipolar disorder: A controlled 10-year follow-up study of offspring of parents with mood disorders.

BACKGROUND: Two major sources of heterogeneity of mood disorders that have been demonstrated in clinical, family and genetic studies are the mood disorder subtype (i.e. bipolar (BPD) and major depressive disorder (MDD)) and age of onset of mood episodes. Using a prospective high-risk study design, our aims were to test the specificity of the parent-child transmission of BPD and MDD and to establish the risk of psychopathology in offspring in function of the age of onset of the parental disorder. METHODS: Clinical information was collected on 208 probands (n=81 with BPD, n=64 with MDD, n=63 medical controls) as well as their 202 spouses and 372 children aged 6-17 years at study entry. Parents and children were directly interviewed every 3 years (mean duration of follow-up=10.6 years). Parental age of onset was dichotomized at age 21. RESULTS: Offspring of parents with early onset BPD entailed a higher risk of BPD HR=7.9(1.8-34.6) and substance use disorders HR=5.0(1.1-21.9) than those with later onset and controls. Depressive disorders were not significantly increased in offspring regardless of parental mood disorder subtype or age of onset. LIMITATIONS: Limited sample size, age of onset in probands was obtained retrospectively, age of onset in co-parents was not adequately documented, and a quarter of the children had no direct interview. CONCLUSIONS: Our results provide support for the independence of familial aggregation of BPD from MDD and the heterogeneity of BPD based on patterns of onset. Future studies should further investigate correlates of early versus later onset BPD.

The use of tricyclic antidepressants in the treatment of temporomandibular joint disorders: systematic review of the literature of the last 20 years

Many therapies have been proposed for the management of temporomandibular disorders, including the use of different drugs. However, lack of knowledge about the mechanisms behind the pain associated with this pathology, and the fact that the studies carried out so far use highly disparate patient selection criteria, mean that results on the effectiveness of the different medications are inconclusive. This study makes a systematic review of the literature published on the use of tricyclic antidepressants for the treatment of temporomandibular disorders, using the SORT criteria (Strength of recommendation taxonomy) to consider the level of scientific evidence of the different studies. Following analysis of the articles, and in function of their scientific quality, a type B recommendation is given in favor of the use of tricyclic antidepressants for the treatment of temporomandibular disorders.

Articulação temporomandibular - aspectos normais e deslocamentos de disco: imagem por ressonância magnética

O deslocamento de disco da articulação temporomandibular tem sido definido como uma relação anormal do disco articular com o côndilo mandibular, fossa e eminência articulares. Os deslocamentos de disco podem estar presentes sem interferir com a função articular a curto prazo. A ressonância magnética tem sido o exame de imagem de primeira escolha para o diagnóstico das anormalidades de tecido mole da articulação temporomandibular, uma vez que apresenta alta acurácia na determinação da posição do disco articular. O objetivo deste trabalho é apresentar uma revisão de literatura, demonstrando os aspectos normais e os diferentes tipos de deslocamentos de disco desta articulação e o seu diagnóstico por imagem, destacando o papel do exame por ressonância magnética.

Avaliação de processos inflamatórios na articulação temporomandibular empregando leucócitos autólogos marcados com tecnécio-99m em modelo animal

OBJETIVO: O objetivo deste estudo foi identificar processos inflamatórios na articulação temporomandibular empregando leucócitos autólogos marcados com tecnécio-99m hexametilpropilenoaminooxima (99mTc-HMPAO). MATERIAIS E MÉTODOS: Foi utilizado um modelo experimental de indução de artrite na articulação temporomandibular de dez coelhos machos da raça Nova Zelândia, por meio da injeção intra-articular de ovalbumina na articulação temporomandibular esquerda de cada animal. Para controle, na articulação contralateral foi injetada solução salina. Após a marcação dos leucócitos com 99mTc-HMPAO e injeção endovenosa deste complexo nos coelhos, imagens cintilográficas foram obtidas. RESULTADOS: Observou-se captação aumentada dos 99mTc-HMPAO-leucócitos na articulação temporomandibular esquerda quando comparada à direita. A análise estatística foi realizada utilizando-se o teste não-paramétrico de Wilcoxon. Houve diferença estatisticamente significativa dos valores das contagens por minuto de radioatividade, relativos à articulação inflamada quando comparados aos valores obtidos na articulação contralateral (p = 0,0073). CONCLUSÃO: O método empregando leucócitos autólogos marcados com 99mTc-HMPAO é capaz de identificar focos inflamatórios de forma precoce e precisa, o que poderá contribuir na conduta terapêutica dos pacientes, antes que alterações estruturais sejam instaladas.

Prevalência de alteração morfológica do processo estilóide em pacientes com desordem temporomandibular

OBJETIVO: Avaliar, radiograficamente, a prevalência de alterações morfológicas do processo estilóide em pacientes com desordens temporomandibulares. MATERIAIS E MÉTODOS: Foram analisadas 1.500 radiografias panorâmicas da articulação temporomandibular de pacientes de ambos os sexos e sem limitação de idade, que foram atendidos pelo Serviço de Desordem Temporomandibular da Faculdade de Odontologia da Universidade Federal de Juiz de Fora, MG, no período de 1997 a 2003. RESULTADOS: Oitenta e três (5,53%) dos pacientes da amostra apresentaram pelo menos um dos lados da articulação com alteração morfológica do processo estilóide, sendo 74 do sexo feminino e 9 do sexo masculino, concentrados na faixa dos 41 a 50 anos de idade (32,5%). Com relação ao tipo morfológico do processo estilóide, verificaram-se 113 alongados, 21 pseudo-articulados e 19 segmentados. Constatou-se, também, que as alterações morfológicas do processo estilóide desenvolvem-se de forma simétrica. CONCLUSÃO: Em pacientes com desordem temporomandibular as alterações do processo estilóide ocorrem de forma diferenciada e de maneira simétrica em cada paciente, independentemente do sexo e da idade.

Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

BACKGROUND: Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD. METHODS: In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset. RESULTS: We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p = .0002). CONCLUSIONS: After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders.

Ressonância magnética e tomografia computadorizada da articulação temporomandibular: além da disfunção

Várias doenças devem ser consideradas no diagnóstico diferencial dos distúrbios que comprometem as articulações temporomandibulares. A disfunção interna é a principal entidade responsável pelos quadros dolorosos desta articulação. Entretanto, os achados clínicos podem ser bastante inespecíficos e diversas outras condições se manifestam com sinais e sintomas semelhantes e, não raramente, indistinguíveis. Neste trabalho demonstramos, por meio de imagens de tomografia computadorizada e ressonância magnética, várias doenças não-disfuncionais, enfatizando a importância dos métodos de imagem no diagnóstico de doenças inflamatórias, neoplásicas e traumáticas desta região. O papel do radiologista é fundamental no diagnóstico diferencial, uma vez que o quadro clínico é, com freqüência, inespecífico.

A mild form of SLC29A3 disorder: a frameshift deletion leads to the paradoxical translation of an otherwise noncoding mRNA splice variant

We investigated two siblings with granulomatous histiocytosis prominent in the nasal area, mimicking rhinoscleroma and Rosai-Dorfman syndrome. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous frameshift deletion in SLC29A3, which encodes human equilibrative nucleoside transporter-3 (hENT3). Germline mutations in SLC29A3 have been reported in rare patients with a wide range of overlapping clinical features and inherited disorders including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, and Faisalabad histiocytosis. With the exception of insulin-dependent diabetes and mild finger and toe contractures in one sibling, the two patients with nasal granulomatous histiocytosis studied here displayed none of the many SLC29A3-associated phenotypes. This mild clinical phenotype probably results from a remarkable genetic mechanism. The SLC29A3 frameshift deletion prevents the expression of the normally coding transcripts. It instead leads to the translation, expression, and function of an otherwise noncoding, out-of-frame mRNA splice variant lacking exon 3 that is eliminated by nonsense-mediated mRNA decay (NMD) in healthy individuals. The mutated isoform differs from the wild-type hENT3 by the modification of 20 residues in exon 2 and the removal of another 28 amino acids in exon 3, which include the second transmembrane domain. As a result, this new isoform displays some functional activity. This mechanism probably accounts for the narrow and mild clinical phenotype of the patients. This study highlights the"rescue" role played by a normally noncoding mRNA splice variant of SLC29A3, uncovering a new mechanism by which frameshift mutations can be hypomorphic.

NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina.

We report two unrelated patients with a multisystem disease involving liver, eye, immune system, connective tissue, and bone, caused by biallelic mutations in the neuroblastoma amplified sequence (NBAS) gene. Both presented as infants with recurrent episodes triggered by fever with vomiting, dehydration, and elevated transaminases. They had frequent infections, hypogammaglobulinemia, reduced natural killer cells, and the Pelger-Huët anomaly of their granulocytes. Their facial features were similar with a pointed chin and proptosis; loose skin and reduced subcutaneous fat gave them a progeroid appearance. Skeletal features included short stature, slender bones, epiphyseal dysplasia with multiple phalangeal pseudo-epiphyses, and small C1-C2 vertebrae causing cervical instability and myelopathy. Retinal dystrophy and optic atrophy were present in one patient. NBAS is a component of the synthaxin-18 complex and is involved in nonsense-mediated mRNA decay control. Putative loss-of-function mutations in NBAS are already known to cause disease in humans. A specific founder mutation has been associated with short stature, optic nerve atrophy and Pelger-Huët anomaly of granulocytes (SOPH) in the Siberian Yakut population. A more recent report associates NBAS mutations with recurrent acute liver failure in infancy in a group of patients of European descent. Our observations indicate that the phenotypic spectrum of NBAS deficiency is wider than previously known and includes skeletal, hepatic, metabolic, and immunologic aspects. Early recognition of the skeletal phenotype is important for preventive management of cervical instability. © 2015 Wiley Periodicals, Inc.

Video Gaming Disorder and Sport and Exercise in Emerging Adulthood: A Longitudinal Study.

Among the negative consequences of video gaming disorder, decreased participation in sport and exercise has received little attention. This study aimed to assess the longitudinal association between video gaming disorder and the level of sport and exercise in emerging adult men. A questionnaire was completed at baseline and 15-month follow-up by a representative national sample of 4,933 respondents. The seven items of the Game Addiction Scale were used to construct a latent variable representing video gaming disorder. Level of sport and exercise was also self-reported. Cross-lagged path modeling indicated a reciprocal causality between video gaming disorder and the level of sport and exercise, even after adjusting for a large set of confounders. These findings support the need for better promotion of sport and exercise among emerging adults in order to contribute to the prevention of video gaming disorder, and to raise the level of sport and exercise activity in addicted gamers.

Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.

BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.AimsWe sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.MethodTo detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.ConclusionsOur findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.

Independent and combined associations of risky single-occasion drinking and drinking volume with alcohol use disorder: Evidence from a sample of young Swiss men.

BACKGROUND: Risky single-occasion drinking (RSOD) is a prevalent and potentially harmful alcohol use pattern associated with increased alcohol use disorder (AUD). However, RSOD is commonly associated with a higher level of alcohol intake, and most studies have not controlled for drinking volume (DV). Thus, it is unclear whether the findings provide information about RSOD or DV. This study sought to investigate the independent and combined effects of RSOD and DV on AUD. METHODS: Data were collected in the longitudinal Cohort Study on Substance Use Risk Factors (C-SURF) among 5598 young Swiss male alcohol users in their early twenties. Assessment included DV, RSOD, and AUD at two time points. Generalized linear models for binomial distributions provided evidence regarding associations of DV, RSOD, and their interaction. RESULTS: DV, RSOD, and their interaction were significantly related to the number of AUD criteria. The slope of the interaction was steeper for non/rare RSOD than for frequent RSOD. CONCLUSIONS: RSOD appears to be a harmful pattern of drinking, associated with increased AUD and it moderated the relationship between DV and AUD. This study highlighted the importance of taking drinking patterns into account, for both research and public health planning, since RSO drinkers constitute a vulnerable subgroup for AUD.

Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism.

Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism. Azorin JM, Bowden CL, Garay RP, Perugi G, Vieta E, Young AH. Source Department of Psychiatry, CHU Sainte Marguerite, Marseilles, France. Abstract About half of all bipolar patients have an alcohol abuse problem at some point of their lifetime. However, only one randomized, controlled trial of pharmacotherapy (valproate) in this patient population was published as of 2006. Therefore, we reviewed clinical trials in this indication of the last four years (using mood stabilizers, atypical antipsychotics, and other drugs). Priority was given to randomized trials, comparing drugs with placebo or active comparator. Published studies were found through systematic database search (PubMed, Scirus, EMBASE, Cochrane Library, Science Direct). In these last four years, the only randomized, clinically relevant study in bipolar patients with comorbid alcoholism is that of Brown and colleagues (2008) showing that quetiapine therapy decreased depressive symptoms in the early weeks of use, without modifying alcohol use. Several other open-label trials have been generally positive and support the efficacy and tolerability of agents from different classes in this patient population. Valproate efficacy to reduce excessive alcohol consumption in bipolar patients was confirmed and new controlled studies revealed its therapeutic benefit to prevent relapse in newly abstinent alcoholics and to improve alcohol hallucinosis. Topiramate deserves to be investigated in bipolar patients with comorbid alcoholism since this compound effectively improves physical health and quality of life of alcohol-dependent individuals. In conclusion, randomized, controlled research is still needed to provide guidelines for possible use of valproate and other agents in patients with a dual diagnosis of bipolar disorder and substance abuse or dependence.

Paranoia and post-traumatic stress disorder in the months after a physical assault: a longitudinal study examining shared and differential predictors.

Background: Being physically assaulted is known to increase the risk of the occurrence of post-traumatic stress disorder (PTSD) symptoms but it may also skew judgements about the intentions of other people. The objectives of the study were to assess paranoia and PTSD after an assault and to test whether theory-derived cognitive factors predicted the persistence of these problems. Method: At 4 weeks after hospital attendance due to an assault, 106 people were assessed on multiple symptom measures (including virtual reality) and cognitive factors from models of paranoia and PTSD. The symptom measures were repeated 3 and 6 months later. Results: Factor analysis indicated that paranoia and PTSD were distinct experiences, though positively correlated. At 4 weeks, 33% of participants met diagnostic criteria for PTSD, falling to 16% at follow-up. Of the group at the first assessment, 80% reported that since the assault they were excessively fearful of other people, which over time fell to 66%. Almost all the cognitive factors (including information-processing style during the trauma, mental defeat, qualities of unwanted memories, self-blame, negative thoughts about self, worry, safety behaviours, anomalous internal experiences and cognitive inflexibility) predicted later paranoia and PTSD, but there was little evidence of differential prediction. Conclusions: Paranoia after an assault may be common and distinguishable from PTSD but predicted by a strikingly similar range of factors.