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1.
Mol Phylogenet Evol ; 140: 106599, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31442496

RESUMO

The Metacrangonyctidae are a small family of amphipod crustaceans of marine origin found only in subterranean continental waters. They display a broad but punctuated distribution between the Caribbean and the Arabian Peninsula, with major disjunctions either due to vicariance by plate tectonics or to occurrence of recent episodes of long-distance transoceanic dispersal. We re-examine the phylogeny of the family and the time frame for its diversification using mitochondrial genomes in the light of two key taxa recently discovered, from Oman (Arabian Peninsula) and the Rif area of Morocco, respectively. We also use a novel fossil calibration scheme of the mitogenome phylogeny. Results of previous analyses based on palaeogeographic calibrations are not contradicted by the new approach, with vicariance by plate tectonics remaining as the main explanatory factor for the amphi-Atlantic distribution displayed by this ancient group of subterranean amphipods.


Assuntos
Anfípodes/classificação , Anfípodes/crescimento & desenvolvimento , Filogenia , Anfípodes/genética , Animais , Teorema de Bayes , Genoma Mitocondrial , Funções Verossimilhança
2.
Psychol Med ; 49(12): 2036-2048, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30303059

RESUMO

BACKGROUND: In a large and comprehensively assessed sample of patients with bipolar disorder type I (BDI), we investigated the prevalence of psychotic features and their relationship with life course, demographic, clinical, and cognitive characteristics. We hypothesized that groups of psychotic symptoms (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations) have distinct relations to risk factors. METHODS: In a cross-sectional study of 1342 BDI patients, comprehensive demographical and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview. In addition, levels of childhood maltreatment and intelligence quotient (IQ) were assessed. The relationships between these characteristics and psychotic symptoms were analyzed using multiple general linear models. RESULTS: A lifetime history of psychotic symptoms was present in 73.8% of BDI patients and included delusions in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic symptoms showed a significant younger age of disease onset (ß = -0.09, t = -3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F11 338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with hallucinations had significant higher levels of childhood maltreatment (ß = 0.09, t = 3.04, p = 0.002). CONCLUSIONS: In this large cohort of BDI patients, the vast majority of patients had experienced psychotic symptoms. Psychotic symptoms in BDI were associated with an earlier disease onset and more frequent hospitalizations particularly for manic episodes. The study emphasizes the strength of the relation between childhood maltreatment and hallucinations but did not identify distinct subgroups based on psychotic features and instead reported of a large heterogeneity of psychotic symptoms in BD.


Assuntos
Transtorno Bipolar/psicologia , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/etiologia , Adulto , Experiências Adversas da Infância , Idoso , Estudos Transversais , Delusões , Feminino , Alucinações , Hospitalização/estatística & dados numéricos , Humanos , Inteligência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prevalência , Transtornos Psicóticos/psicologia , Fatores de Risco
3.
Hippocampus ; 26(8): 1088-95, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27010665

RESUMO

Hippocampal volume deficits have been linked to life stress. However, the degree to which genes and environment influence the association between hippocampal volume and life events is largely unknown. In total, 123 healthy twins from monozygotic and dizygotic twin pairs underwent magnetic resonance imaging (MRI), and 57 healthy twins were interviewed with the Life Events and Difficulties Schedule (LEDS), with an overlap of 54 twins undergoing both MRI and the life events interview. Hippocampal volumes were segmented with Freesurfer software. Data were analyzed with OpenMx software. Smaller hippocampal volume was associated with higher severe life event load (rph = -0.39), where shared environmental factors influencing both measures fully explained the association. Hippocampal volume was not associated with total or mild life event load. Hippocampal volume showed high heritability (range, h(2) : 57%-81%) whereas life event measures were influenced by shared (c(2) ) and unique (e(2) ) environmental factors only (range, c(2) :40%-64%, e(2) : 36%-60%). The results suggested that shared environmental factors influenced the relationship between smaller hippocampal volume and severe (but not mild) stress. This indicated that particularly severe life events that were shared between twins were associated with smaller hippocampal volume. Furthermore, it is suggested to distinguish between mild and severe life events in life event research. © 2016 Wiley Periodicals, Inc.


Assuntos
Hipocampo/diagnóstico por imagem , Estresse Psicológico/diagnóstico por imagem , Adulto , Feminino , Interação Gene-Ambiente , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Modelos Genéticos , Tamanho do Órgão , Software , Gêmeos Dizigóticos , Gêmeos Monozigóticos
4.
Zoolog Sci ; 31(7): 491-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25001920

RESUMO

A survey of biogenic coralline sands in the littoral fringe of a tropical island in Japan brought a new amphipod species to light. This species represents the first record of the subterranean genus Metaniphargus from the West Pacific. The majority of the species in this genus occur in the Caribbean, but a report from Hawaii and now from Japan defies the endemic Caribbean status it kept for so long. Metaniphargus shiroi sp. nov. is described, and morphological comparisons are made with closely resembling species from Hawaii and the Cayman Islands (genus Metaniphargus), and the Great Barrier Reef and California (genus Dulzura). Involvement of non-congeners in the comparisons is necessary as character overlap is abundant. These comparisons suggest that the presence of form-related body types in the shallow marine interstitial realm is circumtropical and follows habitat suitability rather than sudden dispersal or vicariance events.


Assuntos
Crustáceos/anatomia & histologia , Crustáceos/classificação , Animais , Demografia , Ilhas , Japão , Especificidade da Espécie
5.
Brain ; 133(10): 3080-92, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20837502

RESUMO

Structural neuroimaging studies suggest the presence of subtle abnormalities in the brains of patients with bipolar disorder. The influence of genetic and/or environmental factors on these brain abnormalities is unknown. To investigate the contribution of genetic and environmental factors on grey and white matter brain densities in bipolar disorder, monozygotic and dizygotic twins concordant and discordant for bipolar disorder were scanned using 1.5 Tesla magnetic resonance imaging and compared with healthy twin pairs. A total of 232 subjects: 49 affected twin pairs (8 monozygotic concordant, 15 monozygotic discordant, 4 dizygotic concordant, 22 dizygotic discordant) and 67 healthy twin pairs (39 monozygotic and 28 dizygotic) were included. After correcting for the effect of lithium, the liability for bipolar disorder was associated with decreased grey matter density in widespread areas of the brain, but most prominent in frontal and limbic regions, and with decreased white matter density in (frontal parts of) the superior longitudinal fasciculi. The genetic risk to develop bipolar disorder was related to decreased grey matter density in the right medial frontal gyrus, precentral gyrus and insula and with decreased white matter density in the superior longitudinal fasciculi bilaterally. In conclusion, pathology in the frontal lobe, especially in parts of the superior longitudinal fasciculus, may be central to the genetic risk to develop bipolar disorder, while widespread grey matter abnormalities appear related to the illness itself.


Assuntos
Transtorno Bipolar/genética , Transtorno Bipolar/patologia , Encéfalo/patologia , Doenças em Gêmeos , Adulto , Feminino , Predisposição Genética para Doença , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fenótipo , Gêmeos/genética
6.
Am J Med Genet B Neuropsychiatr Genet ; 147B(4): 459-62, 2008 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-17955481

RESUMO

Monozygotic (MZ) twins may be subject to epigenetic modifications that could result in different patterns of gene expression. Several lines of evidence suggest that epigenetic factors may underlie mental disorders such as bipolar disorder (BD) and schizophrenia (SZ). One important epigenetic modification, of relevance to female MZ twins, is X-chromosome inactivation. Some MZ female twin pairs are discordant for monogenic X linked disorders because of differential X inactivation. We postulated that similar mechanisms may also occur in disorders with more complex inheritance including BD and SZ. Examination of X-chromosome inactivation patterns in DNA samples from blood and/or buccal swabs in a series of 63 female MZ twin pairs concordant or discordant for BD or SZ and healthy MZ controls suggests a potential contribution from X-linked loci to discordance within twin pairs for BD but is inconclusive for SZ. Discordant female bipolar twins showed greater differences in the methylation of the maternal and paternal X alleles than concordant twin pairs and suggest that differential skewing of X-chromosome inactivation may contribute to the discordance observed for bipolar disorder in female MZ twin pairs and the potential involvement of X-linked loci in the disorder.


Assuntos
Transtorno Bipolar/genética , Cromossomos Humanos X/genética , Metilação de DNA , Gêmeos Monozigóticos/genética , Doenças em Gêmeos/genética , Feminino , Doenças Genéticas Ligadas ao Cromossomo X , Humanos , Pais , Esquizofrenia/genética , Inativação do Cromossomo X
7.
Zookeys ; (783): 37-54, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30275725

RESUMO

Semi-terrestrial talitrid amphipods of the genus Cryptorchestia (sensu Lowry and Fanini 2013) associated with freshwater-soaked leaf litter were known to occur in inland lakes of Turkey and at the shores of the Black Sea. Before 2013 they had been reported as Orchestiacavimana and later as Cryptorchestiacavimana. In our phylogenetic tree, inferred from a mitochondrial and nuclear gene dataset (cytochrome oxidase I (COI), and histone H3 (H3), respectively), we show that these Turkish populations belong to Cryptochestiagarbinii, a common and widespread continental species, which is closely related to C.cavimana (endemic to Cyprus) and C.ruffoi (endemic to Rhodes). For the Turkish and European populations of C.garbinii, we found low levels of both genetic differentiation and morphological variation, and an age-related size variability (increasing at each moult) of the small lobe in the male gnathopod I merus, the main taxonomically diagnostic character for Cryptorchestia. A mainland (C.garbinii) versus insular isolation and in situ speciation (C.cavimana, and C.ruffoi) in the two east Mediterranean islands of Cyprus and Rhodes is discussed in relation to terrestrial Cryptorchestia species endemic to North East Atlantic volcanic islands (Azores, Canary Islands, and Madeira). The incorporation of five Mediterranean and Atlantic Orchestia species in the Bayesian analysis of the two genes (COI, and H3) indicated that both genera Orchestia and Cryptorchestia are not monophyletic.

8.
Biol Psychiatry ; 62(2): 135-40, 2007 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-17141745

RESUMO

BACKGROUND: Both genetic and environmental factors are involved in the etiology of bipolar disorder; however, biological markers for the transmission of the bipolar genotype ("endophenotypes") have not been found. Autoimmune thyroiditis with raised levels of thyroperoxidase antibodies (TPO-Abs) is related to bipolar disorder and may be such an endophenotype. This study was intended to examine whether autoimmune thyroiditis is related to the disease itself, to the (genetic) vulnerability to develop bipolar disorder, or both. METHOD: Blood was collected from 22 monozygotic (MZ) and 29 dizygotic (DZ) bipolar twins and 35 healthy matched control twins to determine TPO-Abs. RESULTS: The TPO-Abs were positive in 27% of the bipolar index twins, 29% of the monozygotic bipolar cotwins, 27% of the monozygotic nonbipolar cotwins, 25% of the dizygotic bipolar cotwins, 17% of the dizygotic nonbipolar cotwins, and in 16% of the control twins. Repeated measures analysis of covariance on log-transformed absolute TPO-Abs values revealed significantly increased mean TPO-Abs levels in discordant twin pairs as compared with healthy twin pairs, whereas no difference was found between bipolar patients and their (discordant) nonbipolar cotwins. CONCLUSIONS: This study shows that autoimmune thyroiditis is related not only to bipolar disorder itself but also to the genetic vulnerability to develop the disorder. Autoimmune thyroiditis, with TPO-Abs as marker, is a possible endophenotype for bipolar disorder.


Assuntos
Transtorno Bipolar/genética , Doenças em Gêmeos/genética , Predisposição Genética para Doença , Tireoidite Autoimune/genética , Adulto , Autoanticorpos/genética , Autoanticorpos/imunologia , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/imunologia , Comorbidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/imunologia , Marcadores Genéticos/genética , Marcadores Genéticos/imunologia , Genótipo , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Fenótipo , Prevalência , Escalas de Graduação Psiquiátrica , Fatores de Risco , Tireoidite Autoimune/epidemiologia , Tireoidite Autoimune/imunologia , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
9.
Zookeys ; (652): 37-54, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28331390

RESUMO

A new Cryptorchestia species, Cryptorchestia ruffoi Latella & Vonk, sp. n. from the island of Rhodes in south-eastern Greece, can be distinguished on the basis of morphological and phylogenetic data. Morphological analysis and DNA sequencing of mitochondrial and nuclear protein-coding genes indicated that this species is related to Cryptorchestia cavimana (Cyprus) and Cryptorchestia garbinii (Mediterranean regions, with a recent northward expansion). Results supported a genetic separation between the Cryptorchestia species of the east Mediterranean regions and those of the northeast Atlantic volcanic islands examined in this study (Cryptorchestia canariensis, Cryptorchestia gomeri, Cryptorchestia guancha, and Cryptorchestia stocki from the Canary islands, Cryptorchestia monticola from Madeira, and Cryptorchestia chevreuxi from the Azores). The Mediterranean and Atlantic Cryptorchestia species appear to be also morphologically distinct. Cryptorchestia ruffoisp. n., Cryptorchestia cavimana, Cryptorchestia garbinii, and Cryptorchestia kosswigi (Turkish coast) clearly have a small lobe on the male gnathopod 1 merus. This character was the main diagnostic difference between Cryptorchestia (sensu Lowry, 2013) and Orchestia. However, among the six northeast Atlantic island Cryptorchestia species only Cryptorchestia stocki has a small lobe on the merus of gnathopod 1. Reduction or loss of the lobe in the Atlantic Island species cannot be ruled out; however, molecular phylogenetic analysis leads us to presume that this lobe independently evolved between the east Mediterranean Cryptorchestia species and Cryptorchestia stocki from Gran Canaria.

10.
Biol Psychiatry ; 59(4): 317-26, 2006 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-16165108

RESUMO

BACKGROUND: Dendritic cells (DC) are key regulators of the immune system, which is compromised in patients with bipolar disorder. We sought to study monocyte-derived DC in bipolar disorder. METHODS: Monocytes purified from blood collected from DSM-IV bipolar disorder outpatients (n = 53, 12 without lithium treatment) and healthy individuals (n = 34) were differentiated into DC via standard granulocyte-macrophpage colony-stimulating factor/interleukin-4 culture (with/without 1, 5, and 10 mmol/L lithium chloride). The DC were analyzed for DC-specific and functional markers and for T-cell stimulatory potency. RESULTS: Monocytes of bipolar patients showed a mild hampering in their differentiation into fully active DC, showing a weak residual expression of the monocyte marker CD14 and a relatively low potency to stimulate autologous T cells. Lithium treatment abolished this mild defect, and monocyte-derived DC of treated bipolar patients showed signs of activation (i.e., an up-regulated potency to stimulate autologous T cells and a higher expression of the DC-specific marker CD1a). This activated phenotype contrasted with the suppressed phenotype of monocyte-derived DC exposed to lithium in vitro (10 mmol/L) during culture. CONCLUSIONS: Dendritic cells show mild aberrancies in bipolar disorder that are fully restored to even activation after in vivo lithium treatment.


Assuntos
Transtorno Bipolar/patologia , Células Dendríticas/patologia , Monócitos/patologia , Adulto , Antígenos CD/biossíntese , Antígenos CD1/biossíntese , Antimaníacos/uso terapêutico , Autoanticorpos/análise , Autoanticorpos/imunologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/imunologia , Diferenciação Celular/fisiologia , Linhagem da Célula/fisiologia , Técnicas de Cocultura , Células Dendríticas/imunologia , Feminino , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Imunoglobulinas/biossíntese , Interleucina-4/fisiologia , Cloreto de Lítio/uso terapêutico , Masculino , Glicoproteínas de Membrana/biossíntese , Pessoa de Meia-Idade , Monócitos/imunologia , Linfócitos T/imunologia , Linfócitos T/fisiologia , Antígeno CD83
11.
Artigo em Inglês | MEDLINE | ID: mdl-25717427

RESUMO

BACKGROUND: Life events play an important role in the onset and course of bipolar disorder. We will test the influence of life events on first and recurrent admissions in bipolar disorder and their interaction to test the kindling hypothesis. METHODS: We collected information about life events and admissions across the life span in 51 bipolar patients. We constructed four models to explore the decay of life event effects on admissions. To test their interaction, we used the Andersen-Gill model. RESULTS: The relationship between life events and admissions was best described with a model in which the effects of life events gradually decayed by 25% per year. Both life event load and recurrent admissions significantly increased the risk of both first and subsequent admissions. No significant interaction between life event load and number of admissions was found. CONCLUSIONS: Life events increase the risk of both first and recurrent admissions in bipolar disorder. We found no significant interaction between life events and admissions, but the effect of life events on admissions decreases after the first admission which is in line with the kindling hypothesis.

12.
Eur Neuropsychopharmacol ; 25(12): 2197-209, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26481908

RESUMO

The influence of genes and environment on the association between bipolar disorder (BD) and volumes of subcortical brain regions involved in emotion processing has rarely been studied. Furthermore, as far as we know, longitudinal twin studies of subcortical brain volume change in BD have not been carried out at all. In this study, we focused on the genetic and environmental contributions to cross-sectional and longitudinal measures of subcortical brain volumes in BD. A total of 99 twins from monozygotic and dizygotic pairs concordant or discordant for BD and 129 twins from monozygotic and dizygotic healthy control pairs underwent magnetic resonance imaging at baseline. Longitudinal assessment was carried out in 48 twins from monozygotic and dizygotic patient pairs and 52 twins from monozygotic and dizygotic control pairs. Subcortical volume measures were obtained with Freesurfer software and analyzed with structural equation modeling software OpenMx. At baseline, BD was phenotypically and genetically associated with smaller volumes of the thalamus, putamen and nucleus accumbens. BD was not associated with subcortical brain volume change over time in any of the examined regions. Heritability of subcortical volumes at baseline was high, whereas subcortical volume change had low heritability. Genes contributing to BD showed overlap with those associated with smaller volumes of the thalamus, putamen and nucleus accumbens at baseline. Further evaluation of genetic contributions to abnormalities in subcortical brain regions assumed to be involved in emotion processing is recommended.


Assuntos
Transtorno Bipolar/genética , Transtorno Bipolar/patologia , Encéfalo/patologia , Adulto , Análise de Variância , Antidepressivos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Estudos Transversais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
13.
Zookeys ; (449): 69-79, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25408614

RESUMO

A new species of marine interstitial wormshrimp, Ingolfiellamaldivensis, is described from coral sand on the inner and outer reef off Magoodhoo island, Faafu atoll, Maldives. Six females were found and compared to other species from the Maldives and those bordering the Indian Ocean and beyond. Morphological resemblance ties it to a species from the Caribbean island of Curaçao. Both species are found in shallow sublittoral interstitial spaces.

14.
Zookeys ; (302): 1-12, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23794897

RESUMO

Ingolfiella arganoi sp. n. from Abd al Kuri Island in the Arabian Sea is described from two specimens, a male and a female. The western shore of the Indian Ocean was hitherto a vacant spot in the distribution of circumtropical shallow marine interstitial ingolfiellids and therefore the location of the new species fills a meaningful gap in the geography of the family. Morphologically, the new species shows close affinities with Ingolfiella xarifae from the Maldives.

15.
Zookeys ; (365): 25-48, 2013 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-24453549

RESUMO

The mitochondrial cytochrome c oxidase subunit I (COI) can serve as a fast and accurate marker for the identification of animal species, and has been applied in a number of studies on birds. We here sequenced the COI gene for 387 individuals of 147 species of birds from the Netherlands, with 83 species being represented by > 2 sequences. The Netherlands occupies a small geographic area and 95% of all samples were collected within a 50 km radius from one another. The intraspecific divergences averaged 0.29% among this assemblage, but most values were lower; the interspecific divergences averaged 9.54%. In all, 95% of species were represented by a unique barcode, with 6 species of gulls and skua (Larus and Stercorarius) having at least one shared barcode. This is best explained by these species representing recent radiations with ongoing hybridization. In contrast, one species, the Lesser Whitethroat Sylvia curruca showed deep divergences, averaging 5.76% and up to 8.68% between individuals. These possibly represent two distinct taxa, S. curruca and S. blythi, both clearly separated in a haplotype network analysis. Our study adds to a growing body of DNA barcodes that have become available for birds, and shows that a DNA barcoding approach enables to identify known Dutch bird species with a very high resolution. In addition some species were flagged up for further detailed taxonomic investigation, illustrating that even in ornithologically well-known areas such as the Netherlands, more is to be learned about the birds that are present.

16.
Zookeys ; (128): 53-73, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21998551

RESUMO

Psammogammarus wallaceisp. n. is described from the shallow marine interstitial of a sand and coral rubble beach on the Gura Ici islands (North Moluccas; Indonesia). This is the first record of this circum-tropical genus from SE Asia, with the geographically closest relative inhabiting the Ryukyu archipelago in Japan. The new species is highly distinctive by the display of sexual dimorphism on pleopod II, with the medial margin of the male proximal article of exopod provided with a comb of short, blunt curved spinules; no other representative of the genus is known to display sexually-dimorphic appendages aside of the gnathopods. The new species is also noteworthy by the outline of the palm margin of male gnathopod II, hardly excavated, and by showing a carpus broader than long. An overview of the genus Psammogammarus with 14 species to date is provided.

17.
Arch Gen Psychiatry ; 66(9): 957-65, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19736352

RESUMO

CONTEXT: A monocyte pro-inflammatory state has previously been reported in bipolar disorder (BD). OBJECTIVE: To determine the contribution of genetic and environmental influences on the association between monocyte pro-inflammatory state and BD. DESIGN: A quantitative polymerase chain reaction case-control study of monocytes in bipolar twins. Determination of the influence of additive genetic, common, and unique environmental factors by structural equation modeling (ACE). SETTING: Dutch academic research center. PARTICIPANTS: Eighteen monozygotic BD twin pairs, 23 dizygotic BD twin pairs, and 18 monozygotic and 16 dizygotic healthy twin pairs. MAIN OUTCOME MEASURES: Expression levels of monocytes in the previously reported coherent set of 19 genes (signature) reflecting the pro-inflammatory state. RESULTS: The familial occurrence of the association between the monocyte pro-inflammatory gene-expression signature and BD found in the within-trait/cross-twin correlations (twin correlations) was due to shared environmental factors (ie, both monozygotic and dizygotic ratios in twin correlations approximated 1; ACE modeling data: 94% [95% confidence interval, 53%-99%] explained by common [shared] environmental factors). Although most individual signature genes followed this pattern, there was a small subcluster of genes in which genetic influences could dominate. CONCLUSION: The association of the monocyte pro-inflammatory state with BD is primarily the result of a common shared environmental factor.


Assuntos
Transtorno Bipolar/genética , Expressão Gênica/genética , Monócitos/fisiologia , Adulto , Idoso , Transtorno Bipolar/sangue , Transtorno Bipolar/epidemiologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Doenças em Gêmeos/sangue , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/genética , Meio Ambiente , Feminino , Perfilação da Expressão Gênica/estatística & dados numéricos , Predisposição Genética para Doença , Humanos , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Monócitos/metabolismo , Países Baixos/epidemiologia , Fatores de Risco , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
18.
Arch Gen Psychiatry ; 66(2): 142-51, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19188536

RESUMO

CONTEXT: Structural neuroimaging studies suggest the presence of subtle abnormalities in the brains of patients with bipolar disorder. The influence of genetic and/or environmental factors on these brain abnormalities is unknown. OBJECTIVE: To investigate the contribution of genetic and environmental factors on brain volume in bipolar disorder. DESIGN: Magnetic resonance imaging (1.5 T) brain scans of monozygotic (MZ) or dizygotic (DZ) twins concordant and discordant for bipolar disorder were compared with healthy twin pairs. SETTING: Subjects were recruited from the population, the Netherlands Twin Register, and the twin pair cohort at the University Medical Center Utrecht, Utrecht, The Netherlands. PARTICIPANTS: A total of 234 subjects including 50 affected twin pairs (9 MZ concordant; 15 MZ discordant; 4 DZ concordant; 22 DZ discordant) and 67 healthy twin pairs (39 MZ and 28 DZ) were included. MAIN OUTCOME MEASURES: Volumes of the intracranium, cerebrum, cerebellum, lateral and third ventricle, and gray and white matter from the cerebrum and frontal, parietal, temporal, and occipital lobes, both with and without correction for lithium use. To estimate the influence of additive genetic, common, and unique environmental factors, structural equation modeling was applied. RESULTS: Bipolar disorder was associated with a decrease in total cortical volume. Decreases in white matter were related to the genetic risk of developing bipolar disorder (bivariate heritability, 77%; 95% confidence interval, 38% to 100%). Significant environmental correlations were found for cortical gray matter. These relationships all became more pronounced when data were corrected for lithium use. CONCLUSIONS: Focusing on genes controlling white matter integrity may be a fruitful strategy in the quest to discover genes implicated in bipolar disorder. Elucidating the mechanism by which lithium attenuates brain matter loss may lead to the development of neuroprotective drugs.


Assuntos
Transtorno Bipolar/genética , Transtorno Bipolar/psicologia , Encéfalo/patologia , Doenças em Gêmeos/genética , Doenças em Gêmeos/psicologia , Genótipo , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Meio Social , Adulto , Antimaníacos/uso terapêutico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Córtex Cerebral/patologia , Estudos de Coortes , Doenças em Gêmeos/diagnóstico , Doenças em Gêmeos/tratamento farmacológico , Feminino , Predisposição Genética para Doença/genética , Humanos , Carbonato de Lítio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Países Baixos , Tamanho do Órgão , Fenótipo , Gêmeos Dizigóticos/genética , Gêmeos Dizigóticos/psicologia , Gêmeos Monozigóticos/genética , Gêmeos Monozigóticos/psicologia , Adulto Jovem
19.
Arch Gen Psychiatry ; 65(4): 395-407, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18391128

RESUMO

CONTEXT: Mood disturbances are associated with an activated inflammatory response system. OBJECTIVE: To identify a discriminating and coherent expression pattern of proinflammatory genes in monocytes of patients with bipolar disorder. DESIGN: A quantitative polymerase chain reaction (Q-PCR) case-control gene expression study on purified monocytes of bipolar patients, the offspring of bipolar patients, and healthy control participants after having selected 22 discriminating inflammatory genes using whole genome analyses. SETTING: Academic research setting in The Netherlands. PATIENTS: Forty-two bipolar patients with 25 healthy controls, 54 offspring of a bipolar parent (13 had a mood disorder and 3 developed one during follow-up), and 70 healthy children underwent Q-PCR. MAIN OUTCOME MEASURE: Inflammatory gene expression levels in monocytes. RESULTS: We detected in the monocytes of bipolar patients a coherent mutually correlating set (signature) of 19 aberrantly expressed (P < .01) messenger RNAs of inflammatory (PDE4B, IL1B, IL6, TNF, TNFAIP3, PTGS2, and PTX3), trafficking (CCL2, CCL7, CCL20, CXCL2, CCR2, and CDC42), survival (BCL2A1 and EMP1), and mitogen-activated protein kinase pathway (MAPK6, DUSP2, NAB2, and ATF3) genes. Twenty-three of 42 bipolar patients (55%) had a positive signature test result vs 7 of 38 healthy controls (18%) (positive test result: positivity for PDE4B, ie, a messenger RNA 1 SD higher than the mean level found in healthy controls, plus 25% of the other genes with similar positive findings). Positive signature test results were also present in 11 of 13 offspring with a mood disorder (85%), 3 of 3 offspring developing a mood disorder (100%), and 17 of 38 euthymic offspring (45%) vs 13 of 70 healthy children (19%). Lithium carbonate and antipsychotic treatment downregulated the gene expression of most inflammatory genes. CONCLUSIONS: The monocytes of a large proportion of bipolar patients and offspring of bipolar parents showed an inflammatory gene expression signature. This coherent set of genes opens new avenues for biomarker development with possibilities for disease prediction in individuals genetically at risk and for the subclassification of bipolar patients who could possibly benefit from anti-inflammatory treatment.


Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/genética , Citocinas/genética , Expressão Gênica/genética , Monócitos/fisiologia , RNA Mensageiro/genética , Adulto , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Complementar/genética
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