Cohort Studies

Publication Title: 
Schizophrenia Research

Several lines of schizophrenia (SZ) research suggest that a functional downregulation of the prefrontal cortex GABAergic neuronal system is mediated by a promoter hypermethylation, presumably catalyzed by an increase in DNA-methyltransferase-1 (DNMT-1) expression. This promoter hypermethylation may be mediated not only by DNMT-1 but also by an entire family of de novo DNA-methyltransferases, such as DNA-methyltransferase-3a (DNMT-3a) and -3b (DNMT-3b).

Zhubi, A.
Veldic, M.
Puri, N. V.
Kadriu, B.
Caruncho, H.
Loza, I.
Sershen, H.
Lajtha, A.
Smith, R. C.
Guidotti, A.
Davis, J. M.
Costa, E.
Publication Title: 
Autism Research: Official Journal of the International Society for Autism Research

Dysfunction of cerebral cortex in autism is thought to involve alterations in inhibitory neurotransmission. Here, we screened, in prefrontal cortex (PFC) of 15 subjects diagnosed with autism and 15 matched controls the expression of 44 transcripts that are either preferentially expressed in gamma-aminobutyric acidergic interneurons of the mature cortex or important for the development of inhibitory circuitry. Significant alterations in the autism cohort included decreased expression (-45%) of RPP25 (15q24.1), which is located within the autism susceptibility locus, 15q22-26.

Huang, Hsien-Sung
Cheung, Iris
Akbarian, Schahram
Publication Title: 
BMC medical genetics

BACKGROUND: Schizophrenia is considered a language related human specific disease. Previous studies have reported evidence of positive selection for schizophrenia-associated genes specific to the human lineage. FOXP2 shows two important features as a convincing candidate gene for schizophrenia vulnerability: FOXP2 is the first gene related to a language disorder, and it has been subject to positive selection in the human lineage. METHODS: Twenty-seven SNPs of FOXP2 were genotyped in a cohort of 293 patients with schizophrenia and 340 controls.

Tolosa, Amparo
Sanju·n, Julio
Dagnall, Adam M.
MoltÛ, MarÌa D.
Herrero, Neus
de Frutos, Rosa
Publication Title: 
Molecular Psychiatry

Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted.

Hultman, C. M.
Sandin, S.
Levine, S. Z.
Lichtenstein, P.
Reichenberg, A.
Publication Title: 
Schizophrenia Bulletin

Low birth weight (LBW) and hypoxia are among the environmental factors most reliably associated with schizophrenia; however, the nature of this relationship is unclear and both gene-environment interaction and gene-environment covariation models have been proposed as explanations. High-risk (HR) designs that explore whether obstetric complications differentially predict outcomes in offspring at low risk (LR) vs HR for schizophrenia, while accounting for differences in rates of maternal risk factors, may shed light on this question.

Forsyth, Jennifer K.
Ellman, Lauren M.
Tanskanen, Antti
Mustonen, Ulla
Huttunen, Matti O.
Suvisaari, Jaana
Cannon, Tyrone D.
Publication Title: 
Translational Psychiatry

Increasing evidence suggests that epigenetic dysfunction may account for the alteration of gene transcription present in neuropsychiatric disorders such as schizophrenia (SZ), bipolar disorder (BP) and autism.

Dong, E.
Gavin, D. P.
Chen, Y.
Davis, J.
Publication Title: 
Alcoholism, Clinical and Experimental Research

BACKGROUND: Recent studies suggest that protracted and excessive alcohol use induces an epigenetic dysregulation in human and rodent brains. We recently reported that DNA methylation dynamics are altered in brains of psychotic (PS) patients, including schizophrenia and bipolar disorder patients. Because PS patients are often comorbid with chronic alcohol abuse, we examined whether the altered expression of multiple members of the DNA methylation/demethylation network observed in postmortem brains of PS patients was modified in PS patients with a history of chronic alcohol abuse.

Guidotti, Alessandro
Dong, Erbo
Gavin, David P.
Veldic, Marin
Zhao, Weihan
Bhaumik, Dulal K.
Pandey, Subhash C.
Grayson, Dennis R.
Publication Title: 
JAMA psychiatry

IMPORTANCE: Advancing paternal age has been linked to autism. OBJECTIVE: To further expand knowledge about the association between paternal age and autism by studying the effect of grandfathers' age on childhood autism. DESIGN: Population-based, multigenerational, case-control study. SETTING: Nationwide multigeneration and patient registers in Sweden. PARTICIPANTS: We conducted a study of individuals born in Sweden since 1932. Parental age at birth was obtained for more than 90% of the cohort.

Frans, Emma M.
Sandin, Sven
Reichenberg, Abraham
LÂngstrˆm, Niklas
Lichtenstein, Paul
McGrath, John J.
Hultman, Christina M.
Publication Title: 
Molecular Psychiatry

Autism spectrum disorder (ASD) defines a group of common, complex neurodevelopmental disorders. Although the aetiology of ASD has a strong genetic component, there is considerable monozygotic (MZ) twin discordance indicating a role for non-genetic factors. Because MZ twins share an identical DNA sequence, disease-discordant MZ twin pairs provide an ideal model for examining the contribution of environmentally driven epigenetic factors in disease.

Wong, C. C. Y.
Meaburn, E. L.
Ronald, A.
Price, T. S.
Jeffries, A. R.
Schalkwyk, L. C.
Plomin, R.
Mill, J.
Publication Title: 
Molecular Psychiatry

Postpartum depression (PPD) affects ?10-18% of women in the general population and results in serious consequences to both the mother and offspring. We hypothesized that predisposition to PPD risk is due to an altered sensitivity to estrogen-mediated epigenetic changes that act in a cell autonomous manner detectable in the blood. We investigated estrogen-mediated epigenetic reprogramming events in the hippocampus and risk to PPD using a cross-species translational design.

Guintivano, J.
Arad, M.
Gould, T. D.
Payne, J. L.
Kaminsky, Z. A.


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