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Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples.

https://arctichealth.org/en/permalink/ahliterature154634
Source
Mol Psychiatry. 2010 May;15(5):463-72
Publication Type
Article
Date
May-2010
Author
S. Le Hellard
T W Mühleisen
S. Djurovic
J. Fernø
Z. Ouriaghi
M. Mattheisen
C. Vasilescu
M B Raeder
T. Hansen
J. Strohmaier
A. Georgi
F F Brockschmidt
I. Melle
I. Nenadic
H. Sauer
M. Rietschel
M M Nöthen
T. Werge
O A Andreassen
S. Cichon
V M Steen
Author Affiliation
Department of Clinical Medicine, Bergen Mental Health Research Center, University of Bergen, Bergen, Norway. stephanie.le.hellard@helse-bergen.no
Source
Mol Psychiatry. 2010 May;15(5):463-72
Date
May-2010
Language
English
Publication Type
Article
Keywords
Adult
Antipsychotic Agents - therapeutic use
Case-Control Studies
Chromosomes, Human, Pair 17 - genetics
Chromosomes, Human, Pair 22 - genetics
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Germany
Humans
Lipogenesis - drug effects - genetics
Male
Middle Aged
Odds Ratio
Polymorphism, Single Nucleotide - genetics
Scandinavia
Schizophrenia - drug therapy - genetics
Sterol Regulatory Element Binding Protein 1 - genetics
Sterol Regulatory Element Binding Protein 2 - genetics
Abstract
Several studies have reported structural brain abnormalities, decreased myelination and oligodendrocyte dysfunction in schizophrenia. In the central nervous system, glia-derived de novo synthesized cholesterol is essential for both myelination and synaptogenesis. Previously, we demonstrated in glial cell lines that antipsychotic drugs induce the expression of genes involved in cholesterol and fatty acids biosynthesis through activation of the sterol regulatory element binding protein (SREBP) transcription factors, encoded by the sterol regulatory element binding transcription factor 1 (SREBF1) and sterol regulatory element binding transcription factor 2 (SREBF2) genes. Considering the importance of these factors in the lipid biosynthesis and their possible involvement in antipsychotic drug effects, we hypothesized that genetic variants of SREBF1 and/or SREBF2 could affect schizophrenia susceptibility. We therefore conducted a HapMap-based association study in a large German sample, and identified association between schizophrenia and five markers in SREBF1 and five markers in SREBF2. Follow-up studies in two independent samples of Danish and Norwegian origin (part of the Scandinavian collaboration of psychiatric etiology study, SCOPE) replicated the association for the five SREBF1 markers and for two markers in SREBF2. A combined analysis of all samples resulted in highly significant genotypic P-values of 9 x 10(-4) for SREBF1 (rs11868035, odd ration (OR)=1.26, 95% confidence interval (CI) (1.09-1.45)) and 4 x 10(-5) for SREBF2 (rs1057217, OR=1.39, 95% CI (1.19-1.63)). This finding strengthens the hypothesis that SREBP-controlled cholesterol biosynthesis is involved in the etiology of schizophrenia.
PubMed ID
18936756 View in PubMed
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Affective lability mediates the association between childhood trauma and suicide attempts, mixed episodes and co-morbid anxiety disorders in bipolar disorders.

https://arctichealth.org/en/permalink/ahliterature287299
Source
Psychol Med. 2017 Apr;47(5):902-912
Publication Type
Article
Date
Apr-2017
Author
M. Aas
C. Henry
F. Bellivier
M. Lajnef
S. Gard
J-P Kahn
T V Lagerberg
S R Aminoff
T. Bjella
M. Leboyer
O A Andreassen
I. Melle
B. Etain
Source
Psychol Med. 2017 Apr;47(5):902-912
Date
Apr-2017
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Adult Survivors of Child Adverse Events - psychology - statistics & numerical data
Age of Onset
Aged
Anxiety Disorders - epidemiology - physiopathology
Bipolar Disorder - epidemiology - physiopathology
Comorbidity
Female
France - epidemiology
Humans
Male
Middle Aged
Norway - epidemiology
Psychotic Disorders - epidemiology - physiopathology
Suicide, Attempted - psychology - statistics & numerical data
Young Adult
Abstract
Many studies have shown associations between a history of childhood trauma and more severe or complex clinical features of bipolar disorders (BD), including suicide attempts and earlier illness onset. However, the psychopathological mechanisms underlying these associations are still unknown. Here, we investigated whether affective lability mediates the relationship between childhood trauma and the severe clinical features of BD.
A total of 342 participants with BD were recruited from France and Norway. Diagnosis and clinical characteristics were assessed using the Diagnostic Interview for Genetic Studies (DIGS) or the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Affective lability was measured using the short form of the Affective Lability Scale (ALS-SF). A history of childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Mediation analyses were performed using the SPSS process macro.
Using the mediation model and covariation for the lifetime number of major mood episodes, affective lability was found to statistically mediate the relationship between childhood trauma experiences and several clinical variables, including suicide attempts, mixed episodes and anxiety disorders. No significant mediation effects were found for rapid cycling or age at onset.
Our data suggest that affective lability may represent a psychological dimension that mediates the association between childhood traumatic experiences and the risk of a more severe or complex clinical expression of BD.
PubMed ID
27894372 View in PubMed
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Additive effects of childhood abuse and cannabis abuse on clinical expressions of bipolar disorders.

https://arctichealth.org/en/permalink/ahliterature261461
Source
Psychol Med. 2014 Jun;44(8):1653-62
Publication Type
Article
Date
Jun-2014
Author
M. Aas
B. Etain
F. Bellivier
C. Henry
T. Lagerberg
A. Ringen
I. Agartz
S. Gard
J-P Kahn
M. Leboyer
O A Andreassen
I. Melle
Source
Psychol Med. 2014 Jun;44(8):1653-62
Date
Jun-2014
Language
English
Publication Type
Article
Keywords
Adult
Age of Onset
Alcoholism - epidemiology
Bipolar Disorder - epidemiology - physiopathology
Child
Child Abuse - statistics & numerical data
Female
France - epidemiology
Humans
Male
Marijuana Abuse - epidemiology
Middle Aged
Norway - epidemiology
Suicide, Attempted - statistics & numerical data
Abstract
Previous studies of bipolar disorders indicate that childhood abuse and substance abuse are associated with the disorder. Whether both influence the clinical picture, or if one is mediating the association of the other, has not previously been investigated.
A total of 587 patients with bipolar disorders were recruited from Norway and France. A history of childhood abuse was obtained using the Childhood Trauma Questionnaire. Diagnosis and clinical variables, including substance abuse, were based on structured clinical interviews (Structured Clinical Interview for DSM-IV Axis I disorders or French version of the Diagnostic Interview for Genetic Studies).
Cannabis abuse was significantly associated with childhood abuse, specifically emotional and sexual abuse (? 2 = 8.63, p = 0.003 and ? 2 = 7.55, p = 0.006, respectively). Cannabis abuse was significantly associated with earlier onset of the illness (z = -4.17, p
PubMed ID
24028906 View in PubMed
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