| 1. |
- Huezo-Diaz, P, et al.
(författare)
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CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP
- 2012
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Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 26:3, s. 398-407
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Tidskriftsartikel (refereegranskat)abstract
- In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite, N-desmethylescitalopram. We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP, a clinical pharmacogenomic trial. Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer (i.e. IM/PM genotypic category) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers (EMs) ( p = 0.004). Older age was also associated with higher concentrations of escitalopram. Covarying for CYP2D6 and age, we found those homozygous for the CYP2C19*17 allele associated with ultrarapid metabolizer (UM) phenotype had a significantly lower mean escitalopram concentration (2-fold, p = 0.0001) and a higher mean metabolic ratio ( p = 0.0003) than EMs, while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs (1.55-fold, p = 0.008). There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration ( p = 0.0003; p = 0.0012 Bonferroni corrected). In conclusion, we have demonstrated an association between CYP2C19 genotype, including the CYP2C19*17 allele, and steady state escitalopram concentration.
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| 2. |
- Power, R. A., et al.
(författare)
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Fecundity of Patients With Schizophrenia, Autism, Bipolar Disorder, Depression, Anorexia Nervosa, or Substance Abuse vs Their Unaffected Siblings
- 2013
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Ingår i: Jama Psychiatry. - : American Medical Association (AMA). - 2168-622X .- 2168-6238. ; 70:1, s. 22-30
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Tidskriftsartikel (refereegranskat)abstract
- Context: It is unknown how genetic variants conferring liability to psychiatric disorders survive in the Objectives: To examine the reproductive fitness of patients with schizophrenia and other psychiatric Design: We measured the fecundity of patients with schizophrenia, autism, bipolar disorder, Setting: Population databases in Sweden, including the Multi-Generation Register and the Swedish Participants: In total, 2.3million individuals among the 1950 to 1970 birth cohort in Sweden. Main Outcome Measures: Fertility ratio (FR), reflecting the mean number of children compared with Results: Except for women with depression, affected patients had significantly fewer children (FR range Conclusions: Our results suggest that strong selection exists against schizophrenia, autism, and
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| 3. |
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| 4. |
- Tammiste, A, et al.
(författare)
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Whole-exome sequencing identifies a polymorphism in the BMP5 gene associated with SSRI treatment response in major depression
- 2013
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Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 27:10, s. 915-920
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Tidskriftsartikel (refereegranskat)abstract
- Although antidepressants are widely used in the pharmacotherapy of major depressive disorder (MDD), their efficacy is still insufficient as approximately one-third of the patients do not fully recover even after several treatment trials. Inter-individual genetic differences are thought to contribute to the variability in antidepressant response; however, current findings from pharmacogenetic studies are uncertain or not clearly replicated. Here we report the first application of full exome sequencing for the analysis of pharmacogenomics on antidepressant treatment. After 12 weeks of treatment with the selective serotonin re-uptake inhibitor escitalopram, we selected five clear responders and five clear non-responders for exome sequencing. By comparing the allele counts of previously known single nucleotide polymorphisms and novel polymorphisms we selected 38 markers for further genotyping in two independent patient samples treated with escitalopram ( n=116 and n=394). The A allele, carried by approximately 30% of the patients with MDD, of rs41271330 in the bone morphogenetic protein (BMP5) gene showed strong association with worse treatment response in both sample sets ( p=0.001), indicating that this is an promising pharmacogenetic marker for prediction of antidepressant therapeutic outcome.
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| 5. |
- Brooks, Samantha J., et al.
(författare)
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Differential Neural Responses to Food Images in Women with Bulimia versus Anorexia Nervosa
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7, s. e22259-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. Methods: We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). Results: In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. Conclusions: Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.
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| 6. |
- Brooks, Samantha J., et al.
(författare)
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Thinking about Eating Food Activates Visual Cortex with Reduced Bilateral Cerebellar Activation in Females with Anorexia Nervosa : An fMRI Study
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3, s. e34000-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women with anorexia nervosa (AN) have aberrant cognitions about food and altered activity in prefrontal cortical and somatosensory regions to food images. However, differential effects on the brain when thinking about eating food between healthy women and those with AN is unknown. Methods: Functional magnetic resonance imaging (fMRI) examined neural activation when 42 women thought about eating the food shown in images: 18 with AN (11 RAN, 7 BPAN) and 24 age-matched controls (HC). Results: Group contrasts between HC and AN revealed reduced activation in AN in the bilateral cerebellar vermis, and increased activation in the right visual cortex. Preliminary comparisons between AN subtypes and healthy controls suggest differences in cortical and limbic regions. Conclusions: These preliminary data suggest that thinking about eating food shown in images increases visual and prefrontal cortical neural responses in females with AN, which may underlie cognitive biases towards food stimuli and ruminations about controlling food intake. Future studies are needed to explicitly test how thinking about eating activates restraint cognitions, specifically in those with restricting vs. binge-purging AN subtypes.
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| 7. |
- Suda, Masashi, et al.
(författare)
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Functional Neuroanatomy of Body Checking in People with Anorexia Nervosa
- 2013
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Ingår i: International Journal of Eating Disorders. - : Wiley. - 0276-3478 .- 1098-108X. ; 46:7, s. 653-662
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe neural correlates of body checking perceptions in eating disorders have not yet been identified. This functional Magnetic Resonance Imaging study examined the neuroanatomy involved in altered perception and identification with body checking in female with anorexia nervosa (AN). MethodBrain activation while viewing images depicting normal weight individuals involved in either body checking behavior or a neutral (noneating disorder) body action, was compared between 20 females with AN and 15 matched healthy controls (HC). ResultsFemales with AN reported higher anxiety compared to HC during the body checking task. The level of anxiety positively correlated with body shape concern scores. People with AN had less activation in the medial prefrontal cortex (PFC) and right fusiform gyrus compared to HC in response to body checking compared to neutral action images. Body shape concern scores correlated negatively with medial PFC activation in AN group. DiscussionThis preliminary study with modest power suggests that AN patients have reduced activation in cortical areas associated with self-reference, body action perception, and social cognition in females with AN.
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| 8. |
- Suda, Masashi, et al.
(författare)
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Provocation of Symmetry/Ordering Symptoms in Anorexia nervosa : A Functional Neuroimaging Study
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Anorexia nervosa (AN), obsessive-compulsive disorder (OCD), and obsessive-compulsive personality disorder (OCPD) are often co-morbid; however, the aetiology of such co-morbidity has not been well investigated. This study examined brain activation in women with AN and in healthy control (HC) women during the provocation of symmetry/ordering-related anxiety. During provocation, patients with AN showed more anxiety compared to HCs, which was correlated with the severity of symmetry/ordering symptoms. Activation in the right parietal lobe and right prefrontal cortex (rPFC) in response to provocation was reduced in the AN group compared with the HC group. The reduced right parietal activation observed in the AN group is consistent with parietal lobe involvement in visuospatial cognition and with studies of OCD reporting an association between structural abnormalities in this region and the severity of 'ordering' symptoms. Reduced rPFC activation in response to symmetry/ordering provocation has similarities with some, but not all, data collected from patients with AN who were exposed to images of food and bodies. Furthermore, the combination of data from the AN and HC groups showed that rPFC activation during symptom provocation was inversely correlated with the severity of symmetry/ordering symptoms. These data suggest that individuals with AN have a diminished ability to cognitively deal with illness-associated symptoms of provocation. Furthermore, our data also suggest that symptom provocation can progressively overload attempts by the rPFC to exert cognitive control. These findings are discussed in the context of the current neurobiological models of AN.
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