| 1. |
- Athanasiu, L., et al.
(författare)
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A genetic association study of CSMD1 and CSMD2 with cognitive function
- 2017
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Ingår i: Brain Behavior and Immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 61, s. 209-216
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Tidskriftsartikel (refereegranskat)abstract
- The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p <= 1.2 Chi 10(-5)). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease. (C) 2016 The Authors. Published by Elsevier Inc.
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| 2. |
- Bergman, Olle, 1978, et al.
(författare)
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Preliminary evidence that polymorphisms in dopamine-related transcription factors LMX1A, LMX1B and PITX3 are associated with schizophrenia
- 2010
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Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier. - 0278-5846 .- 1878-4216. ; 34:6, s. 1094-1097
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Tidskriftsartikel (refereegranskat)abstract
- The early development of dopaminergic pathways has been attributed importance for the aetiology of schizophrenia. Several transcription factors are involved in the survival and maturation of dopamine neurons, including LMX1A, LMX1B and PITX3. The possibility that polymorphisms in these genes may influence the development and/or the maintenance of dopaminergic neurons prompted us to investigate if five single nucleotide polymorphisms (SNPs) previously linked to Parkinson's disease are associated with this disorder. Preliminary evidence that genetic variation in LMX1A (rs6668493, rs4657411), LMX1B (rs10987386) and PITX3 (rs4919621) may increase the risk of developing schizophrenia is presented.
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| 3. |
- de Frias, Cindy M., et al.
(författare)
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Catechol O-Methyltransferase Val¹-sup-5-sup-8 Met Polymorphism is Associated with Cognitive Performance in Nondemented Adults.
- 2005
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Ingår i: Journal of Cognitive Neuroscience. - : MIT Press - Journals. - 0898-929X .- 1530-8898. ; 17:7, s. 1018-1025
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Tidskriftsartikel (refereegranskat)abstract
- The catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine in the prefrontal cortex. In the present study, we examined the effect of a Val¹-sup-5-sup-8Met polymorphism in the COMT gene on individual differences and changes in cognition (executive functions and visuospatial ability) in adulthood and old age. The participants were 292 nondemented men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula study) tested at two occasions with a 5-year interval. Confirmatory factor analyses were used to test the underlying structure of three indicators of executive functions (verbal fluency, working memory, and Tower of Hanoi). Associations between COMT, age, executive functioning, and visuospatial (block design) tasks were examined using repeated-measures analyses of variance. Carriers of the Val allele (with higher enzyme activity) compared with carriers of the Met/Met genotype (with low enzyme activity) performed worse on executive functioning and visuospatial tasks. Individuals with the /Val genotype declined in executive functioning over the 5-year period, whereas carriers of the Met allele remained stable in performance. An Age × COMT interaction for visuospatial ability located the effect for middle-aged men only. This COMT polymorphism is a plausible candidate gene for executive functioning and fluid intelligence in nondemented middle-aged and older adults.
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| 4. |
- de Frias, Cindy M, et al.
(författare)
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Catechol O-methyltransferase Val158Met polymorphism is associated with cognitive performance in nondemented adults.
- 2005
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Ingår i: Journal of cognitive neuroscience. - Cambridge : MIT Press - Journals. - 0898-929X .- 1530-8898. ; 17:7, s. 1018-25
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Tidskriftsartikel (refereegranskat)abstract
- The catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine in the prefrontal cortex. In the present study, we examined the effect of a Val158Met polymorphism in the COMT gene on individual differences and changes in cognition (executive functions and visuospatial ability) in adulthood and old age. The participants were 292 nondemented men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula study) tested at two occasions with a 5-year interval. Confirmatory factor analyses were used to test the underlying structure of three indicators of executive functions (verbal fluency, working memory, and Tower of Hanoi). Associations between COMT, age, executive functioning, and visuospatial (block design) tasks were examined using repeated-measures analyses of variance. Carriers of the Val allele (with higher enzyme activity) compared with carriers of the Met/Met genotype (with low enzyme activity) performed worse on executive functioning and visuospatial tasks. Individuals with the Val/Val genotype declined in executive functioning over the 5-year period, whereas carriers of the Met allele remained stable in performance. An Age x COMT interaction for visuospatial ability located the effect for middle-aged men only. This COMT polymorphism is a plausible candidate gene for executive functioning and fluid intelligence in nondemented middle-aged and older adults.
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| 5. |
- de Frias, Cindy M, et al.
(författare)
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COMT gene polymorphism is associated with declarative memory in adulthood and old age.
- 2004
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Ingår i: Behavior genetics. - New York : Kluwer Academic Publishers. - 0001-8244 .- 1573-3297. ; 34:5, s. 533-9
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Tidskriftsartikel (refereegranskat)abstract
- Variation in memory performance is to a large extent explained by genes. In the prefrontal cortex, the catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine, a neurotransmitter implicated in cognitive functions. The present study examined the effect of a polymorphism in the COMT gene on individual differences and changes in memory in adulthood and old age. Tests assessing episodic and semantic memory were administered to 286 men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula prospective cohort study) at two occasions followed over a 5-year period. Carriers of the Met/Met genotype (with low enzyme activity) performed better on episodic and semantic memory, as compared to carriers of the Val allele (with higher enzyme activity). Division of episodic memory into its recall and recognition components showed that the difference was specific to episodic recall, not recognition tasks; an effect that was observed across three age groups (middle-age, young-old, and old-old adults) and over a 5-year period. The COMT gene is a plausible candidate gene for memory functioning in adulthood and old age.
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| 6. |
- Kauppi, Karolina, 1985-, et al.
(författare)
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Decreased medial temporal lobe activation in BDNF 66Met allele carriers during memory encoding
- 2013
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Ingår i: Neuropsychologia. - : Elsevier. - 0028-3932 .- 1873-3514. ; 51:12, s. 2462-2468
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Tidskriftsartikel (refereegranskat)abstract
- The Met allele of the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with impaired activity-dependent secretion of BDNF protein and decreased memory performance. Results from imaging studies relating Val66Met to brain activation during memory processing have been inconsistent, with reports of both increased and decreased activation in the Medial Temporal Lobe (MTL) in Met carriers relative to Val homozygotes. Here, we extensively studied BDNF Val66Met in relation to brain activation and white matter integrity as well as memory performance in a large imaging (n=194) and behavioral (n=2229) sample, respectively. Functional magnetic resonance imaging (fMRI) was used to investigate MTL activation in healthy participants in the age of 55–75 years during a face-name episodic encoding and retrieval task. White matter integrity was measured using diffusion tensor imaging.BDNF Met allele carriers had significantly decreased activation in the MTL during encoding processes, but not during retrieval processes. In contrast to previous proposals, the effect was not modulated by age and the polymorphism was not related to white matter integrity. Met carriers had lower memory performance than Val homozygotes, but differences were subtle and not significant. In conclusion, the BDNF Met allele has a negative influence on MTL functioning, preferentially during encoding processes, which might translate into impaired episodic memory function.
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| 7. |
- Kauppi, Karolina, et al.
(författare)
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KIBRA polymorphism is related to enhanced memory and elevated hippocampal processing.
- 2011
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Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - : Society for Neuroscience. - 1529-2401 .- 0270-6474. ; 31:40, s. 14218-22
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have linked the KIBRA rs17070145 T polymorphism to superior episodic memory in healthy humans. One study investigated the effect of KIBRA on brain activation patterns (Papassotiropoulos et al., 2006) and observed increased hippocampal activation in noncarriers of the T allele during retrieval. Noncarriers were interpreted to need more hippocampal activation to reach the same performance level as T carriers. Using large behavioral (N = 2230) and fMRI (N = 83) samples, we replicated the KIBRA effect on episodic memory performance, but found increased hippocampal activation in T carriers during episodic retrieval. There was no evidence of compensatory brain activation in noncarriers within the hippocampal region. In the main fMRI sample, T carriers performed better than noncarriers during scanning but, importantly, the difference in hippocampus activation remained after post hoc matching according to performance, sex, and age (N = 64). These findings link enhanced memory performance in KIBRA T allele carriers to elevated hippocampal functioning, rather than to neural compensation in noncarriers.
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| 8. |
- Melke, Jonas, 1971, et al.
(författare)
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A polymorphism in the serotonin receptor 3A (HTR3A) gene and its association with harm avoidance in women.
- 2003
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Ingår i: Archives of general psychiatry. - : American Medical Association (AMA). - 0003-990X. ; 60:10, s. 1017-23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The brain neurotransmitter serotonin is known to affect various aspects of human behavior, including personality traits. Serotonin receptor type 3 is a ligand-gated channel encoded by 2 different subunit genes, HTR3A and HTR3B. A polymorphism (C178T) in the 5' region of the HTR3A gene has recently been identified and suggested to be of functional importance. OBJECTIVE: To elucidate the possible association between the C178T polymorphism in the HTR3A gene and personality traits in women. DESIGN: Two independent samples of 35- to 45-year-old Swedish women were recruited using the population register. Sample 1 (n = 195) was assessed via the Karolinska Scales of Personality and the Temperament and Character Inventory; sample 2 (n = 175) was assessed using the latter only. Both samples were genotyped with respect to the C178T polymorphism in the HTR3A gene. The A1596G polymorphism in the same gene was also investigated. RESULTS: A significant association between C178T genotype and the Temperament and Character Inventory factor harm avoidance was observed in sample 1 (corrected for multiple comparisons P =.04); this finding was subsequently replicated in sample 2 (P =.004) (pooled populations: P<.001). In the pooled sample, all harm avoidance subscales were found to be significantly associated with the C178T polymorphism: anticipatory worry (P =.001), fear of uncertainty (P<.001), shyness (P<.001), and fatigability and asthenia (P =.008). In addition, a significant association was found in sample 1 between the C178T polymorphism and the Karolinska Scales of Personality nonconformity factor (corrected P =.002), including the subscales of social desirability (P<.001), indirect aggression (P =.002), verbal aggression (P =.05), and irritability (P<.001). Participants homozygous for the less common T allele (<4%) differed from the remaining women by displaying lower ratings on harm avoidance and nonconformity. CONCLUSION: The C178T polymorphism in the HTR3A gene may affect the personality trait of harm avoidance in women.
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| 9. |
- Yonker, Julie E, et al.
(författare)
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Verified hormone therapy improves episodic memory performance in healthy postmenopausal women.
- 2006
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Ingår i: Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition. - Hove : Informa UK Limited. - 1382-5585 .- 1744-4128. ; 13:3-4, s. 291-307
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Tidskriftsartikel (refereegranskat)abstract
- Studies of hormone therapy (HT) and cognition have yielded conflicting results. The aim of this observational study was to examine the effect of estradiol, via serum verified HT (estradiol, estriol, progesterone) and endogenous estradiol, on 108 healthy postmenopausal women's cognitive performance. The results demonstrated that the 43 HT-users performed at a significantly higher level than non-users on episodic memory tasks and on a verbal fluency task, whereas HT-users and non-users did not differ on tasks assessing semantic memory and spatial visualization. In addition, there was a positive relationship between serum estradiol level and episodic memory performance, indicating that postmenopausal HT is associated with enhanced episodic memory and verbal fluency, independent of age and education. These observational results suggest that HT use may be sufficient to exert small, yet positive effects on female sensitive cognitive tasks. Hormone therapy compliance and formulation is discussed as confounding factors in previous research.
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