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| 2. |
- Lonsdorf, Tina B, et al.
(författare)
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The symptomatic profile of panic disorder is shaped by the 5-HTTLPR polymorphism
- 2009
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Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 33:8, s. 1479-1483
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Forskningsöversikt (refereegranskat)abstract
- The short allele of a functional polymorphism (5-HTTLPR) in the serotonin transporter (5-HTT) promoter is associated with reduced serotonin transporter expression, lower in vivo 5-HTT binding, higher neuroticism and amygdala reactivity as well as facilitated fear conditioning and is a candidate variant for panic disorder. However, case-control studies have consistently failed to show an association between 5-HTTLPR and panic disorder. As psychiatric disorders are broadly defined phenotypes merging different symptoms to syndromes, they may not be very well suited for genetic association studies. An alternative approach is to measure symptoms along continuous symptom dimensions which may more appropriately reflect their biological underpinnings and may reveal subpopulations within clinical diagnostic groups. We recorded the symptomatic profile in 73 in panic disorder patients using observer-rated instruments (Panic Disorder Severity Scale, PDSS; Montgomery-Asberg Depression Rating Scale, MADRS) and hypothesized more severe symptoms in patients carrying the 5-HTTLPR s-allele. We observed a strong association between bi- and triallelic 5-HTTLPR polymorphisms and the symptomatic profile. Carriers of the 5-HTTLPR s-allele suffered from most severe panic and depressive symptoms. Our data highlight the importance of defining appropriate phenotypes for psychiatric genetic studies and demonstrate that the 5-HTTLPR genotype may be related to the symptomatic profiles rather than to the vulnerability to develop panic disorder.
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| 3. |
- Paaver, Marika, et al.
(författare)
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The effect of 5-HTT gene promoter polymorphism on impulsivity depends on family relations in girls
- 2008
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Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 32:5, s. 1263-1268
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Forskningsöversikt (refereegranskat)abstract
- The short (S) allele of the 5-HTT gene promoter region polymorphism (5-HTTLPR), in combination with adverse environmental influence, leads to higher likelihood of depression. Impulsivity has been related to low serotonin turnover, poor regulation of affect, and problems in the family, including child maltreatment. The current study explored the effect of the 5-HTTLPR polymorphism in the serotonin transporter gene and adverse family environment on impulsivity in adolescents. Healthy adolescents participating in the Estonian Children Personality Behaviour and Health Study (n=483) filled the Adaptive and Maladaptive Impulsivity Scale (AMIS), Barratt Impulsiveness Scale (BIS-11), a scale measuring family relations, and were genotyped. While genotype alone was not associated with thoughtlessness, BIS-11 impulsiveness, fast decision-making or excitement seeking, 5-HTTLPR S allele carriers, however, had higher scores of disinhibition. In girls carrying the S allele, scores of thoughtlessness and disinhibition depended on family relations, being higher with less warmth in the family. Adverse family relations had no effect on impulsivity in girls with LL genotype. In boys, the effects of family relations on maladaptive impulsivity did not depend on genotype. However, the S allele and high maltreatment in the family both independently increased disinhibition and the BIS-11 score in boys. Family environment and the 5-HTTLPR genotype had no interactive effect on excitement seeking or fast decision-making. In summary, carrying the S allele may lead to high maladaptive impulsivity due to higher sensitivity to environmental adversity, which is more significantly expressed in girls.
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| 4. |
- Pickering, Chris, et al.
(författare)
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Identification of neurotransmitter receptor genes involved in alcohol self-administration in the rat prefrontal cortex, hippocampus and amygdala
- 2007
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Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 31:1, s. 53-64
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Forskningsöversikt (refereegranskat)abstract
- About half of the risk to develop alcoholism is related to genetic background and it is well known that alcohol consumption is highly individualized. In this study, we investigated how individual alcohol consumption behaviour in Wistar rats correlated with mRNA expression of 20 genes in the prefrontal cortex, hippocampus and amygdala. We found that the long-term alcohol consumption of an individual could be estimated by the mean of its consumption on Day 2 and 3. This short exposure minimized changes in gene expression induced by alcohol itself. We found a positive correlation in the prefrontal cortex of GABAA α5 (r = 0.96), GABAB1 (r = 0.96), AMPA GluR1 (r = 0.93), 5-HT3A (r = 0.93) and the α adrenoceptors (α1A r = 1.00, α1B r = 0.93, α2A r = 0.93) with consumption. In the hippocampus, we found negative correlations with the NMDA NR2A subunit (r = − 0.86), the α1A adrenoceptor (r = − 0.89) and the glucocorticoid receptor (r = − 0.86). Finally, in the amygdala there was a negative correlation to NMDA NR2A (r = − 0.79) and a positive correlation with serotonin 5-HT2C (r = 0.79). In conclusion, we have used qPCR to identify specific genes in the brain that correlated to alcohol self-administration of an individual animal. This study suggests that alcohol consumption in the early stages of acquisition depends on the genetic background of the individual and that the prefrontal cortex is particularly important in this behaviour.
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| 5. |
- Pickering, Christopher, 1975, et al.
(författare)
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Sensitization to nicotine significantly decreases expression of GABA transporter GAT-1 in the medial prefrontal cortex.
- 2008
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Ingår i: Progress in neuro-psychopharmacology & biological psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 32:6, s. 1521-6
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated GABA signaling following induction of behavioural sensitization to nicotine. Rats were repeatedly injected with saline, nicotine or hexamethonium for 18 days and gene expression was measured with qPCR. Nicotine upregulated GABAA alpha1 subunit expression in the nucleus accumbens (p<0.05) while no changes were observed for GABAA alpha3, alpha4 or alpha5. In the medial prefrontal cortex, no change in expression of the GABAA subunits was observed. We found that nicotine significantly decreased expression of the transporter GAT-1/SLC6A1 (p<0.05) in the medial prefrontal cortex while the expression of the GAT-3/SLC6A11 (p<0.05) transporter was increased in the nucleus accumbens. This provides the first evidence of neuroadaptive changes in the GABA system after nicotine sensitization and the first demonstration of an effect on GAT-1 or GAT-3 transporters in the addiction field. The GAT-1 findings also provide evidence for an alternative theory of why most schizophrenic individuals also use tobacco products.
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