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- Henningsson, Susanne, 1977
(författare)
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On the influence of serotonin- and sex steroid-related genetic variation on mood, anxiety, personality, autism and transsexualism
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The neurotransmitter serotonin has been related to mood and anxiety, and variation in genes that encode important members of the serotonergic system may hence affect mood- and anxiety-related traits. Sex steroids influence brain development, and variation in genes encoding androgen and estrogen receptors, or enzymes needed for sex steroid synthesis, may be of importance for both personality traits and risk for psychiatric disorders. The specific aims of this thesis were: (i) to investigate the possible influence of serotonin-related genetic variation on the neural correlates of anxiety, and on mood- and anxiety-related phenotypes, including premenstrual dysphoric disorder (PMDD), depression and anxiety-related personality traits, (ii) to investigate the possible influence of sex steroid-related genetic variation on personality, autism spectrum disorder and transsexualism, and (iii) to try to ameliorate the chance of detecting effects of combinations of genetic variations by restricting the statistical analysis to particular patterns. Results: (i) The serotonin transporter (5-HTT) linked polymorphic region (5-HTTLPR) and a polymorphism in an important enzyme for serotonin synthesis (tryptophan hydroxylase 2; TPH2) were associated with amygdala response during presentation of angry faces in subjects with social phobia and controls. (ii) The same polymorphisms were associated with response to placebo and also with placebo-induced changes in amygdala activity during public speaking in subjects with social phobia. (iii) In men, genetic variation in the neurotrophic factor BDNF, which is closely related to the serotonergic system, was associated with the amount of serotonin transporter in the brain. (iv) Polymorphisms in genes that encode proteins important for the development of the serotonergic system (GATA2), for serotonin synthesis (TPH2) and for serotonergic transmission (5-HT3B) were associated with PMDD. (v) The 5-HTTLPR was shown to influence reports of controllable stressful life events in combination with the BDNF Val66Met polymorphism or anxiety-related personality traits in non-depressed men. (vi) Variants that may increase the function of the androgen receptor were associated with extraversion and spiritual acceptance in men. (vii) A variant that is associated with increased androgen receptor function was more common in women with autism spectrum disorder than in controls. (viii) The same androgen receptor polymorphism was associated with transsexualism in combination with polymorphisms in the genes encoding the estrogen receptor ? or the testosterone-converting aromatase enzyme. (ix) A method that restricts the search for genetic combinations to monotone effect patterns was shown to increase the probability of finding gene-gene effects. Conclusions: The results support the notion that variation in genes that encode serotonin-related and sex steroid-related proteins are of importance for the psychiatric traits studied in this thesis.
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| 2. |
- Sandholm, Kerstin, et al.
(författare)
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Early Immune Responses to Borrelia garinii and Borrelia afzeliiin Lyme Borreliosis : Local Complement Activation in Erythema Migrans and in vitro Studies ofComplement Activation, Phagocytosis and Cytokine Profile
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- An optimal eradication of spirochetes in Lyme borreliosis depends on the early immune response, including the potent actions of the complement system. We here assessed possible differences between two Borrelia burgdorferi genospecies in their ability to activate complement, and the consequences of complement activation in terms of phagocytosis and induction of cytokines.Early local complement activation was assessed immunohistochemically in skin biopsies from patients with erythema migrans (EM) caused by B. afzelii or B. garinii. Complement activation, phagocytosis and early cytokine and chemokine release were studied in vitro by incubating clinical isolates of B. afzelii (K78 from a human skin biopsy) and B. garinii (LU59 from human cerebrospinal fluid) in human whole blood.B. afzelii and B. garinii were detected in skin biopsies from EM and deposition of C3-fragments and IgG was found adjacent to the spirochetes. In vitro, B. garinii LU59 induced higher complement activation (measured as the generation of C3a and C5b-9), while B. afzelii K78 recruited more factor H. Phagocytosis by granulocytes and monocytes was demonstrated to be largely dependent on complement activation since phagocytosis was substantially reduced by addition of the C3 inhibitor compstatin or a C5a receptor antagonist. The early cytokine and chemokine release in human blood in response to live spirochetes revealed a rapid and pronounced pro-inflammatory response, mainly associated with the Th1- and Th17-types.We conclude that complement is activated locally in the skin in EM, and that B. garinii LU59 activates complement more than B. afzelii K78. Complement activation is pivotal for efficient phagocytosis of Borrelia spirochetes, especially in early infection before specific antibodies are produced. Both B. garinii LU59 and B. afzelii K78 induce proinflammatory cytokines rapidly, but no clear differences were seen between the two genospecies in this respect.
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| 3. |
- Suchankova, Petra, 1979, et al.
(författare)
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Associations between personality traits and polymorphisms in genes related to inflammation in women
- 2008
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Ingår i: XVIth World Congress on Psychiatric Genetics.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Both inflammation and certain personality traits have been associated with depression; however, studies regarding the relationship between inflammation and general brain functions are not numerous. The present study investigates two single nucleotide polymorphisms located in genes that are associated with inflammation with regards to personality traits in 270 women recruited from the population registry. These women were assessed by means of Karolinska Scale of Personality, a self-reported inventory. The first polymorphism, +1444C>T (rs1130864), is located in the gene coding for C-reactive protein (CRP), a marker of low-grade inflammation, and has previously been linked to raised serum levels of high-sensitivity CRP. The second polymorphism, Y402H (rs1061170), is located in the gene coding for complement factor H (CFH), an important regulator of the complement system. CRP binds to CFH and thereby augments the ability of CFH to down regulate the alternative pathway of complement. The 402H allele has consistently been associated with age-related macular degeneration and was recently linked to Alzheimer’s disease. The +1444T allele was significantly associated with higher scores in the personality traits impulsiveness, monotony avoidance and social desirability (p<0.001, p=0.004 and p=0.012, respectively). The 402H polymorphism was significantly associated with higher levels of the personality trait verbal aggression (p=0.002). In conclusion, the association between the studied CRP and CFH polymorphisms and personality traits further supports the possible involvement of the immune system in mental functions.
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| 4. |
- Suchankova, Petra, 1979, et al.
(författare)
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Associations between personality traits and polymorphisms in genes related to inflammation in women
- 2008
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Ingår i: 49th Annual meeting of the Scandinavian College of Neuro-Psychopharmacology.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Both inflammation and certain personality traits have been associated with depression; however, the mechanisms underlying these connections are unknown. The present study investigates two single nucleotide polymorphisms located in genes that are associated with inflammation with regards to personality traits in order to examine the possible involvement of inflammation in general brain functions. The first polymorphism, +1444C>T (rs1130864), is located in the gene coding for C-reactive protein (CRP), a marker of low-grade inflammation, and has previously been linked to raised serum levels of high-sensitivity CRP. The second polymorphism, Y402H (rs1061170), is located in the gene coding for complement factor H (CFH), an important regulator of the complement system. CRP binds to CFH and thereby augments the ability of CFH to down regulate the alternative pathway of complement. The 402H allele has consistently been associated with age-related macular degeneration and was recently linked to Alzheimer’s disease. The population consisted of 270 women recruited from the population registry. These women were assessed by means of Karolinska Scale of Personality, a self-reported inventory. The +1444T allele was significantly associated with higher scores in the personality traits impulsiveness, monotony avoidance and social desirability (p=0.0016, p=0.016 and p=0.048, respectively). The 402H polymorphism was significantly associated with higher levels of the personality trait verbal aggression (p=0.008). In conclusion, the association between the studied CRP and CFH polymorphisms and personality traits further supports the association between the immune system and mental functions.
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