| 1. |
- Annerbrink, Kristina, 1974, et al.
(författare)
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Acute and chronic treatment with serotonin reuptake inhibitors exert opposite effects on respiration in rats: possible implications for panic disorder.
- 2009
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Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 24:12, s. 1793-1801
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Tidskriftsartikel (refereegranskat)abstract
- Prompted by the suggested importance of respiration for the pathophysiology of panic disorder, we studied the influence of serotonin reuptake inhibitors (SRIs) as well as other serotonin-modulating compounds on respiration in freely moving rats. The effect on respiration after acute administration of compounds enhancing synaptic levels of serotonin, that is, the serotonin reuptake inhibitors paroxetine and fluoxetine, the serotonin-releasing agents m-chlorophenylpiperazine and d-fenfluramine, and the selective 5-HT1A antagonist WAY-100635, were investigated. All serotonin-releasing substances decreased respiratory rate in unrestrained, awake animals, suggesting the influence of serotonin on respiratory rate under these conditions to be mainly inhibitory. In line with a previous study, rats administered fluoxetine for 23 days or more, on the other hand, displayed an enhanced respiratory rate. The results reinforce the assumption that the effect of subchronic administration of a serotonin reuptake inhibitor on certain serotonin-regulated parameters may be opposite to that obtained after acute administration. We suggest that our observations may be of relevance for the fact that acute administration of SRIs, d-fenfluramine, or m-chlorophenylpiperazine often is anxiogenic in panic disorder patients, and that weeks of administration of an SRI leads to a very effective prevention of panic.
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| 2. |
- Annerbrink, Kristina, 1974, et al.
(författare)
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Association between the catechol-O-methyltransferase Val158Met polymorphism and panic disorder: A replication
- 2010
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Ingår i: Psychiatry Research. - : Elsevier Science B.V., Amsterdam.. - 0165-1781 .- 1872-7123. ; 178:1, s. 196-198
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Tidskriftsartikel (refereegranskat)abstract
- The association between the catechol-O-methyltransferase Val158Met polymorphism and panic disorder was studied in a Swedish sample of 211 patients and 452 controls. We found a significant excess of the Val allele in both male and female patients, the latter but not the former finding being in line with previous studies.
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| 3. |
- Annerbrink, Kristina, 1974, et al.
(författare)
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Associations between the angiotensin-converting enzyme insertion/deletion polymorphism and monoamine metabolite concentrations in cerebrospinal fluid
- 2010
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Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 179:2, s. 231-234
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin II has been suggested to influence central dopamine and serotonin turnover. Since the angiotensin-converting enzyme (ACE) plays a key role in angiotensin regulation by converting inactive angiotensin 1 to active angiotensin II, we hypothesised that the functional insertion/deletion (I/D) polymorphism in the ACE gene, which has previously been suggested to be associated with, depression and panic disorder, may influence monoamine activity. A well-established technique for assessing brain monoamine turnover in humans is to measure concentrations of monoamine metabolites in the cerebrospinal fluid (CSF). We thus investigated possible associations between the ACE I/D polymorphism and CSF monoamine metabolite concentrations in a population of healthy male subjects. After having found such an association between the ACE I/D polymorphism and CSF levels of the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid in this sample, I carriers displaying lower levels, we tried to replicate this observation in a population of violent male offenders from which also both CSF and DNA were available. Also in this sample, the same associations were found. Our results suggest that the ACE I/D polymorphism may play a role in the modulation of serotonergic and dopaminergic turnover in men. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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| 4. |
- Annerbrink, Kristina, 1974, et al.
(författare)
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Catechol O-methyltransferase val158-met polymorphism is associated with abdominal obesity and blood pressure in men.
- 2008
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 57:5, s. 708-711
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Tidskriftsartikel (refereegranskat)abstract
- Catechol O-methyltransferase (COMT) degrades catecholamines and estrogens, both of which are of known importance for cardiovascular risk factors such as obesity and hypertension. The gene coding for COMT contains a val158-met polymorphism that exerts a considerable influence on enzymatic activity. We hypothesized that this polymorphism might influence risk factors for cardiovascular disease. Deoxyribonucleic acid samples and data regarding blood pressure and anthropometry were collected from 240 Swedish men, all 51 years old. Subjects homozygous for the low-activity allele (met) displayed higher blood pressure, heart rate, waist-to-hip ratio, and abdominal sagittal diameter as compared with heterozygous subjects, who in turn displayed higher blood pressure, heart rate, waist-to-hip ratio, and abdominal sagittal diameter than subjects homozygous for the high-activity allele (val). All measured variables were significantly correlated; however, the associations between COMT val158-met and cardiovascular variables, and the association between COMT val158-met and anthropometry, respectively, were partly independent of each other, as revealed by multiple linear regression.
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| 5. |
- Annerbrink, Kristina, 1974, et al.
(författare)
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Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene
- 2011
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Ingår i: PSYCHIATRIC GENETICS. - : Rapid Communications of Oxford Ltd. - 0955-8829 .- 1473-5873. ; 21:2, s. 85-89
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Tidskriftsartikel (refereegranskat)abstract
- Background Orexin A and B are neuropeptides influencing, for example, arousal and respiration. Although panic disorder is characterized by both enhanced proneness for arousal and by respiratory abnormalities, the possible influence of orexin-related genes on the risk of developing this disorder has not been studied until now. Methods We have analyzed the Ile408Val polymorphism in the hypocretin receptor 1 (HCRTR1) gene and the Val308Iso (G1246A) polymorphism in the hypocretin receptor 2 (HCRTR2) gene in a sample of 215 panic disorder patients and 454 controls. Results Although the polymorphism in the HCRTR1 did not differ between groups, the Iso allele of the HCRTR2 polymorphism was significantly more frequent in patients than in controls. After the population was divided according to sex, the association between the Iso allele of the Val308Iso polymorphism and panic disorder was observed only in female patients. Conclusion Our results suggest that the HCRTR2 polymorphism may be of importance for the pathophysiology of panic disorder. The results should be regarded as preliminary until replicated in an independent sample. This indicates that further research on the possible role of orexin in panic disorder may prove rewarding.
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| 6. |
- Annerbrink, Kristina, 1974, et al.
(författare)
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Serotonin depletion increases respiratory variability in freely moving rats: implications for panic disorder.
- 2003
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Ingår i: The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). - 1469-5111. ; 6:1, s. 51-6
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate if serotonergic transmission affects respiratory variability, a parameter consistently found increased in patients with panic disorder, we studied the effect of a serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA), on respiratory variability at baseline and during CO2-induced hyperventilation in awake and unrestrained rats. Forty male Wistar rats were given intraperitoneal injections of PCPA (300 mg/kg) or saline 72, 48 and 24 h before registration of respiration in a plethysmograph allowing the animals to move freely. PCPA-treated rats displayed significantly higher tidal volume variability and minute volume variability, both at baseline and during CO2 exposure, compared to controls. The results support the notion that serotonin dysfunction may contribute to the enhanced respiratory variability observed in patients with panic disorder.
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| 7. |
- 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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| 8. |
- 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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| 9. |
- de Frias, Cindy M., et al.
(författare)
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Influence of COMT Gene Polymorphism on fMRI-assessed Sustained and Transient Activity during a Working Memory Task
- 2010
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Ingår i: Journal of cognitive neuroscience. - Cambridge, Mass. : MIT Press. - 0898-929X .- 1530-8898. ; 22:7, s. 1614-1622
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Tidskriftsartikel (refereegranskat)abstract
- The catechol O-methyltransferase (COMT) gene-encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)-contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic-phasic hypothesis, individuals carrying the low-enzyme- activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic-phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic-phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val(158)met polymorphism on different components of working memory.
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| 10. |
- Hansson, Caroline, 1981, et al.
(författare)
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A possible association between panic disorder and a polymorphism in the preproghrelin gene
- 2013
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Ingår i: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123. ; 206:1, s. 22-25
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to investigate whether polymorphisms in the preproghrelin gene are associated with anxiety disorders, such as panic disorder, in humans. Panic disorder is a severe anxiety disorder, characterized by sudden attacks of intense fear or anxiety in combination with somatic symptoms. The preproghrelin gene codes for two gut-derived circulating peptides that have been linked to anxiety-like behaviour in rodents: ghrelin (an orexigenic, pro-obesity hormone) and obestatin. In the present study, we genotyped three missense mutations in the preproghrelin gene in 215 patients suffering from panic disorder and in 451 controls. The A allele of the rs4684677 polymorphism was significantly associated with panic disorder, while there were no significant associations with the two other polymorphisms studied. We conclude that the rs4684677 (Gln90Leu) polymorphism in the preproghrelin gene may be associated with increased risk of panic disorder. It will be important to confirm these findings in additional panic disorder patient groups.
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