| 1. |
- Annerbrink, Kristina, 1974, et al.
(author)
-
Acute and chronic treatment with serotonin reuptake inhibitors exert opposite effects on respiration in rats: possible implications for panic disorder.
- 2009
-
In: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 24:12, s. 1793-1801
-
Journal article (peer-reviewed)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.
|
|
| 2. |
- Annerbrink, Kristina, 1974, et al.
(author)
-
Association between the catechol-O-methyltransferase Val158Met polymorphism and panic disorder: A replication
- 2010
-
In: Psychiatry Research. - : Elsevier Science B.V., Amsterdam.. - 0165-1781 .- 1872-7123. ; 178:1, s. 196-198
-
Journal article (peer-reviewed)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.
|
|
| 3. |
- Annerbrink, Kristina, 1974, et al.
(author)
-
Associations between the angiotensin-converting enzyme insertion/deletion polymorphism and monoamine metabolite concentrations in cerebrospinal fluid
- 2010
-
In: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 179:2, s. 231-234
-
Journal article (peer-reviewed)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.
|
|
| 4. |
- Annerbrink, Kristina, 1974, et al.
(author)
-
Catechol O-methyltransferase val158-met polymorphism is associated with abdominal obesity and blood pressure in men.
- 2008
-
In: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 57:5, s. 708-711
-
Journal article (peer-reviewed)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.
|
|
| 5. |
- Annerbrink, Kristina, 1974
(author)
-
On the association between panic disorder and autonomic regulation – With special focus on the roles of respiration and on the catechol-O-methyltransferase gene
- 2009
-
Doctoral thesis (other academic/artistic)abstract
- Background and aims: Panic disorder is a psychiatric disorder characterized by sudden attacks of intense anxiety. It displays a lot of features suggesting that it may be associated with an underlying aberration in the autonomic regulation of heart activity and respiration: i) the attacks are often characterized by respiratory symptoms and symptoms from the heart, ii) the attacks can be elicited by respiratory stimulants, iii) between attacks, patients with panic disorder often display enhanced respiratory variability and reduced heart rate variability, and iv) patients with panic disorder display enhanced prevalence of respiratory disorders and enhanced mortality in cardiovascular disease. Addressing the reasons for these physiological aberrations may help in elucidating the pathophysiology underlying panic disorder, and shed light on why this disorder is associated with enhanced mortality in cardiovascular disease. Serotonin is believed to be a neurotransmitter of great importance for panic disorder, as well as for the regulation of respiration: one main purpose of the animal studies presented in this thesis hence was to increase our knowledge regarding the role of serotonin in respiratory regulation, the hypothesis being that aberrations in respiration may cause the anxiety attacks, and that serotonin-modulating drugs may prevent panic attacks partly by stabilizing the regulation of respiration. In the first part of the thesis, data is presented on the effects on respiration in freely moving rats of various serotonergic compounds. The second part of this thesis is focused on genetic variations that may be associated with panic disorder. Orexin is a neuropeptide of suggested importance for both respiratory regulation and arousal. We investigated two polymorphisms in the orexin receptors 1 and 2, HCRTR1 Ile408Val and HCRTR2 Val308Iso, in panic disorder patients and healthy controls. Catechol-O-methyltransferase (COMT) is an enzyme that degrades catecholamines such as dopamine and noradrenaline, and may thus be of importance for both autonomic control and psychiatric symptoms. The functional Val158Met polymorphism in this gene has been associated with panic disorder in several studies; in an attempt to replicate this finding, we genotyped this polymorphism in the same group of panic disorder patients. In a separate cohort, we also explored if the same polymorphism is associated with risk factors for cardiovascular disease. Observations: 1) Serotonin depletion with para-chlorophenylalanine decreased respiratory rate and increased respiratory variability. 2) Chronic treatment with serotonin reuptake inhibitors increased respiratory rate. 3) Acute treatment with serotonin reuptake inhibitors, as well as the serotonin releasing drugs d-fenfluramine and m-CPP, and the 5-HT1A antagonist WAY-100635, decreased respiratory rate. 4) The HCRTR2 Val308Iso polymorphism was significantly associated with panic disorder in women. 5) In line with previous studies in Caucasian samples, the COMT Val158 allele was significantly more frequent in PD patients than controls. 6) Met158 allele carriers displayed significantly higher waist-hip-ratio, sagittal diameter, systolic and diastolic blood pressure, and heart rate, than Val158 allele carriers in a population of healthy men. Conclusions: Our results suggest that serotonin exert a modulatory role on respiration, and support the notion that an influence on respiration may contribute both to the anxiogenic and the anti-panic effects of serotonergic drugs. The association between panic disorder and the hypocretin receptor-2 Val308Iso polymorphism is a novel finding in need of replication, whereas the association between panic disorder and the COMT Val158 allele can by now be regarded as confirmed. The association between the COMT Val158Met polymorphism and cardiovascular risk factors is of interest, but does not support the theory that this polymorphism contributes to the enhanced mortality in cardiovascular disease seen in panic disorder patients.
|
|
| 6. |
- Annerbrink, Kristina, 1974, et al.
(author)
-
Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene
- 2011
-
In: PSYCHIATRIC GENETICS. - : Rapid Communications of Oxford Ltd. - 0955-8829 .- 1473-5873. ; 21:2, s. 85-89
-
Journal article (peer-reviewed)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.
|
|
| 7. |
|
|
| 8. |
- Annerbrink, Kristina, 1974, et al.
(author)
-
Serotonin depletion increases respiratory variability in freely moving rats: implications for panic disorder.
- 2003
-
In: The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). - 1469-5111. ; 6:1, s. 51-6
-
Journal article (peer-reviewed)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.
|
|
| 9. |
|
|
| 10. |
- de Frias, Cindy M, et al.
(author)
-
Catechol O-methyltransferase Val158Met polymorphism is associated with cognitive performance in nondemented adults.
- 2005
-
In: Journal of cognitive neuroscience. - Cambridge : MIT Press - Journals. - 0898-929X .- 1530-8898. ; 17:7, s. 1018-25
-
Journal article (peer-reviewed)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.
|
|
