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- Gracias, J., et al.
(författare)
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Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia risk has been associated with the complement component 4 (C4) genes. Here the authors show that C4A is elevated in individuals with schizophrenia. Postsynaptic density is reduced in schizophrenia, and risk variants increasing complement component 4A (C4A) gene expression are linked to excessive synapse elimination. In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in patients with first-episode psychosis (FEP) who develop schizophrenia (FEP-SCZ: median 0.41 fmol/ul [CI = 0.34-0.45], FEP-non-SCZ: median 0.29 fmol/ul [CI = 0.22-0.35], healthy controls: median 0.28 [CI = 0.24-0.33]). We show that the CSF elevation of C4A in FEP-SCZ exceeds what can be expected from genetic risk variance in the C4 locus, and in patient-derived cellular models we identify a mechanism dependent on the disease-associated cytokines interleukin (IL)-1beta and IL-6 to selectively increase neuronal C4A mRNA expression. In patient-derived CSF, we confirm that IL-1beta correlates with C4A controlled for genetically predicted C4A RNA expression (r = 0.39; CI: 0.01-0.68). These results suggest a role of C4A in early schizophrenia pathophysiology.
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- 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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| 10. |
- Melchior, Lydia K, 1979, et al.
(författare)
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Association between estrus cycle-related aggression and tidal volume variability in female Wistar rats.
- 2004
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 29:8, s. 1097-100
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Tidskriftsartikel (refereegranskat)abstract
- Premenstrual dysphoria is characterized by symptoms such as irritability and depressed mood, present during the luteal phase of the menstrual cycle, and disappearing shortly after the onset of menstruation. Subjects with premenstrual dysphoria have previously been reported to display enhanced respiratory variability, and to experience anxiety when exposed to panicogens, such as CO2. In the present study, the possible influence of the estrus cycle and estrus cycle-related aggression on respiratory variability was investigated in female rats of the Wistar strain. The rats were subdivided into two groups: those displaying estrus cycle-related aggression, as evaluated using the resident intruder paradigm, and those not showing aggression throughout the estrus cycle. This model has been developed to serve as an animal model of premenstrual irritability. The former group was found to display higher tidal volume variability in diestrus, as compared to the non-aggressive rats. There was no effect of estrus cycle phase on respiratory variability. These results are well in line with the clinical observation that women with premenstrual dysphoria display higher respiratory variability than controls, and the notion that respiratory variability is a parameter of interest in this context. In our opinion, they also strengthen the concept of this animal model as a model of premenstrual irritability.
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