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Serotonergic gene-t...
Serotonergic gene-to-gene interaction is associated with mood and GABA concentrations but not with pain-related cerebral processing in fibromyalgia subjects and healthy controls
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- Ellerbrock, Isabel (author)
- Karolinska Institutet
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- Sandström, Angelica (author)
- Karolinska Institutet
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- Tour, Jeanette (author)
- Karolinska Institutet
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- Fanton, Silvia (author)
- Karolinska Institutet
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- Kadetoff, Diana (author)
- Karolinska Inst, Dept Clin Neurosci, Nobels Väg 9, S-17177 Stockholm, Sweden; Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden; Löwenströmska Hosp, Stockholm Spine Ctr, Upplands Väsby, Sweden
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- Schalling, Martin (author)
- Karolinska Institutet
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- Jensen, Karin B. (author)
- Karolinska Inst, Dept Clin Neurosci, Nobels Väg 9, S-17177 Stockholm, Sweden; Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden
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- Sitnikov, Rouslan (author)
- Karolinska Institutet
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- Kosek, Eva (author)
- Karolinska Institutet,Uppsala universitet,Institutionen för kirurgiska vetenskaper,Karolinska Inst, Dept Clin Neurosci, Nobels Väg 9, S-17177 Stockholm, Sweden; Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden
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(creator_code:org_t)
- 2021-05-12
- 2021
- English.
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In: Molecular Brain. - : Springer Science and Business Media LLC. - 1756-6606. ; 14:1
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Abstract
Subject headings
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- The neurotransmitter serotonin, involved in the regulation of pain and emotion, is critically regulated by the 5‐HT1A autoreceptor and the serotonin transporter (5-HTT). Polymorphisms of these genes affect mood and endogenous pain modulation, both demonstrated to be altered in fibromyalgia subjects (FMS). Here, we tested the effects of genetic variants of the 5‐HT1A receptor (CC/G-carriers) and 5-HTT (high/intermediate/low expression) on mood, pain sensitivity, cerebral processing of evoked pain (functional MRI) and concentrations of GABA and glutamate (MR spectroscopy) in rostral anterior cingulate cortex (rACC) and thalamus in FMS and healthy controls (HC). Interactions between serotonin-relevant genes were found in affective characteristics, with genetically inferred high serotonergic signalling (5-HT1A CC/5-HTThigh genotypes) being more favourable across groups. Additionally, 5‐HT1A CC homozygotes displayed higher pain thresholds than G-carriers in HC but not in FMS. Cerebral processing of evoked pressure pain differed between groups in thalamus with HC showing more deactivation than FMS, but was not influenced by serotonin-relevant genotypes. In thalamus, we observed a 5‐HT1A-by-5-HTT and group-by-5-HTT interaction in GABA concentrations, with the 5-HTT high expressing genotype differing between groups and 5‐HT1A genotypes. No significant effects were seen for glutamate or in rACC. To our knowledge, this is the first report of this serotonergic gene-to-gene interaction associated with mood, both among FMS (depression) and across groups (anxiety). Additionally, our findings provide evidence of an association between the serotonergic system and thalamic GABA concentrations, with individuals possessing genetically inferred high serotonergic signalling exhibiting the highest GABA concentrations, possibly enhancing GABAergic inhibitory effects via 5-HT.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Serotonin
- GABA
- Genetic polymorphisms
- 5-HT1A
- Serotonin transporter
- Fibromyalgia
- Mood
Publication and Content Type
- ref (subject category)
- art (subject category)
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