The Trajectory of Prefrontal GABA Levels in Initially Antipsychotic-Naïve Patients With Psychosis During 2 Years of Treatment and Associations With Striatal Cerebral Blood Flow and Outcome
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The Trajectory of Prefrontal GABA Levels in Initially Antipsychotic-Naïve Patients With Psychosis During 2 Years of Treatment and Associations With Striatal Cerebral Blood Flow and Outcome. / Bojesen, Kirsten Borup; Rostrup, Egill; Sigvard, Anne Korning; Mikkelsen, Mark; Edden, Richard A.E.; Ebdrup, Bjørn Hylsebeck; Glenthøj, Birte.
I: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The Trajectory of Prefrontal GABA Levels in Initially Antipsychotic-Naïve Patients With Psychosis During 2 Years of Treatment and Associations With Striatal Cerebral Blood Flow and Outcome
AU - Bojesen, Kirsten Borup
AU - Rostrup, Egill
AU - Sigvard, Anne Korning
AU - Mikkelsen, Mark
AU - Edden, Richard A.E.
AU - Ebdrup, Bjørn Hylsebeck
AU - Glenthøj, Birte
N1 - Publisher Copyright: © 2023 Society of Biological Psychiatry
PY - 2024
Y1 - 2024
N2 - Background: GABAergic (gamma-aminobutyric acidergic) function in the prefrontal cortex seems dysfunctional in patients with first-episode psychosis, but the impact of longer-term treatment and relationship to clinical outcomes and striatal activity are unknown. Methods: A longitudinal study of 39 antipsychotic-naïve and benzodiazepine-free patients with psychosis (22.4 ± 5.4 years, 64% women) and 54 matched healthy control participants (HCs) (22.2 ± 4.3 years, 61% women) who were followed up after 6 weeks (28 patients, 51 HCs), 6 months (17 patients, 47 HCs), and 2 years (21 patients, 43 HCs) was completed. GABA levels in the dorsal anterior cingulate cortex and striatal resting cerebral blood flow were assessed on a 3T magnetic resonance scanner at all visits. Results: GABA levels in the dorsal anterior cingulate cortex were significantly lower in patients at baseline and after 6 weeks but not after 6 months or 2 years. Analyses of groups separately revealed decreased GABA levels after 2 years in HCs but stable levels in patients. Treatment increased striatal resting cerebral blood flow after 6 weeks and 6 months but not after 2 years. GABA levels were negatively associated with striatal resting cerebral blood flow in both groups at all visits. Last, lower baseline GABA levels in patients were related to less functional improvement after 2 years. Conclusions: The findings suggest a different trajectory of GABA levels and striatal perfusion in first-episode patients over 2 years of antipsychotic treatment compared with HCs and indicate a downregulatory role of prefrontal GABAergic function on the striatum. Moreover, abnormally low prefrontal GABA level at illness onset may be a marker for a more severe prognosis.
AB - Background: GABAergic (gamma-aminobutyric acidergic) function in the prefrontal cortex seems dysfunctional in patients with first-episode psychosis, but the impact of longer-term treatment and relationship to clinical outcomes and striatal activity are unknown. Methods: A longitudinal study of 39 antipsychotic-naïve and benzodiazepine-free patients with psychosis (22.4 ± 5.4 years, 64% women) and 54 matched healthy control participants (HCs) (22.2 ± 4.3 years, 61% women) who were followed up after 6 weeks (28 patients, 51 HCs), 6 months (17 patients, 47 HCs), and 2 years (21 patients, 43 HCs) was completed. GABA levels in the dorsal anterior cingulate cortex and striatal resting cerebral blood flow were assessed on a 3T magnetic resonance scanner at all visits. Results: GABA levels in the dorsal anterior cingulate cortex were significantly lower in patients at baseline and after 6 weeks but not after 6 months or 2 years. Analyses of groups separately revealed decreased GABA levels after 2 years in HCs but stable levels in patients. Treatment increased striatal resting cerebral blood flow after 6 weeks and 6 months but not after 2 years. GABA levels were negatively associated with striatal resting cerebral blood flow in both groups at all visits. Last, lower baseline GABA levels in patients were related to less functional improvement after 2 years. Conclusions: The findings suggest a different trajectory of GABA levels and striatal perfusion in first-episode patients over 2 years of antipsychotic treatment compared with HCs and indicate a downregulatory role of prefrontal GABAergic function on the striatum. Moreover, abnormally low prefrontal GABA level at illness onset may be a marker for a more severe prognosis.
KW - Antipsychotic-naïve
KW - First-episode
KW - GABA
KW - MRS
KW - pCASL
KW - Striatum
U2 - 10.1016/j.bpsc.2023.12.002
DO - 10.1016/j.bpsc.2023.12.002
M3 - Journal article
C2 - 38145706
AN - SCOPUS:85189088371
JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
SN - 2451-9022
ER -
ID: 388778391