Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis
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Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis. / Bojesen, Kirsten B.; Ebdrup, Bjørn H.; Jessen, Kasper; Sigvard, Anne; Tangmose, Karen; Edden, Richard A.E.; Larsson, Henrik B.W.; Rostrup, Egill; Broberg, Brian V.; Glenthøj, Birte Y.
I: Psychological Medicine, Bind 50, Nr. 13, 2020, s. 2182–2193.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis
AU - Bojesen, Kirsten B.
AU - Ebdrup, Bjørn H.
AU - Jessen, Kasper
AU - Sigvard, Anne
AU - Tangmose, Karen
AU - Edden, Richard A.E.
AU - Larsson, Henrik B.W.
AU - Rostrup, Egill
AU - Broberg, Brian V.
AU - Glenthøj, Birte Y.
PY - 2020
Y1 - 2020
N2 - BackgroundPoor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and 3-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).MethodsThirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.ResultsBefore treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ.ConclusionGlutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.
AB - BackgroundPoor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and 3-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).MethodsThirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.ResultsBefore treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ.ConclusionGlutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.
KW - Anterior cingulate cortex
KW - antipsychotic-naïve
KW - first-episode psychosis
KW - GABA
KW - glutamate
KW - magnetic resonance spectroscopy
KW - thalamus
KW - treatment outcome
U2 - 10.1017/S0033291719002277
DO - 10.1017/S0033291719002277
M3 - Journal article
C2 - 31524118
AN - SCOPUS:85072276740
VL - 50
SP - 2182
EP - 2193
JO - Psychological Medicine
JF - Psychological Medicine
SN - 0033-2917
IS - 13
ER -
ID: 238438463