Brain metabolite abnormalities in ventromedial prefrontal cortex are related to duration of hypercortisolism and anxiety in patients with Cushing's syndrome.
Chronic exposure to excessive glucocorticoid (GC) concentration in Cushing's syndrome (CS) can affect the brain structurally and functionally; ventromedial prefrontal cortex (vmPFC) is rich in GC receptors and therefore particularly vulnerable to excessive GC concentration. Proton magnetic resonance spectroscopy ((1)H-MRS) is a sensitive, non-invasive imaging technique that provides information on brain metabolites in vivo. Our aim was to investigate metabolite concentrations in vmPFC of CS patients and their relationship with clinical outcome. Twenty-two right-handed CS patients (7 active/15 in remission, 19 females, 41.6 ± 12.3 years) and 22 right-handed healthy controls (14 females, 41.7 ± 11 years) underwent brain MRI and (1)H-MRS exams at 3 Tesla. Concentrations of glutamate (Glu), glutamate + glutamine (Glx), creatine (Cr), N-Acetyl-aspartate (NAA), N-Acetyl-aspartate + N-acetylaspartylglutamate (total NAA), choline-containing compounds (Cho) and myoinositol (MI) were determined. Moreover, anxiety and depressive symptoms were evaluated with the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory-II (BDI-II) test, respectively. CS patients had lower concentrations of glutamate and total NAA in the vmPFC than healthy controls (8.6 ± 1.2 vs. 9.3 ± 0.7 mmol/L, and 6.4 ± 0.8 vs. 6.8 ± 0.4 mmol/L, respectively; p < 0.05). Duration of hypercortisolism was negatively correlated with total NAA (r = -0.488, p < 0.05). Moreover, the concentration of total NAA was negatively correlated with anxiety state (r = -0.359, p < 0.05). Brain metabolites are abnormal in the vmPFC of patients with CS. Decreased total NAA and glutamate concentrations indicate neuronal dysfunction that appear to be related with duration of hypercortisolism and anxiety.
Endocrinology/Medicine Departments, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), C/Sant Antoni Maria Claret n.167, 08025, Barcelona, Spain.
Iris
I
Crespo
Endocrinology/Medicine Departments, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), C/Sant Antoni Maria Claret n.167, 08025, Barcelona, Spain.
Alicia
A
Santos
Neuroradiology Unit, Hospital de Sant Pau, and IIB-Sant Pau, UAB, Barcelona, Spain.
Beatriz
B
Gómez-Ansón
Parc de Recerca-UAB, Barcelona, Spain.
Olga
O
López-Mourelo
INNDACYT, Avda. Europa, 20, Planta Baja Puerta, D 08907, Hospitalet de Llobregat, Spain.
Patricia
P
Pires
INNDACYT, Avda. Europa, 20, Planta Baja Puerta, D 08907, Hospitalet de Llobregat, Spain.
Yolanda
Y
Vives-Gilabert
Endocrinology/Medicine Departments, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), C/Sant Antoni Maria Claret n.167, 08025, Barcelona, Spain.
Susan M
SM
Webb
Endocrinology/Medicine Departments, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), C/Sant Antoni Maria Claret n.167, 08025, Barcelona, Spain. eresmini@santpau.cat.
Eugenia
E
Resmini
D000328:Adult; D001007:Anxiety / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003480:Cushing Syndrome / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales
D005973:Glutamine; D018698:Glutamic Acid; D007294:Inositol; D003401:Creatine; D002794:Choline
Anxiety; Brain metabolites; Cushing’s syndrome; Spectroscopy; Ventromedial prefrontal cortex