Title Korelacija terapijskoga odgovora s promjenama nalaza 1H-MRS u liječenju depresije Title (english) Correlation of therapeutic response with changes in 1H-MRS findings in treatment of depression Author Petra Kalember Mentor Neven Henigsberg (mentor)Committee member Marko Radoš (predsjednik povjerenstva)Committee member Ivica Kostović (član povjerenstva)Committee member Rudolf Gregurek (član povjerenstva)Granter University of Zagreb Defense date and country 2024-01-30, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 61 - Medical sciences Abstract Depresija je najčešći psihijatrijski poremećaj sa životnom prevalencijom od preko 10% i povezan je s visokom stopom suicida. Metoda prvog izbora farmakološkog liječenja unutar skupine antidepresiva su selektivni inhibitori ponovne pohrane serotonina (SIPPS), a terapijski odgovor se najčešće opaža tek nakon 4-6 tjedana. Nisu ustanovljeni pouzdani biološki markeri ranog prepoznavanja ili korelacije s kliničkim terapijskim odgovorom. Najčešće korištene ocjenske ljestvice u kliničkoj praksi su Montgomery-Åsbergova ljestvica (MADRS) i Hamiltonova ocjenska ljestvica za depresiju (HAM-D). Konzervativnim pristupom se pozitivnim terapijskim odgovorom smatra smanjenje ukupnog zbroja na MADRS od najmanje 50%.
Spektroskopija protonskom magnetskom rezonacijom (1H-MRS) je ne-ionizirajuća radiološka metoda koja omogućuje višekratne procjene u kraćem vremenskom razdoblju i jedina je metoda koja omogućuje in vivo prepoznavanje razina metabolita u mozgu.
Cilj je istraživanja bio prepoznati korelate kliničkog terapijskog odgovora kod depresije s parametrima mjerenim putem spektroskopije magnetskom rezonancijom, a posebno razine kolina (Cho) u amigdali (AMYG). Istraživanje je uključivalo i druge neurometabolite: N-acetil-aspartat (NAA), kompleks glutamin/glutamat/GABA koji se na 1H-MRS očituje kao Glx vrh, mioinozitol (MI) i kreatin (Cr) koji se zbog svoje relativne stabilne razine smatra referentnim parametrom za određivanje razine pojedinog metabolita. Uz AMYG, druga područja mozga od interesa (ROI) uključivala su dorzolateralni prefrontalni korteks (DLPFC), bazalne ganglije (BG), prednji cingularni korteks (ACC) i hipokampus (HIPPO).
Istraživanje je provedeno na skupini od 59 ispitanika (36 žena i 23 muškarca) koji su u početku istraživanja udovoljavali kliničkim kriterijima depresivnog poremećaja prema DSM-IV, prosječne dobi od 29,4 godine (SD = 7,4), u rasponu od 18,4 godine do 42,5 godina. Mjerenja razina neurometabolita putem 1H-MRS na 3T učinjena su na početku istraživanja, prije započinjanja antidepresivne terapije, i nakon 8 tjedana liječenja.
U početnim razinama Cho u AMYG nisu ustanovljene značajne razlike između skupine ispitanika s pozitivnim terapijskim odgovorom i skupine kod koje nije postignut očekivani terapijski odgovor.
Analizom mješovitim linearnim modelom (LMM) ustanovljena je negativna korelacija razine Cho sa stupnjem depresivne simptomatike nakon 8 tjedana antidepresivne terapije SIPPS. LMM analiza upućuje na značajnu povezanost poboljšanja simptomatike mjerene promjenom ukupnog zbroja na MADRS s efektima Cho (1.48, p = 0.036), vremena liječenja (-11.53, p < 0.001) i promjene Cho izražene interakcijom Cho i vremena istraživanja (-1.95, p = 0.044). Razina Cho na kraju istraživanja bila je značajno viša kod ispitanika kod kojih je postignut pozitivni terapijski odgovor.
Rezultati istraživanja upućuju da je razina Cho mjerena 1H-MRS objektivni korelat kliničke procjene terapijskog odgovora mjerenog putem MADRS, uz značajan inter-individualni varijabilitet u razinama Cho. Razlike po spolu nisu opažene. Prediktivna valjanost Cho nije potvrđena.
Ponovljenim rezultatima na većim skupinama ispitanika, uz češća objektivna vrednovanja putem 1H-MRS i dužim longitudinalnim praćenjem, bilo bi moguće pouzdanije utvrditi korelacijski potencijal Cho mjerenog 1H-MRS kao objektivnog parametra u praćenju terapijskog odgovora.
Abstract (english) Depression is the most common psychiatric disorder with a lifetime prevalence of over 10% and is a disorder associated with a high suicide rate. The method of first choice of pharmacological treatment within the group of antidepressants is selective serotonin reuptake inhibitors (SSRI). The therapeutic response is usually observed only after 4-6 weeks. No reliable biological markers for early recognition or correlation with clinical therapeutic response have been established. The most commonly used rating scales in clinical practice are the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HAM-D). Conservatively, a positive therapeutic response is considered a reduction of the total sum on the MADRS of at least 50%.
Proton magnetic resonance spectroscopy (1H-MRS) is a non-ionizing radiological method that enables multiple assessments in a shorter period of time and is the only method that allows in vivo recognition of metabolite levels in the brain.
The aim of the research was to identify the correlations of clinical therapeutic response in depression with parameters measured by magnetic resonance spectroscopy, and especially choline (Cho) levels in the amygdala (AMYG). The research also included other neurometabolites: N-acetyl-aspartate (NAA), the glutamine/glutamate/GABA complex which appears on 1H-MRS as a Glx peak, myoinositol (MI) and creatine (Cr), which is considered a reference for determining the level of an individual metabolite due to its relatively stable level parameter. In addition to the amygdala, other brain regions of interest (ROIs) included the dorsolateral prefrontal cortex (DLPFC), basal ganglia (BG), anterior cingulate cortex (ACC), and hippocampus (HIPPO).
The research was conducted on a group of 59 subjects (36 women and 23 men) who, at the beginning of the study, met the clinical criteria for a depressive disorder according to DSM-IV, with an average age of 29.4 years (SD = 7.4), in the range of 18.4 years to 42.5 years. Neurometabolite levels were measured by 1H-MRS at 3T at the beginning of the study, before starting antidepressant therapy, and after 8 weeks of treatment.
No significant differences were found in the initial levels of Cho in AMYG between the group of subjects with a positive therapeutic response and the group in which the expected therapeutic response was not achieved.
A linear mixed models (LMM) analysis revealed a negative correlation of Cho level with the degree of depressive symptoms after 8 weeks of SSRI antidepressant therapy. LMM analysis indicates a significant association of improvement in symptoms measured by the change in the total score on the MADRS with the effects of Cho (1.48, p = 0.036), treatment time (-11.53, p < 0.001) and the change in Cho expressed by the interaction of Cho and research time (-1.95, p = 0.044). The level of Cho at the end of the study was significantly higher in subjects who achieved a positive therapeutic response.
Research results suggest that Cho level measured by 1H-MRS is an objective correlate of clinical assessment of therapeutic response measured by MADRS, with significant inter-individual variability in Cho levels. No gender differences were observed. The predictive validity of Cho has not been confirmed.
Repeated results on larger groups of subjects, with more frequent objective evaluations by 1H-MRS and longer longitudinal follow-up, would make it possible to more reliably determine the correlation potential of Cho measured by 1H-MRS as an objective parameter in monitoring the therapeutic response.
Keywords
depresivni poremećaj
antidepresivi
1H-spektroskopija magnetskom rezonancijom
kolin
NAA
amigdala
DLPFC
Keywords (english)
depressive disorder
antidepressants
proton magnetic resonance spectroscopy
choline
NAA
amygdala
DCPFC
Language croatian URN:NBN urn:nbn:hr:105:068774 Project Number: IP-CORONA-2020-12-5588 Project Number: KK.01.1.1.01.0007 Study programme Title: Neuroscience Type of resource Text Extent 139 str. File origin Born digital Access conditions Open access Terms of use Created on 2024-02-08 09:01:55
