Morfološko-funkcionalni korelat depresije kod Parkinsonove bolesti
Morphological-functional correlate of depression in Parkinson's disease
Author
Petrović, Igor N.Mentor
Kostić, VladimirCommittee members
Svetel, Marina
Stefanova, Elka

Žarkov, Marija

Metadata
Show full item recordAbstract
Zasnovanost istraživanja. Parkinsonova bolest (PB) se klinički ispoljava spektrom
neuroloških i psihijatrijskih simptoma. Saznanja o kompleksnosti i varijabilnosti kliničke
ekspresije bolesti, rezultirala su definisanjem specifičnih podtipovima bolesti, kao i
mogućeg specifičnog međuodnos motornih podtipova i psihijatrijskih simptoma.
Pretpostavljeni model neurodegeneracije u PB sugeriše da primarna degeneracija
dopaminergičkih mezokortikalnih i mezolimbičkih neurona dovodi do disfunkcije
orbitofrontalnog korteksa i posledičnog oštećenja serotonergičkih raphe jedara moždanog
stabla. U skladu sa ovim zabeležena hipoehogenost raphe jedara na transkranijalnoj
parenhimskoj ehosonografiji (TPE) mozga ukazuje da ovakav nalaz može biti specifičan
marker idiopatske major depresije, kao i depresivnog raspoloženja u PB. Studije pomoću
magnetne rezonance (MR) mozga ukazuju na moguću ulogu različitih regiona sive i bele
mase mozga kao mogućih morfoloških korelata depresije u PB. Učestalost PB, kao... i
komorbidnih bolesti, uključujući i cerebrovaskularnu bolest (CVB) mozga se povećava sa
starenjem, uz mogućnost uticaja strateški lokalizovanih vaskularnih promena na kliničku
ekspresiju PB. Kod zdravih osoba starijie životne dobi pokazana je povezanost
hiperintenznih promena (HIS) bele mase mozga sa depresijom, ali specifični uticaj ovih
promena na depresiju u PB nije do sada ispitivan.
Ciljevi. Osnovni ciljevi studije su: a) ispitivanje povezanosti između unapred definisanih
motornih podtipova PB sa specifičnim poremećajima afekta, kao i definisanje specifičnih
afektivnih podtipova PB na osnovu cluster analize; b) ispitivanje statusa ehogenosti raphe
jedara kod bolesnika sa različitim afektivnim podtipovima; c) ispitivanje povezanosti HIS
lezija bele mase mozga i depresije u podgrupi bolesnika sa PB starijih od 60. godina; d)
detekcija specifičnog obrasca atrofije sive mase (SM), odnosno bele mase (BM) mozga kod
bolesnika sa PB i depresijom upotrebom voxel-based morfometrijske (MR-VBM) metode.
Metode. Bolesnici. Studijim su obuhvaćeni bolesnici koji su ispunjavali kriterijume
Britanske banke mozgova za PB. Klasifikacija podtipova PB i procena brzine progresije
bazirana je na kriterijumima preporučenim u literaturi. Dijagnoza depresije, anksioznosti i
apatije u delu istraživanja koji se odnosio na analizu afektivnih podgrupa zasnivala se
preporučenim cut-off skorovima Hamiltonovih skala za depresiju (HDRS), anksioznost
(HARS), kao i skali apatije (AS). Dijagnoza depresije u studiji morfoloških korelata
podrazumevala je upotrebu Strukturisanog Klničkog Intervjua (SCID) i DSM-IV preporuka.
Neurovizuelizacione metode. Kvantifikacija i lokalizacija HIS promena bele mase obavljena
je analizom standardnih sekvenci (T2W i FLAIR)MR mozga upotrebom Scheltensove skale.
Analiza topografska distribucija izmene volumena sive i bele mase mozga učinjena je
upotrebom MR-VBM metode i implementacije nalaza u preporučen Statistical Parametric
Mapping (SPM5) sistem za njihovo precizno mapiranje.
Rezultati. Motorni fenotipovi PB i podtipovi poremećaja fekta. U ispitivanoj grupi od 732
bolesnika sa PB najčešći poremećaj afekta je bila apatija (54.3%), dok su anksioznost i
depresija zabeleženi kod 31.8%, odnosno 24.5% bolesnika. Analizom podgrupa (cluster
analiza) identifikovano je pet podtipova poremećaja afekta u PB: depresivni (19.4%),
anksiozno-depresivni (20.3%), anksiozni sa visokim stepenom apatije i kognitivnog deficita
(9.5%) i mešoviti sa visokim stepenom svih afektivnih poremećaja, ali očuvanom
kognicijom (13.3%)...
Background. Parkinson’s disease (PD) is increasingly considered a neuropsychiatric
disorder with complex and variable clinical phenotypic subtypes. It has been suggested
that the various motor presentations of PD are also characterized by a different risk and
severity of specific mood disorders. Unifying model of neurodegeneration in PD suggests
that primary degeneration of dopaminergic mesocortical and mesolimbic neurons leads to
dysfunction of the orbitofrontal cortex, which secondarily affects serotonergic cell bodies
in the dorsal raphe nuclei. Transcranial sonography (TCS) studies suggested that
hypoechogenicity of the midbrain raphe may be a marker of the idiopathic major
depression and depressed mood in PD. However, findings of magnetic resonance imaging
(MRI) studies on depression in PD differ dramatically across the studies. The incidence of
PD increases with age and many age-related comorbid conditions, including
cerebrovascular disease (CVD), can contribute to the clinical c...omplexity of PD. In otherwise
normal older adults white matter lesions (WMLs) have been associated with depression,
however specific impact of WMLs on depression in PD has not been specifically studied.
Aims. The primary aims of the present study were: a) to asses a range of clinical and motor
features suggested by previous research to be associated with depression, apathy and/or
anxiety in a large sample of PD patients. In addition to prespecified clinical or theoretically
defined subgroups, we used data driven methods seek to identify clusters of patients with
specific mood disorders; b) to evaluate raphe nuclei echogenicity in PD patients with
different subclass of mood disorders; c) to assess possible association between CVD and
depression in PD we investigated whether hyperintesity signal (HIS) load on MRI were
associated with depression in patients with PD onset above the age of 60; d) to detect
whether specific patterns of gray matter (GM) and white matter (WM) loss are associated
with depression in patients with PD using MRI voxel-based morphometry (VBM).
Methods. Patients. Patients with idiopathic PD according to the UK PD Brain Bank criteria
were enrolled. Classification of PD subtypes and rate of disease progression was based on
previously reported criteria. Diagnosis of depression, anxiety and apathy in the subclass
analysis was based on suggested cut-off scores on Hamilton scales of depression (HDRS)
and anxiety (HARS), and apathy scale (AS). In MRI and MRI-VBM analysis depression were
diagnosed using the Structured Clinical Interview for DSM-IV Axis I disorders. Image
analysis. WMLs were rated using T2W and FLAIR images and classified using the
semiquantitative visual rating scale of Scheltens. The topographic distribution of brain
tissue loss in patients with PD and controls was assessed using MRI-VBM and implemented
in Statistical Parametric Mapping (SPM5).
Results. Parkinson’s disease motor phenotypes and mood subtypes. In the sample of 732 PD
patients most prevalent mood disorders was apathy (54.3%), while anxiety and depression
were present in 24.5% and 31.8% of patients. Based on a cluster analysis five classes of
mood disorder were identified: depressed (19.4%), anxious-depressed (20.3%), anxious
with high level of apathy and cognitive deficit (9.5%), and mixed with high level of all mood
disorders but preserved cognition (13.3%). The fifth group (37.5%) comprised patients
with low levels of psychiatric disorders. Initial stage of disease (H&Y≤1.5) was
characterized by an isolated depression, while with disease progression affective syndrome
complicated by the emergence of anxiety and apathy...