Parkinsonʼs disease and depression: brain mechanisms and non-invasive brain stimulation based treatment strategies
Date
2021-09-15
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Abstract
Parkinsoni tõbi (PT) on maailmas teine kõige sagedamini esinev neurodegeneratiivne haigus. PT-d iseloomustavad motoorsed ja mittemotoorsed tunnused, viimaste hulka kuuluvad ka neuropsühhiaatrilised häired. Neuropsühhiaatrilised häired (näiteks emotsionaalsed ja kognitiivsed sümptomid) esinevad PT puhul sageli ja neil on oluline mõju inimese elukvaliteedile. Üle maailma esineb kuni 50%-l PT patsientidest kliiniliselt olulisi depressioonisümptomeid, mis on oluliselt kõrgem levimus kui üldpopulatsioonis (hinnanguliselt 13,5%). Suur osa patsientidest ei saavuta neuropsühhiaatriliste häirete ravi käigus täielikku remissiooni erinevatel põhjustel, mille hulka kuuluvad ka ravi puudutavad põhjused nagu ebasobiv ravivalik, ravi kõrvaltoimed, koostoimed teiste ravimitega, vastunäidustused, ravi enneaegne lõpetamine jpt. Mitteinvasiivsed ajustimulatsioonimeetodid nagu korduv transkraniaalne magnetstimulatsioon (rTMS) on näidanud võimekust dorsolateraalse prefrontaalkoore (DLPFK) stimuleerimise kaudu leevendada turvaliselt ja efektiivselt emotsionaalseid, vähesemal määral ka kognitiivseid häireid. Käesoleva doktoritöö peamine eesmärk oli koondada ja laiendada teadmisi tõhusa rTMS ravi kohaldamise kohta patsientidel, kellel on diagnoositud nii PT kui ka depressioon, otsides potentsiaalseid neuropsühhiaatrilisi mõjutusi ka väljaspool meeleoluhäiret (näiteks kognitiivsed probleemid ja kõrgenenud ärevus) ning kaardistada seeläbi võimalikke positiivseid efekte inimese elukvalieedile. Väitekirjas sisalduvate uuringute kokkuvõttena saab esitada järgnevad väited:
1. Depressioonisümptomite raskusaste on oluline PT kliinilisi aspekte ja patsientide elukvaliteeti mõjutav tegur. Ajutüve raphe-tuumade neuroanatoomilised muutused on otseselt seotud depressioonihäirete patogeneesiga ning rõhutavad depressiooni neurokuvamuslike biomarkerite kasvavat tähtsust ja diagnostilist rakendatavust PT kontekstis.
2. DLPFK stimuleerimine rTMS-ga on efektiivne PT’ga seotud depressiooni ravistrateegia, kusjuures võimalik on ka positiivme mõju teistele neuropsühhiatrilistele probleemidele (nt kognitiivsed häired, ärevushäired, apaatsus) − viimaste osas on vajalikud kinnitused edaspidistes kliinilistes uuringutes.
3. Raviresistentse depressiooniga PT patsiendid kujutavad endast keerukat kliinilist valimit, millel on palju, sageli ebapiisavalt kaetud ravivajadusi. Rõhutada tuleb individuaalset varieeruvust nii kliinilises seisundis kui ka võimalikus ravivastuses, mis seeläbi õigustab isikupärastatavaid ravialaseid sekkumisviise, mille hulka sobib nii eraldivõetuna kui ka teiste meetoditega kombinatsioonis rakendatav mitteinvasiivne ajustimulatsioon (sh rTMS).
Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. PD is characterized by motor and non-motor features, the latter including neuropsychiatric disorders. Neuropsychiatric disorders (such as emotional and cognitive symptoms) are common in PD and have a significant impact on a person's quality of life. Worldwide, up to 50% of PD patients have clinically significant depressive symptoms, which is higher in prevalence than in the general population (estimated at 13.5%). A large proportion of patients do not achieve complete remission during treatment for neuropsychiatric disorders for a variety of reasons, including treatment-related causes such as inappropriate treatment options, side effects of treatment, interactions with other drugs, contraindications, premature discontinuation of treatment, and others. Non-invasive brain stimulation methods such as repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC), have been shown to safely and effectively alleviate emotional, and to a lesser extent, cognitive, problems. The main objective of this doctoral dissertation was to gather and expand the knowledge on the application of effective rTMS treatment in patients diagnosed with both PT and depression, also being mindful of potential neuropsychiatric effects outside the mood domain (i.e. cognitive problems and anxiety). The following statements can be stated to summarize the research of the dissertation: 1. The severity of depressive symptoms is an important factor influencing the clinical aspects of PD, and the quality of life of patients. Neuroanatomical changes in the raphe nuclei of the brainstem are directly related to the pathogenesis of depressive disorders and underline the growing importance and diagnostic applicability of brain-based biomarkers of depression in the context of PD. 2. Targeting the DLPFC with rTMS is an effective treatment strategy for PD-related depression, with the potential for positive effects on other neuropsychiatric problems (e.g., cognitive impairment, anxiety disorders, apathy), the latter of which will need to be confirmed in future clinical trials. 3. PD patients with treatment-resistant depression represent a complex clinical sample with many, often insufficiently covered, treatment needs, emphasizing individual variability in both clinical status and potential treatment response, thereby justifying personalized treatment interventions that include rTMS as a standalone method and in combination with others.
Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. PD is characterized by motor and non-motor features, the latter including neuropsychiatric disorders. Neuropsychiatric disorders (such as emotional and cognitive symptoms) are common in PD and have a significant impact on a person's quality of life. Worldwide, up to 50% of PD patients have clinically significant depressive symptoms, which is higher in prevalence than in the general population (estimated at 13.5%). A large proportion of patients do not achieve complete remission during treatment for neuropsychiatric disorders for a variety of reasons, including treatment-related causes such as inappropriate treatment options, side effects of treatment, interactions with other drugs, contraindications, premature discontinuation of treatment, and others. Non-invasive brain stimulation methods such as repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC), have been shown to safely and effectively alleviate emotional, and to a lesser extent, cognitive, problems. The main objective of this doctoral dissertation was to gather and expand the knowledge on the application of effective rTMS treatment in patients diagnosed with both PT and depression, also being mindful of potential neuropsychiatric effects outside the mood domain (i.e. cognitive problems and anxiety). The following statements can be stated to summarize the research of the dissertation: 1. The severity of depressive symptoms is an important factor influencing the clinical aspects of PD, and the quality of life of patients. Neuroanatomical changes in the raphe nuclei of the brainstem are directly related to the pathogenesis of depressive disorders and underline the growing importance and diagnostic applicability of brain-based biomarkers of depression in the context of PD. 2. Targeting the DLPFC with rTMS is an effective treatment strategy for PD-related depression, with the potential for positive effects on other neuropsychiatric problems (e.g., cognitive impairment, anxiety disorders, apathy), the latter of which will need to be confirmed in future clinical trials. 3. PD patients with treatment-resistant depression represent a complex clinical sample with many, often insufficiently covered, treatment needs, emphasizing individual variability in both clinical status and potential treatment response, thereby justifying personalized treatment interventions that include rTMS as a standalone method and in combination with others.
Description
Väitekirja elektrooniline versioon ei sisalda publikatsioone
Keywords
Parkinson's disease, depression (psychology), cerebral cortex, transcranial magnetic stimulation