Increased Risk of Parkinson's Disease in Patients With Schizophrenia Spectrum Disorders

Kuusimäki, Tomi; Al-Abdulrasul, Haidar; Kurki, Samu; Hietala, Jarmo; Hartikainen, Sirpa; Koponen, Marjaana; Tolppanen, Anna‐Maija; Kaasinen, Valtteri

doi:10.1002/mds.28484

Cited by 33 publications

(30 citation statements)

References 60 publications

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“…Also, bipolar disorder [60] has been linked to an increased PD risk, and our results support a role for common epigenetic mechanisms in this context. In contrast, we could not find significant overlap with epigenetic patterns found in schizophrenia [61] and depression [62] which points to a lesser impact of epigenetics linking these disorders to PD. Interestingly, some overlap was seen with epigenetic patterns of rheumatoid arthritis, which reportedly is associated with a decreased PD risk [63][64][65].…”

Section: Discussioncontrasting

confidence: 94%

Butyrate and related epigenetic changes link Parkinson’s disease to inflammatory bowel disease and depressive symptoms

Xie

Ensink

et al. 2021

Preprint

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Background The gut microbiome and its metabolites can impact brain health and are altered in Parkinson's disease (PD) patients. It has been recently demonstrated that PD patients have reduced fecal levels of the potent epigenetic modulator butyrate and its bacterial producers. Here, we investigate whether the changes in the gut microbiome and associated metabolites are linked to PD symptoms and epigenetic markers in leucocytes and neurons. Methods Stool, whole blood samples, and clinical data were collected from 55 PD patients and 55 controls. We performed DNA methylation analysis on whole blood samples and analyzed the results in relation to fecal short-chain fatty acid concentrations and microbiota composition. In another cohort, prefrontal cortex neurons were isolated from control and PD brains. We identified the genome-wide DNA methylation by targeted bisulfite sequencing. Results We show that lower fecal butyrate and reduced Roseburia, Romboutsia, and Prevotella counts are linked to depressive symptoms in PD patients. Genes containing butyrate-associated methylation sites include PD risk genes and significantly overlap with sites epigenetically altered in PD blood leucocytes, predominantly neutrophils, and in brain neurons, relative to controls. Moreover, butyrate-associated methylated-DNA (mDNA) regions in PD overlap with those altered in gastrointestinal, autoimmune, and psychiatric diseases.

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Section: Discussioncontrasting

confidence: 94%

Butyrate and related epigenetic changes link Parkinson’s disease to inflammatory bowel disease and depressive symptoms

Xie

Ensink

et al. 2021

Preprint

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“…The pathway ‘dopamine receptors’ was found to be close to PD drugs contraindicated in SCZ ( Fig. 5 ), indicating that the enhancement in dopamine levels brought about by PD drugs may in fact induce SCZ, which has been linked to a hyperdopaminergic state [57]. The dopamine agonists belonging to this group of PD drugs have been shown to induce psychosis, namely, levodopa (acting on DRD1, DRD2, DRD3, DRD4 and DRD5) and ropinirole (DRD2, DRD3 and DRD4) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The non-comorbid pairs were: (I) Multiple sclerosis -Peroxisomal disorders [44], (II) Schizophrenia -Rheumatoid arthritis [45][46][47], (III) Asthma -Schizophrenia [48]. The comorbid pairs were (IV) Anxiety -Depression [49], (V) Asthma -Hypertension [50,51], (VI) Chronic obstructive pulmonary disorder (COPD) -Heart failure [52,53], (VII) Type 2 diabetes -Obesity [54,55], (VIII) Rheumatoid arthritis -Osteoporosis [56] and (IX) Parkinson's disease -Schizophrenia [57].…”

Section: Resultsmentioning

confidence: 99%

Drug Contraindications in Comorbid Diseases: a Protein Interactome Perspective

Karunakaran

Ganapathiraju

Jain

et al. 2022

Preprint

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Adverse drug reactions (ADRs) are leading causes of death and drug withdrawals and frequently co-occur with comorbidities. However, systematic studies on the effects of drugs in comorbidities are lacking. Drug interactions with the cellular protein-protein interaction (PPI) network give rise to ADRs. We selected 6 comorbid disease pairs, identified the drugs used in the treatment of the individual diseases A and B — 44 drugs in anxiety and depression, 128 in asthma and hypertension, 48 in chronic obstructive pulmonary disease and heart failure, 58 in type 2 diabetes and obesity, 58 in Parkinson′s disease and schizophrenia, and 84 in rheumatoid arthritis and osteoporosis — and categorized them based on whether they aggravate the comorbid condition. We constructed drug target networks (DTNs) and examined their enrichment among genes in disease A/B PPI networks, expressed across 53 tissues and involved in ≈1000 pathways. To pinpoint the biological features characterizing the DTNs, we performed principal component analysis and computed the Euclidean distance between DTN component scores and feature loading values. DTNs of disease A drugs not contraindicated in B were affiliated with proteins common to A/B networks or uniquely found in the B network, similarly regulated common pathways, and disease-B specific pathways and tissues. DTNs of disease A drugs contraindicated in B were affiliated with common proteins or those uniquely found in the A network, differentially regulated common pathways, and disease A-specific pathways and tissues. Hence, DTN enrichment in pathways, tissues, and PPI networks of comorbid diseases will help identify drugs contraindications in comorbidities.

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“…The impact of altered brain perfusion and BBB integrity in ASD may contribute to the onset of neurodegenerative diseases due to the continuous vascular impairments associated with these diseases. Likewise, schizophrenia is associated with an elevated risk for developing Alzheimer's and Parkinson's diseases as they share core features including white matter abnormalities and cognitive deficits (Ribe et al, 2015;Kochunov et al, 2021;Kuusimaki et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

From Neurodevelopmental to Neurodegenerative Disorders: The Vascular Continuum

Ouellette

Lacoste

2021

Front. Aging Neurosci.

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Structural and functional integrity of the cerebral vasculature ensures proper brain development and function, as well as healthy aging. The inability of the brain to store energy makes it exceptionally dependent on an adequate supply of oxygen and nutrients from the blood stream for matching colossal demands of neural and glial cells. Key vascular features including a dense vasculature, a tightly controlled environment, and the regulation of cerebral blood flow (CBF) all take part in brain health throughout life. As such, healthy brain development and aging are both ensured by the anatomical and functional interaction between the vascular and nervous systems that are established during brain development and maintained throughout the lifespan. During critical periods of brain development, vascular networks remodel until they can actively respond to increases in neural activity through neurovascular coupling, which makes the brain particularly vulnerable to neurovascular alterations. The brain vasculature has been strongly associated with the onset and/or progression of conditions associated with aging, and more recently with neurodevelopmental disorders. Our understanding of cerebrovascular contributions to neurological disorders is rapidly evolving, and increasing evidence shows that deficits in angiogenesis, CBF and the blood-brain barrier (BBB) are causally linked to cognitive impairment. Moreover, it is of utmost curiosity that although neurodevelopmental and neurodegenerative disorders express different clinical features at different stages of life, they share similar vascular abnormalities. In this review, we present an overview of vascular dysfunctions associated with neurodevelopmental (autism spectrum disorders, schizophrenia, Down Syndrome) and neurodegenerative (multiple sclerosis, Huntington’s, Parkinson’s, and Alzheimer’s diseases) disorders, with a focus on impairments in angiogenesis, CBF and the BBB. Finally, we discuss the impact of early vascular impairments on the expression of neurodegenerative diseases.

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Increased Risk of Parkinson's Disease in Patients With Schizophrenia Spectrum Disorders

Cited by 33 publications

References 60 publications

Butyrate and related epigenetic changes link Parkinson’s disease to inflammatory bowel disease and depressive symptoms

Butyrate and related epigenetic changes link Parkinson’s disease to inflammatory bowel disease and depressive symptoms

Drug Contraindications in Comorbid Diseases: a Protein Interactome Perspective

From Neurodevelopmental to Neurodegenerative Disorders: The Vascular Continuum

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