Psychotropic drug effects on gene transcriptomics relevant to Parkinson's disease
Psychotropic drugs are widely prescribed in Parkinson's disease (PD) without regard to their pathobiological effects, and these drugs affect the transcription of a large number of genes. Effects of these drugs on PD risk gene transcription were therefore surveyed. Results summarize a comprehens...
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| description | Psychotropic drugs are widely prescribed in Parkinson's disease (PD) without regard to their pathobiological effects, and these drugs affect the transcription of a large number of genes. Effects of these drugs on PD risk gene transcription were therefore surveyed.
Results summarize a comprehensive survey of psychotropic effects on messenger ribonucleic acid (mRNA) expression evident in published data for 70 genes linked to PD risk.
Psychotropic drugs can meaningfully affect PD risk gene mRNA transcription, including antipsychotics (upregulate dopamine receptors D2 and D3 (DRD2, DRD3); downregulate low-density lipoprotein receptor-related protein 8 (LRP8), ubiquitin carboxyl-terminal esterase L1 (UCHL1, also known as PARK5)), haloperidol (upregulates DRD3, parkin (PRKN, also known as PARK2), DRD2; downregulates brain-derived neurotrophic factor (BDNF)), risperidone (upregulates monoamine oxidase B (MAOB), DRD2), olanzapine (upregulates transmembrane protein 163 (TMEM163), BDNF, glutathione S-transferase mu 1 (GSTM1), MAOB, DRD2, solute carrier organic anion transporter family, member 3A1 (SLCO3A1)), aripiprazole (upregulates DRD2), quetiapine, paliperidone, lurasidone, carbamazepine, and many antidepressants (upregulate BDNF), lithium and bupropion (downregulate BDNF), amitriptyline (upregulates DRD3, DRD2), imipramine (upregulates BDNF, DRD3, DRD2), desipramine (upregulates BDNF, DRD3), and fluoxetine (upregulates acid beta-glucosidase (GBA), coiled-coil domain containing 62 (CCDC62), BDNF, DRD3, UCHL1, unc-13 homolog B (UNC13B), and perhaps huntingtin interacting protein 1 related (HIP1R); downregulates microtubule-associated protein tau (MAPT), methylcrotonoyl-coenzyme A carboxylase I (MCCC1), GSTM1, 28kDa calbindin 1 (CALB1)). Fluoxetine effects on BDNF and UCHL1 in GEO Profiles were statistically robust.
This report provides an initial summary and framework to understand the potential impact of psychotropic drugs on PD-relevant genes. Antipsychotics and serotoninergic antidepressants may potentially attenuate PD risk, and lithium and bupropion may augment risk, through MAPT, GBA, CCDC62, HIP1R, BDNF, and DRD2 transcription, with MAPT, GBA, and CCDC62 being strongly associated with PD risk in recent meta-analyses. Limitations of these findings and a research agenda to better relate them to the nigrostriatum and PD are discussed.
► Psychotropics are widely used in treating Parkinson's disease (PD). ► Initial evidence indicates these psychotropics can aff |
| doi_str_mv | 10.1016/j.pnpbp.2012.03.011 |
| format | Article |
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Results summarize a comprehensive survey of psychotropic effects on messenger ribonucleic acid (mRNA) expression evident in published data for 70 genes linked to PD risk.
Psychotropic drugs can meaningfully affect PD risk gene mRNA transcription, including antipsychotics (upregulate dopamine receptors D2 and D3 (DRD2, DRD3); downregulate low-density lipoprotein receptor-related protein 8 (LRP8), ubiquitin carboxyl-terminal esterase L1 (UCHL1, also known as PARK5)), haloperidol (upregulates DRD3, parkin (PRKN, also known as PARK2), DRD2; downregulates brain-derived neurotrophic factor (BDNF)), risperidone (upregulates monoamine oxidase B (MAOB), DRD2), olanzapine (upregulates transmembrane protein 163 (TMEM163), BDNF, glutathione S-transferase mu 1 (GSTM1), MAOB, DRD2, solute carrier organic anion transporter family, member 3A1 (SLCO3A1)), aripiprazole (upregulates DRD2), quetiapine, paliperidone, lurasidone, carbamazepine, and many antidepressants (upregulate BDNF), lithium and bupropion (downregulate BDNF), amitriptyline (upregulates DRD3, DRD2), imipramine (upregulates BDNF, DRD3, DRD2), desipramine (upregulates BDNF, DRD3), and fluoxetine (upregulates acid beta-glucosidase (GBA), coiled-coil domain containing 62 (CCDC62), BDNF, DRD3, UCHL1, unc-13 homolog B (UNC13B), and perhaps huntingtin interacting protein 1 related (HIP1R); downregulates microtubule-associated protein tau (MAPT), methylcrotonoyl-coenzyme A carboxylase I (MCCC1), GSTM1, 28kDa calbindin 1 (CALB1)). Fluoxetine effects on BDNF and UCHL1 in GEO Profiles were statistically robust.
This report provides an initial summary and framework to understand the potential impact of psychotropic drugs on PD-relevant genes. Antipsychotics and serotoninergic antidepressants may potentially attenuate PD risk, and lithium and bupropion may augment risk, through MAPT, GBA, CCDC62, HIP1R, BDNF, and DRD2 transcription, with MAPT, GBA, and CCDC62 being strongly associated with PD risk in recent meta-analyses. Limitations of these findings and a research agenda to better relate them to the nigrostriatum and PD are discussed.
► Psychotropics are widely used in treating Parkinson's disease (PD). ► Initial evidence indicates these psychotropics can affect PD risk-gene transcription. ► Further study of PD risk-gene transcription in PD clinical models is warranted. ► Studies should focus on psychotropic-related modification of PD risk and progression.</description><identifier>ISSN: 0278-5846</identifier><identifier>EISSN: 1878-4216</identifier><identifier>DOI: 10.1016/j.pnpbp.2012.03.011</identifier><identifier>PMID: 22507762</identifier><identifier>CODEN: PNPPD7</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Adult and adolescent clinical studies ; Antidepressants ; Antipsychotics ; Biological and medical sciences ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Gene expression ; Humans ; Medical sciences ; mRNA ; Neurology ; Neuropharmacology ; Organic mental disorders. Neuropsychology ; Parkinson Disease - drug therapy ; Parkinson Disease - genetics ; Parkinson's disease ; Pharmacology. Drug treatments ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psycholeptics: tranquillizer, neuroleptic ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychopharmacology ; Psychotropic Drugs - pharmacology ; Risk ; Transcriptome - drug effects ; Ubiquitin Thiolesterase - genetics ; Ubiquitin-Protein Ligases - genetics</subject><ispartof>Progress in neuro-psychopharmacology & biological psychiatry, 2012-08, Vol.38 (2), p.107-115</ispartof><rights>2012 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-3d0408bf7aea5cb24878397adb75ddd98e12c160d34a0cf044ad029ba2a3b8303</citedby><cites>FETCH-LOGICAL-c389t-3d0408bf7aea5cb24878397adb75ddd98e12c160d34a0cf044ad029ba2a3b8303</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0278584612000681$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26141971$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22507762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lauterbach, Edward C.</creatorcontrib><title>Psychotropic drug effects on gene transcriptomics relevant to Parkinson's disease</title><title>Progress in neuro-psychopharmacology & biological psychiatry</title><addtitle>Prog Neuropsychopharmacol Biol Psychiatry</addtitle><description>Psychotropic drugs are widely prescribed in Parkinson's disease (PD) without regard to their pathobiological effects, and these drugs affect the transcription of a large number of genes. Effects of these drugs on PD risk gene transcription were therefore surveyed.
Results summarize a comprehensive survey of psychotropic effects on messenger ribonucleic acid (mRNA) expression evident in published data for 70 genes linked to PD risk.
Psychotropic drugs can meaningfully affect PD risk gene mRNA transcription, including antipsychotics (upregulate dopamine receptors D2 and D3 (DRD2, DRD3); downregulate low-density lipoprotein receptor-related protein 8 (LRP8), ubiquitin carboxyl-terminal esterase L1 (UCHL1, also known as PARK5)), haloperidol (upregulates DRD3, parkin (PRKN, also known as PARK2), DRD2; downregulates brain-derived neurotrophic factor (BDNF)), risperidone (upregulates monoamine oxidase B (MAOB), DRD2), olanzapine (upregulates transmembrane protein 163 (TMEM163), BDNF, glutathione S-transferase mu 1 (GSTM1), MAOB, DRD2, solute carrier organic anion transporter family, member 3A1 (SLCO3A1)), aripiprazole (upregulates DRD2), quetiapine, paliperidone, lurasidone, carbamazepine, and many antidepressants (upregulate BDNF), lithium and bupropion (downregulate BDNF), amitriptyline (upregulates DRD3, DRD2), imipramine (upregulates BDNF, DRD3, DRD2), desipramine (upregulates BDNF, DRD3), and fluoxetine (upregulates acid beta-glucosidase (GBA), coiled-coil domain containing 62 (CCDC62), BDNF, DRD3, UCHL1, unc-13 homolog B (UNC13B), and perhaps huntingtin interacting protein 1 related (HIP1R); downregulates microtubule-associated protein tau (MAPT), methylcrotonoyl-coenzyme A carboxylase I (MCCC1), GSTM1, 28kDa calbindin 1 (CALB1)). Fluoxetine effects on BDNF and UCHL1 in GEO Profiles were statistically robust.
This report provides an initial summary and framework to understand the potential impact of psychotropic drugs on PD-relevant genes. Antipsychotics and serotoninergic antidepressants may potentially attenuate PD risk, and lithium and bupropion may augment risk, through MAPT, GBA, CCDC62, HIP1R, BDNF, and DRD2 transcription, with MAPT, GBA, and CCDC62 being strongly associated with PD risk in recent meta-analyses. Limitations of these findings and a research agenda to better relate them to the nigrostriatum and PD are discussed.
► Psychotropics are widely used in treating Parkinson's disease (PD). ► Initial evidence indicates these psychotropics can affect PD risk-gene transcription. ► Further study of PD risk-gene transcription in PD clinical models is warranted. ► Studies should focus on psychotropic-related modification of PD risk and progression.</description><subject>Adult and adolescent clinical studies</subject><subject>Antidepressants</subject><subject>Antipsychotics</subject><subject>Biological and medical sciences</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>mRNA</subject><subject>Neurology</subject><subject>Neuropharmacology</subject><subject>Organic mental disorders. Neuropsychology</subject><subject>Parkinson Disease - drug therapy</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson's disease</subject><subject>Pharmacology. Drug treatments</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psycholeptics: tranquillizer, neuroleptic</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Psychotropic Drugs - pharmacology</subject><subject>Risk</subject><subject>Transcriptome - drug effects</subject><subject>Ubiquitin Thiolesterase - genetics</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><issn>0278-5846</issn><issn>1878-4216</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1vEzEQhq0K1Kalv6AS8gXRS5bxR_bjwKGqaItUiSLB2fLas8VhYy-eTaX-exySwo3TzOF55-Nh7EJAJUDUH9bVFKd-qiQIWYGqQIgjthBt0y61FPUrtgBZ-lWr6xN2SrQGAKFAHbMTKVfQNLVcsK8P9Ox-pDmnKTju8_aR4zCgm4mnyB8xIp-zjeRymOa0CY54xhGfbJz5nPiDzT9DpBTfE_eB0BK-Ya8HOxKeH-oZ-37z6dv13fL-y-3n66v7pVNtNy-VBw1tPzQW7cr1Upe7VddY3zcr733XopBO1OCVtuAG0Np6kF1vpVV9W944Y5f7uVNOv7ZIs9kEcjiONmLakhEgley0bruCqj3qciLKOJgph43NzwUyO5dmbf64NDuXBpQpLkvq7WHBtt-g_5t5kVeAdwfAkrPjUDy5QP-4WmjRNbtBH_ccFh1PAbMhFzA69CEX08an8N9DfgNSv5QE</recordid><startdate>20120807</startdate><enddate>20120807</enddate><creator>Lauterbach, Edward C.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20120807</creationdate><title>Psychotropic drug effects on gene transcriptomics relevant to Parkinson's disease</title><author>Lauterbach, Edward C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-3d0408bf7aea5cb24878397adb75ddd98e12c160d34a0cf044ad029ba2a3b8303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult and adolescent clinical studies</topic><topic>Antidepressants</topic><topic>Antipsychotics</topic><topic>Biological and medical sciences</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>mRNA</topic><topic>Neurology</topic><topic>Neuropharmacology</topic><topic>Organic mental disorders. Neuropsychology</topic><topic>Parkinson Disease - drug therapy</topic><topic>Parkinson Disease - genetics</topic><topic>Parkinson's disease</topic><topic>Pharmacology. Drug treatments</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psycholeptics: tranquillizer, neuroleptic</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Psychotropic Drugs - pharmacology</topic><topic>Risk</topic><topic>Transcriptome - drug effects</topic><topic>Ubiquitin Thiolesterase - genetics</topic><topic>Ubiquitin-Protein Ligases - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lauterbach, Edward C.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Progress in neuro-psychopharmacology & biological psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lauterbach, Edward C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Psychotropic drug effects on gene transcriptomics relevant to Parkinson's disease</atitle><jtitle>Progress in neuro-psychopharmacology & biological psychiatry</jtitle><addtitle>Prog Neuropsychopharmacol Biol Psychiatry</addtitle><date>2012-08-07</date><risdate>2012</risdate><volume>38</volume><issue>2</issue><spage>107</spage><epage>115</epage><pages>107-115</pages><issn>0278-5846</issn><eissn>1878-4216</eissn><coden>PNPPD7</coden><abstract>Psychotropic drugs are widely prescribed in Parkinson's disease (PD) without regard to their pathobiological effects, and these drugs affect the transcription of a large number of genes. Effects of these drugs on PD risk gene transcription were therefore surveyed.
Results summarize a comprehensive survey of psychotropic effects on messenger ribonucleic acid (mRNA) expression evident in published data for 70 genes linked to PD risk.
Psychotropic drugs can meaningfully affect PD risk gene mRNA transcription, including antipsychotics (upregulate dopamine receptors D2 and D3 (DRD2, DRD3); downregulate low-density lipoprotein receptor-related protein 8 (LRP8), ubiquitin carboxyl-terminal esterase L1 (UCHL1, also known as PARK5)), haloperidol (upregulates DRD3, parkin (PRKN, also known as PARK2), DRD2; downregulates brain-derived neurotrophic factor (BDNF)), risperidone (upregulates monoamine oxidase B (MAOB), DRD2), olanzapine (upregulates transmembrane protein 163 (TMEM163), BDNF, glutathione S-transferase mu 1 (GSTM1), MAOB, DRD2, solute carrier organic anion transporter family, member 3A1 (SLCO3A1)), aripiprazole (upregulates DRD2), quetiapine, paliperidone, lurasidone, carbamazepine, and many antidepressants (upregulate BDNF), lithium and bupropion (downregulate BDNF), amitriptyline (upregulates DRD3, DRD2), imipramine (upregulates BDNF, DRD3, DRD2), desipramine (upregulates BDNF, DRD3), and fluoxetine (upregulates acid beta-glucosidase (GBA), coiled-coil domain containing 62 (CCDC62), BDNF, DRD3, UCHL1, unc-13 homolog B (UNC13B), and perhaps huntingtin interacting protein 1 related (HIP1R); downregulates microtubule-associated protein tau (MAPT), methylcrotonoyl-coenzyme A carboxylase I (MCCC1), GSTM1, 28kDa calbindin 1 (CALB1)). Fluoxetine effects on BDNF and UCHL1 in GEO Profiles were statistically robust.
This report provides an initial summary and framework to understand the potential impact of psychotropic drugs on PD-relevant genes. Antipsychotics and serotoninergic antidepressants may potentially attenuate PD risk, and lithium and bupropion may augment risk, through MAPT, GBA, CCDC62, HIP1R, BDNF, and DRD2 transcription, with MAPT, GBA, and CCDC62 being strongly associated with PD risk in recent meta-analyses. Limitations of these findings and a research agenda to better relate them to the nigrostriatum and PD are discussed.
► Psychotropics are widely used in treating Parkinson's disease (PD). ► Initial evidence indicates these psychotropics can affect PD risk-gene transcription. ► Further study of PD risk-gene transcription in PD clinical models is warranted. ► Studies should focus on psychotropic-related modification of PD risk and progression.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>22507762</pmid><doi>10.1016/j.pnpbp.2012.03.011</doi><tpages>9</tpages></addata></record> |
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| subjects | Adult and adolescent clinical studies Antidepressants Antipsychotics Biological and medical sciences Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Gene expression Humans Medical sciences mRNA Neurology Neuropharmacology Organic mental disorders. Neuropsychology Parkinson Disease - drug therapy Parkinson Disease - genetics Parkinson's disease Pharmacology. Drug treatments Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psycholeptics: tranquillizer, neuroleptic Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychopharmacology Psychotropic Drugs - pharmacology Risk Transcriptome - drug effects Ubiquitin Thiolesterase - genetics Ubiquitin-Protein Ligases - genetics |
| title | Psychotropic drug effects on gene transcriptomics relevant to Parkinson's disease |
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