Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484)
Meta-analyses, published in 2008–2010, have confirmed abnormally low serum brain-derived neurotrophic factor (BDNF) concentrations in depressed patients and normalization of this by antidepressant treatment. These findings are believed to reflect peripheral manifestations of the neurotrophin hypothe...
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| Veröffentlicht in: | Molecular psychiatry 2014-07, Vol.19 (7), p.791-800 |
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| creator | Molendijk, M L Spinhoven, P Polak, M Bus, B A A Penninx, B W J H Elzinga, B M |
| description | Meta-analyses, published in 2008–2010, have confirmed abnormally low serum brain-derived neurotrophic factor (BDNF) concentrations in depressed patients and normalization of this by antidepressant treatment. These findings are believed to reflect peripheral manifestations of the
neurotrophin hypothesis
, which states that depression is secondary to an altered expression of BDNF in the brain. Since the publication of these meta-analyses, the field has seen a huge increase in studies on these topics. This motivated us to update the evidence on the aforementioned associations and, in addition, to compile the data on serum BDNF concentrations in relation to the symptom severity of depression. Using a manifold of data as compared with earlier meta-analyses, we find low serum BDNF concentrations in 2384 antidepressant-free depressed patients relative to 2982 healthy controls and to 1249 antidepressant-treated depressed patients (Cohen’s
d
=−0.71 and −0.56,
P
-values |
| doi_str_mv | 10.1038/mp.2013.105 |
| format | Article |
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neurotrophin hypothesis
, which states that depression is secondary to an altered expression of BDNF in the brain. Since the publication of these meta-analyses, the field has seen a huge increase in studies on these topics. This motivated us to update the evidence on the aforementioned associations and, in addition, to compile the data on serum BDNF concentrations in relation to the symptom severity of depression. Using a manifold of data as compared with earlier meta-analyses, we find low serum BDNF concentrations in 2384 antidepressant-free depressed patients relative to 2982 healthy controls and to 1249 antidepressant-treated depressed patients (Cohen’s
d
=−0.71 and −0.56,
P
-values <0.0000001). When publication bias is accounted for, these effect-sizes become substantially smaller (
d
=−0.47 and −0.34, respectively,
P
-values<0.0001). We detect between-study heterogeneity in outcomes for which only year of publication and sample size are significant moderators, with more recent papers and larger samples sizes in general being associated with smaller between-group differences. Finally, the aggregated data negate consistent associations between serum BDNF concentrations and the symptom severity of depression. Our findings corroborate the claim that altered serum BDNF concentrations are peripheral manifestations of depression. However, here we highlight that the evidence for this claim is slimmer as was initially thought and amidst a lot of noise.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/mp.2013.105</identifier><identifier>PMID: 23958957</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/378/1686 ; 692/53 ; 692/699/476/1414 ; Adult and adolescent clinical studies ; Antidepressants ; Antidepressive Agents - therapeutic use ; Behavioral Sciences ; Biological and medical sciences ; Biological Psychology ; Biomarkers - blood ; Brain-derived neurotrophic factor ; Brain-Derived Neurotrophic Factor - blood ; Case-Control Studies ; Depression ; Depression - blood ; Depression - drug therapy ; Depression, Mental ; Humans ; Medical sciences ; Medicine ; Medicine & Public Health ; Mental depression ; Meta-analysis ; Miscellaneous ; Mood disorders ; Neuropharmacology ; Neurosciences ; original-article ; Patients ; Pharmacology. Drug treatments ; Pharmacotherapy ; Physiological aspects ; Psychiatric research ; Psychiatric Status Rating Scales ; Psychiatry ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychopharmacology ; Publication Bias - statistics & numerical data ; Systematic review</subject><ispartof>Molecular psychiatry, 2014-07, Vol.19 (7), p.791-800</ispartof><rights>Macmillan Publishers Limited 2013</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2014 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jul 2014</rights><rights>Macmillan Publishers Limited 2013.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c582t-21682d7875ba2fb6f888b517a3c459ddaf820bc8ba8dcac28e306a613c4acc753</citedby><cites>FETCH-LOGICAL-c582t-21682d7875ba2fb6f888b517a3c459ddaf820bc8ba8dcac28e306a613c4acc753</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/mp.2013.105$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/mp.2013.105$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28641620$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23958957$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Molendijk, M L</creatorcontrib><creatorcontrib>Spinhoven, P</creatorcontrib><creatorcontrib>Polak, M</creatorcontrib><creatorcontrib>Bus, B A A</creatorcontrib><creatorcontrib>Penninx, B W J H</creatorcontrib><creatorcontrib>Elzinga, B M</creatorcontrib><title>Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484)</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description>Meta-analyses, published in 2008–2010, have confirmed abnormally low serum brain-derived neurotrophic factor (BDNF) concentrations in depressed patients and normalization of this by antidepressant treatment. These findings are believed to reflect peripheral manifestations of the
neurotrophin hypothesis
, which states that depression is secondary to an altered expression of BDNF in the brain. Since the publication of these meta-analyses, the field has seen a huge increase in studies on these topics. This motivated us to update the evidence on the aforementioned associations and, in addition, to compile the data on serum BDNF concentrations in relation to the symptom severity of depression. Using a manifold of data as compared with earlier meta-analyses, we find low serum BDNF concentrations in 2384 antidepressant-free depressed patients relative to 2982 healthy controls and to 1249 antidepressant-treated depressed patients (Cohen’s
d
=−0.71 and −0.56,
P
-values <0.0000001). When publication bias is accounted for, these effect-sizes become substantially smaller (
d
=−0.47 and −0.34, respectively,
P
-values<0.0001). We detect between-study heterogeneity in outcomes for which only year of publication and sample size are significant moderators, with more recent papers and larger samples sizes in general being associated with smaller between-group differences. Finally, the aggregated data negate consistent associations between serum BDNF concentrations and the symptom severity of depression. Our findings corroborate the claim that altered serum BDNF concentrations are peripheral manifestations of depression. However, here we highlight that the evidence for this claim is slimmer as was initially thought and amidst a lot of noise.</description><subject>631/378/1686</subject><subject>692/53</subject><subject>692/699/476/1414</subject><subject>Adult and adolescent clinical studies</subject><subject>Antidepressants</subject><subject>Antidepressive Agents - therapeutic use</subject><subject>Behavioral Sciences</subject><subject>Biological and medical sciences</subject><subject>Biological Psychology</subject><subject>Biomarkers - blood</subject><subject>Brain-derived neurotrophic factor</subject><subject>Brain-Derived Neurotrophic Factor - blood</subject><subject>Case-Control Studies</subject><subject>Depression</subject><subject>Depression - blood</subject><subject>Depression - drug therapy</subject><subject>Depression, Mental</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mental depression</subject><subject>Meta-analysis</subject><subject>Miscellaneous</subject><subject>Mood disorders</subject><subject>Neuropharmacology</subject><subject>Neurosciences</subject><subject>original-article</subject><subject>Patients</subject><subject>Pharmacology. 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Psychiatry</topic><topic>Psychopharmacology</topic><topic>Publication Bias - statistics & numerical data</topic><topic>Systematic review</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Molendijk, M L</creatorcontrib><creatorcontrib>Spinhoven, P</creatorcontrib><creatorcontrib>Polak, M</creatorcontrib><creatorcontrib>Bus, B A A</creatorcontrib><creatorcontrib>Penninx, B W J H</creatorcontrib><creatorcontrib>Elzinga, B M</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>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Molendijk, M L</au><au>Spinhoven, P</au><au>Polak, M</au><au>Bus, B A A</au><au>Penninx, B W J H</au><au>Elzinga, B M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484)</atitle><jtitle>Molecular psychiatry</jtitle><stitle>Mol Psychiatry</stitle><addtitle>Mol Psychiatry</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>19</volume><issue>7</issue><spage>791</spage><epage>800</epage><pages>791-800</pages><issn>1359-4184</issn><eissn>1476-5578</eissn><abstract>Meta-analyses, published in 2008–2010, have confirmed abnormally low serum brain-derived neurotrophic factor (BDNF) concentrations in depressed patients and normalization of this by antidepressant treatment. These findings are believed to reflect peripheral manifestations of the
neurotrophin hypothesis
, which states that depression is secondary to an altered expression of BDNF in the brain. Since the publication of these meta-analyses, the field has seen a huge increase in studies on these topics. This motivated us to update the evidence on the aforementioned associations and, in addition, to compile the data on serum BDNF concentrations in relation to the symptom severity of depression. Using a manifold of data as compared with earlier meta-analyses, we find low serum BDNF concentrations in 2384 antidepressant-free depressed patients relative to 2982 healthy controls and to 1249 antidepressant-treated depressed patients (Cohen’s
d
=−0.71 and −0.56,
P
-values <0.0000001). When publication bias is accounted for, these effect-sizes become substantially smaller (
d
=−0.47 and −0.34, respectively,
P
-values<0.0001). We detect between-study heterogeneity in outcomes for which only year of publication and sample size are significant moderators, with more recent papers and larger samples sizes in general being associated with smaller between-group differences. Finally, the aggregated data negate consistent associations between serum BDNF concentrations and the symptom severity of depression. Our findings corroborate the claim that altered serum BDNF concentrations are peripheral manifestations of depression. However, here we highlight that the evidence for this claim is slimmer as was initially thought and amidst a lot of noise.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23958957</pmid><doi>10.1038/mp.2013.105</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular psychiatry, 2014-07, Vol.19 (7), p.791-800 |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | 631/378/1686 692/53 692/699/476/1414 Adult and adolescent clinical studies Antidepressants Antidepressive Agents - therapeutic use Behavioral Sciences Biological and medical sciences Biological Psychology Biomarkers - blood Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - blood Case-Control Studies Depression Depression - blood Depression - drug therapy Depression, Mental Humans Medical sciences Medicine Medicine & Public Health Mental depression Meta-analysis Miscellaneous Mood disorders Neuropharmacology Neurosciences original-article Patients Pharmacology. Drug treatments Pharmacotherapy Physiological aspects Psychiatric research Psychiatric Status Rating Scales Psychiatry Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychopharmacology Publication Bias - statistics & numerical data Systematic review |
| title | Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484) |
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