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Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment
Objectives Omega (n)‐3 and n‐6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n‐3 PUFAs would be lower and those of n‐6 PUFAs higher in subjects with bipolar disorder (BD) compared to healthy controls...
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| Published in: | Bipolar disorders 2015-11, Vol.17 (7), p.729-742 |
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| container_title | Bipolar disorders |
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| creator | Saunders, Erika FH Reider, Aubrey Singh, Gagan Gelenberg, Alan J Rapoport, Stanley I |
| description | Objectives
Omega (n)‐3 and n‐6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n‐3 PUFAs would be lower and those of n‐6 PUFAs higher in subjects with bipolar disorder (BD) compared to healthy controls (HCs), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n‐3 but lower n‐6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids.
Methods
This observational, parallel group study compared biomarkers between HCs (n = 31) and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow‐up). Plasma concentrations of five PUFAs [linoleic acid (LA), arachidonic acid (AA), alpha‐linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], two saturated fatty acids (palmitic acid and stearic acid) and two monounsaturated fatty acids (palmitoleic acid and oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFAs, ratios of n‐3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio of n‐6:n‐3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t‐tests, and between the BD group at baseline and follow‐up using paired t‐tests. Comparison of categorical variables was performed using chi‐square tests. Pearson's r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis.
Results
UE EPA was lower in subjects with BD than in HCs, with a large effect size (Cohen's d = 0.86, p |
| doi_str_mv | 10.1111/bdi.12337 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4623957</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1727993014</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4537-694dd954c55cdb97171b56685e97e348fab7163d39b4d99da736a830ed3aa9143</originalsourceid><addsrcrecordid>eNp1kt1u1DAQhSMEoqVwwQsgX7YSaeP4b80FUv-ptCpIgLi0JvZsa0jiYGdZ9tl4OcymXUAC38yR5vibkY-L4jmtDmk-R43zh7RmTD0odinTuhSSzh5u9CxrrnaKJyl9rioq60o8LnZqyWvOqdwtfszDiix7TCNGv_DoXv2WBL0NCQbsR8A-eEvAekf2z98dH5ChhdQBsaG3uR9h9KEnm0J8IpBSsB7GDFn58ZY0fggtROJ8CtFhJDhk5TC9JNA7Ejq8gZL9E5phEQm0eatMa9ZkjAhjl_tPi0cLaBM-u6t7xceL8w-nb8r528ur0-N5ablgqpSaO6cFt0JY12hFFW2ElDOBWiHjswU0ikrmmG6409qBYhJmrELHADTlbK94PXGHZdOhm1ZrzRB9B3FtAnjzd6f3t-YmfDNc1kwLlQH7d4AYvi7zA5vOJ4ttCz2GZTJU1UprVm1mHUxWG0NKERfbMbQyv8I2OWyzCTt7X_y519Z5n242HE2GlW9x_X-SOTm7ukeW0w2ff8H37Q2IX4xUTAnz6frS1Bfv9fUJPzNz9hNrAcgP</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1727993014</pqid></control><display><type>article</type><title>Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment</title><source>Wiley</source><creator>Saunders, Erika FH ; Reider, Aubrey ; Singh, Gagan ; Gelenberg, Alan J ; Rapoport, Stanley I</creator><creatorcontrib>Saunders, Erika FH ; Reider, Aubrey ; Singh, Gagan ; Gelenberg, Alan J ; Rapoport, Stanley I</creatorcontrib><description>Objectives
Omega (n)‐3 and n‐6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n‐3 PUFAs would be lower and those of n‐6 PUFAs higher in subjects with bipolar disorder (BD) compared to healthy controls (HCs), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n‐3 but lower n‐6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids.
Methods
This observational, parallel group study compared biomarkers between HCs (n = 31) and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow‐up). Plasma concentrations of five PUFAs [linoleic acid (LA), arachidonic acid (AA), alpha‐linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], two saturated fatty acids (palmitic acid and stearic acid) and two monounsaturated fatty acids (palmitoleic acid and oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFAs, ratios of n‐3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio of n‐6:n‐3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t‐tests, and between the BD group at baseline and follow‐up using paired t‐tests. Comparison of categorical variables was performed using chi‐square tests. Pearson's r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis.
Results
UE EPA was lower in subjects with BD than in HCs, with a large effect size (Cohen's d = 0.86, p < 0.002); however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between the BD and HC groups after Bonferroni correction for 40 comparisons, at p < 0.001. Neither depressive severity nor mania severity was correlated significantly with any PUFA concentration. Exploratory comparison showed lower UE:E EPA in the BD than the HC group (p < 0.0001). At follow‐up in the BD group, UE, E DHA:ALA, and UE EPA:ALA were decreased (p < 0.002). Exploratory correlations of clinical variables revealed that mania severity and suicidality were positively correlated with UE:E EPA ratio, and that several plasma levels and ratios correlated with panic disorder and psychosis. Depressive severity was not correlated with any ratio. No plasma fatty acid level or ratio correlated with self‐reported n‐3 PUFA intake or use of medication by class.
Conclusions
A large effect size of reduced UE EPA, and a lower plasma UE:E concentration ratio of EPA in the symptomatic BD state may be important factors in vulnerability to a mood state. Altered n‐3 PUFA ratios could indicate changes in PUFA metabolism concurrent with symptom improvement. Our findings are consistent with preclinical and postmortem data and suggest testing interventions that increase n‐3 and decrease n‐6 dietary PUFA intake.</description><identifier>ISSN: 1398-5647</identifier><identifier>EISSN: 1399-5618</identifier><identifier>DOI: 10.1111/bdi.12337</identifier><identifier>PMID: 26424416</identifier><language>eng</language><publisher>Denmark: Blackwell Publishing Ltd</publisher><subject>Adult ; Antidepressive Agents - pharmacology ; Antimanic Agents - pharmacology ; Arachidonic Acid - metabolism ; Behavioral Symptoms - blood ; Behavioral Symptoms - drug therapy ; Biomarkers - blood ; bipolar disorder ; Bipolar Disorder - blood ; Bipolar Disorder - drug therapy ; Bipolar Disorder - psychology ; eicosapentaenoic acid ; Eicosapentaenoic Acid - metabolism ; Eicosapentaenoic Acid - pharmacology ; Fatty Acids, Monounsaturated - metabolism ; Fatty Acids, Omega-3 - blood ; Fatty Acids, Omega-6 - blood ; Female ; Humans ; inflammation ; Longitudinal Studies ; Male ; Middle Aged ; omega-3 ; Severity of Illness Index ; Statistics as Topic ; Suicide - prevention & control ; Synaptic Transmission - drug effects ; Synaptic Transmission - physiology</subject><ispartof>Bipolar disorders, 2015-11, Vol.17 (7), p.729-742</ispartof><rights>2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4537-694dd954c55cdb97171b56685e97e348fab7163d39b4d99da736a830ed3aa9143</citedby><cites>FETCH-LOGICAL-c4537-694dd954c55cdb97171b56685e97e348fab7163d39b4d99da736a830ed3aa9143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26424416$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saunders, Erika FH</creatorcontrib><creatorcontrib>Reider, Aubrey</creatorcontrib><creatorcontrib>Singh, Gagan</creatorcontrib><creatorcontrib>Gelenberg, Alan J</creatorcontrib><creatorcontrib>Rapoport, Stanley I</creatorcontrib><title>Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment</title><title>Bipolar disorders</title><addtitle>Bipolar Disord</addtitle><description>Objectives
Omega (n)‐3 and n‐6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n‐3 PUFAs would be lower and those of n‐6 PUFAs higher in subjects with bipolar disorder (BD) compared to healthy controls (HCs), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n‐3 but lower n‐6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids.
Methods
This observational, parallel group study compared biomarkers between HCs (n = 31) and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow‐up). Plasma concentrations of five PUFAs [linoleic acid (LA), arachidonic acid (AA), alpha‐linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], two saturated fatty acids (palmitic acid and stearic acid) and two monounsaturated fatty acids (palmitoleic acid and oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFAs, ratios of n‐3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio of n‐6:n‐3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t‐tests, and between the BD group at baseline and follow‐up using paired t‐tests. Comparison of categorical variables was performed using chi‐square tests. Pearson's r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis.
Results
UE EPA was lower in subjects with BD than in HCs, with a large effect size (Cohen's d = 0.86, p < 0.002); however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between the BD and HC groups after Bonferroni correction for 40 comparisons, at p < 0.001. Neither depressive severity nor mania severity was correlated significantly with any PUFA concentration. Exploratory comparison showed lower UE:E EPA in the BD than the HC group (p < 0.0001). At follow‐up in the BD group, UE, E DHA:ALA, and UE EPA:ALA were decreased (p < 0.002). Exploratory correlations of clinical variables revealed that mania severity and suicidality were positively correlated with UE:E EPA ratio, and that several plasma levels and ratios correlated with panic disorder and psychosis. Depressive severity was not correlated with any ratio. No plasma fatty acid level or ratio correlated with self‐reported n‐3 PUFA intake or use of medication by class.
Conclusions
A large effect size of reduced UE EPA, and a lower plasma UE:E concentration ratio of EPA in the symptomatic BD state may be important factors in vulnerability to a mood state. Altered n‐3 PUFA ratios could indicate changes in PUFA metabolism concurrent with symptom improvement. Our findings are consistent with preclinical and postmortem data and suggest testing interventions that increase n‐3 and decrease n‐6 dietary PUFA intake.</description><subject>Adult</subject><subject>Antidepressive Agents - pharmacology</subject><subject>Antimanic Agents - pharmacology</subject><subject>Arachidonic Acid - metabolism</subject><subject>Behavioral Symptoms - blood</subject><subject>Behavioral Symptoms - drug therapy</subject><subject>Biomarkers - blood</subject><subject>bipolar disorder</subject><subject>Bipolar Disorder - blood</subject><subject>Bipolar Disorder - drug therapy</subject><subject>Bipolar Disorder - psychology</subject><subject>eicosapentaenoic acid</subject><subject>Eicosapentaenoic Acid - metabolism</subject><subject>Eicosapentaenoic Acid - pharmacology</subject><subject>Fatty Acids, Monounsaturated - metabolism</subject><subject>Fatty Acids, Omega-3 - blood</subject><subject>Fatty Acids, Omega-6 - blood</subject><subject>Female</subject><subject>Humans</subject><subject>inflammation</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Middle Aged</subject><subject>omega-3</subject><subject>Severity of Illness Index</subject><subject>Statistics as Topic</subject><subject>Suicide - prevention & control</subject><subject>Synaptic Transmission - drug effects</subject><subject>Synaptic Transmission - physiology</subject><issn>1398-5647</issn><issn>1399-5618</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp1kt1u1DAQhSMEoqVwwQsgX7YSaeP4b80FUv-ptCpIgLi0JvZsa0jiYGdZ9tl4OcymXUAC38yR5vibkY-L4jmtDmk-R43zh7RmTD0odinTuhSSzh5u9CxrrnaKJyl9rioq60o8LnZqyWvOqdwtfszDiix7TCNGv_DoXv2WBL0NCQbsR8A-eEvAekf2z98dH5ChhdQBsaG3uR9h9KEnm0J8IpBSsB7GDFn58ZY0fggtROJ8CtFhJDhk5TC9JNA7Ejq8gZL9E5phEQm0eatMa9ZkjAhjl_tPi0cLaBM-u6t7xceL8w-nb8r528ur0-N5ablgqpSaO6cFt0JY12hFFW2ElDOBWiHjswU0ikrmmG6409qBYhJmrELHADTlbK94PXGHZdOhm1ZrzRB9B3FtAnjzd6f3t-YmfDNc1kwLlQH7d4AYvi7zA5vOJ4ttCz2GZTJU1UprVm1mHUxWG0NKERfbMbQyv8I2OWyzCTt7X_y519Z5n242HE2GlW9x_X-SOTm7ukeW0w2ff8H37Q2IX4xUTAnz6frS1Bfv9fUJPzNz9hNrAcgP</recordid><startdate>201511</startdate><enddate>201511</enddate><creator>Saunders, Erika FH</creator><creator>Reider, Aubrey</creator><creator>Singh, Gagan</creator><creator>Gelenberg, Alan J</creator><creator>Rapoport, Stanley I</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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><scope>5PM</scope></search><sort><creationdate>201511</creationdate><title>Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment</title><author>Saunders, Erika FH ; Reider, Aubrey ; Singh, Gagan ; Gelenberg, Alan J ; Rapoport, Stanley I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4537-694dd954c55cdb97171b56685e97e348fab7163d39b4d99da736a830ed3aa9143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Antidepressive Agents - pharmacology</topic><topic>Antimanic Agents - pharmacology</topic><topic>Arachidonic Acid - metabolism</topic><topic>Behavioral Symptoms - blood</topic><topic>Behavioral Symptoms - drug therapy</topic><topic>Biomarkers - blood</topic><topic>bipolar disorder</topic><topic>Bipolar Disorder - blood</topic><topic>Bipolar Disorder - drug therapy</topic><topic>Bipolar Disorder - psychology</topic><topic>eicosapentaenoic acid</topic><topic>Eicosapentaenoic Acid - metabolism</topic><topic>Eicosapentaenoic Acid - pharmacology</topic><topic>Fatty Acids, Monounsaturated - metabolism</topic><topic>Fatty Acids, Omega-3 - blood</topic><topic>Fatty Acids, Omega-6 - blood</topic><topic>Female</topic><topic>Humans</topic><topic>inflammation</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Middle Aged</topic><topic>omega-3</topic><topic>Severity of Illness Index</topic><topic>Statistics as Topic</topic><topic>Suicide - prevention & control</topic><topic>Synaptic Transmission - drug effects</topic><topic>Synaptic Transmission - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saunders, Erika FH</creatorcontrib><creatorcontrib>Reider, Aubrey</creatorcontrib><creatorcontrib>Singh, Gagan</creatorcontrib><creatorcontrib>Gelenberg, Alan J</creatorcontrib><creatorcontrib>Rapoport, Stanley I</creatorcontrib><collection>Istex</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Bipolar disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saunders, Erika FH</au><au>Reider, Aubrey</au><au>Singh, Gagan</au><au>Gelenberg, Alan J</au><au>Rapoport, Stanley I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment</atitle><jtitle>Bipolar disorders</jtitle><addtitle>Bipolar Disord</addtitle><date>2015-11</date><risdate>2015</risdate><volume>17</volume><issue>7</issue><spage>729</spage><epage>742</epage><pages>729-742</pages><issn>1398-5647</issn><eissn>1399-5618</eissn><abstract>Objectives
Omega (n)‐3 and n‐6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n‐3 PUFAs would be lower and those of n‐6 PUFAs higher in subjects with bipolar disorder (BD) compared to healthy controls (HCs), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n‐3 but lower n‐6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids.
Methods
This observational, parallel group study compared biomarkers between HCs (n = 31) and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow‐up). Plasma concentrations of five PUFAs [linoleic acid (LA), arachidonic acid (AA), alpha‐linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], two saturated fatty acids (palmitic acid and stearic acid) and two monounsaturated fatty acids (palmitoleic acid and oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFAs, ratios of n‐3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio of n‐6:n‐3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t‐tests, and between the BD group at baseline and follow‐up using paired t‐tests. Comparison of categorical variables was performed using chi‐square tests. Pearson's r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis.
Results
UE EPA was lower in subjects with BD than in HCs, with a large effect size (Cohen's d = 0.86, p < 0.002); however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between the BD and HC groups after Bonferroni correction for 40 comparisons, at p < 0.001. Neither depressive severity nor mania severity was correlated significantly with any PUFA concentration. Exploratory comparison showed lower UE:E EPA in the BD than the HC group (p < 0.0001). At follow‐up in the BD group, UE, E DHA:ALA, and UE EPA:ALA were decreased (p < 0.002). Exploratory correlations of clinical variables revealed that mania severity and suicidality were positively correlated with UE:E EPA ratio, and that several plasma levels and ratios correlated with panic disorder and psychosis. Depressive severity was not correlated with any ratio. No plasma fatty acid level or ratio correlated with self‐reported n‐3 PUFA intake or use of medication by class.
Conclusions
A large effect size of reduced UE EPA, and a lower plasma UE:E concentration ratio of EPA in the symptomatic BD state may be important factors in vulnerability to a mood state. Altered n‐3 PUFA ratios could indicate changes in PUFA metabolism concurrent with symptom improvement. Our findings are consistent with preclinical and postmortem data and suggest testing interventions that increase n‐3 and decrease n‐6 dietary PUFA intake.</abstract><cop>Denmark</cop><pub>Blackwell Publishing Ltd</pub><pmid>26424416</pmid><doi>10.1111/bdi.12337</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Bipolar disorders, 2015-11, Vol.17 (7), p.729-742 |
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| source | Wiley |
| subjects | Adult Antidepressive Agents - pharmacology Antimanic Agents - pharmacology Arachidonic Acid - metabolism Behavioral Symptoms - blood Behavioral Symptoms - drug therapy Biomarkers - blood bipolar disorder Bipolar Disorder - blood Bipolar Disorder - drug therapy Bipolar Disorder - psychology eicosapentaenoic acid Eicosapentaenoic Acid - metabolism Eicosapentaenoic Acid - pharmacology Fatty Acids, Monounsaturated - metabolism Fatty Acids, Omega-3 - blood Fatty Acids, Omega-6 - blood Female Humans inflammation Longitudinal Studies Male Middle Aged omega-3 Severity of Illness Index Statistics as Topic Suicide - prevention & control Synaptic Transmission - drug effects Synaptic Transmission - physiology |
| title | Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment |
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