Adolescents with or at ultra-high risk for bipolar disorder exhibit erythrocyte docosahexaenoic acid and eicosapentaenoic acid deficits: a candidate prodromal risk biomarker.
OBJECTIVE
Mood disorders are associated with low levels of the long-chain omega-3 (LCn-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This study investigated LCn-3 fatty acid biostatus in youth with or at varying risk for developing mania to assess its utility as a prodromal risk biomarker.


METHODS
Erythrocyte fatty acid composition was determined in healthy adolescents (n = 28, HC), asymptomatic adolescents with a biological parent with bipolar I disorder (n = 30; 'high risk', HR), adolescents with a biological parent with bipolar I disorder and major depressive disorder, or depressive disorder not otherwise specified (n = 36; 'ultra-high risk', UHR), and first-episode adolescent bipolar manic patients (n = 35, BP).


RESULTS
Group differences were observed for DHA (P ≤ 0.0001) and EPA (P = 0.03). Compared with HC, erythrocyte EPA + DHA ('omega-3 index') was significantly lower in BP (-24%, P ≤ 0.0001) and UHR (-19%, P = 0.0006) groups, and there was a trend in the HR group (-11%, P = 0.06). Compared with HC (61%), a greater percentage of HR (77%, P = 0.02), UHR (80%, P = 0.005) and BP (97%, P = 0.001) subjects exhibited EPA + DHA levels of ≤4.0%. Among all subjects (n = 130), EPA + DHA was inversely correlated with manic (r = -0.29, P = 0.0008) and depressive (r = -0.28, P = 0.003) symptom severity. The AA/EPA + DHA ratio was significantly greater in BP (+22%, P = 0.0002) and UHR (+16%, P = 0.001) groups.


CONCLUSIONS
Low EPA + DHA levels coincide with the initial onset of mania, and increasing risk for developing bipolar disorder is associated with graded erythrocyte EPA + DHA deficits. Low erythrocyte EPA + DHA biostatus may represent a promising prodromal risk biomarker warranting additional evaluation in future prospective studies.
Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Robert K
RK
McNamara
Department of Pathology, University of Cincinnati, Cincinnati, Ohio, USA.
Ronald
R
Jandacek
Department of Pathology, University of Cincinnati, Cincinnati, Ohio, USA.
Patrick
P
Tso
Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Thomas J
TJ
Blom
Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Jeffrey A
JA
Welge
Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Jeffrey R
JR
Strawn
Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Caleb M
CM
Adler
Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Stephen M
SM
Strakowski
Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Melissa P
MP
DelBello
D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D001714:Bipolar Disorder / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D004281:Docosahexaenoic Acids / Q000172:deficiency*; D015118:Eicosapentaenoic Acid / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D062706:Prodromal Symptoms; D012307:Risk Factors; D055815:Young Adult
D015415:Biomarkers; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
arachidonic acid (AA); eicosapentaenoic acid (EPA); mania; omega-3 index; ultra-high risk