Convergent functional genomic studies of omega-3 fatty acids in stress reactivity, bipolar disorder and alcoholism

Le-Niculescu, Helen; Case, N J; Hulvershorn, Leslie A.; Patel, Sagar P.; Bowker, D; Gupta, Jayanta; Bell, Richard L.; Edenberg, Howard J.; Tsuang, MingT.; Kuczenski, Ronald; Geyer, Mark A.; Za, Rodd; Niculescu, Alexander B.

doi:10.1038/tp.2011.1

Cited by 41 publications

(37 citation statements)

References 217 publications

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“…Of note, adult ADHD is linked with blunted Per2 expression (Baird et al, 2012). It is also interesting that the other clock genes with altered circadian profiles in ENT1 KO mice, Clock and Dbp, are associated with ADHD (Kissling et al, 2008;Roybal et al, 2007;Xu et al, 2010), bipolar disorder (Le-Niculescu et al, 2008;Lee et al, 2010;Shi et al, 2008;Soria et al, 2010), anxiety (Le-Niculescu et al, 2011a), and AUD (Le-Niculescu et al, 2011b;Le-Niculescu et al, 2008). Interestingly, ENT1 KO mice display mania-like behavior (Ruby et al, 2011) similar to Dbp KO mice (Le-Niculescu et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Adenosinergic Regulation of Striatal Clock Gene Expression and Ethanol Intake During Constant Light

Ruby

Vadnie

Hinton

et al. 2014

Neuropsychopharmacol

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Circadian rhythm and sleep disruptions occur frequently in individuals with alcohol use disorders (AUD) and present significant barriers to treatment. Recently, a variant of adenosine transporter, equilibrative nucleoside transporter 1 (ENT1), was associated with the cooccurrence of sleep problems and AUD. We have previously shown that mice lacking ENT1 (ENT1 KO) have reduced adenosine levels in the striatum and drink more alcohol compared with wild types (WT). However, it is unknown whether ENT1 deletion disrupts circadian rhythms, which may contribute to alcohol preference in ENT1 KO mice. Here we used these mice to determine whether endogenous adenosine regulates circadian genetic and behavioral rhythms and influences alcohol intake during chronodisruption. We examined circadian locomotor activity in ENT1 KO vs WT littermates and found that ENT1 KO mice were both active earlier and hyperactive compared with WT mice at night. We used real-time PCR and immunohistochemistry to estimate striatal clock gene levels and found that PER2 expression in the striatum was blunted by ENT1 deletion or A2A receptor (A2AR) antagonism. Next, we exposed ENT1 KO and WT mice to constant light (LL) and found further elevation in ethanol intake in ENT1 KO, but not in WT mice, supporting the notion that circadian dysfunction may contribute to increased alcohol intake in ENT1 KO mice. Finally, we showed that A2AR agonist administration normalized PER1 and PER2 expression and circadian locomotor activity in ENT1 KO mice. Together, our results demonstrate that adenosine signaling regulates cellular and behavioral circadian timing and influences alcohol intake during chronodisruption.

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Section: Discussionmentioning

confidence: 99%

Adenosinergic Regulation of Striatal Clock Gene Expression and Ethanol Intake During Constant Light

Ruby

Vadnie

Hinton

et al. 2014

Neuropsychopharmacol

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“…Crucial genes expressed by leukocytes that have been associated with inflammation, cellular stress and mood states are STMN1, p16 ink4a as well as FOS, DUSP1, TERT and the IL-6 gene. Among these pool of genes, FOS and DUSP1 have been reported good candidates to responses to stress, inflammation and anxiety states 50,51 . Teyssier and collaborators 50 found a strong association of the leukocyte expression of the STMIN1 and p16 ink4a with high scores of anxiety symptoms among patients diagnosed with depression.…”

Section: Anxious-depression As An Inflammatory Phenomenonmentioning

confidence: 99%

Is anxious-depression an inflammatory state?

Camacho

2013

Medical Hypotheses

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For several years, the literature has examined the association of depression and anxiety with inflammatory states such as atherosclerosis and cardiovascular disease, yet this association remains inconclusive. Several possible immune and endocrinological pathways have been postulated that associate depression and anxiety with inflammation and immune dysregulation. Anxiety and depression have usually been envisioned as two separate psychiatric conditions yet they share similar symptoms and are frequently encountered together among individuals. Individuals suffering from anxious-depression are more refractory to treatment and have been reported to have greater disability compared to individuals with anxiety or depression alone. With the current changes in the diagnostic manual for psychiatric disorders placing more emphasis on a dimensional approach for the diagnosis of psychiatric illnesses, the hypothesis presented is that anxious-depression should be considered as a chronic inflammatory phenomenon since it shares common physiopathological pathways and pharmacological treatments with inflammatory states. This hypothesis might help to investigate how different levels of inflammatory biomarkers could be correlated with symptoms of anxious-depression.

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“…It is very interesting that other natural substances such as omega-3 fatty acids have been proposed as adjuvant treatment in alcoholism (Le-Niculescu et al 2011). This is important because it is known that omega-3 fatty acid deficiency results in reduced DA release in the frontal cortex, a relapse site for psychoactive drug abuse.…”

Section: Discussionmentioning

confidence: 99%

Early Intervention of Intravenous KB220IV- Neuroadaptagen Amino-Acid Therapy (NAAT)™ Improves Behavioral Outcomes in a Residential Addiction Treatment Program: A Pilot Study

Miller¹,

Chen

Stokes³

et al. 2012

Journal of Psychoactive Drugs

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Substance use disorders (SUD) are inheritable and the culprit is hypodopaminergic function regulated by reward genes. We evaluated a natural dopaminergic agonist; KB220 intravenous (IV) and oral variants, to improve dopaminergic function in SUD. Our pilot experiment found a significant reduction of chronic symptoms, measured by the Chronic Abstinence Symptom Severity (CASS) Scale. The combined group (IV and oral) did significantly better than the oral-only group over the first week and 30-day follow-up period. Next, the combination was given to129 subjects and three factors; Emotion, Somatic, and Impaired Cognition, with eigenvalues greater than one were extracted for baseline CASS-Revised (CASS-R) variables. Paired sample t-tests for pre and post-treatment scales showed significant declines (p = .00001) from pre- to post-treatment: t = 19.1 for Emotion, t = 16.1 for Somatic, and t = 14.9 for Impaired Cognition. In a two-year follow-up of 23 subjects who underwent KB220IV therapy (at least five IV treatments over seven days) plus orals for 30+ days: 21 (91%) were sober at six months, 19 (82%) having no relapse; 19 (82%) were sober at one year, 18 (78%) having no relapse; and 21 (91%) were sober two-years post-treatment, 16 (70%) having no relapse. We await additional research and advise caution in interpreting these encouraging results.

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Convergent functional genomic studies of omega-3 fatty acids in stress reactivity, bipolar disorder and alcoholism

Cited by 41 publications

References 217 publications

Adenosinergic Regulation of Striatal Clock Gene Expression and Ethanol Intake During Constant Light

Adenosinergic Regulation of Striatal Clock Gene Expression and Ethanol Intake During Constant Light

Is anxious-depression an inflammatory state?

Early Intervention of Intravenous KB220IV- Neuroadaptagen Amino-Acid Therapy (NAAT)™ Improves Behavioral Outcomes in a Residential Addiction Treatment Program: A Pilot Study

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