A Clinical Genetic Method to Identify Mechanisms by Which Pain Causes Depression and Anxiety

Max, Mitchell B.; Wu, Tianxia; Atlas, Steven J.; Edwards, Robert R.; Haythornthwaite, Jennifer A.; Bollettino, A.; Hipp, Heather S.; McKnight, Colin D.; Osman, I.; Crawford, Erin N; Pao, Maryland; Nejim, Jemiel; Kingman, Albert; Aisen, Daniel C; Scully, Michele A.; Keller, Robert B.; Goldman, David; Belfer, Inna

doi:10.1186/1744-8069-2-14

Cited by 53 publications

(48 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another study investigating the role of the COMT Val158Met polymorphism in depression and anxiety in female FM patients confirmed that Met allele was associated with higher levels of both anxiety and depression (Ferna´ndez-de-las-Pen˜as et al, 2012). Pain-gene interactions on postoperative mood have also been observed in surgically treated sciatica patients where common OPRM1 SNPs determined short-term effects of acute sciatica on mood (Max et al, 2006).…”

Section: Genetics Of Variability In Psychosocial Phenotypesmentioning

confidence: 78%

Molecular Genetics of Variability in Human Pain

Belfer

Shnol

Finelli

2013

Encyclopedia of Life Sciences

Self Cite

View full text Add to dashboard Cite

Pain is considered to be an evolutionary‐conserved trait and is employed as a necessary means to survival. Although this trait is common in all humans, it shows great variability among individuals. The underlying mechanisms of pain perception are not fully understood. Functional single nucleotide polymorphism and other types of genetic polymorphisms increase or decrease gene function influencing the encoded product. These polymorphisms (alleles) used to analyse the genetic mechanisms of pain perception may account for up to 50% of the total variability in the human pain phenotype. Interestingly, certain genes (e.g. COMT and OPRM1 ) are reoccurring targets of interest for the variation they cause in experimental and clinical pain perception as well for their effects on analgesia and pain‐related psychosocial traits. Current and future genetic studies of human pain will reveal missing risk factors for painful disorders and will aid focussed clinical trials for improved and innovative pain management in patients at risk. Key Concepts: Variability is a common feature for all pain phenotypes in humans. Genetics account for a big portion of overall variability in human pain. Different pain phenotypes have overlapping genetic background. Both common and rare functional genetic polymorphisms contribute to human pain. Candidate gene studies revealed only of a handful of genetic risk and protective factors for human pain. Unbiased genome‐wide approaches will provide data on additional genetic factors influencing human pain.

show abstract

Section: Genetics Of Variability In Psychosocial Phenotypesmentioning

confidence: 78%

Molecular Genetics of Variability in Human Pain

Belfer

Shnol

Finelli

2013

Encyclopedia of Life Sciences

Self Cite

View full text Add to dashboard Cite

show abstract

“…29 Another reported an association of the G allele with negative mood. 41 According to recent authorities, both these conditions are consistent with a low level of opioid receptor activity. 42 Such an explanation could also be compatible with a lower preference for palatable foods.…”

Section: Discussionmentioning

confidence: 95%

“…40 The rs495491 marker in intron 1 was selected because of its association with alcohol/drug dependence 29 and pain sensitivity. 41 The rs563649 marker was recently reported to affect the translational efficiency of novel isoforms of the mu opioid receptor through a structurally conserved internal ribosomal entry site. 42 The other SNPs were selected from the five tag SNPs reported by Zhang et al, 29 which included rs9322447 and rs648893 (that we have replaced with rs558948 because of assay availability) in addition to rs1799971 and rs495491.…”

Section: Methodsmentioning

confidence: 99%

Opiates, overeating and obesity: a psychogenetic analysis

et al. 2011

View full text Add to dashboard Cite

Objective: This study provides an original perspective on the associations among endogenous opiates, overeating and obesity. The aim was to assess whether variability in the OPRM1 gene, as assessed by seven single-nucleotide polymorphisms, relates to individual differences in the preference for sweet and fatty foods. We also anticipated that these food preferences would be positively associated with binge eating, hedonic eating and emotionally driven eating-patterns of overeating that would, in turn, predict higher body mass index (BMI). Design: Analysis of variance procedures examined genotype differences in food preferences; bivariate correlation coefficients examined the relationships among food preferences and the overeating variables; and a regression analysis tested the combined influences of the overeating variables on BMI. DNA was extracted from whole blood for the genotyping, and measures of food preferences and eating behaviours were obtained from well-validated self-report questionnaires. Subjects: Participants were 300 healthy adult men and women recruited from the community. Results: All the predicted associations were supported by statistically significant results. In particular, the G/G genotype group of the functional A118G marker of the OPRM1 gene reported higher preferences for sweet and fatty foods compared with the other two groups. Food preferences were also related to all overeating measures, which in turn accounted for a substantial proportion of the variance in BMI. Conclusions: Our findings suggest that some of the diversity in the preference for highly palatable foods can be explained by genotypic differences in the regulation of mu opioid receptors. The associations reported in this paper are important from a public-health perspective because of the abuse potential of sweet-fat foods and their strong relationship with obesity.

show abstract

“…previous genetic studies on humans that the galanin system is involved in psychiatric disorders including alcoholism/addiction (43)(44)(45)(46)(47), panic disorder (48,49), and chronic pain-associated depression (50). Furthermore, recent functional studies provided the first evidence that polymorphisms in a highly conserved genetic region upstream from the GAL gene regulates GAL expression in brain areas, such as the amygdala and hypothalamus, implicated in the pathogenesis of depression (51,52).…”

mentioning

confidence: 99%

Brain galanin system genes interact with life stresses in depression-related phenotypes

Juhász

Hullám

Eszlári

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Galanin is a stress-inducible neuropeptide and cotransmitter in serotonin and norepinephrine neurons with a possible role in stress-related disorders. Here we report that variants in genes for galanin (GAL) and its receptors (GALR1, GALR2, GALR3), despite their disparate genomic loci, conferred increased risk of depression and anxiety in people who experienced childhood adversity or recent negative life events in a European white population cohort totaling 2,361 from Manchester, United Kingdom and Budapest, Hungary. Bayesian multivariate analysis revealed a greater relevance of galanin system genes in highly stressed subjects compared with subjects with moderate or low life stress. Using the same method, the effect of the galanin system genes was stronger than the effect of the well-studied 5-HTTLPR polymorphism in the serotonin transporter gene (SLC6A4). Conventional multivariate analysis using general linear models demonstrated that interaction of galanin system genes with life stressors explained more variance (1.7%, P = 0.005) than the life stress-only model. This effect replicated in independent analysis of the Manchester and Budapest subpopulations, and in males and females. The results suggest that the galanin pathway plays an important role in the pathogenesis of depression in humans by increasing the vulnerability to early and recent psychosocial stress. Correcting abnormal galanin function in depression could prove to be a novel target for drug development. The findings further emphasize the importance of modeling environmental interaction in finding new genes for depression.galanin receptors | mood disorders | network-based analysis | neurogenesis | transmitter coexistence M ajor depressive disorder (MDD) is a common and serious disease afflicting more women than men, and a leading cause of disability worldwide, associated with much suffering and major costs for society (1, 2). Environmental psychosocial stressors are important in pathogenesis, because episodes are usually preceded by adverse life events, and early childhood experiences of physical and emotional abuse and parental neglect are important vulnerability factors (3, 4). Genetic vulnerability is significant with a heritability of about 35% (5). We remain ignorant about the brain processes that translate these genetic and environmental influences into depressive symptoms or risk. A major clue is that effective antidepressant drugs act directly or indirectly to enhance neurotransmission in serotonin (5-HT) and norepinephrine monoamine pathways, proving the monoamine hypothesis of depression (6-8). Many other candidate mechanisms have been identified in anatomical, pharmacological, and behavioral studies of stress in rodents. However, the demonstration of stateor trait-related abnormalities in human monoamine or other neural systems remains frustratingly elusive, despite modern brain-imaging methods. To determine whether the neuropeptide galanin has a role in depression, we used a unique Bayesian systems-based analysis to dissect out the influ...

show abstract

A Clinical Genetic Method to Identify Mechanisms by Which Pain Causes Depression and Anxiety

Cited by 53 publications

References 51 publications

Molecular Genetics of Variability in Human Pain

Molecular Genetics of Variability in Human Pain

Opiates, overeating and obesity: a psychogenetic analysis

Brain galanin system genes interact with life stresses in depression-related phenotypes

Contact Info

Product

Resources

About