Home LiteratureArticle Details
PMID: 15457344 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Sex- and lineage-specific inheritance of depression-like behavior in the rat.

Mammalian genome : official journal of the International Mammalian Genome Society ·Vol. 15 ·No. 8 ·2004-08-00 ·Pages 648-62

Solberg LC, Baum AE, Ahmadiyeh N, Shimomura K, Li R, Turek FW, Churchill GA, Takahashi JS, Redei EE

Abstract

The Wistar-Kyoto (WKY) rat exhibits physiological and behavioral similarities to endophenotypes of human depression. In the forced swim test (FST), a well-characterized antidepressant-reversible test for behavioral despair in rodents, WKYs express characteristics of behavioral despair; increased immobility, and decreased climbing. To map genetic loci linked to behavior in the FST, we conducted a quantitative trait loci (QTL) analysis of the segregating F2 generation of a WKY x Fisher 344 (F344) reciprocal intercross. Using linear-model-based genome scans to include covariate (sex or lineage)-by-QTL interaction effects, four significant QTL influencing climbing behavior were identified. In addition, we identified three, seven, and two suggestive QTL for climbing, immobility, and swimming, respectively. One of these loci was pleiotropic, affecting both immobility and climbing. As found in human linkage studies, several of these QTL showed sex- and/or lineage-dependent effects. A simultaneous search strategy identified three epistatic locus pairs for climbing. Multiple regression analysis was employed to characterize the joint contributions of these QTL and to clarify the sex- and lineage-dependent effects. As expected for complex traits, FST behavior is influenced by multiple QTL of small effect, each contributing 5%-10%, accounting for a total 10%-30% of the phenotypic variance. A number of loci mapped in this study share overlapping candidate regions with previously identified emotionality QTL in mice as well as with susceptibility loci recognized by linkage or genome scan analyses for major depression or bipolar disorder in humans. The presence of these loci across species suggests that these QTL may represent universal genetic factors contributing to mood disorders.

MeSH Terms
Animals Chromosome Mapping Crosses, Genetic Depression/genetics Female Genome Male Quantitative Trait Loci Rats Regression Analysis Swimming/physiology
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Solberg Leah C
Department of Psychiatry and Behavioral Science, Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, Illinois 60611, USA.
Baum Amber E
Ahmadiyeh Nasim
Shimomura Kazuhiro
Li Renhua
Turek Fred W
Churchill Gary A
Takahashi Joseph S
Redei Eva E
References (53)
53 references, click to expand
  1. R/qtl: QTL mapping in experimental crosses.
    Bioinformatics. 2003 May 1;19(7):889-90 PMID: 12724300
  2. Genome scan of a second wave of NIMH genetics initiative bipolar pedigrees: chromosomes 2, 11, 13, 14, and X.
    Am J Med Genet B Neuropsychiatr Genet. 2003 May 15;119B(1):69-76 PMID: 12707942
  3. Genome-wide scan and conditional analysis in bipolar disorder: evidence for genomic interaction in the National Institute of Mental Health genetics initiative bipolar pedigrees.
    Biol Psychiatry. 2003 Dec 1;54(11):1265-73 PMID: 14643094
  4. X-linked and lineage-dependent inheritance of coping responses to stress.
    Mamm Genome. 2003 Nov;14(11):748-57 PMID: 14722724
  5. QTL analysis of multiple behavioral measures of anxiety in mice.
    Behav Genet. 2004 May;34(3):267-93 PMID: 14990867
  6. Sex differences and the epidemiology of depression.
    Arch Gen Psychiatry. 1977 Jan;34(1):98-111 PMID: 319772
  7. Depression: a new animal model sensitive to antidepressant treatments.
    Nature. 1977 Apr 21;266(5604):730-2 PMID: 559941
  8. Behavioural despair in rats: a new model sensitive to antidepressant treatments.
    Eur J Pharmacol. 1978 Feb 15;47(4):379-91 PMID: 204499
  9. The tail suspension test: a new method for screening antidepressants in mice.
    Psychopharmacology (Berl). 1985;85(3):367-70 PMID: 3923523
  10. Forced swimming test in rats: effect of desipramine administration and the period of exposure to the test on struggling behavior, swimming, immobility and defecation rate.
    Eur J Pharmacol. 1988 Dec 13;158(3):207-12 PMID: 3253099
  11. "Behavioral despair" test predicts stress ulcer in WKY rats.
    Physiol Behav. 1989 Sep;46(3):483-7 PMID: 2623074
  12. Stress ulcer susceptibility and depression in Wistar Kyoto (WKY) rats.
    Physiol Behav. 1989 Dec;46(6):993-8 PMID: 2634265
  13. Major depression and generalized anxiety disorder. Same genes, (partly) different environments?
    Arch Gen Psychiatry. 1992 Sep;49(9):716-22 PMID: 1514877
  14. Effects of diazepam and desipramine in the forced swimming test: influence of previous experience with the situation.
    Eur J Pharmacol. 1993 May 19;236(2):295-9 PMID: 8319755
  15. Sex and depression in the National Comorbidity Survey. II: Cohort effects.
    J Affect Disord. 1994 Jan;30(1):15-26 PMID: 8151045
  16. Genetic dissection of complex traits.
    Science. 1994 Sep 30;265(5181):2037-48 PMID: 8091226
  17. Empirical threshold values for quantitative trait mapping.
    Genetics. 1994 Nov;138(3):963-71 PMID: 7851788
  18. A genetic linkage map of the laboratory rat, Rattus norvegicus.
    Nat Genet. 1995 Jan;9(1):63-9 PMID: 7704027
  19. Patterns of maternal transmission in bipolar affective disorder.
    Am J Hum Genet. 1995 Jun;56(6):1277-86 PMID: 7762550
  20. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results.
    Nat Genet. 1995 Nov;11(3):241-7 PMID: 7581446
  21. Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect.
    Am J Hum Genet. 1995 Dec;57(6):1384-94 PMID: 8533768
  22. Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants.
    Psychopharmacology (Berl). 1995 Sep;121(1):66-72 PMID: 8539342
  23. Maternal inheritance and chromosome 18 allele sharing in unilineal bipolar illness pedigrees.
    Am J Med Genet. 1996 Apr 9;67(2):202-7 PMID: 8723048
  24. Depression comorbid with anxiety: results from the WHO study on psychological disorders in primary health care.
    Br J Psychiatry Suppl. 1996 Jun;(30):38-43 PMID: 8864147
  25. Identification of a sex-specific quantitative trait locus mediating nonopioid stress-induced analgesia in female mice.
    J Neurosci. 1997 Oct 15;17(20):7995-8002 PMID: 9315917
  26. Quantitative trait locus analysis of contextual fear conditioning in mice.
    Nat Genet. 1997 Nov;17(3):331-4 PMID: 9354800
  27. Quantitative trait loci analysis affecting contextual conditioning in mice.
    Nat Genet. 1997 Nov;17(3):335-7 PMID: 9354801
  28. Anxiety proneness linked to epistatic loci in genome scan of human personality traits.
    Am J Med Genet. 1998 Jul 10;81(4):313-7 PMID: 9674977
  29. The forced swimming test as a model for core and component behavioral effects of antidepressant drugs.
    Behav Pharmacol. 1997 Nov;8(6-7):523-32 PMID: 9832966
  30. Genetic determination of cardiac mass in normotensive rats: results from an F344xWKY cross.
    Hypertension. 1999 Apr;33(4):949-53 PMID: 10205229
  31. Identification of female-specific QTLs affecting an emotionality-related behavior in rats.
    Mol Psychiatry. 1999 Sep;4(5):453-62 PMID: 10523818
  32. Lineage is an epigenetic modifier of QTL influencing behavioral coping with stress.
    Behav Genet. 2005 Mar;35(2):189-98 PMID: 15685431
  33. Strain differences in the behavioral effects of antidepressant drugs in the rat forced swimming test.
    Neuropsychopharmacology. 2000 Feb;22(2):191-9 PMID: 10649831
  34. From mouse to human: fine mapping of quantitative trait loci in a model organism.
    Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12389-90 PMID: 11050190
  35. A genome survey indicates a possible susceptibility locus for bipolar disorder on chromosome 22.
    Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):585-90 PMID: 11149935
  36. Genetic differences in the tail-suspension test and its relationship to imipramine response among 11 inbred strains of mice.
    Biol Psychiatry. 2001 Apr 1;49(7):575-81 PMID: 11297714
  37. Paradoxical hormonal and behavioral responses to hypothyroid and hyperthyroid states in the Wistar-Kyoto rat.
    Neuropsychopharmacology. 2001 Jun;24(6):632-9 PMID: 11331143
  38. Sensitivity of AXB/BXA recombinant inbred lines of mice to the locomotor activating effects of cocaine: a quantitative trait loci analysis.
    Pharmacogenetics. 2001 Apr;11(3):255-64 PMID: 11337941
  39. Genetic risk factors for major depression in men and women: similar or different heritabilities and same or partly distinct genes?
    Psychol Med. 2001 May;31(4):605-16 PMID: 11352363
  40. QTL analysis identifies multiple behavioral dimensions in ethological tests of anxiety in laboratory mice.
    Curr Biol. 2001 May 15;11(10):725-34 PMID: 11378382
  41. Genome-wide epistatic interaction analysis reveals complex genetic determinants of circadian behavior in mice.
    Genome Res. 2001 Jun;11(6):959-80 PMID: 11381025
  42. Finding the molecular basis of quantitative traits: successes and pitfalls.
    Nat Rev Genet. 2001 Jun;2(6):437-45 PMID: 11389460
  43. A statistical framework for quantitative trait mapping.
    Genetics. 2001 Sep;159(1):371-87 PMID: 11560912
  44. A genome screen for genes predisposing to bipolar affective disorder detects a new susceptibility locus on 8q.
    Hum Mol Genet. 2001 Dec 1;10(25):2933-44 PMID: 11741836
  45. Comorbidity of mood and anxiety disorders: the rule, not the exception?
    Am J Psychiatry. 2002 Jan;159(1):3-4 PMID: 11772680
  46. Identification of multiple genetic loci linked to the propensity for "behavioral despair" in mice.
    Genome Res. 2002 Mar;12(3):357-66 PMID: 11875023
  47. Assessing antidepressant activity in rodents: recent developments and future needs.
    Trends Pharmacol Sci. 2002 May;23(5):238-45 PMID: 12008002
  48. Genome survey for susceptibility loci for recurrent, early-onset major depression: results at 10cM resolution.
    Am J Med Genet. 2002 May 8;114(4):413-22 PMID: 11992563
  49. From QTL to gene: the harvest begins.
    Nat Genet. 2002 Jul;31(3):235-6 PMID: 12089518
  50. QTL associated with blood pressure, heart rate, and heart weight in CBA/CaJ and BALB/cJ mice.
    Physiol Genomics. 2002 Jul 12;10(1):5-12 PMID: 12118100
  51. Dopamine D4 receptor and tyrosine hydroxylase genes in bipolar disorder: evidence for a role of DRD4.
    Mol Psychiatry. 2002;7(8):860-6 PMID: 12232779
  52. Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism.
    Am J Hum Genet. 2003 Apr;72(4):879-90 PMID: 12612864
  53. Depressive-like behavior and stress reactivity are independent traits in a Wistar Kyoto x Fisher 344 cross.
    Mol Psychiatry. 2003 Apr;8(4):423-33 PMID: 12740600
Article Info
Journal
Mammalian genome : official journal of the International Mammalian Genome Society
Abbr.
Mamm Genome
ISSN
0938-8990
DOI
10.1007/s00335-004-2326-z
Published
2004-08-00
Pages
648-62
Language
English
Region
United States
NLM ID
9100916
PMCID
PMC3764448
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NIMH NIH HHS · R01 MH060789 · United States
NIMH NIH HHS · R01 MH60789 · United States
External Links
PubMed source DOI: 10.1007/s00335-004-2326-z PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2