Recent research suggests that central corticotropin releasing hormone hyperdrive is an important neurobiological risk factor for developing major depression. The availability of free corticotropin releasing hormone in the central nervous system is tightly regulated by the expression of corticotropin releasing hormone binding protein. Therefore, the gene encoding for corticotropin releasing hormone binding protein is a functional candidate gene for major depression.
We present a systematic study of single nucleotide polymorphisms in the corticotropin releasing hormone binding protein gene and their role in the liability for major depression. Seven single nucleotide polymorphisms were genotyped in a well-diagnosed sample of 89 patients with recurrent major depressions and matched controls.
Two single nucleotide polymorphisms within the corticotropin releasing hormone binding protein gene were significantly associated with the disease (p < .05). An expectation-maximization algorithm estimated a specific haplotype to have a frequency of 53% in patients and 35% in controls (p < .001).
The corticotropin releasing hormone binding protein gene is likely to be involved in the genetic vulnerability for major depression.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Biological Psychiatry
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). 4th ed. American Psychiatric Press, Washington, DC1994
- Dexamethasone suppression test in the diagnosis of depression.JAMA. 1991; 265: 2253-2254
- Excess corticotropin releasing hormone-binding protein in the hypothalamic-pituitary-adrenal axis in transgenic mice.J Clin Invest. 1998; 101: 1439-1447
- Persistent elevations of cerebrospinal fluid concentrations of corticotropin-releasing factor in adult nonhuman primates exposed to early-life stressors.Proc Natl Acad Sci U S A. 1996; 93: 1619-1623
- Genetic analysis of case/control data using estimated haplotype frequencies.Genome Res. 2001; 11: 143-151
- Accuracy of haplotype frequency estimation for biallelic loci, via the expectation-maximization algorithm for unphased diploid genotype data.Am J Hum Genet. 2000; 67: 947-959
- Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse.Am J Psychiatry. 2001; 158: 575-581
- Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood.JAMA. 2000; 284: 592-597
- The combined dexamethasone/CRH test.J Psychiatr Res. 1994; 28: 341-356
- Altered hypothalamic-pituitary-adrenocortical regulation in healthy subjects at high familial risk for affective disorders.Neuroendocrinology. 1995; 62: 340-347
- Altered anxiety and weight gain in corticotropin-releasing hormone- binding protein-deficient mice.Proc Natl Acad Sci U S A. 1999; 96: 11595-11600
- Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation.Endocrinology. 1996; 137: 1212-1218
- Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress.Science. 1997; 277: 1659-1662
- Effects of acute and repeated restraint stress on corticotropin-releasing hormone binding protein mRNA in rat amygdala and dorsal hippocampus.Neurosci Lett. 2001; 302: 81-84
- SNPing away at complex diseases.Am J Hum Genet. 2000; 67: 383-394
- A hospital-based twin register of the heritability of DSM-IV unipolar depression.Arch Gen Psychiatry. 1996; 53: 129-136
- Hormonal response pattern in the combined DEX-CRH test is stable over time in subjects at high familial risk for affective disorders.Neuropsychopharmacology. 1998; 18: 253-262
- Ultrastructural localization of the corticotropin-releasing factor-binding protein in rat brain and pituitary.J Comp Neurol. 1999; 413: 241-254
- Psychoneuroendocrinology of depression. Hypothalamic-pituitary-adrenal axis.Psychiatr Clin North Am. 1998; 21: 293-307
- Cloning and characterization of the cDNAs for human and rat corticotropin releasing factor-binding proteins.Nature. 1991; 349: 423-426
- The central distribution of a corticotropin-releasing factor (CRF)-binding protein predicts multiple sites and modes of interaction with CRF.Proc Natl Acad Sci U S A. 1992; 89: 4192-4196
- GENEPOP (version 1.2).J Hered. 1995; 86: 248-249
Schneider S, Roessli D, Excoffier L (2000): Arlequin ver. 2.000: A software for population genetics data analysis. Available at: http://www.anthro.unige.ch/arlequin Accessed May 27, 2003.
- The Mini-International Neuropsychiatric Interview (M.I.N.I.).J Clin Psychiatry. 1998; 59: 22-33
- A powerful likelihood method for the analysis of linkage disequilibrium between trait loci and one or more polymorphic marker loci.Am J Hum Genet. 1995; 56: 777-787
- The accuracy of statistical methods for estimation of haplotype frequencies.Am J Hum Genet. 2000; 67: 518-522
- Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor.Nature. 1995; 378: 287-292
- Childhood sexual abuse as a risk factor for depression in women.Am J Psychiatry. 1999; 156: 816-828
- Testing association of statistically inferred haplotypes with discrete and continuous traits in samples of unrelated individuals.Hum Hered. 2002; 53: 79-91
- Model-free analysis and permutation tests for allelic associations.Hum Hered. 2000; 50: 133-139
Accepted: April 14, 2003
Received in revised form: March 19, 2003
Received: January 6, 2003
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.