Background
The amygdala is a limbic structure involved in the stress response and the regulation
of emotional behaviors, both of which are disrupted in patients with neuropsychiatric
illnesses. Because glucocorticoids are mediators of the stress response, we hypothesized
that glucocorticoid receptor (GR) messenger ribonucleic acid (mRNA) levels might be
altered in the amygdala. We also hypothesized that estrogen receptor α (ERα) mRNA
expression might be altered in the amygdala, on the basis of observed gender differences
in mental illness.
Methods
Using quantitative film autoradiography after in situ hybridization with human GR
and ERα probes, we measured mRNA levels on adjacent amygdala sections in four groups
(n = 15 each of subjects with schizophrenia, major depressive disorder, and bipolar
disorder, and unaffected control subjects) provided by the Stanley Consortium.
Results
We detected main effects of diagnosis and exposure to antidepressant medication on
the levels of both mRNAs but no main effect of gender. Compared with control subjects,
GR mRNA expression was reduced in the basolateral/lateral nuclei in schizophrenia
and bipolar disorder. Estrogen receptor α mRNA levels were reduced in the basomedial
nucleus in major depressive disorder and bipolar disorder.
Conclusions
Our results support and extend previous findings describing a pattern of steroid hormone
mRNA alterations that differs depending on which brain region is being examined in
a given mental illness.
Key words
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References
- A description of the amygdalo-hippocampal interconnections in the macaque monkey.Exp Brain Res. 1986; 64: 515-526
- Melatonin, cortisol and ACTH in patients with major depressive disorder and healthy humans with special reference to the outcome of the dexamethasone suppression test.Psychoneuroendocrinology. 1985; 10: 173-186
- Amygdalo-entorhinal inputs to the hippocampal formation in relation to schizophrenia.Ann N Y Acad Sci. 2000; 911: 293-304
- Interleukin 1 prevents loss of corticotropic responsiveness to beta-adrenergic stimulation in vitro.Proc Natl Acad Sci U S A. 1988; 85: 5556-5560
- The antidepressants fluoxetine, idazoxan and phenelzine alter corticotropin-releasing hormone and tyrosine hydroxylase mRNA levels in rat brain.Brain Res. 1992; 572: 117-125
- Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications.J Clin Invest. 1991; 87: 831-837
- Multiple feedback regulatory loops upon rat hypothalamic corticotropin-releasing hormone secretion. Potential clinical implications.J Clin Invest. 1988; 82: 767-774
- Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys.J Comp Neurol. 1995; 363: 615-641
- Effects of dexamethasone on central and peripheral ACTH systems in the rat.Neuroendocrinology. 1987; 45: 160-164
- Diagnosis of endogenous depression. Comparison of clinical, research and neuroendocrine criteria.J Affect Disord. 1980; 2: 177-194
- Psychosis and pregnancy.Compr Ther. 1986; 12: 36-41
- The site of the suppressive action of dexamethasone on pituitary-adrenal activity.Endocrinology. 1974; 94: 61-73
- Regulation of gene expression by corticoid hormones in the brain and spinal cord.J Steroid Biochem Mol Biol. 1998; 65: 253-272
- Increased synaptic availability of norepinephrine following desipramine is not essential for increases in GR mRNA. Short communication.J Neural Transm. 1997; 104: 1255-1258
- Limbic pathways and hypothalamic neurotransmitters mediating adrenocortical responses to neural stimuli.Neurosci Biobehav Rev. 1995; 19: 235-240
- The impact of reproductive events on the course of bipolar disorder in women.J Clin Psychiatry. 2002; 63: 284-287
- The extended amygdala and the dopamine system.J Neuropsychiatry Clin Neurosci. 2003; 15: 306-316
- Central glucocorticoid receptors and neuronal plasticity.Meth Neurosci. 1994; 22: 272-382
- Integration of Humoral and Neuronal Signals in Neuroendocrine Regulation, Focus on Interaction of Glucocorticoids with Central Neuropeptide and Monoamine Neurotransmission. Elsevier Science, Amsterdam1989
- Influence of the menstrual cycle phase on the therapeutic response in schizophrenia.Biol Psychiatry. 1994; 36: 137-139
- Cortisol secretion rate in depressive illness.Arch Gen Psychiatry. 1964; 10: 572-575
- New insights into the role of cortisol and the glucocorticoid receptor in severe depression.Biol Psychiatry. 2002; 52: 381-385
- Gender and the expression of schizophrenia.J Psychiatr Res. 1988; 22: 141-155
- Are there sex differences in neuropsychological functions among patients with schizophrenia?.Am J Psychiatry. 1998; 155: 1358-1364
- Sequence and expression of human estrogen receptor complementary DNA.Science. 1986; 231: 1150-1154
- Schizophrenia throughout life.Schizophr Res. 1996; 21: 1-12
- Gender differences in schizophrenia.Psychoneuroendocrinology. 2003; 28: 17-54
- Variation in symptom severity over the menstrual cycle of schizophrenics.Biol Psychiatry. 1993; 33: 207-209
- A modified histochemical technique to visualize acetylcholinesterase-containing axons.J Histochem Cytochem. 1985; 33: 134-140
- The human basal forebrain. Part II.in: Bloom FE Bjorklund A Hokfelt T Handbook of Chemical Neuroanatomy. vol 15. Elsevier Science, Amsterdam1999
- Course of psychiatric disorders across the menstrual cycle.Harv Rev Psychiatry. 1996; 4: 200-207
- The combined dexamethasone/CRH test.J Psychiatr Res. 1994; 28: 341-356
- Human recombinant IL-1 alters glucocorticoid receptor function in Reuber hepatoma cells.J Immunol. 1988; 141: 1522-1528
- Primary structure and expression of a functional human glucocorticoid receptor cDNA.Nature. 1985; 318: 635-641
- Antidepressants and hypothalamic-pituitary-adrenocortical regulation.Endocr Rev. 1996; 17: 187-205
- Corticosteroid inhibition of ACTH secretion.Endocr Rev. 1984; 5: 1-24
- Epidemiology of puerperal psychoses.Br J Psychiatry. 1987; 150: 662-673
- Gender differences in the genetic epidemiology of major depression.J Gend Specif Med. 1998; 1: 28-31
- Vomeronasal and olfactory pathways to the amygdala controlling male hamster sexual behavior.Brain Res. 1982; 240: 27-41
- Women with bipolar illness.Am J Psychiatry. 1996; 153: 163-173
- Corticotropin and cortisol response to human CRH as a probe for HPA system integrity in major depressive disorder.Psychiatry Res. 1988; 24: 25-34
- The 24-hour profiles of cortisol, prolactin and growth hormone secretion in mania.Arch Gen Psychiatry. 1994; 51: 616-624
- A.E. Bennett Research Award. Regulation of serotonin1A, glucocorticoid and mineralocorticoid receptor in rat and human hippocampus: Implications for the neurobiology of depression.Biol Psychiatry. 1998; 43: 547-573
- Increased expression of corticotropin-releasing hormone and vasopressin messenger ribonucleic acid (mRNA) in the hypothalamic paraventricular nucleus during repeated stress.Endocrinology. 1995; 136: 3299-3309
- Topographical organization of amygdaloid projections to the caudatoputamen, nucleus accumbens and related striatal-like areas of the rat brain.Neuroscience. 1991; 44: 15-33
- Differential effects of excitotoxic basolateral and corticomedial lesions of the amygdala on the behavioural and endocrine responses to either sexual or aggression-promoting stimuli in the male rat.Brain Res. 1992; 574: 9-20
- Early environmental regulation of forebrain glucocorticoid receptor gene expression.Dev Neurosci. 1996; 18: 49-72
- Platelet serotonin, plasma cortisol and dexamethasone suppression test in schizophrenic patients.Biol Psychiatry. 1999; 45: 1433-1439
- Estrogen receptors in the human forebrain and the relation to neuropsychiatric disorders.Prog Neurobiol. 2001; 64: 251-267
- The human forebrain has discrete estrogen receptor alpha messenger RNA expression.Neuroscience. 2000; 95: 333-342
- The role of corticotropin-releasing factor in the pathophysiology of affective and anxiety disorders.Ciba Found Symp. 1993; 172 (discussion 308-316): 296-308
- Antidepressant and other centrally acting drugs regulate glucocorticoid receptor messenger RNA levels in rat brain.Psychoneuroendocrinology. 1991; 16: 505-515
- Antidepressant drug action in a transgenic mouse model of the endocrine changes seen in depression.Mol Pharmacol. 1992; 42: 991-995
- Combinatorial amygdalar inputs to hippocampal domains and hypothalamic behavior systems.Brain Res Brain Res Rev. 2001; 38: 247-289
- Neurobiology of emotion perception II.Biol Psychiatry. 2003; 54: 515-528
- Projections from the lateral, basal and accessory basal nuclei of the amygdala to the hippocampal formation in rat.J Comp Neurol. 1999; 403: 229-260
- Connectivity of the rat amygdaloid complex.in: Aggleton J The Amygdala A Functional Analysis.. Oxford University Press, Oxford2000: 31-115
- An autoradiographic study of complementary laminar patterns of termination of afferent fibers to the olfactory cortex.J Comp Neurol. 1973; 150: 87-108
- Effect of estradiol implanted in the corticomedial amygdala on the sexual behavior of castrated male rats.Braz J Med Biol Res. 1991; 24: 1041-1049
- Deficit and hemispheric asymmetry of GABA uptake sites in the hippocampus in schizophrenia.Biol Psychiatry. 1990; 27: 1038-1044
- Can estradiol modulate schizophrenic symptomatology?.Schizophr Bull. 1994; 20: 203-214
- Stress and memory.Neurobiol Learn Mem. 2002; 78: 578-595
- Norepinephrine-independent regulation of GRII mRNA in vivo by a tricyclic antidepressant.Brain Res. 1995; 687: 79-82
- Adrenal gland volume in major depression.Biol Psychiatry. 1996; 40: 89-97
- The dexamethasone/corticotropin-releasing hormone test in depression in bipolar and unipolar affective illness.J Psychiatr Res. 1999; 33: 363-370
- The amygdaloid complex.Physiol Rev. 2003; 83: 803-834
- Down-regulation of neural corticosterone receptors by corticosterone and dexamethasone.Brain Res. 1985; 339: 161-165
- Autoradiographic localization of glucocorticosteroid and progesterone binding sites in the human post-mortem brain.J Steroid Biochem. 1986; 25: 717-721
- Comparison of the efferents of the amygdala and the hippocampal formation in the rhesus monkey: II. Reciprocal and non-reciprocal connections.J Comp Neurol. 1988; 271: 185-207
- Antidepressants increase glucocorticoid and mineralocorticoid receptor mRNA expression in rat hippocampus in vivo.Neuroendocrinology. 1992; 55: 621-626
- The role of estrogen in schizophrenia.J Psychiatry Neurosci. 1996; 21: 123-127
- Psychopathology in women and men.Am J Psychiatry. 1997; 154: 1641-1647
- The role of estrogens in schizophrenia gender differences.Schizophr Bull. 1990; 16: 185-194
- Gender differences in the clinical expression of schizophrenia.Schizophr Res. 1992; 7: 225-231
- Effects of flesinoxan on corticosteroid receptor expression in the rat hippocampus.Eur J Pharmacol. 2000; 404: 111-119
- Topographic organization of cortical inputs to the lateral nucleus of the macaque monkey amygdala.J Comp Neurol. 2000; 421: 52-79
- The Stanley Foundation Brain Collection and Neuropathology Consortium.Schizophr Res. 2000; 44: 151-155
- Regional specificity of brain glucocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders.Mol Psychiatry. 2002; 7 (924): 985-994
- Reduced GAP-43 mRNA in dorsolateral prefrontal cortex of patients with schizophrenia.Cereb Cortex. 2001; 11: 136-147
- Optimization of cRNA probe in situ hybridization methodology for localization of glucocorticoid receptor mRNA in rat brain.Cell Mol Neurobiol. 1990; 10: 145-157
Article info
Publication history
Accepted:
September 8,
2004
Received in revised form:
September 7,
2004
Received:
May 11,
2004
Identification
Copyright
© 2004 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
