https://stevebmd.files.wordpress.com/2011/04/cytokines-sing-the-blues2006.pdf

Cytokines sing the blues: inflammation and the pathogenesis of depression

The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies

Naturally occurring variations in maternal care alter the expression of genes that regulate behavioral and endocrine responses to stress, as well as hippocampal synaptic development. These effects form the basis for the development of stable, individual differences in stress reactivity and certain forms of cognition. Maternal care also influences the maternal behavior of female offspring, an effect that appears to be related to oxytocin receptor gene expression, and which forms the basis for the intergenerational transmission of individual differences in stress reactivity. Patterns of maternal care that increase stress reactivity in offspring are enhanced by stressors imposed on the mother. These findings provide evidence for the importance of parental care as a mediator of the effects of environmental adversity on neural development.

Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations.

The corticosteroid receptor hypothesis of depression.

ContextEvidence suggests that early adverse experiences play a preeminent role
in development of mood and anxiety disorders and that corticotropin-releasing
factor (CRF) systems may mediate this association.ObjectiveTo determine whether early-life stress results in a persistent sensitization
of the hypothalamic-pituitary-adrenal axis to mild stress in adulthood, thereby
contributing to vulnerability to psychopathological conditions.Design and SettingProspective controlled study conducted from May 1997 to July 1999 at
the General Clinical Research Center of Emory University Hospital, Atlanta,
Ga.ParticipantsForty-nine healthy women aged 18 to 45 years with regular menses, with
no history of mania or psychosis, with no active substance abuse or eating
disorder within 6 months, and who were free of hormonal and psychotropic medications
were recruited into 4 study groups (n = 12 with no history of childhood abuse
or psychiatric disorder [controls]; n = 13 with diagnosis of current major
depression who were sexually or physically abused as children; n = 14 without
current major depression who were sexually or physically abused as children;
and n = 10 with diagnosis of current major depression and no history of childhood
abuse).Main Outcome MeasuresAdrenocorticotropic hormone (ACTH) and cortisol levels and heart rate
responses to a standardized psychosocial laboratory stressor compared among
the 4 study groups.ResultsWomen with a history of childhood abuse exhibited increased pituitary-adrenal
and autonomic responses to stress compared with controls. This effect was
particularly robust in women with current symptoms of depression and anxiety.
Women with a history of childhood abuse and a current major depression diagnosis
exhibited a more than 6-fold greater ACTH response to stress than age-matched
controls (net peak of 9.0 pmol/L [41.0 pg/mL]; 95% confidence interval [CI],
4.7-13.3 pmol/L [21.6-60.4 pg/mL]; vs net peak of 1.4 pmol/L [6.19 pg/mL];
95% CI, 0.2-2.5 pmol/L [1.0-11.4 pg/mL]; difference, 8.6 pmol/L [38.9 pg/mL];
95% CI, 4.6-12.6 pmol/L [20.8-57.1 pg/mL]; P<.001).ConclusionsOur findings suggest that hypothalamic-pituitary-adrenal axis and autonomic
nervous system hyperreactivity, presumably due to CRF hypersecretion, is a
persistent consequence of childhood abuse that may contribute to the diathesis
for adulthood psychopathological conditions. Furthermore, these results imply
a role for CRF receptor antagonists in the prevention and treatment of psychopathological
conditions related to early-life stress.

/pdf/pituitary-adrenal-and-autonomic-responses-to-stress-in-women-3frz9dva0e.pdf

Pituitary-Adrenal and Autonomic Responses to Stress in Women After Sexual and Physical Abuse in Childhood

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Physiology and pharmacology of corticotropin-releasing factor.

\s=b\Previous studies have provided evidence that corticotropin releasing factor (CRF) is hypersecreted in patients with major depression. This CRF hypersecretion is believed to contribute at least in part to hyperactivity of the hypothalamicpituitary-adrenal axis in depressed patients. If CRF is chronically hypersecreted in depressed patients, then, due to downregulation, a reduced number of CRF receptor binding sites should be present in patients with profound depressive disorder. To test this hypothesis, we measured the number and affinity of CRF binding sites in the frontal cortex of 26 suicide victims and 29 controls who died of a variety of causes. There was a marked (23%) reduction in the number of CRF binding sites in the frontal cortex of the suicide victims compared with the controls. These data are consistent with the hypothesis that CRF is hypersecreted in depression. (Aren Gen Psychiatry 1988;45:577-579)

https://jamanetwork.com/journals/PSYCH/articlepdf/494315/archpsyc_45_6_009.pdf

Reduced Corticotropin Releasing Factor Binding Sites in the Frontal Cortex of Suicide Victims

Corticotropin-releasing factor (CRF) is the major physiological regulator of the hypothalamic-pituitary-adrenal (HPA) axis. However, considerable evidence indicates that CRF may be responsible for integrating not only the endocrine, but the autonomic and behavioral responses of an organism to stress as well. In addition, clinical studies indicate that CRF of both hypothalamic and extrahypothalamic origin may be hypersecreted in major depression as well as other psychiatric disorders. These findings, taken together, led to the hypothesis that the efficacy of antidepressant and/or anxiolytic drugs may be related to their actions on CRF-containing neural pathways in the central nervous system (CNS). Therefore, alterations of CRF concentrations in 18 rat brain regions were studied after acute administration of a tricyclic antidepressant (imipramine) or one of two triazolobenzodiazepines (alprazolam or adinazolam) that possess anxiolytic properties typical of benzodiazepines, as well as purported antidepressant activity unique to these compounds. Treatment with alprazolam or adinazolam increased hypothalamic CRF concentrations, which was associated with lower plasma ACTH concentrations. In contrast, the concentration of CRF was markedly reduced in the locus coeruleus, amygdala, and several cortical regions by either triazalobenzodiazepine. Acute treatment with imipramine was without effect on CRF concentrations in any brain region studied. Of particular interest is the finding that the two triazolobenzodiazepines exert effects on CRF concentrations in the locus coeruleus and hypothalamus that are opposite to CRF changes seen after stress.

Acute effects of alprazolam and adinazolam on the concentrations of corticotropin-releasing factor in the rat brain.

5a-Pregnane-3a,21-diol-20-one (THDOC) attenuates mild stress-induced increases in plasma corticosterone via a non-glucocorticoid mechanism: comparison with alprazolam

Effects of 5-HT1A receptor agonists on hypothalamo-pituttary-adrenal axis activity and cortlcotropin-releasing factor containing neurons in the rat brain

Michael J. Owens

Papers

Physiology and pharmacology of corticotropin-releasing factor.

Reduced Corticotropin Releasing Factor Binding Sites in the Frontal Cortex of Suicide Victims

Acute effects of alprazolam and adinazolam on the concentrations of corticotropin-releasing factor in the rat brain.

5a-Pregnane-3a,21-diol-20-one (THDOC) attenuates mild stress-induced increases in plasma corticosterone via a non-glucocorticoid mechanism: comparison with alprazolam

Effects of 5-HT1A receptor agonists on hypothalamo-pituttary-adrenal axis activity and cortlcotropin-releasing factor containing neurons in the rat brain