Neurobiological Component Report

Name	Hypothalamic-pituitary-adrenal axis
Description	The hypothalamic-pituitary-adrenal axis (HPA or HTPA axis), also known as the limbic-hypothalamic-pituitary-adrenal axis (LHPA axis) and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland (a pea-shaped structure located below the hypothalamus), and the adrenal (or suprarenal) glands (small, conical organs on top of the kidneys).
No. of Studies (Positive/Negative)	17 (17/0)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
HPA	Aihara, 2007	patients only		These results indicate that depressed patients remitted with...... These results indicate that depressed patients remitted with antidepressant treatment were accompanied by resolution of HPA dysregulation and alteration of regional glucose metabolism in the prefrontal cortical, limbic and paralimbic regions. More...
HPA system	Hatzinger, 2002	patients only		early improvement, early treatment response and beneficial t...... early improvement, early treatment response and beneficial treatment outcome after 6 weeks were associated with a lower HPA system activity and that. in long-term course of depression the HPA system deterioration increases in parallel with the number of previous episodes. More...
HPA axis	Friess, 2008	patients and normal controls		As expected patients with depression showed an overactivity ...... As expected patients with depression showed an overactivity of the HPA axis More...
hypothalamic-pituitary-adrenal (HPA)	Rao, 2008	patients and normal controls		The findings that EEG sleep measures are independent of clin...... The findings that EEG sleep measures are independent of clinical state, whereas HPA variables are state dependent, suggest that sleep and HPA measures make a differential contribution to our understanding of the pathophysiology and prognosis of mood disorders in adolescent patients. More...
hypothalamic-pituitary-adrenal (HPA)	Rao, 2009	high-risk people and normal controls		The findings that REM sleep abnormalities and elevated HPA a...... The findings that REM sleep abnormalities and elevated HPA activity occur before the onset of depression in at-risk adolescents suggest that these variables serve as vulnerability markers for the illness. More...
hypothalamic-pituitary-adrenal axis (HPA)	Klumpers, 2010	patients and normal controls		Major depressive disorder (MDD) has been related to both a d...... Major depressive disorder (MDD) has been related to both a dysfunctional gamma-amino butyric acid (GABA) system and to hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA). More...
hypothalamic-pituitary-adrenal (HPA) axis	Cizza, 2010	patients and normal controls		In cross-correlation analyses, the relationship between cort...... In cross-correlation analyses, the relationship between corticotropin and cortisol concentrations was stronger in women with MDD than in control subjects, a finding consistent with hypothalamic-pituitary-adrenal (HPA) axis activation in MDD. More...

Name in Literature	Related Components
	Level	Approved Name(Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description	All
HPA-axis		rs948854(rs948854)	SNP	Unschuld, 2010	patients and normal controls		This allele was associated with higher HPA-axis activity at ...... This allele was associated with higher HPA-axis activity at admission More...
hypothalamic-pituitary-adrenocortical (HPA) system		ACE(ACE)	gene	Baghai, 2002	patients and normal controls		The Dex/CRH test is one of the most reliable neuroendocrine ...... The Dex/CRH test is one of the most reliable neuroendocrine function tests for hypothalamic-pituitary-adrenocortical (HPA) system dysregulation, angiotensin converting enzyme (ACE) gene D/D genotypes showed a higher cortisol stimulation during the first Dex/CRH test after admission than homozygous I-allele carriers (repeated measurement ANOVA: P=0.034). More...
hypothalamic-pituitary-adrenal axis		Corticoliberin(corticotropin-releasing factor (CRF))	protein	Heim, 2000	patients and normal controls		Our findings suggest that hypothalamic-pituitary-adrenal axi...... Our 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. More...
HPA axis		Somatotropin(growth hormone (GH))	protein	Schmid, 2008	patients only		The activity of the HPA axis appeared to influence the corti...... The activity of the HPA axis appeared to influence the cortisol-induced effects on non-REM sleep and GH levels. More...
hypothalamic-pituitary-adrenal axis (HPA)		gamma-Aminobutyric Acid receptor(GABA(A)-benzodiazepine receptor)	molecule	Klumpers, 2010	patients and normal controls		In the temporal area, [(11)C]FMZ binding showed a strong inv...... In the temporal area, [(11)C]FMZ binding showed a strong inverse correlation with HPA axis activity. The inverse relationship between GABA(A) binding in the temporal lobe and HPA axis activity, suggests that HPA axis hyperactivity is partly due to reduced GABA-ergic inhibition. More...
HPA axis		Non rapid-eye movement (REM) sleep(non rapid-eye movement (REM) sleep)	neurobiological system	Schmid, 2008	patients only		The activity of the HPA axis appeared to influence the corti...... The activity of the HPA axis appeared to influence the cortisol-induced effects on non-REM sleep and GH levels. More...
hypothalamic-pituitary-adrenal axis (HPA)		Gamma-aminobutyric acid (GABA)ergic system(gamma-aminobutyric acid (GABA)ergic system)	neurobiological system	Klumpers, 2010	patients and normal controls		In the temporal area, [(11)C]FMZ binding showed a strong inv...... In the temporal area, [(11)C]FMZ binding showed a strong inverse correlation with HPA axis activity. The inverse relationship between GABA(A) binding in the temporal lobe and HPA axis activity, suggests that HPA axis hyperactivity is partly due to reduced GABA-ergic inhibition. More...
HPA		medial prefrontal cortex (MPFC)(medial prefrontal cortex)	brain morphology and function	Aihara, 2007	patients only		75% of unmedicated MDD patients exhibited a heightened corti...... 75% of unmedicated MDD patients exhibited a heightened cortisol response to the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test, and thus were defined as non-suppressors. Non-suppressors showed a marked hypometabolism in the medial prefrontal cortex as compared with suppressors. After successful pharmacotherapy, enhanced cortisol responsiveness normalized. More...
pituitary-adrenal responses		Increased agitation(anxiety)	symptoms	Heim, 2000	patients and normal controls		Women with a history of childhood abuse exhibited increased ...... Women 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. More...
pituitary-adrenal responses		Depressed mood(depression)	symptoms	Heim, 2000	patients and normal controls		Women with a history of childhood abuse exhibited increased ...... Women 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. More...
stress system (HPA)		Suicide(suicidal intent)	symptoms	Lindqvist, 2008	patients only		Our findings may be attributed to pathophysiological process...... Our findings may be attributed to pathophysiological processes, where a high suicidal intent is revealed during a potential chronic course of MDD, which in turn results in a seemingly normal stress system. More...
hypothalamic-pituitary-adrenal (HPA) axis		Suicide(suicide intent)	symptoms	Mathew, 2003	patients and normal controls		Adolescents who are at risk to make suicide attempts appear ...... Adolescents who are at risk to make suicide attempts appear to display significant elevations of cortisol prior to sleep onset, a time when the hypothalamic-pituitary-adrenal (HPA) axis is normally most quiescent. More...
HPA axis		Psychotic symptoms(somatoform dissociative symptoms)	symptoms	Bob, 2008	patients only	r=-0.40; P-value = 0.014	The results show that cortisol as an index of HPA axis funct...... The results show that cortisol as an index of HPA axis functioning manifests significant relationship to somatoform dissociative symptoms (r=-0.40; p=0.014). More...
HPA axis		Suicide(suicidal behaviour)	symptoms	Jokinen, 2009	patients only		DST(dexamethasone suppression test) non-suppression was asso...... DST(dexamethasone suppression test) non-suppression was associated with suicide attempt and post-dexamethasone serum cortisol at 11:00 p.m. was significantly higher in suicide attempters compared to non-attempters. The DST non-suppressor rate was 39% in young adult suicide attempters compared with 11% in non-attempters. The results add to previous evidence in support of the role of HPA axis hyperactivity and suicidal behaviour. More...
limbic-hypothalamic-pituitary axis (LHPA)		Depressed mood(depression)	symptoms	Marcus, 2011	normal people		When compared to non-depressed women, maternal depressive sy...... When compared to non-depressed women, maternal depressive symptoms, even in the absence of major depressive disorder, appeared to facilitate a different developmental pathway for the infant LHPA and early neurological development. More...
pituitary-adrenal responses		Child abuse(childhood abuse)	environment	Heim, 2000	patients and normal controls		Women with a history of childhood abuse exhibited increased ...... Women with a history of childhood abuse exhibited increased pituitary-adrenal and autonomic responses to stress compared with controls. More...
hypothalamic-pituitary-adrenal axis		Child abuse(child maltreatment)	environment	MacMillan, 2009	normal people		During the reactivity phase, youth in the control group show...... During the reactivity phase, youth in the control group showed an increase in cortisol levels following the TSST (Trier Social Stress Test) and a gradual flattening over time; maltreated youth exhibited an attenuated response. These findings provide further support for hypothalamic-pituitary-adrenal axis dysregulation among maltreated youth. More...

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

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3. The network is generated using Cytoscape Web

Name	Type
Hypothalamus	brain morphology and function
Pituitary gland	brain morphology and function
Paraventricular nucleus	brain morphology and function
Glucocorticoids	molecule
Hydrocortisone	molecule
vasopressin	molecule
adrenal glands	other
vasopressin	protein
Pro-opiomelanocortin	protein
Mineralocorticoid receptor	protein
Glucocorticoid receptor	protein