Childhood stressful events, HPA axis and anxiety disorders

Table 1 Hypothalamic pituitary adrenal axis functioning and its relationship with childhood traumata and psychopathology in post-traumatic stress disordered patients

Author	Control group	Sample	Cortisol levels	ACTH levels	Suppression (DST)	Stress test	Correlations with childhood traumata and psychopathology
Lemieux et al[46], 1995	9 non abused women; 8 abused women w/o PTSD	11 abused women with PTSD	↑ Basal urinary levels	-	-	-	↑ Scores on Impact Event Scale related to cortisol levels in PTSD sample
De Bellis et al[48], 1999	10 non-traumatized children; 24 healthy controls	18 children with PTSD due to childhood maltreatment	↑ Basal urinary levels	-	-	-	↑ Psychopathology
Bremner et al[66], 2003	18 HC	23 patients with abuse-related PTSD	Salivary cortisol: 61% higher	-	-	Cognitive challenge	Neurohormonal response to stress in PTSD subjects is not impaired
			Waiting for test; 46% higher during test
Luecken[52], 1998	31 HC	30 students who lost one parent before age 16	↑ Salivary levels post task	-	-	Video clip depicting the death of a parent + speech task	Altered neurohormonal responses to stress in those who lost one parent
Elzinga et al[53], 2003	12 abused women without PTSD	12 abused women with PTSD	Salivary cortisol: 60% higher waiting for test; 122% higher during test; 69% higher during recovery	-	-	Personalized trauma scripts	Altered neurohormonal responses to stress in PTSD abused women
Rasmusson et al[56], 2001	11 HC	12 outpatients with PTSD	= Plasma basal levels; ↑ plasma and urinary post tests levels	= Basal levels; ↑ post CRF levels	-	CRF and ACTH stimulation tests	Altered neurohormonal responses to stress in PTSD subjects
Santa Ana et al[57], 2006	31 HC	58 subjects with PTSD (25 with childhood trauma)	↓ Plasma basal and post	↓ Post task	-	Cold Pressor Task	-
			Task, if childhood trauma
De Bellis et al[58], 1994	13 HC girls	13 sexually abused girls	= Plasma and salivary basal and post CRH	↓ Basal and post CRH	-	CRH stimulation test	↑ Adult psychopathology and altered hormonal responses to stress
Stein et al[61], 1997	21 non abused women	19 children and/or adolescent with sexual abuse	-	-	↑	Low dose DST (0.5 mg)	↑ Adult psychopathology
Yehuda et al[31], 2004	10 non traumatized subjects	52 traumatized subjects	-	-	↑	Low dose DST (0.5 mg)	-
Jovanovic et al[59], 2010	61 traumatized non PTSD subjects	29 traumatized PTSD subjects	= Basal plasma levels; ↓ post Dex plasma levels	↓ Post Dex	↑	Low dose DST (0.5 mg)	Abnormalities of HPA feedback and ↑ psychopathology
Altemus et al[62], 2003	15 HC	16 women with PTSD due to childhood abuse	= Basal plasma and salivary levels	-	-	-	-
Lindley et al[47], 2004	17 HC	17 subjects with PTSD (88% due to childhood trauma)	↑ Basal salivary levels	-	=	Low dose DST (0.5 mg)	No correlations between cortisol, childhood abuse and psychopathology

HC: Healthy controls; DST: Dexamethasone suppression test; PTSD: Posttraumatic stress disorder; ACTH: Adrenocorticotropin hormone; CRH: Corticotropin releasing hormone; CRF: Corticotropin releasing factor.

Table 2 Hypothalamic pituitary adrenal axis functioning in panic disordered patients

Author	Control group	Sample	Cortisol levels	ACTH levels	DST	Stress test
Woods et al[71], 1987	13 HC	18 drug-free agoraphobic patients	Plasma cortisol not increased during PA	-	-	Exposure to phobic situations
Goldstein et al[76], 1987	61 HC; 38 outpatients with MDE	24 outpatients PD	↑ Basal plasma cortisol vs HC; = plasma cortisol vs MDE	-	=	Dex 1 mg
Cameron et al[74],1987	4 HC	8 PD patients	= In basal conditions; ↑ during spontaneous PA	-	-	-
Kathol et al[77], 1988	37 HC	65 PD subjects	↑ Urinary cortisol	-	-	-
Uhde et al[75], 1988	12 HC	12 drug-free PD patients	= Basal cortisol	-	-	-
Abelson et al[78], 1996	12 HC	20 PD subjects	↑ Overnight plasma cortisol; ↑ amplitude of ultradian secretory episodes	If low frequency of PA→↑ daytime ACTH levels and ↑ ACTH ultradian amplitude. If high frequency of PA→ shifted ACTH circadian cycles	-	-
Schreiber et al[30], 1996	10 MDE subjects, 10 HC	13 PD subjects wth agoraphobia	↑ Plasma cortisol versus controls	= Levels in PD vs controls and MDE subjects	92% non suppressors (higher than MDE subjects and controls)	69% abnormal Dex-CRH test (more than controls, but lesser than MDE subjects)
Bandelow et al[73], 2000	23 HC	23 PD patients	↑ Urinary and salivary cortisol	-	-	-
Coryell et al[81], 1989	38 HC	82 PD patients	-	-	25.6% non suppressors	Dex 1 mg
Coryell et al[80], 1991	-	72 PD patients	-	-	36% non suppressors
Erhardt et al[33], 2006	30 HC	30 PD subjects	↑ Basal plasma levels	↑ Basal	-	17% hyperresponder to Dex-CRH
Petrowski et al[82], 2010	34 HC	34 PD subjects	= Basal salivary levels; abnormally absent cortisol awakening response	-	-	Absent cortisol response to Trier Social Stress Test
Lieberman et al[79], 1983	22 MDE	10 PD	↑ Plasma cortisol	-	=	DST

HC: Healthy controls; DST: Dexamethasone suppression test; PA: Panic attack; MDE: major depressive episode; ACTH: Adrenocorticotropin hormone; PD: Panic disorder; Dex: Dexamethasone; CRH: Corticotropin releasing hormone.

Table 3 Hypothalamic pituitary adrenal axis functioning and its correlation with psychopathology in obsessive compulsive disordered patients

Author	Control group	Sample	Cortisol levels	Other hormones levels	DST	Correlations with psychopathology
Monteleone et al[91], 1994	13 HC	13 drug-free OCD patients	↑ Plasma cortisol cyrcadian rhythm	-	-	↑ Severity of OCD symptoms
Kluge et al[86], 2007	9 HC	9 OCD inpatients w/o comorbid depression	↑ Plasma levels	↑ Plasma ACTH	-	-
Catapano et al[89], 1990	20 HC	18 OCD patients	-	-	27.7% non-suppression	Correlated with sex (all non suppressors were males) and independently of depression
Coryell et al[92], 1989	82 panic disordered patients	20 OCD outpatients	-	-	=	-
Altemus et al[90], 1992	25 HC	12 OCD subjects	-	↑ CSF CRH; ↑ plasma and CSF AVP	-	↑ Psychopathology

HC: Healthy controls; DST: Dexamethasone suppression test; CSF: Cerebrospinal fluid; CRH: Corticotropin releasing hormone; AVP: Arginine vasopressin; OCD: Obsessive-compulsive disorder; ACTH: Adrenocorticotropin hormone.

Table 4 Hypothalamic pituitary adrenal axis functioning and its correlation with psychopathology and childhood traumata in social phobia patients

Author	Control group	Sample	Cortisol levels	CRH levels	Stress test	Correlations with childhood traumata and psychopathology
Potts et al[100], 1991	15 HC	10 SP	= Urinary	-	-	-
Levin et al[103], 1993	14 HC	36 (28 generalized SP + 8 specific SP)	= Plasma	-	Ten-minute talk	-
Uhde et al[101], 1994	-	54-64 SP patients	= Plasma and urinary	-	= DST (Dex 1 mg)	-
Martel et al[105], 1999	21 HC	27 SP	= Salivary basal and task-related	-	Modified TSST	Correlated to anticipatory anxiety in both groups
Furlan et al[104], 2001	17 HC	18 SP	After speech task: ↑ 90% increase in salivary levels in 7 SP; ↓ 32% in salivary LE in 11 SP. After exercise task: =	-	Public speaking task and physical exercise task	-
Condren et al[32], 2002	15 HC	15 SP	↑ Plasma cortisol after test; = plasma cortisol basal	= Basal and after test	Public mental arithmetic and short term memory test	-
van West et al[106], 2008	25 HC	25 SP	↑ Salivary cortisol after test	-	Public speaking test	Correlated to trait but not state anxiety levels
Roelofs et al[107], 2009	22 HC, 17 patients with PTSD	18 SP	↑ Salivary cortisol after test	-	Social approach-avoidance task in social stress condition (TSST)	Cortisol increase correlated to the social avoidance behavior
Elzinga et al[99], 2010	16 SAD w/o CA, 16 HC, 16 PTSD with CA	9 SAD with CA	↑ Salivary cortisol after test; = salivary cortisol basal	-	TSST	CA is associated with ↑ cortisol reactivity to TSST
Lanzenberger et al[102], 2010	18 HC	12 subjects with SP	↓ Plasma levels	-	-	Negative correlations with 5HT binding in brain regions and positive correlation with trait anxiety

HC: Healthy controls; DST: Dexamethasone suppression test; TSST: Trier social stress test; SAD: Separation anxiety disorder; CA: Childhood abuse; SP: Social phobia; PTSD: Posttraumatic stress disorder; Dex: Dexamethasone.

Table 5 Hypothalamic pituitary adrenal axis functioning and its correlations with psychopathology in generalized anxiety disordered patients

Author	Control group	Sample	Cortisol levels	DST	Correlations with psychopathology
Mantella et al[114], 2008	42 HC	71 GAD subjects	↑ Morning basal and peak salivary cortisol	-	↑ Psychopathology
Steudte et al[118], 2011	15 HC	15 GAD patients	↓ Cortisol in the first and second 3-cm hair segments; = salivary diurnal cortisol profiles	-	-
Schweizer et al[112], 1986	-	79 GAD subjects	-	27% non-suppression	-
Tiller et al[113], 1988	13 HC	30 GAD patients	-	27% non-suppression	Normalization of HPAA suppression after successful non drug behavioral treatment
Tafet et al[115], 2005	8 non treated GAD outpatients	17 treated GAD outpatients	= Morning plasma cortisol; ↑ evening plasma cortisol	-	↓ Evening plasma cortisol level after cognitive treatment
Pomara et al[116], 2005	90 HC	41 GAD patients	↑ Plasma cortisol levels	-	↓ Plasma cortisol after acute and chronic treatment with diazepam
Rosenbaum et al[117], 1983	22 HC	22 GAD subjects	= 24 h urinary cortisol levels	-	-

HC: Healthy controls; DST: Dexamethasone suppression test; GAD: Generalized anxiety disorder; HPAA: Hypothalamic pituitary adrenal axis.