Table 3.
Summary of the findings related to the hypothalamic–pituitary–adrenal axis involved in GAD, PDA, and SAD.
| Biomarker | Finding | |
|---|---|---|
| General anxiety disorder | ||
| Basal levels | Plasma ACTH concentration | ↑ vs. HCs [140] |
| Plasma cortisol level | =vs. HCs [140,141] | |
| ↑ vs. HCs [142] | ||
| Salivary cortisol levels | =vs. HCs [107,143] | |
| ↑ vs. HCs and positively correlated with symptoms [144] | ||
| Hair cortisol levels | ↓ vs. HCs [145,146] | |
| sAA/cortisol ratio | ↑ vs. HCs [147] | |
| Salivary cortisol awakening response | ↑ in GAD with comorbid MDD vs. HCs [148] | |
| ↓ vs. HCs in adults (>65 years) with long-lasting ADs [149] | ||
| Plasma DHEAS levels | =vs. HCs [141] | |
| Cortisol/ DHEAS ratio | =vs. HCs [141] | |
| After stress-tests/treatments | Plasma cortisol levels (after stress-test) | =vs. HCs [140] |
| Plasma ACTH concentration (after stress-test) | =vs. HCs [140] | |
| Salivary cortisol levels (after a common stressful situation) | In males, ↓ decline rate of post-stress cortisol increases vs. HCs [143] | |
| In females, ↑ post-stress cortisol secretion and ↓ recuperation capacity correlated with clinical severity [143] | ||
| Plasma cortisol levels (following CBT, escitalopram, and treatments refocusing patients’ attention) | ↓ vs. HCs [150,151,152] | |
| Plasma cortisol levels (after treatment with buspirone, alprazolam, or diazepam) | =pre vs. post treatment [153,154,155,156] | |
| sAA/cortisol ratio (after mental arithmetic challenge) | ↓ vs. HCs [147] | |
| HPA axis modifications (after dexamethasone suppression test) | =vs. MDD [142,157,158,159,160] | |
| Panic disorders with or without agoraphobia | ||
| Basal levels | Cortisol plasma levels | ↑ vs. HCs [161,162,163,164] |
| =vs. HCs [165,166] | ||
| Urinary free cortisol levels | =vs. HCs [167] | |
| ↑ vs. HCs [168] | ||
| ↑ in complicated PDA vs. HCs [169] | ||
| =in active (paroxetine) vs. placebo treatment [170] | ||
| Plasma ACTH concentration | ↑ vs. HCs [166] | |
| After stress-tests/treatments | Plasma ACTH concentration (response to CRH) | ↓ vs. HCs [162,166,171] |
| = vs. HCs [172] | ||
| Plasma cortisol levels (response to CRH) | ↓ vs. HCs [162,166] | |
| =vs. HCs [171,172] | ||
| Plasma cortisol levels (after spontaneous panic attacks) | =vs. HCs [173] | |
| Plasma cortisol levels (after feared situations) | =vs. HCs [174] | |
| Plasma cortisol levels (during panic attacks induced by lactate infusion) | =vs. HCs [175,176,177,178,179,180] | |
| ↑ vs. HCs [181] | ||
| ↓ vs. HCs [59] | ||
| Plasma cortisol levels (after yohimbine-induced panic attacks) | ↑ vs. HCs [182] | |
| Plasma cortisol levels (after caffeine or mCPP administration) | =vs. HCs [183,184] | |
| Salivary cortisol levels (during spontaneous panic attacks) | ↑ vs. after [185] | |
| Plasma ACTH concentrations (after feared situations) | =vs. HCs [174] | |
| Plasma ACTH concentrations (during panic attacks induced by lactate infusion) | =vs. HCs [175,176,177,178,179,180] | |
| Social anxiety disorder | ||
| Basal levels | Urinary free cortisol levels | =vs. HCs [186,187] |
| Salivary cortisol levels | =vs. HCs [188,189,190] | |
| =in female adolescents vs. HCs [191] | ||
| risk factor for SAD onset [192] | ||
| Salivary cortisol awakening response | ↑ in SAD patients with comorbid MDD [148] | |
| ↑ in children vs. HCs and significantly predicted SAD onset [193] | ||
| Plasma cortisol levels | =vs. HCs [188] | |
| sAA/cortisol ratio | ↑ vs. HCs [189,190] | |
| After stress-tests/treatments | Salivary cortisol levels (after TSST) | =vs. HCs [188] |
| Salivary cortisol levels (after dexamethasone) | =vs. HCs [187] | |
| Salivary cortisol levels (after intravenous citalopram, CCK-4 or mCPP) | =vs. HCs [194,195,196] | |
| Salivary cortisol levels (after administration of fenfluramine or mCPP) | ↑ vs. HCs [59,197] | |
| Salivary cortisol levels (after stress test) | ↑ vs. HCs [198,199] | |
| Plasma cortisol levels (after TSST) | =vs. HCs [188,200] | |
| ↑ in SAD patients with comorbid MDD vs. HCs [200] | ||
| sAA/cortisol ratio (after TSST) | =vs. HCs [188] | |
| sAA/cortisol ratio (after electrical stimulation) | ↑ vs. HCs [190] | |
| sAA/cortisol ratio (after dexamethasone) | ↑ vs. HCs [189] | |
| sAA/cortisol ratio (after public speaking task) | ↑ vs. HCs [201] | |
| Hair cortisol concentration (after TSST) | =vs. HCs [188] | |
| Plasma ACTH concentration (after TSST) | ↑ in SAD patients with MDD vs. HCs [200] | |
| =vs. HCs [200] | ||
Note: ACTH: adrenocorticotropic hormone; ADs: Anxiety disorders; CBT: cognitive-behavioral therapy; CRH: corticotropin-releasing hormone; DHEAS: dehydroepiandrosterone; DST: dexamethasone suppression test; GAD: generalized anxiety disorder; HCs: healthy controls; MDD: major depressive disorder; mCPP: meta-chlorophenylpiperazine; PDA: panic disorder with or without agoraphobia; sAA: salivary alpha-amylase; SAD: social anxiety disorder; TSST: trier social stress test; ↑: increased; ↓: decreased.