1. Hypothalamic-pituitary-adrenal axis activity
in major depressive disorder
Carmilla Licht & Nicole Vogelzangs

2. Cardiovascular disease
Depression
Biological black box
Metabolic changes,
atherosclerosis
Cardiovascular disease

3. Cardiovascular disease
Depression
inflammation autonomic HPA-axis
nervous system
Metabolic changes,
atherosclerosis
Cardiovascular disease

4. Cardiovascular disease
Depression
inflammation autonomic HPA-axis
nervous system
Metabolic changes,
atherosclerosis
Cardiovascular disease

5. Hypothalamic-pituitary-adrenal axis

6. Function HPA axis
Acute
versus
Chronic
Hersenen: oa geheugen

7. Function cortisol
Primary defense mechanism in reaction to stress, to regain homeostatis, including lowering cortisol
Essential for optimal emotional and cognitive functioning  removing stressor
Hersenen: oa geheugen

8. Role of HPA axis in depression?

9. Some indications Stress and depression
Cushing’s disease and depression
Somatic consequences of depression
Symptoms of depression

10. What is the evidence?

11. Depression and Cortisol
Increased HPA-as activity
Caroll (1976), Holsboer (1984), Nemeroff (1984), Gold (1986), Young (1994), Bhagwagar (2005)
Decreased HPA-as activity
Chrousos en Gold (1992), Asnis (1995), McGinn (1996), Levitan (2002), Stetler en Miller (2005)
No association
Schlechte (1986), Strickland (1998), Anisman (1999), Posener (2000), Young (2002)

12. Why investigate HPA-axis?
Knowledge pathophysiology depression
Identifying risk groups
Medication?

13. How investigate HPA-axis?
CRH, ACTH, cortisol
Liquor, blood, urine, saliva
95% bound, 5% free
Stress versus basal

14. Diurnal rhythm => multiple time points CAR, basal
Cortisol nmol/l
Awakening Sleep Awakening

15. Major depressive disorder and Hypothalamic-pituitary-adrenal axis activity
Sophie Vreeburg
WJG Hoogendijk, J van Pelt, RH de Rijk, JCM Verhagen,
R van Dyck, JH Smit, FG Zitman, BWJH Penninx
Supported by the Geestkracht program of ZonMW and matching funds of participating organisations

16. Research question
Do cortisol levels (Cortisol Awakening Response, evining level and DST) differ between depressive persons and controls in a large sample?
Do remitted and current cases differ?
What is the role of comorbid anxiety?

17. Assessment of cortisol in saliva
Saliva collected at home
73% of samples returned to lab LUMC
7 samples:
Cortisol awakening response (CAR):
T1: at awakening
T2: +30 minuten
T3: +45 minuten
T4: +60 minuten
Evening: T5: 22:00u
T6: 23:00u
DST: 0.5 mg dexamethason at 23:05 T7: at awaking
Most previous studies are rather small, no extensive psychiatric studies => NESDA

18. Cortisol measures
CAR
Evening level
DST

19. area under the curve (AUC)
AUC to increase
Cortisol nmol/l
AUC to ground
Minutes after awakening

20. Cortisol measures CAR Evening level: T5 at 22.00u and T6 at 23.00u
DST Mean of 2 measures

21. Cortisol measures CAR Avond waarde DST: 0.5 mg dexamethason
Cortisol suppression
Ratio T1/T7

22. Covariates Sociodemografic factors Sex, age, SES Health factors
Smoking, physical activity
Sampling factors
Work status, weekday, season, time at awakening, sleep duration

23. Current vs remitted MDD

24. Cortisol Awakening Response
MDD+anxiety (n=830)
MDD (n=450)
Anxiety (n=255)
Controls (n=308)
Cortisol (nmol/l)
direct groepseffect tijd*groep effect
MDD+anxiety vs controles p< p=.03
MDD lifetime vs controles p= p=.04
Anxiety lifetime vs controles p=.03 p=.67

25. Evening cortisol REF Cortisol (nmol/l)
p= p= p=.05
Cortisol (nmol/l)
REF
controles anxiety MDD MDD+anxiety

26. Cortisol, after dexamethason (T7)
p= p= p=.21
p=0.10
p=0.81
Cortisol (nmol/l)
REF
controles anxiety MDD MDD+anxiety

27. Conclusions
Persons with depression or anxiety show a modest but significant higher cortisol awakening response
Persons with comorbid anxiety+MDD also have higher evening cortisol levels
No difference between current and remitted MDD