hpa axis activity hpa axis activity in delinquent male in delinquent male

adolescentsadolescents

arne popmadepartment of

child and adolescent

psychiatry vu amsterdam

outlineoutline

backgroundbackground literatureliterature

overall projectoverall project study 1study 1 study 2study 2 study 3study 3

conclusionconclusion discussiondiscussion

backgroundbackground

disruptive behaviour disorders (dbd): disruptive behaviour disorders (dbd): oppositional defiant disorder (odd)oppositional defiant disorder (odd) conduct disorder (cd)conduct disorder (cd)

- high prevalence - high prevalence - high risk for problems in adulthood- high risk for problems in adulthood - major public health problem- major public health problem

- resistant to treatment- resistant to treatment

theoretical frameworktheoretical framework

underarousalunderarousal

fearlessness sensation seekingfearlessness sensation seeking (zuckermann,1977) (raine, 1993)(zuckermann,1977) (raine, 1993)

biological parametersbiological parameters

biological parameters: the biological parameters: the ansans

autonomic nervous system activityautonomic nervous system activity in antisocial children:in antisocial children:

low basal heart rate (hr):low basal heart rate (hr): (ortiz & raine, 2004) (ortiz & raine, 2004)

smaller increase during stress:smaller increase during stress:(van goozen (van goozen al.al., 1998 & 2000), 1998 & 2000)

biological paramaters: biological paramaters: cortisolcortisol

cortisol cortisol in antisocial children:in antisocial children:

low basal cortisol (???)low basal cortisol (???) (Mc Burnett et al., 2000; Shoal et al., 2003)(Mc Burnett et al., 2000; Shoal et al., 2003)

blunted cortisol reaction during stressblunted cortisol reaction during stress (Van Goozen et al., 1998 & 2000; Moss al.,1995)(Van Goozen et al., 1998 & 2000; Moss al.,1995)

overall project: aimoverall project: aim- non clinically referred groupnon clinically referred group- early in adolescence (follow-up)early in adolescence (follow-up)- study 1: diurnal cortisol cyclestudy 1: diurnal cortisol cycle- study 2: hpa/ans: psychosocial stress teststudy 2: hpa/ans: psychosocial stress test

- hpa/ans: frustrating stress testhpa/ans: frustrating stress test- interactions between hormones in relation to interactions between hormones in relation to subtypes of aggressionsubtypes of aggression

overall project: study overall project: study populationpopulation

12-14 year old boys from (n = 110)12-14 year old boys from (n = 110)delinquency diversion project (DP) in amsterdamdelinquency diversion project (DP) in amsterdam(petty crime: shoplifting, vandalism, aggression)(petty crime: shoplifting, vandalism, aggression)

normal control boys (n = 35)normal control boys (n = 35)

matched group wise on age, ses, ethnicity, IQmatched group wise on age, ses, ethnicity, IQ

overall project: instrumentsoverall project: instruments

diagnostic interwiew schedule for diagnostic interwiew schedule for childrenchildren

child behavior checklistchild behavior checklist

wechsler intelligence scalewechsler intelligence scale

subjectssubjects

normal controls:normal controls: NCNCdiversion project without DBD:diversion project without DBD: DP-DP-diversion project with DBD:diversion project with DBD: DP+DP+

DBD = ODD ór CDDBD = ODD ór CD

study 1: diurnal cycle of cortisol, incl. CAR

aimaim

measuring cortisol levels in saliva measuring cortisol levels in saliva - in the first hour after waking up:in the first hour after waking up: the cortisol awakening response (CAR)the cortisol awakening response (CAR)- during the dayduring the dayhypotheses:hypotheses: smaller CAR and lower cortisol levels over smaller CAR and lower cortisol levels over the day in DP+ compared to NCthe day in DP+ compared to NC

0

2

4

6

8

10

12

14

7:00 8:00 9:00 10:00 11:00 12:00 13:00 14:00 15:00 16:00 17:00 18:00 19:00 20:00 21:00

time

cort

isol

(nm

ol/l)

NC (n = 32)

DP- (n = 61)

DP+ (n = 20)

study 1: diurnal cycle of cortisol, incl CAR

resultsresults

study 2: psychosocial stress test

aimaim

measuring salivary cortisol, HRmeasuring salivary cortisol, HRhypotheses:hypotheses: DP+DP+ lower basal cortisol and HR,lower basal cortisol and HR,

smaller increase cortisol and HRsmaller increase cortisol and HRas compared with NCas compared with NC

study 2: psychosocial stress test

timeschedule timeschedule

initial resting period psychosocial stress test post-test resting period

t = -50 min t = -25 t = 0 t = 10 t = 15 t = 35 t = 55 t =75

HR and SCL saliva saliva saliva saliva saliva saliva saliva nms 1 nms nms nms nms nms nms 1 Von Zerssen negative mood scale

study 2: psychosocial stress test

salivary cortisolsalivary cortisol

0

0,5

1

1,5

2

2,5

3

3,5

4

-40 -30 -20 -10 0 10 20 30 40 50 60 70 80

time

cort

isol

(nm

ol/l)

NC (n = 30)DP- (n = 45)DP+ (n = 21)

prepare speaking

study 2: psychosocial stress test

heartrateheartrate

72

74

76

78

80

82

84

86

88

90

-40 -30 -20 -10 0 10 20 30 40 50 60 70 80time

hear

trat

e (b

pm)

NC (n = 30)DP- (n = 49)DP+ (n = 21)

prepare speaking

study 2: psychosocial stress test

negative affectnegative affect

0

1

2

3

4

5

-40 -30 -20 -10 0 10 20 30 40 50 60 70 80

time

nega

tive

moo

d NC (n = 30)DP- (n = 50)DP+ (n = 22)

prepare speaking

study 2: psychosocial stress test

resultsresults

in resting situation:in resting situation: no differences cortisol, HR negative mood no differences cortisol, HR negative mood during stress:during stress: DP+DP+ smaller increase in cortisol and HR, smaller increase in cortisol and HR, but similar increase in negative mood but similar increase in negative mood during psychosocial stressorduring psychosocial stressoras compared with NCas compared with NC

conclusionconclusion

delinquent boys with a disruptive behavior delinquent boys with a disruptive behavior disorder show differences in cortisol levels,disorder show differences in cortisol levels,1 in the first hours after waking up 1 in the first hours after waking up 2 during a psychosocial stressor 2 during a psychosocial stressor as compared with normal controlsas compared with normal controls

conclusionconclusion

when studying HPA activity when studying HPA activity in relation to disruptive behavior in relation to disruptive behavior it is important to take into account it is important to take into account diurnal variation diurnal variation and basal versus stress conditionsand basal versus stress conditions

testosterone and cortisoltestosterone and cortisol

evidence from studies in animals that evidence from studies in animals that testosterone influences HPA-functioning testosterone influences HPA-functioning (Luine 2002)(Luine 2002)ánd cortisol influences testosterone ánd cortisol influences testosterone levels (Viau 2002)levels (Viau 2002)

aggressionaggression

The Buss-Durkee Hostility Inventory (BDHI; The Buss-Durkee Hostility Inventory (BDHI; Buss-Durkee and Baer 1956) Buss-Durkee and Baer 1956)

- self-report questionnaire - self-report questionnaire - translated and validated for the - translated and validated for the Netherlands by Lange et al (1995)Netherlands by Lange et al (1995)

bdhi: itemsbdhi: items overt aggression:overt aggression: feeling angry and displaying aggression, feeling angry and displaying aggression,

often impulsive and poorly controlledoften impulsive and poorly controlled

- ”When I am angry, I slam doors” - ”When I am angry, I slam doors” - “I have known people who pushed me - “I have known people who pushed me so far that we came to blows”so far that we came to blows” - “When I really lose my temper, I am - “When I really lose my temper, I am capable of slapping someone” capable of slapping someone”

behavioral measure: behavioral measure: itemsitems

covert aggression:covert aggression: feeling angry without expressing openly, is feeling angry without expressing openly, is

more hidden and controlledmore hidden and controlled

- “I am irritated a great deal more than - “I am irritated a great deal more than people are aware of”people are aware of” - “Although I don’t show it, I am - “Although I don’t show it, I am sometimes eaten up with jealousy”sometimes eaten up with jealousy” - “If I let people see the way I feel, I’d be - “If I let people see the way I feel, I’d be considered a hard person to get along considered a hard person to get along with”with”

study populationstudy population

12-14 year old boys (12-14 year old boys (n = 103; m.a.13.68 ± n = 103; m.a.13.68 ± 0.74)0.74)

from delinquency diversion project in from delinquency diversion project in amsterdamamsterdam

(petty crime: shoplifting, vandalism, (petty crime: shoplifting, vandalism, aggression)aggression)

27 participants had a DBD diagnosis (26%)27 participants had a DBD diagnosis (26%)

instrumentsinstruments

linear regression analyses were performed linear regression analyses were performed with aggression (overt and covert aggressionwith aggression (overt and covert aggressionrespectively) as dependent variable and with respectively) as dependent variable and with testosterone, cortisol and testosterone xtestosterone, cortisol and testosterone xcortisol as independent variablescortisol as independent variables

testosteron x cortisol > overt testosteron x cortisol > overt aggressionaggression

6

8

10

12

14

0 50 100 150 200 250

Testosterone (pmol/l)

Ove

rt A

ggre

ssio

n

Cortisol 1SD below mean

Cortisol mean

Cortisol 1 SD above mean

discussiondiscussion

how to understand this interaction?how to understand this interaction?

1: cortisol related to psychosocial factors 1: cortisol related to psychosocial factors (social withdrawal, inhibition) that (social withdrawal, inhibition) that influence influence the testosterone-aggression relationshipthe testosterone-aggression relationship

discussiondiscussion

2: high cortisol protective against aggression2: high cortisol protective against aggression (Shirtcliff 2005)(Shirtcliff 2005)

3: cortisol directly influences effects of 3: cortisol directly influences effects of testosterone, for example on receptor leveltestosterone, for example on receptor level (Viau 2002)(Viau 2002)

future plansfuture plansfollow up:do HPA and ANS (re)activity predict (persistency of) disruptive behavior?how do environmental factors (ie traumatic events) interact with these biological factors in relation to disruptive behavior? which subtypes op disruptive behavior correlate best with HPA activity

thank you!thank you!Theo Doreleijers

Herman van Engeland Robert Vermeiren

Lucres JansenStephanie van Goozen

Wim van den BrinkThomas RinneHans SteinerAdrian Raine