Bases neurobiológicas de la depresión infantil · Bases neurobiológicas de la depresión...

Bases neurobiológicas de la depresión infantil: el papel de la respuesta biológica de estrés

Dr. Enrique F. Maldonado Profesor Titular de Universidad

Laboratorio de Neuropsicología Infanto-‐Juvenil (LNIJ) Dpto. Psicobiología y Metodología de las CC.C.

Universidad de Málaga

Laboratorio de Neuropsicología Infanto-Juvenil

Hospital Virgen de la Victoria, Málaga

Neurobiological bases of child depression: the role of the biological stress response

Dr. Enrique F. Maldonado Lecturer

Child and Adolescent Neuropsychology Laboratory (CANL) Deparment of Psychobiology and Behavioral Sciences

University of Malaga

Child and AdolescentNeuropsychology Lab Hospital Virgen de la Victoria,

Málaga

Introduc)on

•  Why child depression is an important health problem today?

•  Best predictors of the first episode of child or adolescent depression: –  Depressive symptomatology –  Morning free corBsol levels –  Searching new biological markers???

Introduc)on •  The biological stress response and its associaLon with depression in child populaLons: the role of LC-‐NA-‐SAM system

Introduc)on •  The biological stress response and its associaLon with depression in child populaLons: the role of HPA-‐axis

Morning levels of: -‐CorLsol -‐sAA AcLvity/Output -‐RaLo sAA/CorLsol

TRF internalizing scores: -‐Depression-‐Withdrawal -‐Anxiety-‐Depression -‐PsychosomaBc -‐Total Internalizing

Study 1 Association of Salivary Morning Alpha-Amylase Activity

with Internalizing Psychopathology Scores in Boys and Girls 8-11 y.o.

Objec)ves

•  1. What´s the best salivary marker of depressive symptoms in a communitary child sample of 8-‐11 y.o.?

•  2. Can gender/sex modulate this associaLon between salivary markers and number of depressive symptoms?

•  A communitary and healthy sample (n = 99) with scarce gender/sex-‐differences in SES and in anthropometric variables was recruited in Malaga:

•  Low-‐medium socioeconomic status with respect to the city of Malaga

•  Low levels of perceived stress

•  Low levels of internalizing psychopathology


Child and AdolescentNeuropsychology Lab

Association of Salivary Morning Alpha-Amylase Activity with Internalizing Psychopathology Scores in Boys and Girls

8-11 y.o.

Salivary measurements: free cor)sol

Figure 1. Awakening corLsol response (in observaLon days 1, 2, and mean ± SEM).

Diurnal rhythm of free cor1sol Clow, Thorn, Evans & Hucklebridge (2004)

Salivary measurements: alpha-‐amylase ac)vity

Figure 2. Alpha-‐amylase (acLvity) awakening response (observaLon days 1, 2, and mean ± SEM).

Diurnal rhythm of sAA Nater et al. (2007)

Salivary measurements: alpha-‐amylase output

Figure 3. Alpha-‐amylase (output) awakening response (in observaLon days 1, 2, and mean ± SEM).

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Diurnal rhythm of sAA Nater et al. (2007)

Salivary measurements: Ra)o sAA / free cor)sol

Bauer, Quas y Boyce (2002) Figure 4. RaLo Alpha-‐amylase (acLvity/output) / CorLsol

Study 1: Main Results

ParLal correlaLons between TRF scores and salivary measurements (n = 99)

Table 5.

Partial correlations between Teacher´s Report Form scores and salivary markers after controlling for age and body mass index in the full

sample (n = 99).

TRFanxiety TRFdepression-withdrawal TRFpsychosomatic TRFtotal

Mean cortisol -0.079 0.009 0.005 -0.042

Mean delta cortisol 0.062 0.065 -0.133 0.019

Mean sAA activity -0.182 † -0.213 * -0.125 -0.222 *

Mean sAA output -0.138 -0.155 -0.121 -0.179 †

Ratio sAA activity/cortisol -0.061 -0.190 † -0.111 -0.153

Ratio sAA output/cortisol -0.046 -0.137 -0.090 -0.121

† p = 0.10; * p < 0.05; ** p < 0.01

Girls (n = 54)

Table 7.

Partial correlations between Teacher´s Report Form scores and salivary markers after controlling for age and body mass index in girls (n

= 54).

TRFanxiety TRFdepression-withdrawal TRFpsychosomatic TRFtotal

Mean cortisol 0.009 -0.053 -0.056 -0,035

Mean delta cortisol 0.016 0.128 -0.126 0.009

Mean sAA activity -0.148 -0.343 * -0.171 -0.284 †

Mean sAA output -0.169 -0.137 -0.204 -0.216

Ratio sAA activity/cortisol 0.169 -0.314 * -0.127 -0.257 †

Ratio sAA output/cortisol 0.194 -0.153 -0.193 -0.232 †

† p = 0.10; * p < 0.05; ** p < 0.01

ModeraLon analysis: sex X (sAA X TRF)

Figure 5. Squared-‐root transformed values of mean morning salivary alpha-‐amylase acLvity on squared-‐root transformed values of the TRFdepression-‐withdrawal subscale (n = 99).

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1

2

3

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5

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8

9

Non-clinical Clinical

Squa

red-

root

tran

sfor

med

val

ues

of s

AA

activ

ity

Figure 6. Comparison of Squared-‐root transformed values of sAA acLvity between parLcipants showing clinical (n = 8) and non-‐clinical (n = 91) scores in the TRFdepression-‐withdrawal subscale.




8-11 y.o.

*

* P < 0.05

•  I “Feel” depressed vs “Look” depressed… Hospital Virgen de la Victoria,

MálagaChild and AdolescentNeuropsychology Lab


8-11 y.o.

Study 2

Neuropsychological Assessment Sesion (± 1 h)

ENFEN

5 DIGITS

WISC-‐IV

-‐Digits

-‐Inverse Digits

Relaxa)on Relaxa)on

CDI

CogniLve & Psychosocial Stress

Association of Salivary Alpha-Amylase Activity and Executive Functions in Boys and Girls 7-12 Years Old (A Pilot Study)

TRF

CBCL

N = 16

Objec)ves

•  1. What´s the associaLon between mean levels of sAA acLvity and depressive scores (TRF and CBCL) in a communitary child sample of 7-‐12 y.o.?

•  2. What´s the associaLon between mean levels of sAA acLvity and execuLve funcLons in a communitary child sample of 7-‐12 y.o.?

Study 2: Main Results

•  CorrelaLons between sAA Levels and TRF Scores: •  r = .625; p = .030; n = 12

Figure 1. CorrelaBon between mean sAA AcBvity and Total TRF Internalizing Scores

1.

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TRF anxiety-‐depression: r = .559; p = .059; n = 12 TRF depression-‐withdrawal: r = .426; p = .168; n = 12 TRF psychosomaLc: r = .508; p = .092; n = 12




Diurnal rhythm of sAA and its response to stressors Nater et al. (2007)

•  CorrelaLons between AAs Levels and ExecuBve FuncBons: •  r = .755; p = .030; n = 11

Figure 2. CorrelaBon between mean sAA AcBvity and Working Memory Scores obtained through the Inverse Digits Test of the WISC-‐IV aTer controlling for BMI, sex and Time of TesBng

2.

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WISC-‐IV: Digits n.s. 5 DIGITS: n.s. ENFEN: Errores Anillas r = .699; p = .054; n = 6

Selected References

•  Cubala, W.J. & Landowski, J. (2014). Low baseline salivary alpha-‐amylase in drug-‐naïve pa)ents with short-‐illness-‐dura)on first episode major depressive disorder. Journal of Affec1ve Disorders, 157, 14-‐17.

•  Vigil, J.M., Geary, D.C., Granger, D.A., Flinn, M.V. (2010). Sex differences in salivary cor)sol, alpha-‐amylase, and psychological func)oning following Hurricane Katrina. Child Development, 81, 1228-‐1240.

•  Oei, N.Y., Tollenaar, M.S., Elzinga, B.M., & Spinhoven, P. (2010). Propanolol reduces emo)onal distrac)on in working memory: a par)al media)ng role of propranolol-‐induced cor)sol increases? Neurobiology of Learning and Memory, 18(2), 178-‐187.

Gracias¡¡¡ Thank you¡¡¡ Madrid (Spain)



Neurobiological bases of child depression: the role of the biological stress response

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