Bases neurobiológicas de la depresión infantil · Bases neurobiológicas de la depresión...
Transcript of 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
Hospital Virgen de la Victoria, Málaga
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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Non-clinical Clinical
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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.
Hospital Virgen de la Victoria, Málaga
Child and AdolescentNeuropsychology Lab
Association of Salivary Morning Alpha-Amylase Activity with Internalizing Psychopathology Scores in Boys and Girls
8-11 y.o.
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* P < 0.05
• I “Feel” depressed vs “Look” depressed… Hospital Virgen de la Victoria,
MálagaChild and AdolescentNeuropsychology Lab
Association of Salivary Morning Alpha-Amylase Activity with Internalizing Psychopathology Scores in Boys and Girls
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
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Hospital Virgen de la Victoria, Málaga
Child and AdolescentNeuropsychology Lab
Association of Salivary Alpha-Amylase Activity and Executive Functions in Boys and Girls 7-12 Years Old (A Pilot Study)
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
Hospital Virgen de la Victoria, Málaga
Child and AdolescentNeuropsychology Lab
Association of Salivary Alpha-Amylase Activity and Executive Functions in Boys and Girls 7-12 Years Old (A Pilot Study)
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
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Hospital Virgen de la Victoria, Málaga
Child and AdolescentNeuropsychology Lab
Association of Salivary Alpha-Amylase Activity and Executive Functions in Boys and Girls 7-12 Years Old (A Pilot Study)
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)
Hospital Virgen de la Victoria, Málaga
Child and AdolescentNeuropsychology Lab
Neurobiological bases of child depression: the role of the biological stress response