AAPI 2003

Neurobiología en Estrés y
Trauma

Dr. Enrique De Rosa

Informes@consultapsi.com
www.consultapsi.com
www.estrestraumatico.com
 Fuentes de estrés:
• Gastos, la falta de dinero, la persistente recensión económica,
• Desocupación,
• Desbordes sociales, Incremento del delito, Inseguridad
• Demandas y frustraciones de la escuela,
• Cambios en sus cuerpos,
• Problemas con sus amigos
• el vivir en un ambiente/vecindario poco seguro,
• Peleas frecuentes entre los padres
• Separación o divorcio de sus padres,
• Enfermedad crónica o problemas severos en la familia,
• Muerte de un ser querido- (Hoy suicidios, víctimas v. urbana
etc)
• Mudarse o cambiar de escuela
• Llevar a cabo demasiadas actividades o tener expectativas
demasiado altas

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 Trauma.
1.Lesión duradera producida por un agente
mecánico, generalmente externo.
2. Choque emocional que produce un daño
duradero en el inconsciente.
3. Emoción o impresión negativa, fuerte y
duradera.

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 Espectro de las reacciones al
estrés
• Trastorno por estrés agudo
• Psicosis reactiva breve
• Trastornos disociativos
– fuga disociativa
– amnesia disociativa
– personalidad múltiple
• Trastornos conversivos
• Trastornos adaptativos
• Trastornos fóbicos
• Trastornos depresivos
– depresión reactiva
– depresión postraumática
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• Trastorno de despersonalización
• Trastornos del sueño
• Trastornos por somatización
• Trastornos de personalidad
– borderline
– antisocial
– depresiva
• Cambio de personalidad
– catastrófica
– TEENE
• DESNOS (trastorno de estrés
extremo no especificado)
Patología psiquiátrica postraumática
• Trastornos de ansiedad
• Síndrome de Stress postraumático
• Trastorno por estrés agudo
• Trastornos del estado de ánimo
• Síndromes depresivos
• Trastornos adaptativos
• Trastornos disociativos
• Psicosis
• Trastornos Psiquiátricos debidos a una condición médica
• Epilepsia
• Demencia
• Síndrome Postconmocional de los traumatizados de
cráneo
• Trastornos relacionados con abuso de sustancias
• Trastornos Somatoformes
• Dismorfofobia
• Somatizaciones o enfermedades psicosomáticas
• Síndromes Conversivos
 PTSD: Síntomas nucleares

Aumento de la respuesta autónomica (H)

Reexperiencia del hecho traumático (I)

Evitamiento (A)

Anestesia efectiva

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1. SNV.
2. Eje Hipotálamo-
Hipófisis-
Suprarrenal
3. Locus Coeruleus.
4. Amígdala/
hipocampo
5. Corteza prefrontal

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 gustativa auditiva olfativa
visual kinestética

Cortex
Pre-frontal TÁLAMO

HIPOCAMPO
Cognitive map Amígdala
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 Prenatal stress produces learning deficits
associated with an inhibition of neurogenesis in
the hippocampus
Lemaire,Koehl, Le Moal & Abrous Bordeaux II
Early experiences such as prenatal stress significantly influence
the development of the brain and the organization of behavior. In
particular, prenatal stress impairs memory processes but the
mechanism for this effect is not known. Hippocampal granule
neurons are generated throughout life and are involved in
hippocampal-dependent learning. Here, we report that prenatal
stress in rats induced lifespan reduction of neurogenesis in the
dentate gyrus and produced impairment in hippocampal-related
spatial tasks. Prenatal stress blocked the increase of learning-
induced neurogenesis. These data strengthen pathophysiological
hypotheses that propose an early neurodevelopmental origin for
psychopathological vulnerabilities in aging.
 TEPT
Cuadros clínicos que se estructuran
posteriormente a un trauma real o imaginario único
o repetido y de alta o baja intensidad.
Es diametralmente diferente a un cuadro por estrés
La sintomatología se estructura alrededor de 3 ejes:
alerta (arousal)
evitamiento
revivir el hecho traumático

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 TEPT en los niños
DSM IV
A - Si ha vivido o presenciado,
acontecimientos de muerte o amenazas
para su integridad física o de su entorno
(violencia familiar, abuso sexual).
– Pueden manifestarse con trast. Del
comportamiento o agitación psicomotriz

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 TEPT en los niños
DSM IV
B
– El trauma es reexperimentado
• En niños pequeños:
– juegos y dibujos repetitivos donde aparecen temas o
aspectos del trauma
– Sueños terroríficos (pesadillas)
– Dramatización del acontecimiento traumático
– Malestar psicológico intenso (Llantos, temores obsesivos,
fobias)
– Quejas psicosomáticas

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 TEPT en los niños
DSM IV
C
– Evitación ante estímulos asociados al trauma.
• El niño no cuenta lo sucedido
• Evita los lugares asociados al hecho traumático
• Temor ante el abusador
• Sensación de desapego
• Aislamiento
• Incapacidad para expresar afectos
• Sensación de culpabilidad por lo sucedido

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 TEPT en los niños
DSM IV
D
– Síntomas persistentes de aumento de
activación ( arousal )
• Dificultad para conciliar o mantener el sueño
• Irritabilidad y ataques de ira
• Menor concentración
• Hipervigilancia
• Respuestas exageradas de sobresalto

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 TEPT en los niños
DSM IV
E
– Las alteraciones se prolongan por más de 1 mes
(Criterios B-C-D)

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Cuadros clínicos de estrés post traumáticos
más habituales en niños para el DSM IV

• Estrés agudo
– Menos de 1 mes

• TEPT
– Más de 1 mes

• Trastorno Disociativo

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 Tipos de trauma

• Directo
• Indirecto
– Presencial (violencia doméstica)
– Ser testigo (accidente de tránsito)
– Ser informado (relatos)
– (virtual) imágenes por TV, PC
– Transgeneracional
– Vicario (“contagio del trauma”)
– Varios: desgaste laboral en menores

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 Síntomas comunes en los niños
• Temores obsesivos
• Alteraciones del sueño
• Hipervigilancia
• Tendencia al llanto
• Falta de entusiasmo
• Impulsividad
• Agresividad excesiva
• Conflicto con compañeros
• Quejas psicosomáticas
• Enfermedad o accidentes frecuentes

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 Abuso Infantil
• Son fenómenos con altísima incidencia socio-
cultural
• Es un concepto que continúa en evolución según
investigaciones médicas, sociológicas y
psicológicas
• Incluye negligencia, daño emocional abusos
físicos, explotación y abuso sexual.
• Es un área de abordaje escencialmente
interdisciplinaria

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 Síntomas de abuso Infantil según la edad
• Preescolar:
– Ansiedad
– Retraimiento
– Culpabilidad
– Quejas somáticas
– Alteración del apetito
– Ansiedad de separación
– Alteraciones del sueño
– Pesadillas
– Hiperactividad
– Mentiras
– Falta de confianza
– Fobias
– Regresiones
– Conocimiento sexual inapropiado para la edad
– Agresividad
– Ausencia de síntomas

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• Edad escolar y adolescentes.
– Ansiedad
– Retraimiento
– Culpabilidad
– Quejas somáticasAlteración del apetito
– Alteraciones del sueño
– Enuresis encopresis
– Pesadillas
– Depresión
– Fobias
– Dificultades escolares
– Crisis de angustia
– Mala relación con los compañeros
– Huida del hogar
– Intentos de suicidio
– Tics
– Hostilidad y negativismo
– Agresividad
– Pasividad
– Delincuencia
– Conducta sexual
– Obsesiones Psicosis
– Ausencia de síntomas

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 Secuelas
• Mayor cantidad de síntomas psiquiátricos en los adultos
• Menor cociente intelectual a expensas del CI verbal en los
test estandarizados
• Mayor incidencia de intentos de suicidio
• En los estudios neurocognitivos
• Alteraciones de la memoria, sensopercepción y conducta
• Alteraciones del eje hipotálamo-hipófiso suprarrenal-
amígdalo-hipocámpico-corteza frontal contralateral.

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 Tipos de Abuso Infantil
• Negligencia
• Abuso emocional
• Abuso físico
• Abuso sexual

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Niveles
 Memoria
Áreas de importancia
Diencéfalo:
- Núcleos :
- dorsomedial
- medial
- Hipocampo
- Núcleo dentado
- Hipocampo
- Gyrus parahipocámpico
Núcleos Amígdalinos
Talámico medial
Mediales lóbulo temporal
Hipocampo
Amigdala
• Corpus Callosum (CC)
• Lateral Ventricle (LV)
• Fornix (F, both dorsally and
ventrally)
• Body of Caudate (C)
• Stria Terminalis (ST)
• Stria Medullaris Thalami
(SMT)
• Choroid Plexus forming roof of
(3V)
• Mediodorsal N (MD)
• Lateral Dorsal N (LD)
• Internal Medullary Lamina
(IML)
• Ventral Lateral N (VL)
• External Medullary Lamina
(EML)
• Reticular Nucleus (R) and Zona
Incerta (ZI)
• External Medullary Lamina
(EML)
• Reticular Nucleus (R) and Zona
Incerta (ZI)
• Subthalamic Nucleus (STN)
• Internal Capsule (IC)
• Extreme Capsule (ExmC)
• Claustrum (Cl)
• External Capsule (ExlC)
• Putamen (P)
• Globus Pallidus (GP)
• Optic Tract (OT)
• Amygdala
• Lenticular Fasciculus (LF)
• Thalamic Fasciculus (TF,
Mammillothalamic Tract
(MTT)
• Tuber cinereum (TC,)
Estrés:  cortisol  hipocampo
(pérdida neuronal-overpruning)

Trauma  cortisol 
 aguda
 crónica
• Sensibilidad a los receptores de
glucocorticóides  atrofia hipocámpica
• Depresión resistencia a los glucocort.
No hay atrofia

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Psicofisiológicos
+++ respuesta autónoma a est.traumáticos
++ resp.est. Neutros > intens. (pérdida
discriminación).
• No habituación startle response
• Resp. debajo umbral en + sonoros
(timbre, teléfono)
Neuroanatómicos
 volumen hipocámpico
Activación áreas sensitivas y amigdala
Menor actividad de Broca
Mayor act. Hemisferio no dominante
Est., como respuesta física, emocional y no
verbal
 Janet 1889 - Emoción
intensa disocia de la
conciencia y se guarda
como sensaciones .
Cuando las emociones son
intensas, no pueden ser
integradas en una
narrativa

•Fragmentarias-
•L'Automatisme
Psychologique.

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 La naturaleza
disociartiva de la
memoria traumática es
lo que la distingue de la
experoencia cotidiana

La D. En el momento
del trauma se
transformó en el
predictor más
importante de
desarrollo de PTSD
 Freud fijación
tuviera base
biológica
Introduction to
Psychoanalysis and
the War Neuroses

Pavlov CR. Los

eventos ocurren una
y otra vez
( recuerdos)

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 gustativa auditiva olfativa
visual kinestética

Cortex
Pre-frontal TÁLAMO

HIPOCAMPO
Cognitive map Amígdala
PsyGnos – Centro de Estudios y Terapias Cognitivas
• Más temprano el trauma, mayor
elemento disociativo, más amnesia,
más temprano
• Alteración en el proceso de
plasticidad neuronal Attachment

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 Estrés-Trauma-PTSD:
Espectro clínico
Conjunto de Elementos y respuestas

•Cognitivas
•Comportamentales
•Emocionales
•Fisiológicos
•Anatómicos
-----------------------
•Sociales
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 Organización de la experiencia
auditiva Miedo

Corteza Auditiva

Hipocampo

Tálamo
auditivo
Amigdala
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 Trauma.
• 1. m. Lesión duradera producida por un
agente mecánico, generalmente externo.
• 2. m. Choque emocional que produce un
daño duradero en el inconsciente.
• 3. m. Emoción o impresión negativa,
fuerte y duradera.

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 Sucesos Vitales

Soportes Calidad
Vulnerabilidad de
Afectivos
Vida

Enfermedad

Gatillador

Zukerfeld R y Zukerfeld Z. Psicoanálisis Tercera tópica y

vulnerabilidad somática. Lugar 1999: 47.
 Stress-induced changes in cerebral metabolites,
hippocampal volume, and cell proliferation
prevented by tianeptine
Boldizsár Czéh, October 2, 2001, 10.1073 /pnas.211427898
Stress-induced structural remodeling in the adult hippocampus, involving
debranching and shortening of dendrites and suppression of neurogenesis,
provides a cellular basis for understanding the impairment of neural plasticity in
the human hippocampus in depressive illness. Accordingly, reversal of structural
remodeling may be a desirable goal for antidepressant therapy. Animals were
subjected to a 7-day period of psychosocial stress to elicit stress-induced
endocrine and central nervous alterations before the onset of daily oral
administration of tianeptine (50 mg/kg).
Chronic psychosocial stress significantly decreased in vivo concentrations of
N-acetyl-aspartate ( 13%), creatine and phosphocreatine ( 15%), and choline-
containing compounds ( 13%). The proliferation rate of the granule precursor
cells in the dentate gyrus was reduced ( 33%). These stress effects were
prevented by the simultaneous administration of tianeptine.
In stressed animals treated with tianeptine, hippocampal volume increased
above the small decrease produced by stress alone. These findings provide a
cellular and neurochemical basis for evaluating antidepressant treatments with
regard to possible reversal of structural changes in brain that have been reported
in depressive disorders.
 Prenatal stress produces learning deficits
associated with an inhibition of neurogenesis
in the hippocampus
Lemaire,Koehl, Le Moal & Abrous Bordeaux II
Early experiences such as prenatal stress significantly influence the
development of the brain and the organization of behavior. In particular,
prenatal stress impairs memory processes but the mechanism for this effect is
not known. Hippocampal granule neurons are generated throughout life and
are involved in hippocampal-dependent learning. Here, we report that prenatal
stress in rats induced lifespan reduction of neurogenesis in the dentate gyrus
and produced impairment in hippocampal-related spatial tasks. Prenatal stress
blocked the increase of learning-induced neurogenesis. These data strengthen
pathophysiological hypotheses that propose an early neurodevelopmental
origin for psychopathological vulnerabilities in aging.

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 Experimental diabetes in rats causes
hippocampal dendritic and synaptic
reorganization and increased glucocorticoid
reactivity to stress
Magariños and McEwen The Rockefeller University
Chronic stressor that produces retraction and simplification of apical dendrites
of hippocampal pyramidal neurons. Diabetes also induces morphological
changes in the presynaptic mossy fiber terminals that form excitatory synaptic
contacts with the proximal apical dendrites. One effect, synaptic vesicle
depletion, occurs in diabetes as well as after repeated stress and Cort treatment.
However, diabetes produced other MFT structural changes that differ
qualitatively and quantitatively from other treatments. Furthermore, whereas
7 d of repeated stress was insufficient to produce dendritic or synaptic
remodeling in nondiabetic rats, it potentiated both dendritic atrophy and MFT
synaptic vesicle depletion in STZ rats. These changes occurred in concert with
adrenal hypertrophy and elevated basal Cort release as well as hypersensitivity
and defective shutoff of Cort secretion after stress. Thus, as an endogenous
stressor, STZ diabetes not only accelerates the effects of exogenous stress to
alter hippocampal morphology; it also produces structural changes that overlap
only partially with those produced by stress and Cort in the nondiabetic state.
 Adptación-Eje
Limbic-hypothalamic-pituitary-adrenal axis in depression:
literature review
Twardowska K; Rybakowski J
Kliniki Psychiatrii Dorosych w Poznaniu. Psychiatr Pol, 1996 Sep,
30:5, 741-55
Increased cortisol concentration has until now been the best
documented biochemical abnormality in depression. Pathological
results of the Dexamethasone Suppression Test pointing to
hyperactivity of LHPA axis are found in about half of depressive
patients. According to most recent research, primary disturbance of
LHPA axis concerns hypothalamus and limbic system. An association
was found between disturbances of LHPA axis in depression and
immune system abnormalities in this illness. Disturbances of
serotonergic and noradrenergic neurotransmission in depression may
also partially result from LHPA axis dysfunction. Influencing LHPA
axis may underlie the mechanism of new antidepressant drug,
tianeptine. Recently, it was found that classical tricyclic antidepressant
drugs as well as electroconvulsive may also act on LHPA in regulatory
way.
 Adptación-Eje
Watanabe Y, Gould E, Daniels DC, Cameron H, McEwen BS.
Laboratory of Neuroendocrinology, Rockefeller University, New York,
NY 10021.
Repeated 6-h daily restraint stress over 21 days reduces length and number
of branch points of hippocampal CA3c pyramidal dendrites in the
hippocampal formation of adult male rats. This effect is mimicked by daily
injections of 40 mg/kg corticosterone. Daily treatment with tianeptine (15
mg/kg) prior to stress sessions or the corticosterone treatment prevented
these effects of stress or corticosterone, respectively. Tianeptine treatment
did not prevent the effects of stress to increase adrenal/body weight ratio,
nor did it prevent the effects of stress to decrease body weight gain,
indicating that its actions are not mediated solely by effects on stress-
induced secretion of corticosterone. Because tianeptine is known to
enhance neural uptake of serotonin, these results suggest that the
serotonergic system may be involved in modulating stress and
corticosterone effects on dendritic morphology.
 Adptación-Eje
Delbende C, Contesse V, Mocaer E, Kamoun A, Vaudry H.
European Institute for Peptide Research, CNRS URA 650.
The possible effect of tianeptine, a novel antidepressant agent, on the
neuroendocrine response to stress was investigated in adult male rats. Tube
restraint stress for 30 min induced a marked increase of plasma ACTH and
corticosterone. A single i.p. injection of tianeptine (10 mg/kg), 120 min
before stress caused a significant decrease of ACTH and corticosterone
levels. In order to investigate the kinetics of the effect of tianeptine, the drug
was injected at various times (from 15 min to 12 h) before restraint stress.
The inhibitory effect of tianeptine on stress-induced elevations of plasma
ACTH and corticosterone occurred from 1 to 3 h after the injection.
Administration of increasing doses of tianeptine revealed that only the
highest doses (10 and 20 mg/kg) had a significant effect on stress-evoked
stimulation of ACTH and corticosterone secretion. These results show that
the antidepressant, tianeptine, reduces the activation of the hypothalamo-
pituitary-adrenal (HPA) axis induced by restraint stress. Since depressed
patients generally exhibit an elevated cortisol level, the present data suggest
that part of the therapeutic properties of tianeptine could be accounted for
by the effect of this antidepressant to modulate the activity of the HPA axis.
 Stress facilitates classical conditioning in
males, but impairs classical conditioning in
females through ovarian hormones
Gwendolyn E. Wood and Tracey J. Shors Princeton University
Exposure to restraint and brief intermittent tailshocks facilitates associative learning of
the classical conditioned eyeblink response in male rats. Based on evidence of sex
differences in learning and responses to stressful events, we investigated sexually
dimorphic effects of a stressor of restraint and intermittent tailshock on classical eyeblink
conditioning 24 h after stressor cessation. Our results indicate that exposure to the acute
stressor had diametrically opposed effects on the rate of acquisition of the conditioned
response in male vs. female rats. Exposure to the stressor facilitated acquisition of the
conditioned response in males, whereas exposure to the same stressful event dramatically
impaired acquisition in females. We further demonstrate that the stress-induced
impairment in female conditioning is dependent on the presence of ovarian hormones.
Conditioning of stressed sham-ovariectomized females was significantly impaired
relative to the unstressed controls, whereas conditioning in stressed ovariectomized
females was not impaired. We present additional evidence that estrogen mediates the
stress-induced impairment in female acquisition. Females administered sesame oil
vehicle and then stressed were significantly impaired relative to their unstressed controls,
whereas females administered the estrogen antagonist tamoxifen prior to stress were not
impaired. In summary, these results indicate that exposure to the same aversive event can
induce opposite behavioral responses in males vs. females. These effects underscore sex
differences in associative learning and emotional responding, and implicate estrogen in
the underlying neuronal mechanism
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