Presentació

INVESTIGACIÓN EN
PSIQUIATRÍA DEL NIÑO Y DEL
ADOLESCENTE
Celso Arango M.D., Ph.D
[email protected]
25 de mayo de 2010
www.hggm.es/ua
www.cibersam.es
Criterios nosológicos en psiquiatría.
Limitaciones
“La extraordinaria diversidad de los cuadros clínicos que corresponden a un
mismo trastorno básico, demuestra que las condiciones de su puesta en
marcha deben ser muy complejas. Incluso cuando un trauma externo muy
concreto, como una herida en la cabeza, o una intoxicación, son los
responsables de la aparición de un cuadro clínico, este cuadro deja
comprobar numerosos factores históricos y personales. La estructuración
general del sistema nervioso, la predisposición del sexo, y el destino personal
del enfermo hacen, todos juntos, que este cuadro sea característicamente
personal"
Kraepelin, 1919
Concepto de enfermedad/trastorno mental
Enfermedades frente a trastornos
Desventaja biológica
Método empírico-estadístico
Definición de Trastorno Mental
El Trastorno mental viene definido no sólo por
la presencia de síntomas y/o la desviación de
la conducta normal, sino porque bajo tales
fenómenos subyacen mecanismos que
comportan una restricción de libertad. Existe
una pérdida de las posibilidades de
autorrealización y una clara interferencia en la
vida cotidiana del paciente y en sus relaciones
interpersonales.
Ciencia, filosofía y psiquiatría
“La psiquiatría se preocupa de áreas de la
experiencia y comportamientos humanos como la
emoción, deseos, voluntad y creencias con gran
carga de valores”
Bill Fulford
“Si el cerebro fuese tan simple que nosotros
pudiésemos comprenderlo, nosotros seríamos tan
simples que no lo entenderíamos”
Albert Einstein
Fundamentos de la psiquiatría
Toda la medicina clínica es parte Ciencia y parte
Arte. El Arte consiste en adaptar el conocimiento
científico a las necesidades particulares de un
paciente.
Fundamentos de la psiquiatría
“ Si la especialidad de psiquiatría resiste lo suficiente
en sus esfuerzos actuales puede encontrarse algún día
ante los trastornos de personalidad y las listas de
síntomas con la misma nostalgia con la que ahora
mira la medicina basada en el diván”
Editorial, Science 31 de octubre de 2003
Causas de los Trastornos mentales
Factores predisponentes (vulnerabilidad):
¿Por qué enferma?
Factores precipitantes o desencadenantes
¿ Por qué ahora?
Factores de mantenimiento:
¿Por qué se mantiene?
IMPACT OF MENTAL DISEASES
Maternal conditions
Respiratory infections
Malaria
Childhood diseases
Diarrhoeal diseases
HIV/AIDS
Tuberculosis
Other CD causes
Injuries
Congenital abnormalities
Musculoskeletal diseases
Perinatal conditions
Nutritional deficiencies
Other NCDs
Malignant neoplasms
Diabetes
Neuropsychiatric
disorders
Sense organ disorders
Cardiovascular diseases
Respiratory diseases
Digestive diseases
Diseases of the genitourinary system
Disease burden measured by Disability Adjusted Life
Years (DALYs)
Source: WHO 2005
Global Inability: 15-44 years
Mental illness: Main cause for Disability in Young
Adults
Anemia
Schizophrenia
Violence
Years of healthy life lost
Wars
Bipolar disorder
Self-injury
Alcohol use
Traffic accidents
Tuberculosis
Mayor depression
0
12500
25000
37500
50000
Years of life with disability adjusted; thousands
DALYs = One DALY is equal to one day of healthy life lost.
Murray Cl, Lopez AD, editors. The Global Burden of Disease. Harvard University Press, 1999.
Porcentaje estimado del porcentaje de AVAD por causa sobre el
total. España 2000. Instituto de Salud Carlos III
Enfermedades no
transmisibles
86%
Accidentes y
lesiones
8,6%
Enfermedades
transmisibles,
maternales, perinatales
y nutricionales
5,4%
Fuente: Área Salud Internacional. ISCIII
COVERED AREAS OF KNOWLEDGE IN THE
NETWORK
DEPRESSION
EPIDEMIOLOGY
CLINICAL RESEARCH
NEUROPSYCOPHARMACOLOGY
POST-MORTEM STUDY
BIOCHEMISTRY
GENETICS
NEUROIMAGING
DEPRESSION IN CHILDREN
AND ADOLESCENTS
PSYCHOGERIATRICS
SCHIZOPHRENIA
EPIDEMIOLOGY
CLINICAL RESEARCH
NEUROPSYCOPHARMACOLOGY
GENETICS
NEUROIMAGING
PSYCHOSIS IN CHILDHOOD
AND ADOLESCENCE
PSYCHOSOCIAL FACTORS
COMORBIDITY
BIPOLAR DISORDER
EPIDEMIOLOGY
CLINICAL RESEARCH
NEUROPSYCOPHARMACOLOGY
GENETICS
NEUROIMAGING
NEUROPSYCHOLOGY
PSYCHOSIS IN CHILDHOOD
AND ADOLESCENCE
PSYCHO-EDUCATION
FUNCTIONAL ADAPTATION
Paus et al., Nature Neuroscience 2008
Salud Mental Infanto-Juvenil
Unidad de Adolescentes
UNIDAD DE ADOLESCENTES
DPTO. PSIQUIATRIA
H. G .U. G. MARAÑON
www.hggm.es/ua/
www.cibersam.es
ASISTENCIA, INVESTIGACIÓN, DOCENCIA
INVESTIGACIÓN
CLÍNICA
AMBULATORIO
AMI-TEA
INGRESO
HOSPITALARIO
PEP
PRIMEROS EPISODIOS
PSICÓTICOS, PEP
NEUROPSICOFARMACOLOGÍA
DEL DESARROLLO
COGNICIÓN EN TRASTORNOS
DEL NEURODESARROLLO
NEUROBIOLOGÍA
DE LOS TGD
GENÉTICA
TGD
BIOQUÍMICA
TRATAMIENTO GRUPAL
NEUROPSICOLOGÍA
ADOLESCENTES
ANTIPSICÓTICOS
INFANCIA
ADOLESCENCIA
FAMILIARES
PEP
ALTO RIESGO
NEUROIMÁGEN
ANTIOXIDANTES
REHABILITACIÓN
COGNITIVA
INTRODUCTION
The first episode of psychosis
is a critical period in the course
of each patient’s illness and
perhaps the most important
opportunity for therapeutic
intervention
Even at Conversion to Psychosis might be a critical point
Adapted from Pantelis C et al. Lancet. 2003;361:281
Why to study EOP:
• Early-onset psychotic disorders (EOP, onset prior to 18 years) are
more severe and disabling than those beginning in adulthood
(Ballageer et al. 2005; Volkmar, 1996)
• EOP has usually an insidious onset with symptomatic overlap
between different diagnoses, starting during a crucial period in
development (Menezes and Milovan, 2000)
• Although EOP can be diagnosed with the adult criteria, specific
ethiopatological, prognostic, diagnostic and treatment features
need to be further studied (Arango et al, 2004)
• Few studies of first-episode EOP: ethical concerns, difficult
recruitment…Previous studies: assessment and sample
limitations (Nicolson et al, 2000; McKenna et al.1994; McClellan et al. 2002)
Advantages of Studying First- episode EOP
• Methodological advantages:
– less confounding variables (adverse life events,
exposure to drugs or medications, effect of
progression of illness)
– more homogeneous sociodemographic factors
(most attend compulsory school)
– higher genetic loading
• Study of EOP may clarify etiology and
prognosis of the different psychotic disorders
Relevance of findings in normal brain
development for the
neurodegenerative vs.
neurodevelopmental
hypotheses
Thompsom et al., 2001
Diagnostic stability of first-episode EOP
DSM-IV diagnoses
Follow-up
Positive predictive value (%)
Baseline
(N=24)
1-yr FU
(N=24)
2-yr FU
(N=23)
B to 1-yr FU
1-2 yr FU
B to 2-yr FU
Schizophrenia
16.7%
33.3%
33.3%
100
100
100
Bipolar Disoder
29.2%
37.5%
33.3%
71.4
100
71.4
Schizoaffective
disorder
8.3%
8.3%
8.3%
50.0
100
50.0
Psychosis NOS
25.0%
8.3%
4.2%
16.7
50
16.7
Schizophreniform/
brief psychosis
16.7%
8.3%
12.5%
50.0
100
50.0
Depression with
psychotic features
4.2%
4.2%
4.2%
100
100
100
-Diagnostic stability was remarkably high for schizophrenia,
moderate for bipolar disorder, and low for other diagnoses
Fraguas et al. Child Psychiatry Hum Dev 2008; 39(2):137-45
INTRODUCTION
Changes in neurocognitive outcomes over 2-years in first-episode
EOP and controls
LONGITUDINAL ASSESSMENT
EOP (N=22)
Controls (N=29)
Attention
F= 5.74
p= 0.02*
F= 3.91
p= 0.05
Working
memory
F= 0.25
p= 0.61
F= 1.96
p= 0.17
Executive
function
F= 3.01
p= 0.09
F= 6.35
p= 0.01
Learning
& memory
F= 15.15
p= 0.001*
F= 0.80
p= 0.37
Global
F= 13.25
p= 0.002*
F= 9.77
p= 0.004
* In EOP, significance disappeared when controlling for changes on
symptomatology over the FU period
Mayoral et al. Eur Psychiatry 2008; 23(5):375-83
NEURODEVELOPMENT
Actual developmental theories:
a subtle disease process affects critical circuits
during early development..…remains clinically
silent until the normal maturation of the
affected structures brings the “lesion” to the
symptomatic stage.
NEURODEVELOPMENT
* p ≤ 0.01 schizophrenia vs bipolar
Parellada et al 2006
NEURODEVELOPMENT
Desarrollo premórbido en
esquizofrenia de inicio muy temprano
Lenguaje
49 pacientes (<12)
Datos retrospectivos
Motor
Social
Area de alteración en el
desarrollo
Educational
Nicolson et al., 2000
NEURODEVELOPMENT
At least one psychomotor developmental deviance.-
%
p=0.069, schizophrenia vs bipolar
Parellada et al 2006
NEURODEVELOPMENT
IQ and academic achievement.-
**
*
**
*
*p<0.05 vs controls
**p<0.001 vs controls
Corrected by parents´ studies
patients vs controls achievement, OR=4
Parellada et al 2006
NEURODEVELOPMENT
Abnormal dermatoglyphic patterns.
Dissociations.-
NEURODEVELOPMENT
Controls
(n=41)
Patients
(n=39)
5 (12.2)
9 (23.7)
Controls
Schizoph.
Bipolar
Other
Males (n=57)
4 (14.8)
6 (42.9)*
2 (22.2)
1 (14.3)
Females (n=21)
1
0
0
0
*OR=4.32, p=0.04, schizophrenia vs control
Dissociations.• 13/14 dissociations were present in males (p=0.048)
• None of the six schizophrenic patients with dissociations had a family history of psychosis (Fisher exact 0.093
bilateral, 0.058 unilateral)
NEURODEVELOPMENT
Neurological soft signs.Mean
S.D.
CONTROLS
(n=47)
PATIENTS
(n=49)
Pts. vs
Controls
Between
groups
Sch. vs
controls
Tot. NES
11.98
6.11
25.69
9.35
p<0.001
ns
p<0.001
Sen. Int
2.68
2.10
5.22
2.75
p<0.001
ns
p=0.001
SCMT
1.47
1.73
4.73
3.45
p<0.001
ns
p<0.001
Motor Coord
2.06
1.48
3.78
2.2
p<0.001
ns
p=0.02
Others
5.77
3.08
11.96
4.31
p<0.001
ns
p<0.001
At least 2
NSS
71.1
95.9
p<0.01
ns
p=0.07
All patients´ groups differed independently from controls
Mayoral et al 2009
NEURODEVELOPMENT
Changes in neurocognitive outcomes over 2-years in first-episode
EOP and controls
LONGITUDINAL ASSESSMENT
EOP (N=22)
Controls (N=29)
Attention
F= 5.74
p= 0.02*
F= 3.91
p= 0.05
Working
memory
F= 0.25
p= 0.61
F= 1.96
p= 0.17
Executive
function
F= 3.01
p= 0.09
F= 6.35
p= 0.01
Learning
& memory
F= 15.15
p= 0.001*
F= 0.80
p= 0.37
Global
F= 13.25
p= 0.002*
F= 9.77
p= 0.004
* In EOP, significance disappeared when controlling for changes on
symptomatology over the FU period
Mayoral et al. Eur Psychiatry 2008; 23(5):375-83
NEURODEVELOPMENT
Brain volume differences between first-episode EOP
and controls at baseline assessment
-First-episode EOP (N=23) and healthy controls (N=37)
-Duration of illness 13.91 (12.74) weeks
Male patients showed:
-Larger volumes in overall CSF (p = .044), and left
frontal
(p = .024), and right parietal sulci CSF (p = .042)
-Lower volumes of GM in the right frontal (p = .012)
and
left frontal (p = .006) lobes
No significant differences between different EOP
diagnoses
Moreno et al. J Am Acad Child Adolesc Psychiatry 2005; 44:1151-1157
NEURODEVELOPMENT
Structural brain abnormalities in 92 children and
adolescents with a recent-onset first episode of
psychosis, and 94 healthy controls. Baseline evaluation
In male patients:
- GM volume was reduced in: whole brain (E.S.=0.77),
frontal (0.98 and 0.79 in right and left) and parietal
lobes (0.61 and 0.42).
- Total CSF volume was increased (E.S.=0.81).
- CSF was also increased in frontal, temporal, and
right parietal lobes.
Bipolar patients showed fewer differences than other
diagnoses.
Reig et al, in press
Results (II)
NEURODEVELOPMENT
• Are local gray matter volumes different between
patients who eventually develop schizophrenia or
bipolar disorder?
•
Schizo – controls:
Medial frontal
•
Schizo – controls:
Left middle frontal
•
Bipolar – controls:
Medial frontal
•
Others – controls:
Insula
Janssen et al JAACAP 2009
Even ‘early’ might already be too Late!
Normal
Subjects
Subjects With
Schizophrenia
Difference
P Value
.00002
.0001
.0005
.001
.005
.01
.05
Adapted from: Thompson PM, et al. Proc Natl Acad Sci USA. 2001;98(20):11650-11655.
Results (I)
Gray matter volume abnormalities be detected in patients
with recent-early-onset first episode psychosis?
•
Medial frontal cortex
•
Left middle frontal gyrus
•
•
Left insula
All brains in standard space, permitting localization of blobs.
JAACAP 2009
Results (II)
• Are local gray matter volumes different between
patients who eventually develop schizophrenia or
bipolar disorder?
•
Schizo – controls:
Medial frontal
•
Schizo – controls:
Left middle frontal
•
Bipolar – controls:
Medial frontal
•
Others – controls:
Insula
JAACAP 2009
Progression of brain volume changes in firstepisode EOP and controls over 2-years
SIGNIFICANT RESULTS:
1.2%
2.9%
FRONTAL GRAY MATTER
0.7%
2.0%
MALES
Patients
(n=16)
Controls
(n=21)
Time x group p=0.02
Group P p<0.01
Group C p<0.05
Time x group p=0.02
Group P ns
Group C ns
In the frontal lobe, rate of GM volume loss was higher in EOP patients (L: 2.9 and R: 2.0%) than in Controls
(L: 1.2 and R: 0.7%)
Reig et al.. Schizophrenia Bulletin. 2009
Unpublished data
Left Frontal GM Volume
FEMALES
MALES
PAT VS CONT
*
BASAL
PAT VS CONT
*
% CHANGE IN
2YR
males:
p = 0.0405
females: ns
males:
p = 0.0254
females
p= 0.0240
* ANCOVA for differences between PAT and CONT using age and scanner as cofactors of no interest
Rate of GM volume loss within the 2 yr follow-up was higher in
patients (-3.3% ; -3.2% -for males and females respectively) than in
controls (-0.7% ; -0.3% -for males and females respectively).
Unpublished data
Left Frontal CSF Volume
FEMALES
MALES
PAT VS
CONT *
BASAL
males:
p = 0.0139
females: ns
PAT VS
CONT *
% CHANGE
IN 2YR
males:
p = 0.0050
Females
p= 0.0195
* ANCOVA for differences between PAT and CONT using age and scanner as cofactors of no interest
(Males) Significant increase of CSF volume within the 2 yr follow up (6.5% ; 5.4% -for
males and females respectively), than in controls (2.3% ; 2.6% -for males and
females respectively).
2 year followup
spectroscopy
study
Longitudinal
change
Controls = 2.2
%
Patients = 0.7
%
Unpublished data
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à|ááâxáÊ
Emil Kraepelin, The manifestations of Insanity, 1920
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Emil Kraepelin, The manifestations of Insanity, 1920
RELATIONSHIP BETWEEN OXIDATIVE CELL DAMAGE
AND BRAIN VOLUMES
CONTROL
N=78
SCHIZOPH
N=26
BIPOLAR
N=14
Intracranial volume
B=-0.008, t=-0.647
(C.I. 95% B: -0.031 - 0.016)
P=0.520
B=0.021, t=-0.644
(C.I. 95% B: -0.039 - 0.080)
P=0.478
B=-0.057, t=-1.464
(C.I. 95% B: -0.148 - 0.035)
P=0.187
Frontal grey matter
B=0.003, t=0.321
(C.I. 95% B: -0.015 - 0.021)
P=0.749
B=-0.013, t=-0.705
(C.I. 95% B: -0.050 - 0.025)
P=0.490
B=-0.004, t=-0.161
(C.I. 95% B: -0.070 - 0.062)
P=0.877
Parietal grey matter
B=-0.005, t=-0.644
(C.I. 95% B: -0.022 - 0.011)
P=0.521
B=-0.004, t=0.252
(C.I. 95% B: -0.040 - 0.032)
P=0.804
B=-0.027, t=-1.070
(C.I. 95% B: -0.089 - 0.035)
P=0.326
Temporal grey matter
B=0.006, t=0.690
(C.I. 95% B: -0.011 - 0.022)
P=0.492
B=-0.026, t=-0.966
(C.I. 95% B: -0.082 - 0.030)
P=0.347
B=0.073, t=1.532
(C.I. 95% B: -0.043 - 0.189)
P=0.176
Total sulcal CSF
B=0.017, t=0.851
(C.I. 95% B: -0.022 - 0.056)
P=0.398
B=0.006, t=0.146
(C.I. 95% B: -0.074 - 0.085)
P=0.886
B=-0.015, t=-0.187
(C.I. 95% B: -0.215 - 0.185)
P=0.858
Lateral ventricles
B=0.003, t=0.076
(C.I. 95% B: -0.071 - 0.077)
P=0.940
B=0.239, t=3.863
(C.I. 95% B: -8.141 - -1.997)
P=0.001
B=0.021, t=0.098
(C.I. 95% B: -0.501 - 0.543)
P=0.925
±
Regression analyses included brain volumes as dependent variables, and levels of LOOH, total intracranial volume (except for
intracranial volume), age, gender, daily smoking status (as dichotomous variable yes/no), IQ, psychopathology (as total PANSS
score; only for EOP patients), and time since onset of psychotic symptoms (only for EOP patients) as covariables.
Significant value (P<0.0033, after Bonferroni correction) are in boldface.
For statistical analyses brain volumes and LOOH were log-transformed
Fraguas et al submitted
Clusters of cortical thinning in first episode early onset
schizophrenia
Biol Psych 2009
Outcome and Progressive
Brain Changes
Ventricle / Brain ratio
Ventricle Change Over 5 Years
1.7
Scan date
1.6
Year 1
Year 5
1.5
1.4
1.3
1.2
Left
Ventricle
Right
Ventricle
Kraepelinian
Davis KL et al. Biol Psychiatry. 1998;43:783-793.
Left
Ventricle
Right
Ventricle
Non-Kraepelinian
EXPLORATORY ANALYSIS FOR
PROGNOSTIC PREDICTION
r = 0.769
(p = 0.0003)
• Poor sensory integration: thalamus
BJP 2009
• Poor motor coordination and
sequencing of complex motor
caudate nucleus
poor
acts:
• We generate a t-map at t=3.22 (p<0.001) and after use small volume correction to
test only voxels within ROIs.
• Clusters of any size containing a voxel of p<0.05 corrected are considered
statistically significant
BJP 2009
Results – shape analysis – groupwise
Shape differences in the thalamus, colored areas (not grey) indicate sigificant
differences in thalamic shape
•
Left
Right
SubmItted 2010
Gyral and sulcal based cortical metrics: What
constitutes the frontal lobe differences between patients
Sulcal span
and controls?
A
Superior
frontal
gyrus
Superior
frontal
sulcus
Sulcal depth
Lateral
Left
Left
Frontal
- Anterior
C
C
Kochunov et al 2008
Sulcal depth
• Gyrus:
• Thickness, surface, gyrification
• Sulcus:
• Sulcal span and sulcal depth
• Male patients have less thickness, surface and gyrification in superior frontal gyrus
• Male patients have larger sulcal span and shallower sulcal depth in superior frontal
gyrus
Longitudinal neuroimaging: 0-25 years
What questions can we answer?
I. Changes in connectivity
Diffusion tensor imaging (DTI) allows for assessment of
white matter connectivity.
The pediatric use of antipsychotics has
dramatically increased
• In 2002, 93% of all antipsychotics were atypicals.
• In 2004, 99% were atypicals.
Cognition: Tasks grouped in cognitive domains
Z-scores
(SD)
Executive functions
2.0
1.5
1.0
0.5
0.0
-0.5
-1.0
-1.5
Quetiapine
Olanzapine
-2.0
Attention Working memory Executive Verbal fluencyVisuoconstructiveLearning and
functioning
ability
memory
•
•
No cognitive improvement was observed in any of the groups
No differences between groups
Robles et al 2009
Change in weight over time by treatment
group olanzapine/quetiapine
WEIGHT
80.00
75.00
WEIGHT
70.00
quetiapine
65.00
olanzapine
60.00
55.00
50.00
basal
day 7 day 15 day 30 day 90
day
180
Arango et al, 2009
Metabolic side effects in young people treated with
second-generation antipsychotics
The aim of this study was to evaluate
metabolic side effects in children and
adolescents after 6 months of treatment with
3 different second-generation antipsychotics
(RIS, OLZ, QTP)
Sample: 66 patients
antipsychotic-naïve (n=25) or
quasi-naïve patients* (n=41).
• Mean age=15.2 (SD=2.9), range 4-18 yr.
• 66.7% male
• 51.5% schizophrenia or other psychosis
No baseline differences between treatment
groups
*Quasi-naïve patients: fewer than 30 days with any
antipsychotic
Fraguas et al, J Clin Psychiatry 2008
Metabolic side effects in young people treated with
second-generation antipsychotics
At risk for adverse health outcome
BMI≥95 or
BMI>85 +
•hypertension >90th or
•fasting cholesterol≥ 200mg/dl or
•LDL cholesterol > 130 or
•HDL cholesterol <40 or
•TGC≥150 or
•Hyperglycaemia ≥110 mg/dl)
Significant weight gain
Defined as > 0.5 increase in body
mass index (BMI) z-score (adjusted
for age and gender) at 6 months
RIS: 50%
OLZ: 75%*
QTP: 29%
At risk adverse
Baseline
6 month
RIS
OLZ
QTP
22.7%
15.0%
12.5%
36.4%
60.0%*
20.8%
* p<0.05
• Total cholesterol increased in patients
receiving olanzapine (p=0.047) and quetiapine
(p=0.016).
•Treatment with quetiapine was associated
with a decrease in free thyroxin (p=0.011).
*p<0.01
Fraguas et al, J Clin Psychiatry 2008
Abnormal Involuntary Movements
-60 children and adolescents who had taken antipsychotic medication for
less than one month and 66 who had been receiving treatment with
antipsychotic for more than 12 months.
- Age=15.62 (SD=1.85).
Short-term exposure
Long-term
exposure
Statistics
Total dyskinesia score
2-9
27(45%)
52 (78.8%)
χ²=10.241
p=0.002
Total dyskinesia score
10-19
0
5 (7.57)
χ²=10.241
p=0.002
Total Parkinson score
2-9
20 (33.3%)
52 (78.8%)
χ²=5.385
ns
Total Parkinson score
12-14
0
2 (3.03%)
χ²=5.385
ns
Laita et al, 2007
Endocrine Side Effects
ENDOCRINE SIDE EFFECTS
NORMAL RANGE
SHORT-TERM
LONG-TERM EXPOSURE
Prolactin
2-20 ng/dL
34.2 (SD 22.6)
25.8 (SD 24.4)
Glycosylated hemoglobin
3-6.5% total Hb
4.6 (SD 0.3)
4.7 (SD 0.37)
Thyroid hormone T4
0.8-2 ng/dL
1.5 (SD 0.9)
1.4 (SD 1.3)
TSH
0.5-4.5 ng/dL
1.8 (SD 0.8)
2.8 (SD 1.2)
-Prolactin levels were elevated in 78.6% of the
sample in short-term group, and in 48.5% in the
longer-term group (χ²= 7.892, p=0.019)
-In the longer-term group, treatment with
risperidone correlated with prolactin levels
(p=0.021).
Laita et al, 2007
DESARROLLO DEL ENSAYO
Fase 1 (8 semanas)
Grupo A: EFA-3(DHA+EPA+VIT E)
Firma CI
s0
s2
s4
s6
s8
Lavado (2 semanas)
Fase 2 (8 semanas)
Grupo B: EFA-3 (DHA+EPA+VIT E)
s10
s12
s14
s16
s18
Selección
Fase 2 (8 semanas)
Grupo A: Placebo
( aceite inerte+ VIT E)
Fase 1 (8 semanas)
Grupo B: Placebo
( aceite inerte+ VIT E)
Firma CI
s0
s2
s4
s6
s8
s10
s12
s14
s16
s18
ECG
Analítica, constantes vitales,
medidas antropométricas
CGI, ABC, SRS, FADS,
MEDFICTS, Omega 3
fatty acid inventory, UKU
Analítica, constantes vitales,
medidas antropométricas
CGI, ABC, SRS, FADS,
MEDFICTS, Omega 3
fatty acid inventory, UKU
Cannabis
Incremento en el uso de cannabis en
adolescencia
Estudios longitudinales demuestran por primera
vez relación causa- efecto en la relación
consumo de cannabis-psicosis
El uso de cannabis se asocia con menor edad de
inicio de los síntomas psicóticos, más síntomas
positivos en el momento basal y mayor mejoría si
cesa el consumo a los 6 meses después del
episodio.
Baeza et al, 2009
Psicoeducación
•
Intervención de tipo psicoeducativo comparada con “intervención no
estructurada”
•
Dirigida a padres y pacientes adolescentes con primeros episodios
psicóticos, en grupos separados
•
En ambos grupos, 3 sesiones individuales y 12 grupales que se
añaden al tratamiento habitual.
•
Objetivos:
1.
2.
3.
Comparar los cambios en la evolución de la enfermedad (recaídas…)
Comparar los cambios en variables familiares (carga familiar…)
Estimación del coste-beneficio
Baeza et al, 2009
Heredabilidad de los trastornos mentales
Trastorno
Heredabilidad (%)
Trastorno
Heredabilidad (%)
Alzheimer
Alcoholismo
Esquizofrenia
Depresión
mayor
T Bipolar
T Pánico
> 60
50 - 60
60 - 89
70 - 89
33 - 75
45
TOC
Rasgos
personalidad
Autismo
TDAH
Gilles Tourette
Suicidio
45 - 65
40 - 50
90
80 - 90
90
45
Factores de riesgo para el desarrollo de
esquizofrenia
Familiar esquizofrénico
•
•
•
•
•
•
Migración
Estrés social
Ciudad
Drogas (cannabis)
Obstétricos
Fecha de nacimiento
0
10
Murray, 2002
20
30
40
50
Genéticos
Sociales
Tóxicos
Lesionales
¿Infecciosos?
Otros
Estudios familiares en esquizofrenia
Parentesco con el paciente esquizofrénico
Genes compartidos:
0% población general
12,5% familiar de tercer grado
25% familiar de segundo grado
50% familiar de primer grado
100% gemelo monocigótico
Riesgo de desarrollar esquizofrenia
Gottesman, 1991
SGENE consortium
Genome-wide scan for susceptibility genes
conferring risk of schizophrenia
Basic-Clinical colaboration
Basic Research
New therapeutic targets
Data processing
Diagnosis aid
Training in neuroscience
Clinical Investigation
Predisposición
genética
Fenotipo
vulnerable
Hiperactividad
eje HPA/CRF
Traumas o
acontecimient
os vitales
diarios en
edad adulta
Acontecimientos
vitales negativos
en la infancia
(estrés)
Hipocampo:
Alteración de la
neurogénesis
Neurotoxicidad
Locus Ceruleus:
Hiperactividad NA
Vunerabilidad al estrés
y acontecimientos vitales
Alteraciones biológicas
Cambios emocionales y conductuales
CONCLUSIONES
• Es el producto de las patologías cerebrales
diferentes o más complejo
• Estudio de enfermedades complejas:
marcadores de riesgo
• Investigación colaborativa traslacional y
multicéntrica
ACKNOWLEDGEMENTS
Clinical Psychiatrists:
Mara Parellada
Dolores Moreno
Carmen Moreno
Mar Alvarez
Cloe Llorente
Ana Espliego
Nuria Martínez
Miguel Moreno
Psychologists:
María Mayoral
Jessica Merchán
Marta Leiva
Marta Rapado
Research
Nurses:
Marisa Giráldez
Cecilia Tapia
Data Manager:
Jose de Arriba
CAFEPS group
Patients and their
families
Adolescent Unit, Department of Psychiatry
http://www.hggm.es/ua/
www.cibersam.es