Applied pha macogene ics o
p edic esponse o ea men
o fi s psycho ic episode:
s udy p o ocol
Se gi Mas
1,2,3
*, Lau a Julià
2
, Manuel J. Cues a
3,4,5
,
Benedic o C espo-Faco o
3,6,7,8
, Ja ie Va
´zquez-Bou gon
3,9,10
,
Ca los Spuch
3,11
, Ana Gonzalez-Pin o
3,12
, Angela Ibañez
3,13
,
Judi h Usall
14,15
, C is ina Rome o-Lo
´pez-Albe ca
3,16
,
Ana Ca alan
3,17,18,19,20
, Anna Mane
´
3,21,22,23
and Miquel Be na do
2,3,24,25
1
Depa men o Clinical Founda ions, Pha macology Uni , Uni e si y o Ba celona, Ba celona, Spain,
2
Ins i u d’in es igacions Biomèdiques Augus Pi i Sunye (IDIBAPs), Ba celona, Spain,
3
Cen o de
In es igación Biomédica en Red en Salud Men al (CIBERSAM), Mad id, Spain,
4
Depa amen o de
Psiquia ı
´a, Hospi al Uni e si a io de Na a a, Pamplona, Spain,
5
Ins i u o de In es igacio
´n Sani a ia de
Na a a (IdiSNA), Pamplona, Spain,
6
Unidad de Ges ión Clínica de Salud Men al, Hospi al Uni e si a io
Vi gen del Rocı
´o, Se illa, Spain,
7
Ins i u o de Biomedicina de Se illa (IBiS), Hospi al Uni e si a io VI gen
del Rocio/Cen o Supe io de In es igaciones Cine íficas (HUVR/CSIC)/Uni e sidad de Se illa,
Se ille, Spain,
8
Depa men o Psychia y, Uni e sidad de Se illa, Se ille, Spain,
9
Depa amen o de
Psiquai ia, Ma que
´s de Valdecilla Uni e si y Hospi al –IDIVAL, San ande , Spain,
10
Depa amen o de
Medicina y Psiquia ia, Uni e sidad de Can ab ia, San ande , Spain,
11
T ansla ional Neu oscience
Resea ch G oup, Galicia Su Heal h Resea ch Ins i u e (IIS-Galicia Su ), Se izo Galego de Saúde/
Uni e sidad de Vigo (SERGAS-UVIGO), Vigo, Spain,
12
BIOARABA, Depa men Psychia y, Hospi al
Uni e si a io Ala a, Uni e sidad del Paı
´s Vasco/Euskal He iko Unibe si a ea Vi o ia (UPV/EHU),
Vi o ia, Spain,
13
Depa men o Psychia y, Hospi al Uni e si a io Ramo
´n y Cajal, Uni e sidad de Alcala
´,
Ins i u o Ramón y Cajal de In es igación Sani a ia (IRYCIS), Mad id, Spain,
14
Ins i u de Rece ca San
Joan de De
´u, Esplugues de Llob ega , Ba celona, Spain,
15
Cen e de Salu Men al, Pa c Sani a i San
Joan de De
´u, San Boi de Llob ega , Ba celona, Spain,
16
Depa amen de Ciències Expe imen als i de
la Salu , Depa men o Psychology, Uni e si y o Cadiz, Cádiz, Spain,
17
Psychia y Depa men ,
Basu o Uni e si y Hospi al, Osakide za, Basque Heal h Se ice, Bilbao, Spain,
18
Biobizkaia Heal h
Resea ch Ins i u e, OSI Bilbao-Basu o, Bilbao, Spain,
19
Neu oscience Depa men , Uni e si y o he
Basque Coun y, Leioa, Spain,
20
Depa men o Psychosis S udies, Ins i u e o Psychia y, Psychology
& Neu oscience, King’s College London, London, Uni ed Kingdom,
21
Ins i u de Salud Men al, Hospi al
del Ma , Ba celona, Spain,
22
Hospi al del Ma Resea ch Ins i u e, Ba celona, Spain,
23
Uni e si a
Pompeu Fab a (UPF), Ba celona, Spain,
24
Ba celona Clinic Schizoph enia Uni , Hospi al Clı
´nic de
Ba celona, Ba celona, Spain,
25
Depa amen de Medicina, Ins i u de Neu ociències (UBNeu o),
Uni e si a de Ba celona (UB), Ba celona, Spain
The applica ion o pe sonalized medicine in pa ien s wi h fi s -episode psychosis
(FEP) equi es ools o classi yingpa ien sacco ding o hei esponse o
ea men , conside ing bo h ea men e ficacy and oxici y. Howe e , se e al
limi a ions ha e hinde ed i s ansla ion in o clinical p ac ice. He e, we desc ibe
he a ionale, aims and me hodology o Applied Pha macogene ics o P edic
Response o T ea men o Fi s Psycho ic Episode ( he Fa maPRED-PEP p ojec ),
which aims o de elop and alida e p edic i e algo i hms o classi y FEP pa ien s
acco ding o hei esponse o an ipsycho ics, he eby allowing he mos
app op ia e ea men s a egy o be selec ed. These p edic o s will in eg a e,
h ough machine lea ning echniques, pha macogene ic (measu ed as polygenic
isk sco es) and epigene ic da a oge he wi h clinical, sociodemog aphic,
en i onmen al, and neu oana omical da a. To do his, he Fa maPRED-PEP
p ojec will use da a om wo al eady ec ui ed coho s: he PEPS coho om
he “Geno ype-Pheno ype In e ac ion and En i onmen . Applica ion o a
F on ie s in Psychia y on ie sin.o g01
OPEN ACCESS
EDITED BY
Michal Assa ,
Olin Neu opsychia y Resea ch Cen e
(ONRC), Uni ed S a es
REVIEWED BY
Je ey Bishop,
Uni e si y o Minneso a Twin Ci ies,
Uni ed S a es
Jacopo Sapienza,
San Ra aele Scien ific Ins i u e (IRCCS), I aly
*CORRESPONDENCE
Se gi Mas
[email p o ec ed]
RECEIVED 17 Sep embe 2024
ACCEPTED 10 Decembe 2024
PUBLISHED 07 Janua y 2025
CITATION
Mas S, Julià L, Cues a MJ, C espo-Faco o B,
Va
´zquez-Bou gon J, Spuch C,
Gonzalez-Pin o A, Ibañez A, Usall J,
Rome o-Lo
´pez-Albe ca C, Ca alan A,
Mane
´A and Be na do M (2025) Applied
pha macogene ics o p edic esponse
o ea men o fi s psycho ic
episode: s udy p o ocol.
F on . Psychia y 15:1497565.
doi: 10.3389/ psy .2024.1497565
COPYRIGHT
©2025Mas,Julià,Cues a,C espo-Faco o,
Va
´zquez-Bou gon, Spuch, Gonzalez-Pin o,
Ibañez, Usall, Rome o-Lo
´pez-Albe ca, Ca alan,
Mane
´andBe na do.Thisisanopen-access
a icle dis ibu ed unde he e ms o he
C ea i e Commons A ibu ion License (CC BY).
The use, dis ibu ion o ep oduc ion in o he
o ums is pe mi ed, p o ided he o iginal
au ho (s) and he copy igh owne (s) a e
c edi ed and ha he o iginal publica ion in
his jou nal is ci ed, in acco dance wi h
accep ed academic p ac ice. No use,
dis ibu ion o ep oduc ion is pe mi ed
which does no comply wi h hese e ms.
TYPE S udy P o ocol
PUBLISHED 07 Janua y 2025
DOI 10.3389/ psy .2024.1497565
P edic i e Model in Fi s Psycho ic Episodes”s udy ( he PEPs s udy om he
Spanish abb e ia ion) (N=335) and he PAFIP coho om “Clinical P og am on
Ea ly Phases o Psychosis”(PAFIP om he Spanish abb e ia ion) (N = 350). These
coho s will be used o c ea e he p edic o , which will hen be alida ed in a new
coho , he Fa maPRED coho (N = 300). The Fa maPRED-PEP p ojec has been
designed o o e come se e al o he limi a ions iden ified in pha macogene ic
s udies in psychia y: (1) he sample size; (2) he pheno ype he e ogenei y and i s
defini ion; (3) he complexi y o he pheno ype and (4) he gende pe spec i e.
The global each o he Fa maPRED-PEP p ojec is o acili a e he e ec i e
deploymen o p ecision medicine in na ional heal h sys ems.
KEYWORDS
pe sonalized medicine, an ipsycho ic, p edic ion, psychosis, Pha macogene ics
In oduc ion
Schizoph enia (SZ) is he mos pa adigma ic psycho ic diso de .
The cou se o he illness is o en ch onic and highly a iable,
causing a significan loss o quali y o li e o he pa ien and hei
amily membe s (1). I also has a high cos o socie y, accoun ing
o 10% o he global bu den o men al diso de s in Eu ope (2).
The e is g ea a iabili y in he e ficacy o an ipsycho ic d ugs (APs)
in he ea men o SZ as well as in he suscep ibili y o pa ien s o
he side e ec s o hese d ugs. On a e age, be ween 20% and 30% o
pa ien s do no espond app op ia ely o AP ea men and less han
40% achie e symp om emission (3), wi h a 70% ea men
discon inua ion a e. This leads o elapses ha en ail new
admissions, he eby wo sening he p ognosis, nega i ely a ec ing
he pa ien ’s quali y o li e, and educing li e expec ancy (4).
Fu he mo e, app oxima ely 30% o pa ien s de elop ea men -
esis an SZ (TRS). I is essen ial o elucida e he unde lying
pa hophysiology o TRS o iden i y bioma ke s o i s ea ly
de ec ion and ea men . As an example, plasma le els o
me aboli es in ol ed in he Kynu enine pa hway, a he c oss oad
be ween neu oinflamma ion and glu ama e gic neu o ansmission,
has been p oposed as bioma ke o TRS (5). Howe e , he a es o
long- e m eco e y o fi s -episode psychosis (FEP) a e mo e
a o able since abou 51% o pa ien s may achie e ei he
symp oma ic, unc ional, and pe sonal eco e y (6). Selec ing he
bes compound o each pa ien is a challenging p ocedu e (7), and
i s selec ion, un o una ely, la gely elies on clinical expe ience and
a ial-and-e o s a egy ha exposes he pa ien s o a highe isk o
ad e se eac ions, p olongs he eco e y ime, and wo sens he
long- e m esponse (8).
In his con ex , he sea ch o bioma ke s o selec he mos
sui able AP o each pa ien in he ea ly s ages is a p io i y a ea in
psychia y (9). Pha macogene ics (PGx) has become one o he
main ools in his sea ch o bioma ke s (3). Howe e , PGx esul s
a e cha ac e ized by a lack o eplicabili y, hus limi ing hei
ansla ion in o clinical p ac ice. These s udies ha e elied on he
knowledge o pha macokine ic and/o pha macodynamic
p ocesses. The pha macokine ic s udies ha e shown he mos
p omising esul s o clinical implemen a ion as he gene ic
a iabili y in me abolism- ela ed genes explains a significan
pe cen age o he a iabili y in he plasma le els o some APs.
Geno yping hese genes can be e y use ul in imp o ing APs
e ficacy and ole abili y (10). In his ega d, in e na ional
guideline g oups, such as he Du ch Pha macogene ics Wo king
G oup (DPWG), ha e published pha macogene ic guidelines o
gene-d ug in e ac ions in ol ing CYP2D6, CYP3A4, and CYP1A2
wi h an ipsycho ics (11), while he Clinical Pha macogene ics
Implemen a ion Conso ium (CPIC) is de eloping simila
guidelines (h ps://cpicpgx.o g/p io i iza ion-o -cpic-guidelines/).
Addi ionally, egula o y agencies like he Food and D ug
Adminis a ion (FDA) ha e iden ified 41 pha macogenomic
bioma ke s ele an o psychia y in d ug labeling (h ps://
www. da.go /d ugs/science-and- esea ch-d ugs/ able-
pha macogenomic-bioma ke s-d ug-labeling). By con as , he
pha macodynamic s udies ha e been a ely eplica ed in
independen popula ions, o en explaining a small pe cen age o
he obse ed a iabili y ha limi s hei p edic i e capaci y (12).
The candida e gene app oach is u he limi ed by he lack o
unde s anding o he mechanism o ac ion o he APs. The
pha macological esponse o APs can be defined as a complex
pheno ype wi h polygenic inhe i ance in ol ing mul iple loci wi h
small e ec s. Polygenic isk sco es (PRS) a e cons uc ed by
summing he mul iple isk alleles associa ed wi h a pheno ype
and a e weigh ed by he magni ude o hei es ima ed e ec in
genome-wide associa ion s udies (GWAS) using la ge coho s wi h
su ficien s a is ical powe (13). In psychia y, hese PRS ha e been
calcula ed o es ima e he gene ic isk o a ious condi ions, such as
SZ, majo dep ession, and bipola diso de (14). Se e al s udies
ha e demons a ed ha he PRS calcula ed o psychopa hologies
can be use ul in pha macogenomic s udies (14–17) as p edic o s o
Mas e al. 10.3389/ psy .2024.1497565
F on ie s in Psychia y on ie sin.o g02
he esponse o APs (18–22). Addi ionally, he PRS calcula ed o
pheno ypes ela ed o he pha macological esponse o APs, such as
cogni i e pe o mance o me abolic al e a ions, can also be
associa ed wi h he e ficacy o oxici y o AP ea men s (14,23–
25). The clinical applica ion o PRS and hei inclusion in heal hca e
sys ems a e some o he mos p omising aspec s in implemen ing
PGx in clinical p ac ice (13). Howe e , PRS ha e limi ed p ecision
in hei p edic i e capaci y, as he e a e many o he
sociodemog aphic, en i onmen al, clinical, and pha macological
ac o s in ol ed in his complex pheno ype. Despi e hese
limi a ions, he e is e idence o he clinical applicabili y o PRS,
mainly o pa ien iden ifica ion and s a ifica ion (13,17). In hese
examples, PRS ha e been inco po a ed in o isk algo i hms and a e
al eady used in clinical p ac ice in some cases, inc easing hei
p edic i e capaci y. The in eg a ion o PRS in o algo i hms ha
include o he isk ac o s (i.e., sociodemog aphic, en i onmen al,
clinical, and pha macological) ep esen s he u u e o
pe sonalized medicine.
Applied pha macogene ics o p edic
esponse o ea men o fi s
psycho ic episode
PGx s udies ha e been hinde ed by limi a ions such as di ficul ies in
ec ui ing la ge coho s, as hey equi e de ailed in o ma ion and
longi udinal ollow-up o assess he esponse o pha macological
ea men . Addi ionally, PGx s udies in SZ a e cons ained by
disease-specificlimi a ions(14) such as diagnos ic he e ogenei y
(mul iple and a iable symp oms accompanied by neu opsychological
and unc ional impai men s) (26), mul iple como bidi ies, and
pha macological he e ogenei y (mul iple APs wi h di e en
p ope ies, a iable doses, AP combina ions, and concomi an
medica ions) (27,28). Fu he mo e, he e is he e ogenei y in he
defini ion o esponse pheno ypes ha is usually defined as a
pe cen age o imp o emen in o e all symp oma ology o a h eshold
alue measu ed in c oss-sec ional s udies, wi hou he conside a ion o
he di e en symp oms and dimensions o psychia ic diso de s, hei
longi udinal e olu ion, o yea s o ea men . Acco dingly, se e al
au ho s p oposed adding unc ioning and pe sonal eco e y measu es
o he lis o ou come indica o s o FEP, expanding i beyond
symp oma ologic emission (29).
The “Applied Pha macogene ics o P edic Response o
T ea men o Fi s Psycho ic Episode”(Fa maPRED-PEP om
he Spanish abb e ia ion) p ojec is a mul icen e s udy designed
o allow he de elopmen and alida ion o a p edic i e algo i hm
o he applica ion o pe sonalized medicine in pa ien s wi h fi s -
episode psychosis (FEP). The pu pose o his p edic o will be o
classi y FEP pa ien s acco ding o hei esponse pheno ype o APs,
he eby allowing he mos app op ia e ea men s a egy o be
selec ed. This p edic o will in eg a e, h ough machine lea ning
echniques, pha macogene ic (measu ed as polygenic isk sco es)
and epigene ic da a wi h clinical, sociodemog aphic,
en i onmen al, and neu oana omical da a. To do his, he
Fa maPRED-PEP p ojec will use he da a om wo al eady
ec ui ed coho s o pa ien s wi h FEP and a longi udinal ollow-
up: he PEPS coho om “Geno ype-Pheno ype In e ac ion and
En i onmen . Applica ion o a P edic i e Model in Fi s Psycho ic
Episodes”( he PEPs s udy om he Spanish abb e ia ion; PI08/
0208) (N = 335) (30) and he PAFIP coho om “Clinical P og am
on Ea ly Phases o Psychosis”(PAFIP om he Spanish
abb e ia ion)”(N = 350) (31). These coho s will allow esponse
pheno ypes o be defined using longi udinal da a, aking in o
accoun no only he symp oma ological dimensions o he
pa hology, bu also he neu ocogni i e dimensions and ad e se
e ec s. These coho s will be used o c ea e as well as in e nally
alida e he p edic o . This p edic o will be ex e nally alida ed in a
new p ospec i e coho o pa ien s wi h FEP and a longi udinal
ollow-up, he Fa maPRED coho (N = 300).
S udy design
S udy design
Fa maPRED-PEP is an obse a ional, na u alis ic, and
longi udinal s udy examining clinical ajec o ies and he
p edic o s o clinical esponse o APs in FEP coho s (Figu e 1).
P ojec aims
The specific aims o he Fa maPRED-PEP s udy a e o:
1. Define ea men esponse pheno ypes o an ipsycho ics in
wo coho s o pa ien s wi h fi s -episode psychosis (N =
700) using s a is ical echniques applied o longi udinal
da a on symp oma ology, neu ocogni ion, and ad e se
e ec s, be o e alida ing hese pheno ypes in a new
p ospec i e coho (N = 300).
2. Reach consensus on clinical ecommenda ions o he
defined ea men esponse pheno ypes.
3. De elop and pe o m in e nal, ex e nal, and p ospec i e
alida ion o he p edic i e algo i hms o he defined
esponse pheno ypes using machine lea ning echniques
ha in eg a e pha macogene ic a iables (measu ed as PRS)
and epigene ic da a along wi h clinical, sociodemog aphic,
en i onmen al, and neu oana omical da a.
4. De elop p edic i e algo i hms o an ipsycho ic esponses
specifically adap ed o each gende .
5. De elop a compu e applica ion ha con ains he
p edic i e algo i hms o he ea men esponse
pheno ypes and he clinical ecommenda ions o each.
6. S udy he easibili y o he clinical applicabili y o he
p edic i e algo i hms in coo dina ion wi h heal hca e sys ems.
7. P omo e educa ional p og ams on pe sonalized and
p ecision medicine in psychia y.
8. Explo e s a egies o p omo e access o genomic and heal h
da a, and hei po en ial isks and benefi s in psychia ic
pa ien s.
Mas e al. 10.3389/ psy .2024.1497565
F on ie s in Psychia y on ie sin.o g03
To achie e hese objec i es, he Fa maPRED-PEP s udy has
es ablished a na ional esea ch ne wo k ha is ocused on ec ui ing
FEP pa ien s om 12 na ional s udy si es (Figu e 2), wi h eigh wo k
packages ha ing al eady been designed (Table 1). The eams om hese
si es a e membe s o he Biomedical Resea ch Ne wo king Cen e in
Men al Heal h (CIBERSAM om he Spanish abb e ia ion), a Spanish
ne wo k ocusing on ansla ional esea ch on he neu oscien ific
aspec s ela ed o heal h and men al illness (www.cibe sam.es)(32).
FIGURE 1
Fa maPRED-PEP s udy design and wo kflow.
FIGURE 2
Fa maPRED-PEP esea ch ne wo k and s udy si es.
Mas e al. 10.3389/ psy .2024.1497565
F on ie s in Psychia y on ie sin.o g04
Rec ui ed samples
The Fa maPRED-PEP s udy will ake ad ance o wo al eady
ec ui ed Spanish coho s o FEP pa ien s wi h longi udinal
assessmen and is cu en ly ec ui ing a hi d coho . The wo
coho s p e iously ec ui ed a e: he PEPS coho (N = 335) (30)
and he PAFIP coho (N = 350) (31). A comple e desc ip ion o
hese coho s can be ound elsewhe e (30,33).
P ospec i e sample
The Fa maPRED-PEP esea ch ne wo k is ec ui ing he
Fa maPRED coho . The inclusion c i e ia a e: aged be ween 16
and 35 yea s a he ime o fi s e alua ion; a du a ion o posi i e
symp oma ology ha does no exceed 12 mon hs; a du a ion o AP
ea men ha does no exceed 3 mon hs; fluency in Spanish; and
signed in o med consen o he s udy ( o mino s, by a legal
gua dian i he pa ien ag ees o pa icipa e). The exclusion
c i e ia a e: a neu ological diso de ; auma ic b ain inju y wi h a
loss o consciousness; in ellec ual disabili y, no only an IQ < 70, bu
also poo unc ioning; soma ic pa hology wi h a men al impac ;
oxic psychosis; o a e usal o unde go gene ic es ing.
The s udy was app o ed by he esea ch e hics commi ees o all
he pa icipa ing clinical cen e s (HCB/2022/0079). In o med
consen is o be ob ained om all he pa icipan s. In o med
consen has been designed acco ding o he ecommenda ions o
he Spanish P ecision Medicine In as uc u e Associa ed wi h
Science and Technology (IMPaCT) (h ps://impac .isciii.es/) and
he Ca los III Heal h Ins i u e (Spain) o ensu e p ope da a sha ing
and o p omo e open science.
P ima y clinical endpoin
Clinical ajec o ies, de i ed om longi udinal da a ha
cha ac e ize AP esponse pheno ypes, will se e as he p ima y
clinical endpoin . These ajec o ies will u ilize da a collec ed a
baseline, 3, 6, and 12 mon hs and will be iden ified ia clus e ing
and la en a iable analyses. Response pheno ypes will be based on
TABLE 1 Fa maPRED-PEP wo k packages.
Wo k package Func ion
WP1. Fa maPRED coho ec ui men Task 1. Decide clinical assessmen s and ime-poin s
Task 2. Design and de elop a web-based EDC
Task 3. Rec ui 300 pa ien s expe iencing FEP a 12 clinical cen e s. Longi udinal ollow-up will consis o ou isi s
(baseline, a 3, 6 and 12 mon hs a e s udy inclusion) du ing which clinical and neu opsychological assessmen s will
be conduc ed and he occu ence o ad e se e ec s and plasma le els o APs will be assessed. A he baseline isi ,
sociodemog aphic da a and amily his o y will be collec ed, a biological sample o DNA ex ac ion will be ob ained,
and magne ic esonance imaging (MRI) will be pe o med.
WP2. Defini ion o esponse pheno ypes and
clinical ecommenda ions
Task 1. De elop da a p ep ocessing p o ocols, including da a ans o ma ion, da a impu a ion, and da a
ha moniza ion, among he h ee coho s included in he p esen s udy.
Task 2. Define esponse pheno ypes o APs in FEP using 12-mon h longi udinal da a on symp oma ology,
neu ocogni ion, and ad e se e ec s h ough clus e ing and la en a iable analyses.
Task 3. De elop a guide o clinical ecommenda ions o each o he esponse pheno ypes.
WP3. Pha macogene ic s udy Task 1. De elop and apply quali y con ol p o ocols o gene ic and epigene ic da a.
Task 2. Calcula e selec ed polygenic isk sco es using whole-genome geno yping ollowing p e iously desc ibed
s anda d p o ocols.
Task 3. Calcula e epigene ic clocks and epigene ic isk sco es using whole-genome me hyla ion da a acco ding o
s anda d p o ocols.
Task 4. Pe o m a pha macokine ic s udy o he candida e genes in ol ed in he abso p ion, dis ibu ion, me abolism,
and exc e ion o APs and i s ela ionship o AP plasma le els.
WP4. De elopmen and alida ion o
p edic i e algo i hms
De elop p edic i e algo i hms o he iden ified AP esponse pheno ypes using baseline da a. The PEPS coho will be
used o c ea e he p edic ion model and he PAFIP coho will be used as an independen alida ion sample. The
mos obus model will be selec ed and fine- uned by me ging he PEPS and PAFIP coho s be o e being ex e nally
alida ed using he Fa maPRED coho . Explainable a ificial in elligence (AI) me hods ha de i e in o ma i e
p edic ions will be used.
WP5. De elopmen o a clinical decision
suppo sys em
In coo dina ion wi h a specialized company, a compu e applica ion ha in eg a es he p edic i e algo i hms (WP4)
and he clinical ecommenda ions (WP2) o he iden ified esponse pheno ypes will be de eloped. This applica ion
mus in eg a e he a ious algo i hms and ecommenda ions sequen ially: (1) p edic ion o symp om ajec o y; (2)
p edic ion o neu ocogni i e ajec o y; (3) p edic ion o ad e se e ec s; (4) he apeu ic s a egy ecommenda ions and
APs; and (5) dosing ecommenda ions and he need o moni o ing plasma le els.
WP6. S udy o clinical applicabili y and
easibili y o in eg a ion in o he Spanish
Na ional Heal h Sys em
In coo dina ion wi h he e i o ial men al heal h manage s o each pa icipa ing au onomous communi y, bo h he
clinical applicabili y and in eg a ion in o he Spanish Na ional Heal h Sys em o he findings om his s udy will
be assessed.
WP7. Educa ion and eaching o pe sonalized
and p ecision medicine in psychia y
A p og am will be de eloped o p omo e he eaching o pe sonalized and p ecision medicine in psychia y using he
ne wo k o CIBERSAM cen e s as a p omo ion pla o m.
WP8. Dissemina ion o esul s P epa a ion o publica ions and communica ions.
Mas e al. 10.3389/ psy .2024.1497565
F on ie s in Psychia y on ie sin.o g05

longi udinal changes ac oss mul iple domains, including psycho ic
symp oma ology (posi i e, nega i e, and gene al symp oms),
a ec i e symp oms, and side e ec s. All measu es used o define
hese ajec o ies a e de ailed below.
Me hods
Diagnosis
The diagnosis o a psycho ic diso de will be es ablished using
semi-s uc u ed in e iews based on he age o he pa ien : he
Schedule o A ec i e Diso de s and Schizoph enia o School-Age
Child en - P esen and Li e ime Ve sion (K-SADS-PL) (< 18 yea s
old) (34) and he Mini-In e na ional Neu opsychia ic In e iew
(MINI) (> 18 yea s old) (35). To e ospec i ely cha ac e ize and
da e he ini ial symp oms o a psycho ic illness, he Symp om Onse
in Schizoph enia (SOS) in en o y will be used (36).
Demog aphic and en i onmen al ac o s
A baseline, a comple e pe sonal and amily his o y will be
aken, including a his o y o d ug use. En i onmen al ac o s and
s esso s will also be eco ded using se e al measu es ha include
he Lewis-Mu ay Obs e ic Complica ions Scale (37), he Lis o
Th ea ening Expe iences Ques ionnai e (38) and he Childhood
T auma Ques ionnai e (39), wi h in o ma ion on u banici y and he
socioeconomic s a us also being collec ed using he Hollingshead-
Redlich index. The P emo bid Adjus men Scale (PAS) (40) will be
used o assess p emo bid adjus men , one o he mos s udied
ac o s in ela ion o he p ognosis o psycho ic diso de s. In each
e alua ion, weigh , heigh , he body mass index (BMI), blood
p essu e, and he abdominal pe ime e will also be eco ded, wi h
he aim o moni o ing he physical heal h indica o s.
T ea men da a
In each e alua ion, in o ma ion on he d ugs p esc ibed will be
eco ded, including he ype o d ug, he du a ion o ea men , and
dosage. In o ma ion on psychological ea men will also be
collec ed. To assess ad e se d ug eac ions, se e al measu es will
be included: he Ud alg ü Kliniske Unde sogelse (UKU) side
e ec a ing scale (41), he Simpson-Angus scale, and gene al blood
es s ( o al choles e ol, LDL, HDL, iglyce ides, glucose, and
p olac in). AP plasma le els will be measu ed a each isi . The
analysis o plasma le els oge he wi h he comple e geno yping o
he cy och omes and anspo e s will allow he iden ifica ion o
genuine non- esponde s, di e en ia ing hem om non-adhe e s o
ea men . Adhe ence will be measu ed using he Mo isky G een
Le ine Medica ion Adhe ence Scale (42).
Clinical measu es
A baseline and in each e alua ion, a comp ehensi e assessmen
o psychopa hology will be pe o med ha will include well-
es ablished measu es such as he Posi i e and Nega i e Synd ome
Scale (PANSS) (43), he B ie Nega i e Symp om Scale (BNSS) (44),
he Young Mania Ra ing Scale (YMRS) (45), and he Mon gome y
—Asbe g Dep ession Ra ing Scale (MADRS) (46). The assessmen
o global unc ioning will include he Clinical Global Imp ession
(CGI) Scale (47), he Global Assessmen o Func ioning (GAF)
Scale and Func ional Assessmen S aging (FAST) (48).
Cogni ion
The neu opsychological assessmen ba e y will be applied in
he h ee-mon h e alua ion o ensu e ha he pa ien is clinically
s able. The neu opsychological assessmen ba e y will be epea ed
in he one-yea ollow-up isi . The s udy will use he MATRICS
Consensus Cogni i e Ba e y (MCCB) (49) consis ing o 10
indi idually adminis e ed es s ha measu e cogni i e
pe o mance in se en domains: speed o p ocessing (BACS:
symbol coding; ca ego y fluency: animal naming; T ail Making
Tes - Pa A), a en ion/ igilance (CPT-IP), wo king memo y
(WMS®-III: Spa ial Span; Le e -Numbe Span), e bal lea ning
(HVLT-R™), isual lea ning (BVMT-R™), easoning and p oblem
sol ing (NAB®: Mazes), and social cogni ion (MSCEIT™:
Managing Emo ions). The MCCB will be complemen ed by
se e al es s o acili a e he ha moniza ion o he cogni i e da a
among he coho s. These es s include: he Vocabula y and Ma ix
Reasoning sub es s o he Wechsle Adul In elligence Scale –
Fou h Edi ion (WAIS-IV) (50) o measu e cu en IQ; he
Backwa d Digi Span sub es o he WAIS-IV (50) o measu e
wo king memo y; and he T ail Making Tes - Pa B (51) o
measu e execu i e unc ions. Addi ionally, a baseline, he
Cogni i e Rese e Assessmen Scale in Heal h (CRASH) (52) will
be used o measu e cogni i e ese e.
Neu oimaging
The mul imodal neu oimaging p o ocol is designed o a 3T
MRI scanne and includes s uc u al imaging and es ing-s a e
unc ional MRI ( MRI). Images will be collec ed a baseline o in
he h ee-mon h e alua ion o ensu e ha he pa ien is clinically
s able. The e a e cu en ly 11 MRI scanning si es wi h a a ie y o
endo s and pla o ms. Da a will be collec ed om each cen e and
p ocessed a one si e. Upon a i al a he da a analysis cen e ,
quali y con ol (QC) will check he consis ency o he da a and
adhe ence o he specified imaging p o ocol. Following QC, he da a
will be ma hema ically ha monized o elimina e esidual si e e ec s
and will hen be p ocessed using obus analysis s eams.
Mas e al. 10.3389/ psy .2024.1497565
F on ie s in Psychia y on ie sin.o g06
Gene ics and epigene ics
In all e alua ions, blood samples will be collec ed in whole-blood
EDTA ubes. The blood samples will be p ocessed using a s anda dized
p o ocol o ob ain aliquo s o plasma ( o plasma AP assessmen ) and
bu y coa ( o DNA ex ac ion). Samples will be s o ed in -80°C
eeze s. The ele an me ada a will include he as ing du a ion, he
ime since he las AP dosage, and ecen illnesses o inflamma o y
condi ions. DNA will be ex ac ed om bu y coa samples ollowing
es ablished s anda d p o ocols. No malized DNA concen a ions will
be sen o he Spanish Na ional Geno yping Cen e (CeGen). Whole-
genome geno yping will be unde aken using he Axiom™Spain
Biobank A ay (de eloped in he Uni e si y o San iago de
Compos ela, Spain) (The mo Fishe Scien ific) and da a will be
analyzed o ob ain polygenic isk sco es (PRS) o schizoph enia and
o he psychopa hologies as well as o he condi ions including
cogni ion, pe sonali y ai s, and me abolic o inflamma o y ai s.
GWAS summa y esul s will be downloaded om he Psychia ic
Genomics Conso ium and he Science Gene ic Associa ion
Conso ium. S anda d pipeline analysis (p e iously desc ibed (25))
will be pe o med, allowing e ficien quali y con ol, ela edness es ing,
p incipal componen analysis, and geno ype impu a ion. The selec ed
PRSs will be compu ed using he PRS con inuous sh inkage (PRS-CS)
so wa e, a Bayesian-based me hod ha in e s an upda ed pos e io
SNP e ec size by applying con inuous sh inkage o he disco e y
GWAS summa y s a is ics. The ex e nal linkage disequilib ium (LD)
e e ence panel will be cons uc ed using a publicly a ailable subsample
o he UK Biobank. The de i ed PRSs will be s anda dized o z-sco es
wi h mean 0 and a s anda d de ia ion o 1. The geno yping o specific
pha macogene ic genes (including cy och omes and anspo e s) will
be conduc ed wi h he Pha macoScan a ay (The mo Fishe Scien ific).
Only genes wi h meaning ul impac s on AP me abolism, as pe CPIC
le els A–B o gene-d ug in e ac ions (h ps://cpicpgx.o g/genes-d ugs/),
will be included. Gene ic a ian s will be anno a ed using s a (*)
alleles, whe e applicable, ia he Pha mVa da abase (h ps://
www.pha m a .o g/). Fo s a is ical analysis, geno ype- o-
pheno ype ansla ions will ollow consensus ecommenda ions
(e.g., CYP2D6) (53) o , i absen , CPIC-defined pheno ypes. DNA
me hyla ion will be assessed using he Illumina Infinium
Me hyla ionEPIC 2.0 ki (Illumina) and analyzed o calcula e
di e en epigene ic clocks (54)andme hyla ionp ofile sco es
(MPS) (55) acco ding o s anda d p o ocols ha include quali y
con ol, be a- alue compu a ion, no maliza ion, and singula alue
decomposi ion o iden i y and emo e unwan ed sou ces o
a ia ion (56,57). We will use publicly a ailable da a om
me hyla ion-wide associa ion s udies as a disco e y sample o
calcula e me hyla ion p ofile sco es using simila app oaches o
hose used o he cons uc ion o PRS. We de eloped a code o
compu ing MPS accessible ia he ollowing public eposi o y on
Gi Hub: h ps://gi hub.com/agonse/me hylsco e.
Da a collec ion
Pheno ypic da a will be collec ed and managed using
Lib eClinica, an open-sou ce elec onic da a cap u e (EDC)
sys em o clinical ials based on he OpenClinica(R) (OC) 3
communi y edi ion. A web-based EDC has been designed
specifically o he collec ion o da a om all he measu es and
ques ionnai es. Real- ime da a alida ion and quali y ules will be
defined o ensu e ha he da a a e en e ed accu a ely and as
comple ely as possible. Clinical a e s will di ec ly en e he
ques ionnai e da a using he co esponding da a en y o ms.
Each da a en y will hen be ca e ully double-checked by an
ex e nal p ojec managemen eam ha will esol e any
disc epancy o que y. S anda d ope a ing p ocedu es will be
es ablished o ensu e p ope da a collec ion and compa abili y
ac oss he s udy si es.
Da a analysis
The analyses will ocus on wo main goals: (1) he
cha ac e iza ion o AP esponse pheno ypes using longi udinal
da a and (2) he p edic ion o hese pheno ypes. Clinical
ajec o ies u ilizing da a om baseline, 3-, 6-, and 12-mon h
ollow-ups will iden i y AP esponse pheno ypes based on he
longi udinal change in di e en psycho ic symp om domains
(posi i e, nega i e, and gene al) as well as in a ec i e symp oms
and side e ec s. T ajec o y analyses will include all he in o ma ion
a ailable om all he ime-poin s and will apply s a e-o - he-a
clus e ing and la en a iable analyses. The PEPS coho (N = 300)
will be used o iden i y hese AP esponse pheno ypes and o
pe o m hei clinical cha ac e iza ion. P edic ions will be based
on he da a collec ed a baseline and he cogni ion in o ma ion
collec ed in he 3-mon h ollow-up. To ensu e ou abili y o es he
obus ness o he p edic ion models in an unbiased manne , he
PEPS coho will be used o c ea e he p edic ion model, while
he PAFIP coho (N = 350) will be used as an unseen independen
alida ion sample. Explainable machine lea ning me hods will be
used. The mos obus model will hen be selec ed and fine- uned by
me ging he PEPS and PAFIP coho s be o e being ex e nally
alida ed using he Fa maPRED coho .
Sample size and powe
We used a ecen ly-desc ibed me hod o de e mine sample size
o de eloping a clinical p edic ion model using a adi ional
likelihood-based app oach (e.g., logis ic eg ession) (58). Sample
sizes we e de i ed o he scena ios o low, medium o high
p edic ion pe o mance (Nagelke ke R-squa ed alue o 0.25/0.40/
0.55), wi h he numbe o pa ame e s in he model being 10. The
minimum expec ed equency o he AP esponse clus e was 15%
acco ding o p e ious s udies wi h he PEPS coho (59). Using he
R package ‘pmsampsize’, we es ima ed he sample sizes equi ed o
bina y ou comes. Fo a bina y ou come, he e a e h ee c i e ia o
de e mining sample size: (1) a small o e fi ing defined by an
expec ed sh inkage o p edic o e ec s by 10% o less; (2) a small
absolu e di e ence o 0.05 in he model’s appa en and adjus ed
Nagelke ke R-squa ed alue; and (3) a p ecise es ima ion (wi hin
+/- 0.05) o he a e age ou come isk in he popula ion o a key
Mas e al. 10.3389/ psy .2024.1497565
F on ie s in Psychia y on ie sin.o g07
ime-poin o in e es o p edic ion. Each c i e ion may equi e a
di e en sample size and he chosen sample size is he la ges o he
h ee. Fo his s udy, when he ou come is conside ed bina y, he
c i e ion wi h he la ges equi ed sample size will be c i e ion 1 o
a low p edic i e pe o mance and 2 o medium and high
pe o mances. Assuming a pheno ype equency o 15% and a
maximum o 10 pa ame e s o be included in he p edic i e
model, he minimum sample size o a model is es ima ed o be
be ween 290 and 310.
Discussion
The Fa maPRED-PEP p ojec has been designed o o e come
se e al o he limi a ions iden ified in PGx s udies in
psychia y, including:
1. Sample size. As commen ed p e iously, he ec ui men o
la ge coho s wi h longi udinal ollow-ups and deep
pheno yping is challenging and di ficul o achie e. He e,
he aim o he s udy is o collec da a om 1000 pa ien s
h ough he in eg a ion o h ee coho s o FEP pa ien s: he
PEPS coho , he PAFIP coho , and he Fa maPRED
coho . The assessmen ins umen s and measu emen
ime-poin s o be used in he Fa maPRED coho we e
decided ia a wo king g oup discussion o acili a e he
ha moniza ion o clinical and neu ocogni i e da a among
he coho s.
2. Pheno ype he e ogenei y and defini ion. One ac o
hinde ing he iden ifica ion o p edic o s o AP esponse
is he inconsis ency in how AP esponse pheno ypes a e
defined ac oss a ious s udies (28,59). Many esea che s
adop bina y classifica ions o measu e e ec i eness
(ca ego izing subjec s as ei he esponde s o non-
esponde s) o e alua e oxici y (de e mining whe he an
ad e se e ec is p esen o absen ), al hough he e is no
consensus ega ding he ideal cu -o alues o hese
a iables. Such bina y classifica ions ail o cap u e he
complex na u e o AP esponses, which a e influenced by
bo h he e ec i eness o he ea men (encompassing
mul iple aspec s such as clinical symp oms,
neu ocogni i e pe o mance, and quali y o li e) and he
side e ec s in ol ed. Addi ional challenges in p edic ing
AP esponses include he di e se p og ession o he disease
i sel . P edic ing esponse ou comes using pa ien s wi h
ch onic condi ions in oduces mo e a iabili y and limi s
he applicabili y o he findings due o di e ences in illness
du a ion, diagnos ic c i e ia, and p e ious ea men s.
Con e sely, pa ien s expe iencing hei fi s episode o
schizoph enia gene ally show less a ia ion in hei p io
use o an ipsycho ics, making hem mo e app op ia e
subjec s o s udying p edic o s o ea men ou comes
(60,61). The aim o he Fa maPRED-PEP s udy is o
define he pheno ype o esponse o APs using
longi udinal da a om o e he cou se o one yea a e
he FEP and conside ing ha his esponse is a complex
pheno ype encompassing no only he emission o he
a ious symp oms ha cha ac e ize he pa hology, bu also
he neu ocogni i e aspec s and he eme gence o
ad e se e ec s.
3. The complexi y o he pheno ype. The AP esponse is a
complex pheno ype wi h a polygenic basis ha could be
pa ially cap u ed using PRS. Howe e , as is he case wi h
o he isk ac o s used in heal hca e (e.g., choles e ol
le els), PRS ha e a p edic i e capaci y wi h limi ed
accu acy, meaning hey canno p edic a clinical a iable
o in e es wi h su ficien p ecision a he indi idual le el.
E en i he PRS cap u ed all he gene ic a iabili y in a
pha macological esponse a ibu able o common gene ic
a ian s, hei p edic i e capaci y would s ill be impe ec ,
mainly o wo easons. Fi s ly, gene ic ac o s a e no he
only isk ac o s ha explain a iabili y in a
pha macological esponse as he e a e many o he
sociodemog aphic, en i onmen al, clinical, and
pha macological ac o s in ol ed in his complex
pheno ype (62,63). Secondly, PRS only accoun o he
con ibu ion o common gene ic a ian s, each wi h a small
e ec , wi hou conside ing he e ec s o a e gene ic
a ian s, which a e less equen bu ha e a la ge impac ,
o he e ec s a ibu able o epigene ic modifica ions.
Al hough he inclusion o a e gene ic a ian s,
iden ifiable h ough massi e sequencing echniques, is no
expec ed o inc ease he p edic i e capaci y o he PRS in
he sho e m (13), he inclusion o epigene ics in
pha macogenomic s udies is expec ed o help explain
much o he missing he i abili y, ha is, he he i abili y o
a pheno ype ha is no cap u ed by gene ic a ian s (3). In
his ega d, a iables such as epigene ic clocks ha e ecen ly
been shown o be ela ed no only o schizoph enia, bu also
o he esponse o APs (56,64,65).
4. The gende pe spec i e. The s udy assumes a gende -based
app oach as a c oss-cu ing axis o imp o e heal h
in e en ions. The e o e, i s objec i e is o de elop
p edic i e algo i hms o he esponse o AP, especially
ailo ed o each gende . The di e ences be ween women
and men in he incidence o FEP a e well known, bu less
s udied in ela ion o he esponse o AP. In his sense, he
s udy will no be limi ed o conside ing gende as a simple
ca ego ical a iable o in oduc ion in o s a is ical models,
bu aims o conduc an in-dep h s udy o he impac ha
gende has on pha macological esponse in FEP and i s
in e ac ion wi h o he heal h de e minan s (e.g., age,
socioeconomic s a us, educa ional le el, e c.). The e o e,
his s udy will p omo e he sea ch, de ec ion, and analysis
o di e ences, as well as simila i ies, be ween men and
women, bo h in e ms o e ficacy and in e ms o he
equency and ype o ad e se e ec s. Thus, i aims o
de e mine whe he he imp o emen in psycho ic
symp oma ology, bu also in neu ocogni i e
cha ac e is ics, as well as he equency and se e i y o
ad e se e ec s, a e exclusi e o one o he wo sexes, mo e
p e alen in one o he wo sexes, wi h di e en
Mas e al. 10.3389/ psy .2024.1497565
F on ie s in Psychia y on ie sin.o g08
cha ac e is ics be ween bo h sexes, o e en i hey ecei e
di e en esponses om he sys em depending on whe he
hey a e men o women. To a oid some o he gende biases
and common malp ac ices in heal h esea ch, he s udy
da a will be collec ed and analyzed disagg ega ed by gende
and will be p esen ed in epo s and publica ions de i ed in
he same way.
O e coming hese limi a ions, he aim o he Fa maPRED-PEP
s udy is o de elop algo i hms o p edic AP esponse pheno ypes using
gene ic and epigene ic da a (measu ed as isk sco es) oge he wi h
clinical, sociodemog aphic, en i onmen al, and neu oana omical da a.
The u u e o medicine is ocused on o e ing a comp ehensi e
app oach o heal h, aking in o accoun all he de e mining ac o s
o heal h o illness. The gene a ion o la ge amoun s o heal h da a
has exceeded he capaci y o manage all a ailable in o ma ion in
eal ime; he e o e, a ificial in elligence can become a suppo ool
o heal hca e p o essionals, who, howe e , mus always ha e he
final say in decision-making. Machine lea ning sys ems, and mo e
specifically deep lea ning ones, a e capable o ex ac ing pa e ns
and gene a ing conclusions om a la ge amoun o da a using
complex o mulas and associa ions, making hem less in ui i e. This
ac limi s he unde s anding and comp ehension o he sys ems by
heal hca e p o essionals, making i di ficul o in eg a e hem in o
wo kflows and gene a ing a lack o confidence in he esul s hey
can p o ide. Ou p ojec will be ocus in explainable a ificial
in elligence me hods ha de i e in o ma i e p edic ions ha can
be mapped back o indi idual ea u es and bioma ke s, as opposed
o some deep lea ning and o he “black-box” echniques ha may
no be app op ia e o achie ing in e p e abili y.
The applica ion o p ecision medicine in psychia y has been
defined as a mul i-s age p ocess (66), whe e PRS play a significan
ole in each s age, such as in: (1) p edic ing he isk o de eloping
he diso de o design p e en i e s a egies; (2) s a i ying pa ien s
based on hei own cha ac e is ics, bo h clinical and gene ic, o
iden i y he mos e ec i e ea men , ea men - esis an pa ien s,
and suscep ibili y o de eloping ad e se e ec s; and (3) op imizing
dosage egimens o ensu e ea men e ficacy and ole abili y based
on d ug kine ics and pa ien gene ic cha ac e is ics. The
Fa maPRED-PEP s udy ocuses on he second and hi d s ages o
his s a egy.
Al hough he Fa maPRED s udy has been designed o add ess
se e al limi a ions commonly ound in pha macogenomics (PGx)
s udies, ce ain cons ain s should be conside ed when in e p e ing
u u e findings. Fi s ly, as a na u alis ic s udy, ea men
he e ogenei y and he non- andom selec ion o specific
ea men s could ac as po en ial con ounde s. Secondly, while
allowing p io an ipsycho ic (AP) ea men o less han h ee
mon hs aims o acili a e sample ec ui men and ensu e adequa e
s a is ical powe , i may also in oduce a iabili y ha could
con ound clinical ajec o ies. Thi dly, al hough ea men
adhe ence will be moni o ed, no in e en ions o enhance
adhe ence a e planned; as a esul , adhe ence a iabili y may
u he con ound he esponse pheno ypes based on clinical
ajec o ies. Finally, despi e he implemen a ion o igo ous da a
ha moniza ion p o ocols o ensu e compa abili y ac oss he h ee
coho s in ol ed in he s udy, uncon olled di e ences be ween
coho s may s ill influence he findings.
The applica ion o hese s a egies in pe sonalized and p ecision
medicine is especially ele an in pa ien s wi h FEP, as eco e y
a e FEP has become he p ima y goal o any ea men s a egy
(61), wi h hei p og ess du ing he fi s yea o ea men
conside ed c ucial o disease p ognosis and elapse p e en ion.
Al hough SZ is a po en ially disabling and se ious men al illness, an
app op ia e mul idisciplina y app oach o FEP can con ibu e o
comple e eco e y (67). A c i ical pe iod o 2 o 5 yea s a e FEP
has been defined, du ing which he apeu ic in e en ions may be
mo e success ul in p e en ing elapses and achie ing unc ional
eco e y in pa ien s (68). P e en ing elapses in he ea ly s ages o
he disease has become a majo challenge due o he c i ical impac
ha a elapse can ha e on unc ional p ognosis (69). Non-
adhe ence o APs and a lack o disease knowledge a e e y
common in pa ien s wi h FEP and a e associa ed wi h an
inc eased isk o elapse, leading o a wo se disease cou se and
unc ionali y (70–72).
Psycho ic diso de s encompass schizoph enia, schizoph eni o m
diso de , schizoa ec i e diso de , b ie psycho ic diso de , and
subs ance-induced psycho ic diso de . Addi ionally, o he men al
heal h condi ions, such as majo dep essi e diso de , bipola
diso de , obsessi e-compulsi e diso de (OCD), pos auma ic
s ess diso de (PTSD), and au ism spec um diso de , may also
p esen wi h sho - o medium- e m psycho ic symp oms. Gi en he
gene ic pleio opy sha ed among hese condi ions -cap u ed h ough
polygenic isk sco es- and he widesp ead use o APs o ea hem,
he findings o he Fa maPRED-PEP s udy ha e he po en ial o o e
ansdiagnos ic insigh s ha ex end beyond fi s -episode psychosis
(FEP) pa ien s.
Pha macogenomic s udies and pe sonalized and p ecision
medicine in he field o psycho ic diso de s will need o add ess he
challenges ha mus be aced o ensu e hei u u e applicabili y in
clinical p ac ice. These challenges ha e been defined by he
In e na ional Conso ium o Pe sonalized Medicine (ICPe Med)
(h ps://www.icpe med.eu/index.php) and include, among o he s,
he managemen o genomic and heal h da a in e ms o ensu ing
confiden iali y as well as access o ci izens and esea che s, he
in ol emen o heal h au ho i ies in p omo ing pe sonalized
medicine o acili a e i s implemen a ion in heal hca e sys ems,
he educa ion and in ol emen o heal hca e p o essionals o ensu e
knowledge, access, and applica ion o pe sonalized and p ecision
medicine s a egies, he mul idisciplina y in eg a ion o esea che s
and clinicians o de elop pe sonalized medicine s a egies, and he
collec ion o da a and hei use o a mo e e ficien pa ien -cen e ed
heal hca e sys em. These challenges a e also he pilla s o IMPaCT
(h ps://impac .isciii.es/) o he Ca los III Heal h Ins i u e (Spain),
he ounde o he Fa maPRED-PEP s udy. The aims o ou s udy
a e aligned wi h he mission o IMPaCT o acili a e he e ec i e
deploymen o p ecision medicine in he Spanish Na ional Heal h
Sys em, ensu ing scien ific and echnical quali y, equi y, and
e ficiency in he use o a ailable scien ific esou ces o mee he
needs o he ci izen y.
Mas e al. 10.3389/ psy .2024.1497565
F on ie s in Psychia y on ie sin.o g09