GRUP DE RECERCA UNITAT DE TRASTORNOS DE LA CONDUCTA ALIMENTARIA INFANTO-JUVENIL

Hospital Clínic de Barcelona (Barcelona)

Directora: Josefina Castro-Fornieles, Directora de l’Institut de Neurosciències de l’Hospital Clínic, Psiquiatra Consultora Sènior

mtplana@clinic.ub.es

(+34) 932 27 99 70 – (+34) 932 27 99 74

Web del grup: http://www.hospitalclinic.org

Actualització fitxa tècnica del grup: octubre 2017

MEMBRES DEL GRUP INVESTIGADOR

Josefina Castro-Fornieles. Psiquiatra, Directora Institut de Neurociències, Hospital Clínic de Barcelona. Universitat de Barcelona. IDIBAPS
A/e: jcastro@clinic.cat

Maria Teresa Plana Turró. Psiquiatra, Coordinadora Grup de Treball de Tr. Conducta Alimentària, Hospital Clínic de Barcelona.
A/e: mtplana@clinic.cat

Luisa Lázaro Garcia. Psiquiatra, Cap de Servei de Psiquiatria i Psicologia Infantil i Juvenil, Hospital Clínic de Barcelona
A/e: llazaro@clinic.cat

Esteve Martínez Mallén. Psicòleg, Especialista del Grup de Treball de Tr. Conducta Alimentària. Hospital Clínic de Barcelona.
A/e: martinez@clinic.cat

Elena Moreno Pérez. Psicòloga, Especialista del Grup de Treball de Tr. Conducta Alimentària, Hospital Clínic de Barcelona.
A/e: emoreno@clinic.cat

Susana Andrés Perpiñá. Psicòloga, Especialista del Grup de Treball de Tr. Conducta Alimentària, Hospital Clínic de Barcelona.
A/e: sandres@clinc.cat

Itziar Flamarique Valencia. Psiquiatra, Especialista del Grup de Treball de Tr. Conducta Alimentària Hospital Clínic de Barcelona.
A/e: iflamarique@clinic.cat

Ines Hilker. Psicòloga, Especialista del Grup de Treball de Tr. Conducta Alimentària. Hospital Clínic de Barcelona.
A/e: hilker@clinic.cat

ACTIVITATS I CAPACITATS DEL GRUP DE RECERCA

Els aspectes de major interès per la nostra unitat es basen fins ara en: a) recerca basada amb la clínica (repercussions de la desnutrició, factors predictors del curs clínic, imatge corporal), b) recerca basada l’estudi de nous tractaments (psicològics i amb fàrmacs) així com c) recerca basada en neuromiatge, neuropsicologia i recerca bàsica en genètica.

Pels propers tres anys, els principals objectius són:

  1. Examinar les anomalies del cervell en aquests pacients mitjançant noves tècniques de neuroimatge que ens permetran avaluar el gruix cortical, la girificatió i el volum del cervell. A més a més, utilitzarem imatges de ressonància magnètica funcional (f-MRI) per estudiar els correlats cerebrals de les dificultats cognitives observades en els nostres estudis previs en aquestes mostres.
  2. Estudiar les conseqüències biològiques d’aquests trastorns, especialment les conseqüències cardíaques, hormonals i bioquímiques. Aquests trastorns presenten les majors taxes de mortalitat i morbiditat en totes les condicions psiquiàtriques i poc se sap de quina manera la detecció precoç podria ajudar a reduir aquestes taxes.
  3. Concloure l’estudi de seguiment de vint anys de pacients diagnosticats d’anorèxia nerviosa. Aquest estudi inclou avaluacions clíniques, neuropsicològiques i de neuroimatge d’una mostra de dones diagnosticades d’anorèxia nerviosa al nostre Departament de Psiquiatria de Nens i Adolescents fa vint anys.
  4. Anàlisi genètica d’aquests pacients per delimitar subgrups amb característiques diferenciades, específicament atenent a la simptomatologia obsessiva.

LÍNIES DE RECERCA

Línia: Examinar les anomalies del cervell en aquests pacients mitjançant noves tècniques de neuroimatge.
Investigador principal: Josefina Castro-Fornieles

Línia: Estudiar les conseqüències biològiques d’aquests trastorns, especialment les conseqüències cardíaques, hormonals i bioquímiques.
Investigadors principals: Maria Teresa Plana Turró. Itziar Flamarique Valencia

Línia: Estudi de seguiment de vint anys de pacients diagnosticats d’anorèxia nerviosa.
Investigador principal: Susana Andrés Perpiñá

Línia: La relació clínica i genètica de pacients amb anorèxia nerviosa i pacients amb trastorn obsessiu compulsiu.
Investigador principal: Luisa Lázaro García

Línia: Estudis vinculats a l’avaluació de l’auto imatge i la imatge a terceres persones en pacients amb trastorns de la conducta alimentària en població infanto-juvenil.
Investigador principal: Maria Teresa Plana Turró

MILLORS PUBLICACIONS DEL GRUP (2015-2017)

Gassó P, Rodríguez N, Blázquez A, Monteagudo A, Boloc D, Plana MT, Lafuente A, Lázaro L, Arnaiz JA, Mas S.
Epigenetic and genetic variants in the HTR1B gene and clinical improvement in children and adolescents treated with fluoxetine.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Apr 3;75:28-34.
PMID: 28025020
Abstract
The serotonin 1B receptor (5-HT1B) is important to both the pathogenesis of major depressive disorder and the antidepressant effects of selective serotonin reuptake inhibitors. Although fluoxetine has been shown to be effective and safe in children and adolescents, not all patients experience a proper clinical response, which has led to further study into the main factors involved in this inter-individual variability. Our aim was to study the effect of epigenetic and genetic factors that could affect 5-hydroxytryptamine receptor 1B (HTR1B) gene expression, and thereby response to fluoxetine. A total of 83 children and adolescents were clinically assessed 12weeks after of initiating an antidepressant treatment with fluoxetine for the first time. We evaluated the influence of single nucleotide polymorphisms (SNPs) specifically located in transcription factor binding sites (TFBSs) on their clinical improvement. A combined genetic analysis considering the significant SNPs together with the functional variant rs130058 previously associated in our population was also performed. Moreover, we assessed, for the first time in the literature, whether methylation levels of the HTR1B promoter region could be associated with the pharmacological response. Two, rs9361233 and rs9361235, were significantly associated with clinical improvement after treatment with fluoxetine. The heterozygous genotype combination analysis showed a negative correlation with clinical improvement. The lowest improvement was experienced by patients who were heterozygous for all three SNPs. Moreover, a negative correlation was found between clinical improvement and the average methylation level of the HTR1B promoter. These results give new evidence for the role of epigenetic and genetic factors which could modulate HTR1B expression in the pharmacological response to antidepressants.

Blázquez A, Gassó P, Mas S, Plana MT, Lafuente A, Lázaro L.
One-Year Follow-up of Children and Adolescents with Major Depressive Disorder: Relationship between Clinical Variables and Abcb1 Gene Polymorphisms.
Pharmacopsychiatry. 2016 Nov;49(6):248-253. Epub 2016 Jun 16.
PMID: 27309038
Abstract
Introduction: Differences in response to fluoxetine (FLX) may be influenced by certain genes that are involved in FLX transportation (ABCB1). We examined remission and recovery from the index episode in a cohort of patients treated with FLX, and also investigated associations between genetic variants in ABCB1 and remission, recovery, and suicide risk. Methods: This was a naturalistic 1-year follow-up study of 46 adolescents diagnosed with major depressive disorder (MDD). At 12 months they underwent a diagnostic interview with the K-SADS-PL. Results: It was found that remission was around 69.5% and recovery 56.5%. Remission and recovery were associated with lower scores on the CDI at baseline, with fewer readmissions and suicide attempts, and with lower scores on the CGI and higher scores on the GAF scale. No relationship was found between ABCB1 and remission or recovery. However, a significant association was observed between the G2677T ABCB1 polymorphism and suicide attempts. Conclusion: Other factors such as stressful events, family support, and other genetic factors are likely to be involved in MDD outcome.

Herpertz-Dahlmann B, Van Elburg A, Castro-Fornieles J, Schmidt U.
ESCAP Expert Paper: New developments in the diagnosis andtreatment of adolescent anorexia nervosa–a European perspective.
Eur Child Adolesc Psychiatry. 2015 Oct;24(10):1153-67
PMID: 26226918
Abstract
Anorexia nervosa is a potentially life-threatening disorder with a typical onset in adolescence and high rates of medical complications and psychiatric comorbidity. This article summarizes issues relating to classification in DSM-5 and presents a narrative review of key evidence-based medical and behavioral interventions for adolescent AN and subthreshold restricting eating disorders, mainly, but not exclusively published between 2012 and 2014. In addition, it systematically compares the clinical guidelines of four European countries (Germany, Spain, The Netherlands, and United Kingdom) and outlines common clinical practice, in relation to treatment settings, nutritional rehabilitation, family-oriented and individual psychotherapy, and psychopharmacological treatment. With the exception of family-based treatment, which is mainly evaluated and practiced in Anglo-American countries, the evidence base is weak, especially for medical interventions such as refeeding and pharmacological intervention. There is a need for common European research efforts, to improve the available evidence base and resulting clinical guidance.

Gassó P, Rodríguez N, Mas S, Pagerols M, Blázquez A, Plana MT, Torra M, Lázaro L, Lafuente A.
Effect of CYP2D6, CYP2C9 and ABCB1 genotypes on fluoxetine plasma concentrations and clinical improvement in children and adolescent patients.
Pharmacogenomics J. 2014 Oct;14(5):457-62. doi: 10.1038/tpj.2014.12. Epub 2014 Mar 25.
PMID: 24663076
Abstract
There is little known about pharmacogenetic of fluoxetine in children and adolescents. In this study, we evaluate, for the first time, the influence of CYP2D6, CYP2C9 and ABCB1 genotypes on the steady-state plasma concentrations of fluoxetine and its active metabolite (S)-norfluoxetine, and on the clinical improvement in children and adolescent patients receiving fluoxetine treatment. The assessment was performed in 83 patients after 8 and 12 weeks of treatment. Fluoxetine/(S)-norfluoxetine ratio was negatively correlated with the number of active CYP2D6 alleles (r: -0.450; P<0.001). Regarding the G2677T ABCB1 polymorphism, T allele carriers showed significantly higher improvements on the majority of scales including the Clinical Global Impression-Improvement scale (P<0.001). Our results confirm the influence of CYP2D6 genetic variants in fluoxetine pharmacokinetics and provide evidence for the potential effect of the ABCB1 genotype on the clinical improvement in children and adolescent patients treated with fluoxetine. Lozano-Serra E, Andrés-Perpiña S, Lázaro-García L, Castro-Fornieles J. Adolescent Anorexia Nervosa: cognitive performance after weight recovery.
J Psychosom Res. 2014. 76(1):6-11.
PMID: 24360134
Abstract
OBJECTIVE: Although there is no definitive consensus on the impairment of neuropsychological functions, most studies of adults with Anorexia Nervosa (AN) find impaired functioning in cognitive domains such as visual-spatial abilities. The objective of this study is to assess the cognitive functions in adolescents with AN before and after weight recovery and to explore the relationship between cognitive performance and menstruation.
METHODS: Twenty-five female adolescents with AN were assessed by a neuropsychological battery while underweight and then following six months of treatment and weight recovery. Twenty-six healthy female subjects of a similar age were also evaluated at both time points.
RESULTS: Underweight patients with AN showed worse cognitive performance than control subjects in immediate recall, organization and time taken to copy the Rey’s Complex Figure Test (RCFT). After weight recovery, AN patients presented significant improvements in all tests, and differences between patients and controls disappeared. Patients with AN and persistence of amenorrhea at follow-up (n=8) performed worse on Block Design, delayed recall of Visual Reproduction and Stroop Test than patients with resumed menstruation (n=14) and the control group, though the two AN groups were similar in body mass index, age and psychopathological scale scores.
CONCLUSION: Weight recovery improves cognitive functioning in adolescents with AN. The normalization of neuropsychological performance is better in patients who have recovered at least one menstrual cycle. The normalization of hormonal function seems to be essential for the normalization of cognitive performance, even in adolescents with a very short recovery time.

INSTITUCIONS QUE RECONEIXEN AL GRUP DE RECERCA

El Servei de Psiquiatria i Psicologia Infantil i Juvenil de l’Hospital Clínic de Barcelona ha tingut una especial dedicació amb els trastorns de la conducta alimentària (TCA) des de fa molts d’anys. La Unitat de TCA del nostre servei ha estat designada per la Conselleria de Sanitat com a centre de referència a Catalunya per TCA en adolescents. Consta de diferents dispositius assistencials destacant l’Hospital de Dia (amb diferents programes d’intervenció), Hospitalització complerta. Disposa d’una Guia Clínica de TCA desenvolupada pels integrants de la unitat, de la que es basa el treball assistencial amb aquests pacients, englobant aspectes del diagnòstic, mesures d’avaluació psicomètriques, de l’abordatge terapèutic, integrant la vessant mèdico-nutricional com els aspectes del tractament psicològic, i psicoeducació a pacients i familiars.

A part de la tasca assistencial, des de la nostra unitat s’estan desenvolupant diferents estudis d’investigació entorn diferents aspectes dels trastorns alimentaris. El grup està integrat majoritàriament per membres del Servei de Psiquiatria i Psicologia Infantil, però està integrat en el Institut d’Investigacions biomèdiques August Pi i Sunyer (IDIBAPS) dins del grup Bases biològiques del Trastorn Psíquic (Coordinador M. Bernardo), i en el CIBER-SAM (Centro de Invesitgación Biomédicas en Red de Salut Mental del Instituto de Salud Carlos III) dins del grup de l’Hospital Clínic coordinat pel Dr. M Bernardo. També és part del Grup de Recerca Consolidat en Psiquiatria i Psicologia Infantil de l’Agència de Gestió d’Ajuts Universitaris de Recerca (AGAUR) de la Generalitat de Catalunya.