WP 4 Translation to clinical practice ERANET NEURON Project: Linking synaptic dysfunction to disease mechanisms in schizophrenia - a multi-level investigation (SYNSCHIZ) WP 4 Translation to clinical practice Obregia Clinical Hospital of Psychiatry

OBJECTIVE The objective of the first phase of the project was the initiation of the patients group. Start data – 01.05.2018

METHODS A. Elaboration of the documents for obtaining the approval from Ethics Committee of the Clinical Hospital Of Psychiatry "Prof. Dr. Alex. Obregia". Specific documents, which included informed consent for the patient or his / her legal representative and a description of the project, were submitted to the Ethics Commission of the Clinical Psychiatric Hospital "Prof. Dr. Alex. Obregia ". The Ethics Commission approved the project activities.

METHODS B. Methodology for clinical evaluation of patients with schizophrenia A working protocol was developed for constitution of the patient group.

Visit 1 Inclusion criteria: diagnosis of schizophrenia including all subtypes according to DSM IV and ICD 10. Exclusion criteria: psychoactive substance use that can induce psychosis. The patient / legal representative is informed about the present study. The patient / legal representative signs the Informed Consent in 2 copies in the presence of the doctor and keeps a copy. Patient code Sex Date of birth Ethnicity Clinical and psychiatric evaluation Diagnosis: Schizophrenia with all the subtypes according to DSM IV TR and ICD 10 Patient history Family history Personal medical history – comorbidities (medical documents to prove) with associated medication Psychiatric history - data on the age at onset, number of episodes, the degree of remission of inter-episodes symptomatology, the previous neuroleptic treatment, the mentioning of possible suicide attempts Scales: PANSS, Calgary Scale, Sheehan Disability Scale (SDS), Addenbrooke’s Cognitive Examination Blood taking for: Complete blood count; Hormones: TSH, fT4, prolactin; Inflammation markers: ESR, CRP; Biochemistry: TGP, TGP, GGT, LDL-cholesterol, HDL-cholesterol, triglycerides, total lipids, glycaemia, HbA1c; Ionogram: Na, K, Cl Blood for DNA extraction Setting up a schedule for EEG, MRI

RESULTS In the current stage, 230 patients with schizophrenia were clinically evaluated: 221 - adult patients with paranoid schizophrenia 9 - adolescents with schizophrenia or acute psychosis.

The anamnesis included: - history of the disease: onset of symptoms, evolution, trigger factors; - family history: the existence of other relatives with schizophrenia or other mental illness in the patient's family; - personal history: school and professional route, drugs consumption, association of other medical conditions.

49 patients donated blood for genetic studies 43 adults 6 adolescents

Adult patients 30 females 13 males

Adult patients Age distribution: 21 – 69 yrs.

Adult patients Familial history positive for psychiatric diseases – 13 patients

Adult patients Comorbidities – 20 patients 7

Adult patients Marital status: 5 patients – married 5 patients – divorced 1 patient – widow 31 patients – no partner

Adult patients Education 30 – high school 5 - faculty 3 – 10 yrs school 2 – primary school 2 – secondary school

Adolescent patients 5 females 1 male Age – 14 – 17 yrs.: 1 – 14 yrs.

Adolescent patients Familial history positive for psychiatric diseases – 3 patients Personal history – 1 patient – premature birth with mild delayed psychomotor development 5 patients – high school students with good results 1 patient – abandoned the school

Schizophrenia in children and adolescents The study included children and adolescents with schizophrenia or acute psychosis admitted to the Child and Adolescent Psychiatry Clinic from January 2017 to May 2019

116 patients aged from 11 to 17 years 74 males and 42 females

62 of adolescents had at least one first-degree or second-degree relative with psychiatric history.

Comorbidities: - epileptic seizures in 8 children, - ADHD in 6 children, - 16 patients associated intellectual disability, mostly the mild form (12 patients).

The disorder’s onset was due to the use of drugs in 10 patients. In most cases (81 patients), the primary symptoms were hallucinations or delusions; other symptoms included social withdrawal, depressive disposition, aggressivity, and negativism.