The study protocol was submitted to ERA-NET NEURON for funding on 28/06/2023. Description of the Israeli responsibilities was extracted from the full submitted research protocol. The protocol includes two studies (CHS1 and CHS2). At the time of the study registration CHS1 was partially analyzed whereas CHS2 has not been initiated. See below the full description of the two studies' protocols. To explore the probability of mental illness (MI) onset or psychiatric relapse following infections, we will utilize two databases from the CHS registries from Israel (n=50,000, n=69,594). Participants with a high load of past infections (cohort 1, n=50,000) will be identified and matched in a 1:1 ratio to controls by age and sex. Probability of MI onset across a broad range of psychiatric disorders, including depression, bipolar disorder, anxiety and psychotic disorders will be explored. The probability of psychiatric relapse among individuals with pre-existing mental disorder following infection will be investigated in a cohort of 34,797 individuals with schizophrenia matched randomly to age and sex controls with no diagnosis of schizophrenia (n = 34,797) (cohort 2, total n=69,594, 5). Socio and sociodemographic factors which might serve as vulnerability or resilience factors will be assessed across both cohorts, and will include environmental factors such as socioeconomic status, familial status, healthcare utilization information and demographic factors. In addition, The CHS databases (n=50,000, n=69,594) will be utilized to study outcomes of infections in SMI. From the CHS databases in Israel, outcome of infections will be assessed in the two previously described cohorts. Severe outcomes will be defined as hospital admission \~two weeks after a diagnosis of an infection, among individuals with pre-existing anxiety, depression, bipolar diagnosis (n=50,000), and among patients with schizophrenia (n=69,594), as well as all-cause mortality. The following infections will be considered: Epstein Barr Virus, Cytomegalovirus, Toxoplasma Gondii, COVID-19, and Herpes viruses. Environmental protective and risk factors and their moderating role in the association between infection and outcome will include marital status, number of siblings, and sociodemographic factors. Vulnerability factors such as smoking, obesity, and comorbid physical illness will also be examined. The presence of pre-existing viral infections will be assessed as a potential vulnerability factor.
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CHS 1: Mental Illness
Timeframe: Up to 30 years.
CHS 2: Post-infection relapse
Timeframe: 3 months post infection