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The incidence of psychotic disorders varies in different geographic areas. As there has been no report from Turkey, this study aimed to provide the treated incidence rate of first-episode psychosis (FEP) in a defined area. All individuals, aged 15-64 years, presenting with FEP (ICD-10 F20-29, F30-33) to mental health services in a defined catchment-area in Sinop which is located in the Black Sea region of the northern Turkey were recorded over a 4-year period (2009 to 2012). Incidence rates of psychotic disorders and their 95% confidence intervals (CIs) were estimated. Poisson regression was applied to estimate the differences in incidence rate ratio (IRR) by age, sex, and urbanicity. One hundred and fifteen FEP participants were identified during the 4 years. Crude incidence rates of all psychoses, schizophrenia, other psychotic disorders, and affective psychotic disorders were respectively 38.5 (95% CI 27.1-49.9), 10.7 (95% CI 6.6-14.8), 10.0 (95% CI 5.7-14.3) and 17.7 (95% CI 11.3-24.2) per 100 000 person-years. After age-sex standardisation the rates increased slightly. There were no gender differences in the incidence rates. IRR of any psychotic disorder was highest in the youngest age group (15-24 years) compared to the oldest age group (55-64 years), 7.9 (95% CI 2.8-30.5). In contrast with previous studies, the incidence rate of any psychotic disorder was not significantly increased in urban areas compared with rural areas. The current study, the first of its kind from Turkey, indicates that the risk of schizophrenia and other psychotic disorders in a lowly urbanised area of Turkey is comparable to those reported in Western European cities.

Social capital is thought to represent an environmental factor associated with the risk of psychotic disorder (PD). This study aims to investigate the association between neighbourhood-level social capital and clinical transitions within the spectrum of psychosis. In total, 2175 participants, representative of a community-based population, were assessed twice (6 years apart) to determine their position within an extended psychosis spectrum: no symptoms, subclinical psychotic experiences (PE), clinical PE, PD. A variable representing change between baseline (T1) and follow-up (T2) assessment was constructed. Four dimensions of social capital (informal social control, social disorganisation, social cohesion and trust, cognitive social capital) were assessed at baseline in an independent sample, and the measures were aggregated to the neighbourhood level. Associations between the variable representing psychosis spectrum change from T1 to T2 and the social capital variables were investigated. Lower levels of neighbourhood-level social disorganisation, meaning higher levels of social capital, reduced the risk of clinical PE onset (OR 0.300; z = -2.75; p = 0.006), persistence of clinical PE (OR 0.314; z = -2.36; p = 0.018) and also the transition to PD (OR 0.136; z = -2.12; p = 0.034). The other social capital variables were not associated with changes from T1 to T2. Neighbourhood-level social disorganisation may be associated with the risk of psychosis expression. Whilst replication of this finding is required, it may point to level of social disorganisation as a public health target moderating population psychosis risk.

Exposures constitute a dense network of the environment: exposome. Here, we argue for embracing the exposome paradigm to investigate the sum of nongenetic “risk” and show how predictive modeling approaches can be used to construct an exposome score (ES; an aggregated score of exposures) for schizophrenia. The training dataset consisted of patients with schizophrenia and controls, whereas the independent validation dataset consisted of patients, their unaffected siblings, and controls. Binary exposures were cannabis use, hearing impairment, winter birth, bullying, and emotional, physical, and sexual abuse along with physical and emotional neglect. We applied logistic regression (LR), Gaussian Naive Bayes (GNB), the least absolute shrinkage and selection operator (LASSO), and Ridge penalized classification models to the training dataset. ESs, the sum of weighted exposures based on coefficients from each model, were calculated in the validation dataset. In addition, we estimated ES based on meta-analyses and a simple sum score of exposures. Accuracy, sensitivity, specificity, area under the receiver operating characteristic, and Nagelkerke’s R2 were compared. The ESMeta-analyses performed the worst, whereas the sum score and the ESGNB were worse than the ESLR that performed similar to the ESLASSO and ESRIDGE. The ESLR distinguished patients from controls (odds ratio [OR] = 1.94, P < .001), patients from siblings (OR = 1.58, P < .001), and siblings from controls (OR = 1.21, P = .001). An increase in ESLR was associated with a gradient increase of schizophrenia risk. In reference to the remaining fractions, the ESLR at top 30%, 20%, and 10% of the control distribution yielded ORs of 3.72, 3.74, and 4.77, respectively. Our findings demonstrate that predictive modeling approaches can be harnessed to evaluate the exposome.

Dear Editor, The Covid-19 pandemic affected human life globally, inducing much stress on daily living (Çakıroğlu et al. 2020). Although assessments of general mental health during the Covid-19 pandemic have been widely reported, there is not adequate research on how schizophrenia patients have been affected. According to the World Health Organization (2020), individuals with chronic diseases who do not pay attention to their personal hygiene and the rules of protection from COVID-19 have a higher risk of getting infected than the healthy individuals who observe these measures. It is well known that the risk of Covid-19 infection is raised among schizophrenia patients due to negligence on the requisite control of personal hygiene and health conditions related to smoking and diabetes ( Cohn et al., 2004; Dinan et al., 2004; Krieger et al. 2019). The cognitive impairment in this disorder which reduces the perceptions on the necessity of self protection and the awareness of the risks proposed to underlie this raised risk of COVID-19 positivity (Yao et al. 2020). These patients have difficulty in following the preventive regulations (Palomar-Ciria et al., 2020). Apart from the risk of infection, there is also the risk of pandemic related development of auditory or visual hallucinations and delusional symptoms by acute and chronic psychosis patients during and after the pandemic (Brown et al. 2020, Cowan 2020). Therefore, this survey has been organised to evaluate the reaction developed by schizophrenia patients to the pandemic conditions. The first Covid-19 case was reported in Turkey on 11 March 2020 (Anadolu Agency, 11.03.2020) which was followed by the gradual increase in case numbers. In order to prevent the spread of Covid-19 and maintain the existing public health, the Republic of Turkey Ministry of Health established a 'Scientific Committee'' and prepared effective strategies including social isolation, quarantine, school closures, social distancing and wearing face mask in the community. During this process, the approximately 250 schizophrenia and schizoaffective disorder patients followed up by the Psychosis Outpatient Unit of Dokuz Eylul University Hospital Psychiatry Department (DEUPD) were instructed to visit the outpatient unit only in emergency conditions. It was determined that there were 176 schizophrenia patients whose follow up visit appointments for the period of April 1 - June 22, 2020, scheduled before the announcement of the pandemic, were cancelled. Therefore, the survey reported here was conducted with the schizophrenia patients of the DEUPD online and by telephone connections during 10- 20 May, 2020, the 9th and the 10th weeks of the pandemic. Only 76 (43.19%) of the 176 patients joined the survey, since 4 (2.27%) refused to participate and 96 (54.4%) could not be contacted. The survey aimed to determine the incidence of Covid-19 diagnosis among these schizophrenia patients and their attitude to the preventive measures against the infection during the first 2 months of the pandemic, together with how they felt and their needs for psychiatric consultation on outpatient basis during this period. The surveyed 76 patients consisted of 49 (64%) males and 27 (35%) females, with 73 (96.1%) dwelling in urban and 3 (3.9%) in suburban areas; and only 11 (14.5%) employed while 65 (85.5%) were not working. Only two patients reported consulting emergency services for Covid-19 symptoms. The rest of the patients did not report consulting a healthcare facility for suspecting Covid-19 symptoms or   Table 1. Data on the demographic, clinical and social features of the schizophrenia patients during the COVID-19 pandemic   n=76           Mean SD   Gender (F/M) 27 (35.5%) / 49 (64.5%)     Age   44.54 12.21   Disease duration   16.62 9.96   Patients living /with         Alone   3 (3.9%)     Parent(s)   43 (56.6%)     Spouse/children 25 (32.9%)     Sibling (s) 1 (1.3%)     Relative(s) 2 (2.6%)     Friend(s)   2 (2.6%)           Yes No Need to see a psychiatrist     23 (30.3%) 53 (69.7%) Subjective psychiatric complaints     32 (42.1%) 44 (57.9%) Consultation with an emergency service     2 (2.6%) 74 (97.4%) Planning to go to the hospital in the post-quarantine period   58 (76.3%) 18 (23.7%) Wearing a mask in community     67 (88.2%) 4 (5.3%) Keeping social distancing     68 (89.5%) 3 (3.9%) Expressed feeling         Loneliness   26 (34.2%) 49 (64.5%) Depressed   31 (40.8%) 44 (57.9%) Despaired   22 (28.9%) 52 (68.4%) Anxious     25 (32.9%) 49 (64.5%) Difficulty of going to the hospital in the quarantine period   53 (69.7%) 23 (30.3%)   hospital admission for Covid-19 infection or psychotic attack or incidences of Covid-19 related hallucination or delusions. During this 2-month period, 4 patients had experienced fatigue, 2 had episodes of dry cough and 7 had experienced shortness of breath, which can be associated with the nature of schizophrenia, the sedentary life style.and cigarette smoking. Medication was prescribed by a psychiatrist for 10 patients and by a family doctor for 16 patients or supplied directly by pharmacies for 45 patients on the basis of prescriptions with 1-year validity issued by the hospital* (Table 1). Much as it had been aimed to contact all patients with cancelled appointments, this objective was not attainable The patients who were not reached are likely to include those with low awareness and difficulty of adapting to infection prevention strategies. On the other hand, regardless of the level of awareness of the pandemic and compliance with the rules, phone use by these patients might have been limited by economic and environmental reasons, as well as the difficulties imposed by the pandemic. In conclusion, it is possible to say that most of the patients with schizophrenia were aware of the risk of COVID-19 infection, and understood and mostly obeyed the general health rules and advices of healthcare professionals even if they had difficulty in doing so. This could also have resulted from the nature of schizophrenia with preference for social isolation even if this can worsen the prognosis. On the other hand, patients need to be in contact with a mental healthcare professional in extraordinary situations of a pandemic. This survey did not find a remarkable increase in positive symptom severity in association with COVID-19 as most patients included in the survey had not seen a psychiatrist or mental healthcare professional for two months with 53 patients stating that they did not have to need.   However, 58 patients also stated that despite planning to make a consultation after normalization of the quarantine measures, the anxiety of contagion outweighed the option of visiting outpatient clinics. This anxiety over Covid-19 infection, however, may make it difficult for patients to understand the level of the need to see a psychiatrist and may be associated with the assumption that the pandemic would be taken under control in the normalization process with a decrease in the risk of contagion. On the results of this survey, it may be concluded that strategies for prevention of COVID-19 spread were effective among schizophrenia patients and that there is need to develop a system that reaches all patients and keeps them socially connected during the COVID-19 pandemic. *In Turkey, prescription reports with 1-year validity are issued for patients with chronic disorders. The medications can only be prescribed by a specialist, and in the case of pyshchiatric disorders, by a consultant psychiatrist. When the report is confirmed by a hospital committee of specialists, a family doctor is able to issue prescriptions. According to the decision of the Ministry of Health, patients who have medication prescription reports valid for one year would be able to get their medicines directly from pharmacies without having to consult a psychiatrist or family doctor during the pandemic.               REFERENCES Anadolu Agency (2020, Mach 11). Sağlık Bakanı Koca Türkiye'de ilk koronavirüs vakasının görüldüğünü açıkladı, https://www.aa.com.tr/tr/kor onavir us/ saglik-bakani-koca-turkiyede-ilk-koronavirus-vakasinin-goruldugunu- acikladi/1761466. Accessed 28 May 2020.   Brown E, Gray R, Lo Monaco S et al (2020) The potential impact of COVID-19 on psychosis: A rapid review of contemporary epidemic and pandemic research. Schizophr Res 222:79-87. Cohn T, Prud'homme D, Streiner D et al (2004) Characterizing coronary heart disease risk in chronic schizophrenia: High prevalence of the metabolic syndrome. Can J Psychiatry 49:753-60. Cowan, HR (2020) Is schizophrenia research relevant during the COVID-19 pandemic?. Schizophr Res 220:271-2. Çakıroğlu S, Ertaş E, and Alyanak B (2020) Letter To The Editor - The Covid-19 Pandemic And Mental Health As Issues Considered Within The Context Of Adjustment Disorder And Psychosocial Interventions. Turk Psikiyatri Derg 31:148-50. Dinan T, Holt R, Kohen D et al (2004) \"Schizophrenia and diabetes 2003\" expert consensus meeting, Dublin, 3-4 october 2003: Consensus summary. Br J Psychiatry 184 (Suppl. 47): 0-2. Krieger I, Bitan DT, Comaneshter D et al (2019) Increased risk of smoking- related illnesses in schizophrenia patients: A nationwide cohort study. Schizophr Res 212:121-5. Palomar-Ciria N, del Valle PB, Hernández-Las Heras MÁ et al (2020) Schizophrenia and COVID-19 delirium. Psychiatry Res 290:113137. Yao H, Chen JH, and Xu YF (2020) Patients with mental health disorders in the COVID-19 epidemic. Lancet Psychiatry 7: e21. World Health Organization (2020, Mart 25). Covid-19: Vulnerable and High Risk Group, Geneva, Switzerland: World Health Organization, https:// www.who.int/westernpacific/emergencies/covid-19/information/high-risk- groups. Accessed 28 May 2020.

The relationship between childhood trauma (CT) and psychotic symptoms in patients with schizophrenia (SCZ), and subthreshold psychotic experiences in non-clinical populations is well-established. However, little is known about the relationship between subtypes of trauma and specific symptoms in patients, their siblings, and controls. It is also not clear which variables mediate the relationship between trauma and psychotic symptoms. Seven hundred and forty-two patients with SCZ, 718 of their unaffected siblings and 1039 controls from three EU-GEI sites were assessed for CT, symptom severity, and cognitive schemas about self/others. CT was assessed with the Childhood Trauma Questionnaire, and cognitive schemas were assessed by The Brief Core Schema Scale. Patients with psychosis were affected by CT more than their siblings and controls in all domains. Childhood emotional abuse and neglect were more common in siblings than controls. CT was related to negative cognitive schemas toward self/others in patients, siblings, and controls. We found that negative schemas about self-mediated the relationship between emotional abuse and thought withdrawal and thought broadcasting. Approximately 33.9% of the variance in these symptoms was explained by the mediator. It also mediated the relationship between sexual abuse and persecutory delusions in SCZ. Our findings suggest that childhood abuse and neglect are more common in patients with schizophrenia than their siblings and healthy controls, and have different impacts on clinical domains which we searched. The relationship between CT and positive symptoms seems to be mediated by negative cognitive schemas about self in schizophrenia.

Psychotic experiences (PEs) may predict a range of common, non-psychotic disorders as well as psychotic disorders. In this representative, general population-based cohort study, both psychotic and non-psychotic disorder outcomes of PE were analysed, as were potential moderators. Addresses were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighbourhoods at baseline (n = 4011). Participants were interviewed with the Composite International Diagnostic Interview (CIDI) both at baseline and at 6-year follow-up. Participants with PE at baseline were clinically re-interviewed with the SCID-I at follow-up. The role of socio-demographics, characteristics of PE, co-occurrence of mood disorders and family history of mental disorders were tested in the association between baseline PE and follow-up diagnosis. In the participants with baseline PE, the psychotic disorder diagnosis rate at follow up was 7.0% - much lower than the rates of DSM-IV mood disorders without psychotic features (42.8%) and other non-psychotic disorders (24.1%). Within the group with baseline PE, female sex, lower socio-economic status, co-occurrence of mood disorders, family history of a mental disorder and persistence of PE predicted any follow-up DSM diagnosis. Furthermore, onset of psychotic v. non-psychotic disorder was predicted by younger age (15-30 years), co-presence of delusional and hallucinatory PE and family history of severe mental illness. The outcome of PE appears to be a consequence of baseline severity of multidimensional psychopathology and familial risk. It may be useful to consider PE as a risk indicator that has trans-diagnostic value.

There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation. We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 ( = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI ( = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls. The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, = 0.037] and in EUGEI (RERI = 3.39, = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, = 0.003; EUGEI: RERI = 4.16, = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, = 0.284; EUGEI: -0.37, = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, < 0.001; EUGEI: 6.44, < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, < 0.001; EUGEI: 5.43, = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, < 0.001; EUGEI: 0.54, = 0.465). The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

Purpose This paper aims to investigate associations between early childhood and current indicators of socioeconomic inequality and the onset (incident), persistence and progression (increase in severity) of psychotic experiences (PEs) in a longitudinal follow-up of a community-based population. Methods Households in the metropolitan area of Izmir, Turkey were contacted in a multistage clustered probability sampling frame, at baseline (T 1 , n  = 4011) and at 6-year follow-up (T 2 , n  = 2185). Both at baseline and follow-up, PEs were assessed using Composite International Diagnostic Interview 2.1. The associations between baseline socioeconomic features and follow-up PEs were analysed using logistic regression models. Indicators of social inequality included income, educational level, current socioeconomic status (SES), social insurance, the area resided, ethnicity, parental educational level, and SES at birth. Results The risk of onset of PEs was significantly higher in lower education, lower SES, and slum-semi-urban areas. The persistence of PEs was significantly associated with the lowest levels of education and current SES, and rural residency. Persistent PEs were significantly and negatively associated with paternal SES at birth. Progression of PEs was significantly higher among respondents with educational achievements lower than university level and lower levels of SES, who have no social insurance and who reside in slum-semi-urban areas. Parental education and paternal SES at birth were not associated with the persistence of PEs. Conclusion Indicators of social inequality (low education, low SES, low income, and poverty in the neighbourhood) were associated with the onset and persistence of PEs and progression along the extended psychosis phenotype. The early indicators seem to have a modest life-long impact on the psychosis phenotype.

First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes. We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS. In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group. The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene-environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.

Background Psychotic experiences (PEs) are not exclusive to psychotic disorders and highly correlated with mood episodes. In this representative general population-based study, longitudinal bidirectional associations between the extended psychosis phenotype and mood episodes were investigated, accounting for other possible causes. Methods Households were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighbourhoods at baseline ( n  = 4011) and at 6-year follow-up ( n  = 2185). Participants were interviewed with the relevant sections of the composite international diagnostic interview both at baseline and at follow-up. Sociodemographic, familial and environmental risk factors associated with the extended psychosis phenotype and mood episodes were assessed. Logistic regression and cross-lagged panel correlation models were used for the associations between the extended psychosis phenotype and mood episodes. Results PEs were associated with subsequent depressive and manic episodes. There was bidirectionality in that mood episodes were associated with subsequent PEs, and PEs were associated with subsequent mood episodes. The associations occurred in a sub-additive pattern. There were substantial synchronous and cross-lagged correlations between these psychopathology domains, with reciprocally similar cross-lagged correlations. Familial risk and adverse life events were associated with both psychopathology domains, whereas some sociodemographic risk factors and alcohol/cannabis use were associated with only one domain. Conclusion The sub-additive bidirectional associations between PEs and mood episodes over time and the similarity of cross-lagged correlations are suggestive of mutually causal connections between affective and psychotic domains of psychopathology.