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 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 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, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 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.

This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation.

Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses.

JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences.

These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.

Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing.

We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8–18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task.

Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression.

Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment.

The aim of this longitudinal study was to determine whether the depot formulation of an antipsychotic reduces violence in outpatients with schizophrenia as compared to oral administration of the same antipsychotic.

Forty-six previously violent patients with schizophrenia were randomised to receive treatment with oral or depot zuclopenthixol for 1 year. Clinicians interviewed patients at baseline and every month thereafter to assess treatment adherence. An interviewer blinded to treatment assignments interviewed an informant about any violent behaviour during the previous month.

Violence during the follow-up year was inversely proportional to treatment adherence, better compliance, and greater reduction of positive symptoms. Lower frequency of violent acts was observed in the depot group. The level of insight at baseline was not significantly associated with violence recidivism. Regardless of route of administration, treatment non-adherence was the best predictor of violence.

Some patients with schizophrenia and prior violent behaviour may benefit from the depot formulation of antipsychotic medication.

To determine the change in prevalence of posttraumatic stress disorder (PTSD) symptoms in victims of the March 11 attacks and their relatives, 1 and 6 months after the attacks.

Evaluation of PTSD symptoms using the Davidson Trauma Scale (DTS) and General Health Questionnaire (GHQ) in a sample of 56 patients admitted to an emergency room of a general hospital, and assessment of PTSD symptoms in relatives of the patients.

At Month 1, 41.1% of patients (31.3% of males and 54.2% of females) presented with PTSD. At Month 6, this figure was 40.9% (30.4% of males and 52.4% of females). There was a significant improvement in perception of health among females between Month 1 and Month 6. Relatives presented similar DTS scores at baseline and at 6 months.

We verified that rates of PTSD did not vary substantively between the two evaluations. PTSD symptoms positively correlated with psychological health involvement. This correlation points out that both PTSD symptoms and subjective general health involvement are part of the psychological response to trauma.

The prevalence of PTSD symptoms was high and remained stable between Month 1 and Month 6, while subjective perception of health improved significantly.

This study assessed the prevalence of MS in patients treated with antipsychotics using two proposed NCEP-ATP-III definitions.

A retrospective, cross-sectional, multicenter study was carried out by 117 Spanish Psychiatrists (The CLAMORS Collaborative Group). Consecutive outpatients meeting DSM-IV criteria for Schizophrenia, Schizophreniform or Schizoaffective Disorder, under antipsychotic treatment for at least 12 weeks, were recruited. MS was defined as fulfilment of at least 3 of the following components: waist circumference >102(men) / >88(women)cm (NCEP-ATP-III definition), or BMI>=28.8 kg/m2, (revised NCEP-ATP-III definition); tryglicerides>=150mg/dL; HDL-cholesterol <40mg/dL(men) / <50mg/dL(women); blood pressure >=130/85; fasting glucose >=110mg/dL. Kappa coefficients and bivariate logistic regression models were applied.

1452 evaluable patients (863 men, 60.9%), 40.7+12.2 years (mean+SD) were included. MS was presented in 24.6% [23.6%(men), 27.2%(women); p=0.130)] (NCEP-ATP-III definition), and in 25.5% [25.6%(men), 25.6%(women); p=0.9924)] (revised NCEP-ATP-III definition). Kappa coefficient between both definitions was 0.81 [0.81(men), 0.84(women)]. Obesity component was present in 42.4% of patients [34.3%(men), 54.5%(women); p<0.001] when defined by waist circumference (NCEP-ATP-III definition), and in 38.2% [36.7%(men), 39.4%(women); p=0.3156] when defined by BMI (revised NCEP-ATP III definition). Obesity component was less associated to presence of MS when it was defined by waist circumference (OR=9.99, 95%CI:7.37-13.55), than when it was defined by BMI (OR=11.19, 95%CI:8.42-14.87).

Obesity plays a central role in the NCEP-ATP-III definition of MS. Prevalence of the abdominal obesity component may be assessed by either the measurement of the waist circumference or by calculation of the body mass index without losing reliability.

On behalf of the CLAMORS Collaborative Group.

This study assessed the factors associated to persistence of negative symptoms in patients treated with antipsychotics.

A retrospective, cross-sectional, multicenter study was carried out by 117 Spanish Psychiatrists (The CLAMORS Collaborative Group). Consecutive outpatients meeting DSM-IV criteria for Schizophrenia, Schizophreniform or Schizoaffective Disorder, under antipsychotic treatment for at least 12 weeks, were recruited. Negative symptoms were assessed using the PANSS scale (1-blunted affect; 2-emotional withdrawal; 3-poor rapport; 4-social withdrawal; 5-abstract thinking; 6-verbal fluency; 7-stereotyped thinking). Persistence of a negative symptom was defined by severity score >3. Multivariate logistic regression models were applied including gender, age, civil status, work situation, BMI, time on antipsychotic treatment and dose, CGI and Total and Positive PANSS scores, cardiovascular risk by SCORE (10-year death) and Framingham (10-year all CV events) equations and Metabolic Syndrome.

1452 evaluable patients (863 men, 60.9%), 40.7+12.2 years (mean+SD) were included. Negative symptoms (one or more) were presented in 60.3% of patients. All negative symptoms were associated to worst clinical severity (higher CGI and Total PANSS scores). Negative symptoms were also associated to gender (symptoms 4), age (symptoms 1,2,4,5), civil status (symptoms 2,4), work situation (symptoms 3,4,5), time on antipsychotic treatment (symptoms 1,2,3,6,7), and dose (symptom 2).

Persistence of negative symptoms plays an important role in patients treated with antipsychotics, being all of them associated to clinical severity but also to other sociodemographic and time and dose with current antipsychotic treatment.

On behalf of the CLAMORS Collaborative Group.

This study assessed the persistence of negative symptoms in patients treated with antipsychotics.

A retrospective, cross-sectional, multicenter study was carried out by 117 Spanish Psychiatrists (The CLAMORS Collaborative Group). Consecutive outpatients meeting DSM-IV criteria for Schizophrenia, Schizophreniform or Schizoaffective Disorder, under antipsychotic treatment for at least 12 weeks, were recruited. Negative symptoms were assessed using the PANSS scale (1-blunted affect; 2-emotional withdrawal; 3-poor rapport; 4-social withdrawal; 5-abstract thinking; 6-verbal fluency; 7-stereotyped thinking). Persistence of a negative symptom was defined by severity score > 3. Persistence of primary negative symptoms was defined when: not present extrapyramidal symptom (EPS); not present items 2 (anxiety) or 6 (depression) of General Psychopathology PANSS scale (<=3); dose of haloperidol non higher than 15 mg/d; and not present antiparkinsonian treatment.

1452 evaluable patients (863 men, 60.9%), 40.7+12.2 years (mean+SD) were included. Negative symptoms (one or more) were presented in 60.3% of patients. The most frequent negative symptoms were social withdrawal (45.8%), emotional withdrawal (39.1%), poor rapport (35.8%) and blunted affect (33.1%). Primary negative symptoms (one or more) were present in 33.1% of patients. The most frequent primary negative symptoms were also social withdrawal (18.2%), emotional withdrawal (14.8%), poor rapport (14.8%) and blunted affect (12.8%).

Persistence of negative symptoms plays an important role in most patients treated with antipsychotics, being near half of them primary negative symptoms.

On behalf of the CLAMORS Collaborative Group.

To describe a generalizable stochastic-simulation model for schizophrenia treatment related with the cardiovascular associate risk of SGA.

A model to simulate the expected 10-year occurrence of all-type cardiovascular events (CVE) in a hypothetical cohort of 100.000 patients with schizophrenia treated with SGA drugs in Spain was developed. The model considered, as a baseline health state, outpatient treated with SGA with characteristics of patients enrolled in the CLAMORS study; a cross-sectional study in schizophrenia spectrum disorders aimed to ascertain prevalence of metabolic syndrome in such patients together with CHD. Three other states were considered: suffering a CVE, death due to CVE and death due to other causes. The CVE risk for each SGA drugs was estimated through a locally-adjusted Framingham risk equation. Treatment outcomes were simulated using the expected mean change of the cardiovascular (CV) risk factors from the CATIE clinical trial. Death by CVE or others causes were estimated from published literature.

The 10-year rate of CVE following SGA treatment was 0.181, 0.179, 0.176 and 0.172 for olanzapine, quetiapine, risperidone and ziprasidone, respectively. Relative risk was calculated relative to no-treatment, and the corresponding values were 1.03, 1.02, 1.00 and 0.97. The total estimated CVE were 25,269 events; 25,157; 24,883 and 24,514, respectively.

A generalizable, flexible model was developed through stochastic simulation of the CV risk for SGA drugs. The estimated clinical outcomes suggest different levels of CVE risk for each SGA drugs. Ziprasidone showed the lower rate with no association with increased risk for CHD.

Brain volume abnormalities and oxidative cell damage have been reported to be pathological characteristics of schizophrenia patients. This study aims to assess a potential relationship between these two characteristics in child and adolescent patients with first-episode psychosis.

26 child and adolescent patients with first-episode early-onset schizophrenia, and 78 age- and gender-matched healthy controls were assessed. Magnetic resonance imaging (MRI) scans were used for volumetric measurements of five cerebral regions: gray matter of the frontal, parietal, and temporal lobes, sulcal cerebrospinal fluid (CSF), and lateral ventricles. Oxidative cell damage was traced by means of a systemic increase in lipid hydroperoxides (LOOH).

Lateral ventricle volumes were significantly higher in schizophrenia patients than in controls. In schizophrenia patients, a significant positive relationship was found between oxidative cell damage (LOOH levels) and the abnormal enlargement of the lateral ventricles, after controlling for total intracranial volume, age, gender, daily smoking status, intelligence quotient (IQ), psychopathology, and time since onset of psychotic symptoms. No association was found between brain volumes and oxidative cell damage in control subjects.

Our results suggest that, in patients with first-episode early-onset schizophrenia, enlargement of the lateral ventricles is associated with chronic oxidative cell damage.

Thirty-six OCD patients on maintenance treatment were evaluated using the Y-BOCS, SF-36, and DAS-S. Their SF-36 scores were compared to Spanish norms and to those obtained from U.S. OCD patients, schizophrenic outpatients, depressed outpatients, heroin dependents, patients on hemodialysis, and kidney transplant recipients.

Early-onset psychosis (EOP) are a heterogeneous group, with high diagnostic stability for schizophrenia and bipolar disorder, in contrast to the lack of diagnostic stability of other EOP.

We recruited 24 adolescents consecutively admitted, who presented a first psychotic episode, in the adolescent psychiatric unit of the Gregorio Marañón General Hospital in Madrid, between May 2002 and May 2003, for a two year follow-up. Only one was lost at the two-year assessment.

Diagnosis of the psychotic disorders was assessed using the Kiddie-Sads-Present and Lifetime Version (K-SADS-PL).

The agreement between the baseline and the one-year follow-up diagnoses was 54.2%. Positive Predictive Value (PPV) was 100% for schizophrenia and depression with psychotic features, and 71.4% for bipolar disorder, while only 50.0% for schizo-affective disorder and 16.7% for psychosis NOS. From the one-year to the two-year follow-up, only one patient changed the diagnosis, so the agreement was 95.7%.

Eight patients were diagnosed with schizophrenia at the follow-up, but only four of them had received this diagnosis at the baseline assessment. The diagnosis of bipolar disorder was given at the follow-up to eight patients, from whom only four subjects received this diagnosis at baseline.

The results of the our longitudinal study on diagnostic stability support the Kraepelinean distinction between dementia praecox and manic-depressive psychosis.

To assess the prevalence of metabolic syndrome (MS) and the coronary heart disease (CHD) risk in patients with schizoaffective disorder treated with antipsychotics.

Schizoaffective patients from a multicentre cross-sectional study, in which 117 psychiatrists recruited consecutive outpatients meeting DSM-IV criteria for schizophrenia, schizophreniform or schizoaffective disorder and receiving antipsychotic treatment in monotherapy for at least 12 weeks. MS was defined as fulfilment of at least 3 of the following components (NCEP-ATP-III definition): waist circumference >102(men)/>88(women) cm; triglycerides >=150mg/dL; HDL-cholesterol < 40mg/dL(men)/< 50mg/dL(women); blood pressure >=130/85; fasting glucose >=110mg/dL. CHD risk was assessed by SCORE (10-year CV death) and Framingham (10-year all CV events) functions.

268 valuable patients with schizoaffective disorder (127 men, 48.1%), 41.9±12.3 years (mean±SD) were examined. MS was presented in 26.5% (95%CI:21.2-31.8) of subjects [26.8% in men (19.1-34.5), 27.0% (19.6-34.4) in women (p=0.966)]. the overall 10-year CV risks (CV death or any event) were 0.8±1.6 (SCORE) and 6.5±6.8 (Framingham), respectively. the 8.4% (95%CI:5.0-11.8) and 20.1% (95%CI:15.2-24.9) of patients showed high/very-high risk according to SCORE (≥3%) and Framingham (≥10%), respectively. A high/very-high risk of any CV event (Framingham≥10%) was associated with age above 40(men)/45(women) years [OR: 32.44 (9.59-109.71, p< 0.001)], and CGI-S=3-4; [OR: 4.32 (1.15-16.26, p=0.03)]. Women showed lower risk of any CV event [OR: 0.30 (0.14-0.65, p=0.002)].

MS prevalence and CHD risk were high among patients with schizoaffective disorder treated with antipsychotics. Gender, age and poor disease control could be associated with CHD risk.

*On behalf of the CLAMORS Collaborative Group.

Psychosis with onset prior to 18 years of age, or early-onset psychosis (EOP), have a poorer prognosis than adult-onset psychosis. Further, a worse functional outcome of patients with EOP has been related to diagnosis of schizophrenia, severity of negative symptoms, behavioral problems, premorbid functioning, childhood onset, and insidious onset. We aim to examine the functional outcome of patients with EOP over a two-year follow-up.

A total of 24 patients with first episode psychosis were enrolled. Subjects underwent a cross-sectional evaluation at the baseline visit that consisted of collecting sociodemographic data, including parental socioeconomic status as measured by the Hollingshead-Redlich Scale. Psychotic symptoms were assessed using the Spanish version of the Positive and Negative Syndrome Scale (PANSS). Social disability was measured with the Global Assessment of Functioning disability scale (GAF). Patients were assessed at a two-year follow-up. A linear regression analysis was used to predict the level of functioning (based on GAF scores) over the two-year follow-up. Variables entered into this equation were: GAF at two-year follow-up (as dependent variable), and gender, age at first onset, parental socioeconomic status, diagnosis, positive symptoms at baseline, and negative symptoms at baseline (as independent variables).

Negative symptoms at baseline were the only significant variable that predict the functional outcome at the two-year follow-up (p= 0.010).

Functional prognosis of early-onset psychosis depends on the severity of negative symptoms, independently of diagnosis.

To assess the coronary heart disease (CHD) risk and prevalence of the metabolic syndrome (MS) in patients with schizoaffective disorder (SD) receiving antipsychotics.

Patients meeting DSM-IV criteria for SD and receiving antipsychotic treatment were recruited in a retrospective, cross-sectional, multicenter study (the CLAMORS study). MS was defined as at least three of the following components: waist circumference greater than 102cm (men)/greater than 88cm (women); serum triglycerides greater or equal to 150mg/dl; HDL cholesterol less than 40mg/dl (men)/less than 50mg/dl (women); blood pressure greater or equal to 130/85mmHg; fasting blood glucose greater or equal to 110mg/dl. The 10-year CHD risk was assessed by the Systematic coronary risk evaluation (SCORE) (cardiovascular mortality) and Framingham (any cardiovascular event) functions. Clinical severity was assessed using the PANSS and CGI-S scales.

A total of 268 valuable patients with SD (127 men, 48.1%), 41.9±12.3years (mean±S.D.), were analyzed. The 10-year overall cardiovascular mortality and CV-event risk were 0.8±1.6 (SCORE) and 6.5±6.8 (Framingham), respectively. A high/very high risk of any CV event (Framingham≥10%) was associated with severity [CGI-S=3–4; OR: 4.32 (1.15–16.26), P = 0.03)]. MS was present in 26.5% (95%CI: 21.2–31.8) of subjects, without gender differences, but significantly associated with patient's impression of severity: CGI=3–4; OR=1.90 (0.83–4.36), and CGI=5–7; OR=3.13 (1.06–9.24), P = 0<0.001, and age [OR=1.91 (1.09–3.34), P<0.024)].

CHD risk and MS prevalence were high among patients with SD, being MS prevalence associated with age and severity of disease.

Previous studies have reported progressive brain changes and cognitive deficits in early-onset psychosis (EOP). Little is known on the relationship between longitudinal changes in brain structure and neurocognition.

Naturalistic 5-year prospective study comparing frontal gray matter (GM) volume and executive functions in adolescents with a first episode of EOP and a sample of healthy controls at baseline, 2-year and 5-year follow-up.

Thirty-six patients (age at baseline 15.8 ±.7, 66.6% male) and 34 controls (15.4±1.4, 55.9% male) comprised the study sample. Both patients and controls presented with frontal GM loss during the first five years of follow-up. During the first two years, patients presented with significantly greater GM loss than controls in the left (F=9.642, p=0.003) and right frontal lobe (F=7.585, p=0.008), with no significant differences between year 2 and 5. Patients with EOP performed significantly worse in executive tasks than controls in all visits. During the first two years of follow-up, controls, but not patients, presented with a significant improvement in executive functioning (F=7.523, p=0.009), with similar evolution of cognitive functioning between years 2 and 5 in both groups (F=0.908, p=0.346). Changes in frontal GM volume and executive functioning were not significantly correlated within the entire follow-up period.

Over the first two years of illness, patients with EOP show greater frontal GM loss and less improvement in executive functions than expected. This could be a critical period for the development of deficits in EOP, in which more intensive interventions would be warranted.

Earlier studies have examined the symptom dimensions of the PANSS (Positive And Negative Syndrome Scale) in patients with chronic schizophrenia, regardless predominance of symptoms. The aim of this study was to examine the component structure of the PANSS in patients with schizophrenia spectrum disorders and predominantly negative syndrome.

Data of PANSS were extracted from a cross-sectional and retrospective multicenter study in 1,704 adult psychiatric outpatients meeting DSM-IV criteria for schizophrenia, schizophreniform or schizoaffective disorder. We used 5 items of the PANSS negative subscale to individually determine the presence of a negative syndrome when the score on all of the 5-items were >3, with no extrapyramidal symptoms, anxiety, or depression and dose of haloperidol, when applicable, ≤15mg/day. Exploratory factor analysis was carried out using principal component analysis to extract domains. Eigenvalues above 1 according with Kaiser K1 rule were applied to extract factors. Items with a loading of ≥ 0.4 were considered to load on a component.

A total of 307 [61% men, mean age: 41 (SD:12) years] fulfilled criteria for inclusion in the analysis. Principal component analysis of the PANSS revealed four components: positive, negative (all negative items of the original PANSS plus items 15 and 16 of the general psychopathology subscale), mood and disorganization, explained 58% of the total variance. Internal consistency (Cronbach-alpha) of these 4 domains was high: 0.897, 0.874, 0.819 and 0.833, respectively.

This analysis suggest a four component structure of the PANSS in patients with schizophrenia spectrum disorders and predominantly negative syndrome.

To develop a Support Vector Machine (SVM) algorithm as a predictive tool for diagnostic outcome in patients with FE-EOP, based on clinical and biomedical data at the emergence of the illness.

Two-year, prospective longitudinal study, where 81 patients (9-17 years of age) with a FE-EOP and stable diagnosis at follow-up and 41 age and sex-matched healthy controls (HC) were included. Structured diagnostic interviews, clinical and cognitive scales, a MRI scan and biochemical tests were conducted at baseline. Three SVM classification algorithms were developed (SSD vs HC group, non-SSD vs HC group, and SSD vs non-SSD group). Jackknifing was used to validate the algorithms and to calculate performance estimates. Enhanced-Recursive Feature Elimination was performed in order to gain information about the predictive weight for diagnosis of each variable.

The SSD-versus-non-SSD classifier achieved an overall accuracy of 83.1%, sensitivity of 86.6% and specificity of 77.8%. The variables during a FE-EOP with higher predictive value for a diagnosis of SSD were clinical variables such as negative symptoms preceding or during the psychotic onset, poor insight and duration of illness until first psychiatric contact. Biochemical, neuroimaging, and cognitive variables at baseline did not provide any additional predictive value.

SVM may serve as a predictive tool for early diagnosis of SSD during a FE-EOP. The most discriminative variables during a FE-EOP for a future diagnosis of SSD are clinical variables.