Long-term diagnostic stability, predictors of diagnostic change, and time until diagnostic change of first-episode psychosis: a 21-year follow-up study.

BACKGROUND: Although diagnostic instability in first-episode psychosis (FEP) is of major concern, little is known about its determinants. This very long-term follow-up study aimed to examine the diagnostic stability of FEP diagnoses, the baseline predictors of diagnostic change and the timing of diagnostic change. METHODS: This was a longitudinal and naturalistic study of 243 subjects with FEP who were assessed at baseline and reassessed after a mean follow-up of 21 years. The diagnostic stability of DSM-5 psychotic disorders was examined using prospective and retrospective consistencies, logistic regression was used to establish the predictors of diagnostic change, and survival analysis was used to compare time to diagnostic change across diagnostic categories. RESULTS: The overall diagnostic stability was 47.7%. Schizophrenia and bipolar disorder were the most stable diagnoses, with other categories having low stability. Predictors of diagnostic change to schizophrenia included a family history of schizophrenia, obstetric complications, developmental delay, poor premorbid functioning in several domains, long duration of untreated continuous psychosis, spontaneous dyskinesia, lack of psychosocial stressors, longer duration of index admission, and poor early treatment response. Most of these variables also predicted diagnostic change to bipolar disorder but in the opposite direction and with lesser effect sizes. There were no significant differences between specific diagnoses regarding time to diagnostic change. At 10-year follow-up, around 80% of the diagnoses had changed. CONCLUSIONS: FEP diagnoses other than schizophrenia or bipolar disorder should be considered as provisional. Considering baseline predictors of diagnostic change may help to enhance diagnostic accuracy and guide therapeutic interventions.

The association of adverse childhood experiences with long-term outcomes of psychosis: a 21-year prospective cohort study after a first episode of psychosis.

BACKGROUND: Evidence suggests a possible relationship between exposure to childhood adversity (CA) and functional impairment in psychosis. However, the impact of CA on long-term outcomes of psychotic disorders remains poorly understood. METHODS: Two hundred and forty-three patients were assessed at their first episode of psychosis for CA and re-assessed after a mean of 21 years of follow-up for several outcome domains, including symptoms, functioning, quality of life, cognitive performance, neurological dysfunction, and comorbidity. The unique predictive ability of CA exposure for outcomes was examined using linear regression analysis controlling for relevant confounders, including socioeconomic status, family risk of schizophrenia, and obstetric complications. RESULTS: There were 54% of the patients with a documented history of CA at mild or higher levels. CA experiences were more prevalent and severe in schizophrenia than in other psychotic disorders (p < 0.001). Large to very large effect sizes were observed for CA predicting most role functioning variables and negative symptoms (ΔR2 between 0.105 and 0.181). Moderate effect sizes were observed for positive symptoms, personal functioning, impaired social cognition, impaired immediate verbal learning, poor global cognition, internalized stigma, poor personal recovery, and drug abuse severity (ΔR2 between 0.040 and 0.066). A dose-response relationship was observed between levels of CA and severity of outcome domains. CONCLUSION: Our results suggest a strong and widespread link between early adversity exposure and outcomes of psychotic disorders. Awareness of the serious long-term consequences of CA should encourage better identification of those at risk and the development of effective interventions.

Social exclusion as a major outcome domain of psychotic disorders: early predictors, and associations with non-recovery and clinical staging 21 years after a first episode of psychosis.

PURPOSE: People with psychotic disorders have high levels of social exclusion; however, little is known about its early predictors. We present a long-term observational cohort study aimed at examining early risk factors for later social exclusion. METHODS: A total of 243 subjects were assessed at their first psychotic episode for early risk factors including sociodemographic variables, familial risk of major mental disorders, perinatal complications, childhood factors, and adolescent factors and re-assessed after a mean follow-up of 21 years for 12 social exclusion domains: leisure activities, housing, work, income, neighborhood deprivation, educational attainment, physical and mental health, family and social support, legal competence, and discrimination. The ability of risk factors to predict social exclusion was examined using hierarchical linear regression. RESULTS: Overall social exclusion was independently predicted by low parental socio-economic status, length of follow-up, familial risk of schizophrenia, obstetric complications, neurodevelopmental delay, poor childhood adjustment, childhood adversity, poor adolescent social networks, poor adolescent adjustment, and low premorbid IQ. The model explained 58.2% of the variance in total social exclusion score. Each social exclusion domain was predicted by a different set of variables, which explained between 17.8 and 57.0% of their variance, although low socio-economic status, familial risk of schizophrenia, obstetric complications, childhood adversity, and poor social networks predicted most of the social exclusion domains. CONCLUSION: Early risk factors strongly predicted later social exclusion. A multifaceted approach to preventing later social exclusion is crucial in people with a first episode of psychosis and early risk factors of social exclusion.

The effect of anticholinergic burden of psychiatric medications on major outcome domains of psychotic disorders: A 21-year prospective cohort study.

BACKGROUND: Most medications used to treat psychotic disorders possess anticholinergic properties. This may result in a considerable anticholinergic burden (ACB), which may have deleterious effects on long-term outcomes. The extent to which cumulative ACB over years of treatment with psychotropic medications impacts different outcome domains remains unknown. METHODS: This was a naturalistic study of 243 subjects with first-episode psychosis aimed at examining the cumulative effect of ACB of psychotropic medications administered over the illness course (ACB-years exposure) on several outcome domains assessed after a mean 21-year follow-up. Associations between ACB and the outcomes were modelled accounting for relevant confounding factors by using hierarchical linear regression analysis. RESULTS: Over the study period, 81.9 % of the participants were dispensed at least one drug with strong anticholinergic effects for at least 1 year; at the follow-up visit, 60.5 % of the participants continued to take medications with strong ACB. ACB-years exposure was uniquely related to severity of negative symptoms (ß = 0.144, p = 0.004), poor psychosocial functioning (ß = 0.186, p < 0.001) and poor cognitive performance (ß = -0.273, p < 0.001). This association pattern was independent of a schizophrenia diagnosis. Most of the associations between ACB at the follow-up visit and the outcomes were accounted for ACB-years exposure. CONCLUSION: Lifetime ACB of psychotropic medications has deleterious effects on the outcome of psychotic disorders. Clinicians should avoid prescribing medications with strong ACB, since there are numerous alternatives within each psychotropic drug group for prescribing medications with low ACB.

Long-term trajectories of clinical staging in first-episode psychosis and their associated cognitive outcome: A 21-year follow-up study.

Cognitive deficits are already present before psychosis onset but are a key feature of first-episode psychosis (FEP). The objective of this study was to investigate the cognitive outcomes of a cohort of FEP patients who were diagnosed using the clinical staging approach and were followed for up to 21 years. We analyzed data from 173 participants with first-admission psychosis who were followed-up for a mean of 20.9 years. The clinical staging assessment was adapted from the clinical staging framework developed by McGorry et al.1 Cognitive assessment was performed using the MATRICS Consensus Cognitive Battery (MMCB) at the end of follow-up. FEP patients who were longitudinally diagnosed in the lowest clinical stages (stages 2A and 2B) showed better performance in attention, processing speed, and MCCB overall composite score than those in the highest clinical stages (stages 4A and 4B). There was a significant linear trend association between worsening of all MCCB cognitive functions and MCCB overall composite score and progression in clinical staging. Furthermore, the interval between two and five years of follow-up appears to be associated with deficits in processing speed as a cognitive marker. Our results support the validation of the clinical staging model over a long-term course of FEP based on neuropsychological performance. A decline in some cognitive functions, such as processing speed, may facilitate the transition of patients to an advanced stage during the critical period of first-episode psychosis.

Psychopathological networks in psychosis: Changes over time and clinical relevance. A long-term cohort study of first-episode psychosis.

BACKGROUND: First-episode psychosis is a critical period for early interventions to reduce the risk of poor outcomes and relapse as much as possible. However, uncertainties about the long-term outcomes of symptomatology remain to be ascertained. METHODS: The aim of the present study was to use network analysis to investigate first-episode and long-term stages of psychosis at three levels of analysis: micro, meso and macro. The sample was a cohort of 510 patients with first-episode psychoses from the SEGPEP study, who were reassessed at the long-term follow-up (n = 243). We used the Comprehensive Assessment of Symptoms and History for their assessments and lifetime outcome variables of clinical relevance. RESULTS: Our results showed a similar pattern of clustering between first episodes and long-term follow-up in seven psychopathological dimensions at the micro level, 3 and 4 dimensions at the meso level, and one at the macro level. They also revealed significant differences between first-episode and long-term network structure and centrality measures at the three levels, showing that disorganization symptoms have more influence in long-term stabilized patients. CONCLUSIONS: Our findings suggest a relative clustering invariance at all levels, with the presence of two domains of disorganization as the most notorious difference over time at micro level. The severity of disorganization at the follow-up was associated with a more severe course of the psychosis. Moreover, a relative stability in global strength of the interconnections was found, even though the network structure varied significantly in the long-term follow-up. The macro level was helpful in the integration of all dimensions into a common psychopathology factor, and in unveiling the strong relationships of psychopathological dimensions with lifetime outcomes, such as negative with poor functioning, disorganization with high antipsychotic dose-years, and delusions with poor adherence to treatment. These results add evidence to the hierarchical, dimensional and longitudinal structure of psychopathological symptoms and their clinical relevance in first-episode psychoses.

A clinical staging model of psychotic disorders based on a long-term follow-up of first-admission psychosis: A validation study.

We examined the empirical validity of a staging model of psychotic disorders primarily based on their long-term course. The model distinguished 6 consecutive stages (2A, 2B, 3A, 3B, 4A, 4B) based on symptom recurrence, persistence and progression, such as functional decline. We analyzed data from 243 participants with first-admission psychosis who were followed-up for a mean of 20.9 years and assessed for 22 baseline variables, 23 construct-related variables and 31 outcome variables. Later stages scored significantly poorer than early stages on most validators by showing generally medium to large effect sizes and a dose-response pattern, thus confirming the validity of the model. For each set of validators, differences between consecutive stages were especially evident for stages 2 and 3A, although many variables from each validation realm also differentiated between the consecutive stages 3A and above. Baseline predictors including familial load of schizophrenia, neurodevelopmental impairment, childhood adversity, treatment delay, negative symptoms, neurological impairment and poor early response to treatment, independently accounted for 49.9% of the variance of staging. A staging model of psychosis based primarily on its long-term course has sound construct, outcome and predictive validity, which may inform about stage indicators and predictors of clinical stages from psychosis onset.

Psychometric analysis of the Psychiatric Diagnostic Screening Questionnaire (PDSQ) and determinants of psychopathology in two outpatient clinics in Navarre (Spain).

BACKGROUND: The self-report Psychiatric Diagnostic Screening Questionnaire PDSQ is designed to screen Axis I psychiatric disorders. We aim to determine its psychometric properties in Spanish outpatients and assess its relationship with two interviews (for psychopathology and for personality disorders) and clinical/demographic variables. METHODOLOGY: We administered the study questionnaire, the Mini International Neuropsychiatric Interview Plus (MINI-Plus), the Standardised Assessment of Personality Abbreviated Scale (SAPAS), and the List of Threatening Experiences Questionnaire (LTE-Q) to 375 patients at two public outpatient centres. Reliability of the study questionnaire was evaluated (Cronbach's alpha, ?) and known-group validity measured by comparing groups based on demographic and clinical variables (binary logistic regression analysis) and MINI-Plus diagnoses (Mann-Whitney U). The diagnostic accuracy of the study questionnaire score was analysed taking the MINI-Plus diagnoses as the gold standard (ROC analysis). RESULTS: Internal consistency was adequate across all PDSQ scales (? >0.7; mean ?=0.85). Known-group comparisons were satisfactory. Female and male patients showed higher prevalence of internalizing and externalizing diagnoses, respectively. Younger age, more life events and limitations, higher SAPAS scores, and lower economic levels were linked to a greater number of PDSQ diagnoses. Inter-group differences were found for all PDSQ scales based on the corresponding MINI-Plus diagnoses. Mean values of sensitivity, AUC, and negative predictive value were 88.7, 0.82, and 96.7, respectively. CONCLUSIONS: When applied to a sample of Spanish outpatients, the PDSQ exhibits satisfactory psychometric properties and adequate relationships with the psychopathology and personality interviews, and clinical and demographic variables. The study questionnaire is suitable for assessing comorbidity and psychopathology dimensions.

Neuromotor dysfunction as a major outcome domain of psychotic disorders: A 21-year follow-up study.

BACKGROUND: The long-term stability of neuromotor domains assessed at the first episode of psychosis (FEP) and their ability for predicting a number of outcomes remains largely unknown, and this study addressed these issues. METHODS: This was a longitudinal study of 243 participants with FEP who were assessed at baseline for background variables and parkinsonism, dyskinesia, neurological soft signs (NSS) and catatonia, and reassessed 21 years later for the same neuromotor variables, psychopathology, functioning, personal recovery, cognitive performance and medical comorbidity. Stability of neuromotor ratings was assessed using the intraclass correlations coefficient and associations between the predictors and outcomes were examined using univariate and multivariate statistics. RESULTS: Baseline dyskinesia and NSS ratings showed excellent stability over time whereas that for parkinsonism and catatonia was relatively low. Neuromotor dysfunction at follow-up was independently predicted by a family history of schizophrenia, obstetric complications, neurodevelopmental delay, low premorbid IQ and baseline ratings of dyskinesia and NSS. Moreover, baseline dyskinesia and NSS ratings independently predicted more positive and negative symptoms, poor functioning and less personal recovery; catatonia predicted less personal recovery and more medical comorbidity. Baseline neuromotor ratings explained between 4% (for medical comorbidity) and 34% (for neuromotor dysfunction) of the variance in the outcomes. Lastly, neuromotor dysfunction at baseline highly predicted clinical staging at follow-up. CONCLUSION: Baseline neuromotor domains show variable stability over time and relate distinctively to very long-term outcomes. Both baseline dyskinesia and NSS are trait markers of the disease process and robust predictors of the outcomes.

Long-Term Outcomes of First-Admission Psychosis: A Naturalistic 21-Year Follow-Up Study of Symptomatic, Functional and Personal Recovery and Their Baseline Predictors.

This study was aimed at characterizing long-term outcomes of first-admission psychosis and examining their baseline predictors. Participants were assessed at baseline for 38 candidate predictors and re-assessed after a median follow-up of 21 years for symptomatic, functional, and personal recovery. Associations between the predictors and the outcomes were examined using univariate and multivariate Cox regression models. At baseline, 623 subjects were assessed for eligibility, 510 met the inclusion/exclusion criteria and 243 were successfully followed-up (57.3% of the survivors). At follow-up, the percentages of subjects achieving symptomatic, functional, and personal recovery were 51.9%, 52.7%, and 51.9%, respectively; 74.2% met at least one recovery criterion and 32.5% met all three recovery criteria. Univariate analysis showed that outcomes were predicted by a broad range of variables, including sociodemographics, familial risk, early risk factors, premorbid functioning, triggering factors, illness-onset features, neurological abnormalities, deficit symptoms and early response to treatment. Many of the univariate predictors became nonsignificant when entered into a hierarchical multivariate model, indicating a substantial degree of interdependence. Each single outcome component was independently predicted by parental socioeconomic status, family history of schizophrenia spectrum disorders, early developmental delay, childhood adversity, and mild drug use. Spontaneous dyskinesia/parkinsonism, neurological soft signs and completion of high school remained specific predictors of symptomatic, functional, and personal outcomes, respectively. Predictors explained between 27.5% and 34.3% of the variance in the outcomes. In conclusion, our results indicate a strong potential for background and first-episode characteristics in predicting long-term outcomes of psychotic disorders, which may inform future intervention research.

Prospective Long-Term Cohort Study of Subjects With First-Episode Psychosis Examining Eight Major Outcome Domains and Their Predictors: Study Protocol.

Background: Our current ability to predict the long-term course and outcome of subjects with a first-episode of psychosis (FEP) is limited. To improve our understanding of the long-term outcomes of psychotic disorders and their determinants, we designed a follow-up study using a well-characterized sample of FEP and a multidimensional approach to the outcomes. The main goals were to characterize the long-term outcomes of psychotic disorders from a multidimensional perspective, to address the commonalities and differential characteristics of the outcomes, and to examine the common and specific predictors of each outcome domain. This article describes the rationale, methods, and design of a longitudinal and naturalistic study of subjects with epidemiologically defined first-admission psychosis. Methods: Eligible subjects were recruited from consecutive admissions between January 1990 and December 2009. Between January 2018 and June 2021, we sought to trace, re-contact, and re-interview the subjects to assess the clinical course, trajectories of symptoms and functioning, and the different outcomes of psychotic disorders. Since this is a naturalistic study, the research team will not interfere with the subjects' care and treatment. Predictors include antecedent variables, first-episode characteristics, and illness-related variables over the illness course. We assess eight outcome domains at follow-up: psychopathology, psychosocial functioning, self-rated personal recovery, self-rated quality of life, cognitive performance, neuromotor dysfunction, medical and psychiatric comorbidities, and mortality rate. The range of the follow-up period will be 10-31 years with an estimated mean of 20 years. We estimate that more than 50% of the baseline sample will be assessed at follow-up. Discussion: The study design was driven by the increasing need to refine the ability to predict the different clinical outcomes in FEP, and it aims to close current gaps in knowledge, with a broad approach to both the definition of outcomes and their determinants. To the best of our knowledge, this study is one of the few attempting to characterize the very long-term outcome of FEP and the only study addressing eight major outcome domains. We hope that this study helps to better characterize the long-term outcomes and their determinants, enabling better risk stratification and individually tailored, person-based interventions.