Additive effects of a family history of schizophrenia spectrum disorders and an environmental risk score for the outcome of patients with non-affective first-episode psychosis.

BACKGROUND: First-episode psychotic disorders comprise a heterogeneous phenotype with a complex etiology involving numerous common small-effect genetic variations and a wide range of environmental exposures. We examined whether a family of schizophrenia spectrum disorder (FH-Sz) interacts with an environmental risk score (ERS-Sz) regarding the outcome of patients with non-affective first episode psychosis (NAFEP). METHODS: We included 288 patients with NAFEP who were evaluated after discharge from an intensive 2-year program. We evaluated three outcome measures: symptomatic remission, psychosocial functioning, and personal recovery. We analyzed the main and joint associations of a FH-Sz and the ERS-Sz on the outcomes by using the relative excess risk due to interaction (RERI) approach. RESULTS: A FH-Sz showed a significant association with poor symptomatic remission and psychosocial functioning outcomes, although there was no significant interaction between a FH-Sz and the ERS-Sz on these outcomes. The ERS-Sz did not show a significant association with poor symptomatic remission and psychosocial functioning outcomes, even though the magnitude of the interaction between ERS-Sz and FH-Sz with the later outcome was moderate (RERI = 6.89, 95% confidence interval -16.03 to 29.81). There was no association between a FH-Sz and the ERS-Sz and personal recovery. CONCLUSIONS: Our results provide further empirical support regarding the contribution of FH-Sz to poor symptomatic remission and poor psychosocial functioning outcomes in patients with NAFEP.

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.

20-Year trajectories of six psychopathological dimensions in patients with first-episode psychosis: Could they be predicted?

Patients with first-episode psychoses (FEP) exhibit heterogeneity in clinical manifestations and outcomes. This study investigated the long-term trajectories of six key psychopathological dimensions (reality-distortion, negative, disorganization, catatonia, mania and depression) in patients diagnosed with FEP. A total of 243 patients were followed up for 20 years and the trajectories of the dimensions were analysed using growth mixture modelling. These dimensions showed varied course patterns, ranging from two to five trajectories. Additionally, the study examined the predictive value of different factors in differentiating between the long-term trajectories. The exposome risk score showed that familial load, distal and intermediate risk factors, acute psychosocial stressors and acute onset were significant predictors for differentiating between long-term psychopathological trajectories. In contrast, polygenic risk score, duration of untreated psychosis and duration of untreated illness demonstrated little or no predictive value. The findings highlight the importance of conducting a multidimensional assessment not only at FEP but also during follow-up to customize the effectiveness of interventions. Furthermore, the results emphasize the relevance of assessing premorbid predictors from the onset of illness. This may enable the identification of FEP patients at high-risk of poor long-term outcomes who would benefit from targeted prevention programs on specific psychopathological dimensions.

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.

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.

Effectiveness of the early intervention service for first-episode psychosis in Navarra (PEPsNa): Broadening the scope of outcome measures.

BACKGROUND: This study compares the effectiveness of a new early intervention service for firstepisode psychosis (FEP) in patients under conventional treatment. Six primary and 10 secondary outcome measures are used to better characterize the comparative effectiveness between two FEP groups. METHODS: This study plans to enroll 250 patients aged 15-55 years with FEP from all inpatient and outpatient mental health services and primary health care from January 2020 until December 2022. The control group will be composed of 130 FEP patients treated in mental health centers in the 2 years prior to the start of PEPsNa (Programa de Primeros Episodios de Psicosis de Navarra). The primary outcome measures are symptomatic remission, functional recovery, personal recovery, cognitive performance, functional capacity in real-world settings, and costs. The secondary outcome measures are duration of untreated psychosis, substance abuse rate, antipsychotic monotherapy, minimal effective dose of antipsychotic drugs, therapeutic alliance, drop-out rate, number of relapses, global mortality and suicidality, resource use, and general satisfaction in the program. DISCUSSION: This study arises from the growing need to broaden the scope of outcome measures in FEP patients and to account for unmet needs of recovery for FEPs. It aims to contribute in the dissemination of the NAVIGATE model in Europe and to provide new evidence of the effectiveness of early intervention services for stakeholders of the National Health Service.

The network structure of cognitive deficits in first episode psychosis patients.

Network analysis is an important conceptual and analytical approach in mental health research. However, few studies have used network analysis to examine the structure of cognitive performance in psychotic disorders. We examined the network structure of the cognitive scores of a sample of 207 first-episode psychosis (FEP) patients and 188 healthy controls. Participants were assessed using a battery of 10 neuropsychological tests. Fourteen cognitive scores encompassing six cognitive domains and premorbid IQ were selected to perform the network analysis. Many similarities were found in the network structure of FEP patients and healthy controls. Verbal memory, attention, working memory and executive function nodes were the most central nodes in the network. Nodes in both groups corresponding to the same tests tended to be strongly connected. Verbal memory, attention, working memory and executive function were central dimensions in the cognitive network of FEP patients and controls. These results suggest that the interplay between these core dimensions is essential for demands to solve complex tasks, and these interactions may guide the aims of cognitive rehabilitation. Network analysis of cognitive dimensions might have therapeutic implications that deserve further research.

Assessment of cognitive impairment in psychosis spectrum disorders through self-reported and interview-based measures.

Self-reported and interview-based measures can be considered coprimary measures of cognitive performance. We aimed to ascertain to what extent cognitive impairment in psychotic disorders, as assessed with a neuropsychological battery, is associated with subjective cognitive complaints compared to difficulties in daily activities caused by cognitive impairment. We assessed 114 patients who had a psychotic disorder with a set of neuropsychological tests and two additional measures: the Cognitive Assessment Interview-Spanish version (CAI-Sp) and the Frankfurt Complaint Questionnaire (FCQ). Patients also underwent a clinical assessment. The CAI-Sp correlated significantly with all the clinical dimensions, while the FCQ correlated only with positive and depressive symptoms. The CAI-Sp correlated significantly with all cognitive domains, except for verbal memory and social cognition. The FCQ was associated with attention, processing speed and working memory. The combination of manic and depressive symptoms and attention, processing speed, working memory and explained 38-46% of the variance in the patients' CAI-Sp. Education and negative symptoms, in combination with attention, processing speed, and executive functions, explained 54-59% of the CAI-Sp rater's variance. Only negative symptoms explained the variance in the CAI-Sp informant scores (37-42%). Depressive symptoms with attention and working memory explained 15% of the FCQ variance. The ability to detect cognitive impairment with the CAI-Sp and the FCQ opens the possibility to consider these instruments to approximate cognitive impairment in clinical settings due to their ease of application and because they are less time-consuming for clinicians.

A network analysis and empirical validation of executive deficits in patients with psychosis and their healthy siblings.

BACKGROUND: Psychopathological symptoms and cognitive impairment are core features of patients with psychotic disorders. Executive dysfunctions are commonly observed and typically assessed using tests like the Wisconsin Card Sorting Test (WCST). However, the structure of executive deficits remains unclear, and the underlying processes may be different. This study aimed to explore and compare the network structure of WCST measures in patients with psychosis and their unaffected siblings and to empirically validate the resulting network structure of the patients. METHODS: The subjects were 298 patients with a DSM 5 diagnosis of a psychotic disorder and 89 of their healthy siblings. The dimensionality and network structure of the WCST were examined by means of exploratory graph analysis (EGA) and network centrality parameters. RESULTS: The WCST network structure comprised 4 dimensions: perseveration (PER), inefficient sorting (IS), failure to maintain set (FMS) and learning (LNG). The patient and sibling groups showed a similar network structure, which was reliably estimated. PER and IS showed common and strong associations with antecedent, concurrent and outcome validators. The LNG dimension was also moderately associated with these validators, but FMS did not show significant associations. CONCLUSIONS: Four cognitive processes underlying WCST performance were identified by the network analysis. PER, IS and LNG were associated with and shared common antecedent, concurrent and outcome validators, while FMS was not associated with external validators. These four underlying dysfunctions might help disentangle the neurofunctional basis of executive deficits in psychosis.

The network and dimensionality structure of affective psychoses: an exploratory graph analysis approach.

BACKGROUND: The dimensional symptom structure of classes of affective psychoses, and more specifically the relationships between affective and mood symptoms, has been poorly researched. Here, we examined these questions from a network analysis perspective. METHODS: Using Exploratory Graph Analysis (EGA) and network centrality parameters, we examined the dimensionality and network structure of 28 mood and psychotic symptoms in subjects diagnosed with schizoaffective disorder (n=124), psychotic bipolar disorder (n=345) or psychotic depression (n=245), such as in the global sample of affective psychoses. RESULTS: EGA identified four dimensions in subjects with schizoaffective or bipolar disorders (depression, mania, positive and negative) and three dimensions in subjects with psychotic depression (depression, psychosis and activation). The item composition of dimensions and the most central symptoms varied substantially across diagnoses. The most central (i.e., interconnected) symptoms in schizoaffective disorder, psychotic bipolar disorder and psychotic depression were hallucinations, delusions and depressive mood, respectively. Classes of affective psychoses significantly differed in terms of network structure but not in network global strength. LIMITATIONS: The cross-sectional nature of this study precludes conclusions about the causal dynamics between affective and psychotic symptoms. CONCLUSION: EGA is a powerful tool for examining the dimensionality and network structure of symptoms in affective psychoses showing that both the interconnectivity pattern between affective and psychotic symptoms and the most central symptoms vary across classes of affective psychoses. The findings outline the value of specific diagnoses in explaining the relationships between mood and affective symptoms.

Utility of the MoCA for cognitive impairment screening in long-term psychosis patients.

Cognitive impairment is a key feature in patients with psychotic disorders. The Montreal Cognitive Assessment (MoCA) is a brief tool that has been shown to be effective in identifying mild cognitive impairment and early dementia. This study explores the usefulness of this instrument to detect cognitive impairment in long-term psychotic disorders. One hundred-forty stabilized patients were re-evaluated more than 15 years after a First Episode of Psychosis (FEP). Patients were psychopathologically assessed, and the MoCA test and MATRICS Consensus Cognitive Battery (MCCB) were administered. Two cut-off scores for cognitive impairment using the MCCB were applied (T score <40 and < 30). Concurrent validation was found between the total scores of the MoCA and MCCB. We also found significant associations between 5 out of 7 MoCA subtests (visuospatial-executive, attention, language, abstraction and delayed recall) and MCCB subtests but not for the naming and orientation MoCA subtests. Receiver operating characteristic (ROC) analysis suggested a <25 cut-off for cognitive impairment instead of the original <26. Our results suggest that the MoCA test is a useful screening instrument for assessing cognitive impairment in psychotic patients and has some advantages over other available instruments, such as its ease-of-use and short administration time.