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Consistent evidence supports the involvement of genetic and environmental factors, and their interactions, in the etiology of psychosis. First-episode psychosis (FEP) comprises a group of disorders that show great clinical and long-term outcome heterogeneity, and the extent to which genetic, familial and environmental factors account for predicting the long-term outcome in FEP patients remains scarcely known.
Methods
The SEGPEPs is an inception cohort study of 243 first-admission patients with FEP who were followed-up for a mean of 20.9 years. FEP patients were thoroughly evaluated by standardized instruments, with 164 patients providing DNA. Aggregate scores estimated in large populations for polygenic risk score (PRS-Sz), exposome risk score (ERS-Sz) and familial load score for schizophrenia (FLS-Sz) were ascertained. Long-term functioning was assessed by means of the Social and Occupational Functioning Assessment Scale (SOFAS). The relative excess risk due to interaction (RERI) was used as a standard method to estimate the effect of interaction of risk factors.
Results
Our results showed that a high FLS-Sz gave greater explanatory capacity for long-term outcome, followed by the ERS-Sz and then the PRS-Sz. The PRS-Sz did not discriminate significantly between recovered and non-recovered FEP patients in the long term. No significant interaction between the PRS-Sz, ERS-Sz or FLS-Sz regarding the long-term functioning of FEP patients was found.
Conclusions
Our results support an additive model of familial antecedents of schizophrenia, environmental risk factors and polygenic risk factors as contributors to a poor long-term functional outcome for FEP patients.
First-episode psychosis is a critical period for early interventions to reduce the risk of poor outcomes and relapse as much as possible. There are now many studies revealing the patterns of course in the short and medium terms, but uncertainties about the long-term outcomes of symptomatology remain to be ascertained.
Objectives
First, we ascertained whether the structure of psychopathological symptoms, dimensions and domains of psychopathology remains invariant over time between first-episode psychosis and long-term follow-up. Second, we analysed the changes in the interrelationships of psychopathological symptoms, dimensions and domains of psychopathology between FEP and long-term follow-up at three levels.
Methods
We performed 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 (CASH) for their assessments.
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.
Conclusions
Our findings suggest that disorganization symptoms have more influence in long-term stabilized patients. The main results of the current study add evidence to the hierarchical, dimensional and longitudinal structuring of first-episode psychoses.
Cognitive deficits are common, clinically relevant and closely linked to poor functional outcomes in everyday functioning in patients with schizophrenia and other psychoses.
Objectives
To ascertain to which extent a polydiagnostic assessment of schizophrenia is associated with clinically-derived criteria of cognitive impairment and gold-standard neuropsychological assessment.
Methods
We assessed 98 patients with a psychotic disorder. We tested if patients met criteria for schizophrenia according to five diagnostic classifications: Krapelin, Bleuler, Schneider, ICD-10 and DSM-IV. Also, we applied a set of clinically-derived criteria to assess cognitive impairment associated with psychosis (CIAPs). Gold-standard neuropsychological assessment was administered, covering the cognitive domains included in the MATRICS Cognitive Battery: attention, processing speed, verbal memory, visual memory, working memory, executive function and social cognition. MANOVAs were performed to test the association between polydiagnostic and clinically-derived criteria and neuropsychological assessment.
Results
MANOVA profile analyses revealed that patients who met CIAPs criteria showed cognitive impairment in all the cognitive domains except for social cognition. Patients diagnosed with Kraepelin’s criteria showed significant differences in processing speed, visual memory, working memory and GCI. Patients fulfilling Bleuler and DSM-IV criteria showed significant deficits in processing speed and verbal memory, respectively. Schneider and ICD-10 diagnostic criteria did not reveal differences in cognition between patients who fulfilled these criteria.
Conclusions
CIAPs criteria were the most accurate classifying patients with cognitive impairment, followed by Kraepelin’s criteria, which were the ones among diagnostic criteria which better differentiated patients regarding cognitive impairment. These criteria take into consideration the outcome in addition to symptoms.
Disclosure
This work was supported by the Government of Navarra (grants 17/31, 18/41, 87/2014) and the Carlos III Health Institute (FEDER Funds) from the Spanish Ministry of Economy and Competitivity (14/01621 and 16/02148). Both had no further role in the study des
Cognitive impairment is a core feature of schizophrenia and other psychotic disorders and executive deficits are within the most impaired cognitive functions The Wisconsin Card Sorting test (WCST) has been extensively used in literature on schizophrenia and psychosis. The underlying structure of executive impairment may have important implications for our understanding of the complex connections between executive dysfunction and the psychopathology and neurofunctional basis of psychosis.
Objectives
The objective was to empirically validate the dimensions of the WCST network structure of patients regarding antecedent, concurrent and outcome variables.
Methods
Subjects were 298 patients with a DSM 5 diagnosis of psychotic disorder. To assess the empirical validation of network structure of the WCST antecedent, concurrent and outcome variables were selected from the CASH interview and other scales of patients.
Results
Pearson coefficient correlations between the 4 network loadings (NL) of WCST, namely perseveration, inefficient sorting, failure to maintain the set and learning, and antecedent, concurrent and outcome validators are shown in the table. PER and IS showed common and strong associations with antecedent, concurrent and outcome validators. LNG dimension was also moderately associated and FMS did not show significant associations.
Conclusions
‘Perseveration’ and ‘Inefficient sorting’ dimensions achieve and share common antecedent, concurrent and outcome validators. While ‘Learning’ dimension achieves partial validation in terms of antecedent and outcome validators and ‘Failure to maintain the set’ dimension was not associated with external validators. These four underlying dysfunctions might help to disentangle the neurofunctional basis of executive deficits in psychosis.
Even though cognitive impairment is considered a hallmark of schizophrenia, it has not been included as a criterion into major diagnostic systems.
Objectives
To test whether a set of clinical-defined cognitive impairment criteria can have utility in the assessment of psychosis patients in clinical practice.
Methods
We assessed 98 patients with a psychotic disorder, diagnosed using DSM 5 criteria. We developed a set of cognitive impairment associated with psychosis (CIAPs) criteria following the format of current DSM criteria and based on previous literature. The CIAPs criteria include: A) criterion for evidence of cognitive impairment after the beginning of illness; B) cognitive impairment clinically evidenced, affecting functioning in everyday activities in at least two out of six cognitive domains; C) and D) exclusion criterion for either delirium or other neurocognitive disorders, respectively, as causal agents of the cognitive impairment. The psychosis patients dichotomized by the CIAPs criteria were tested regarding the neuropsychological performance in attention, speed of processing, verbal memory, visual memory, working memory, executive function and social cognition tasks. Also a Global Cognitive Index was calculated.
Results
Forty-three patients with psychosis fulfilled the CIAPs criteria (43.9%). MANOVA profile analyses revealed a pattern of statistically significant deficits in all the cognitive dimensions except for social cognition in CIAPs+ patients regarding CIAPS-, with prominent deficits in processing speed and memory functions.
Conclusions
The CIAPs criteria could be an auxiliary method for clinicians to assess cognitive impairment. It may also permit clinical estimation of the influence of cognitive deficits on the ecological functioning of patients.
Conflict of interest
This work was supported by the Government of Navarra (grants 17/31, 18/41, 87/2014) and the Carlos III Health Institute (FEDER Funds) from the Spanish Ministry of Economy and Competitivity (14/01621 and 16/02148). Both had no further role in the study des
Psychosis are complex disorders due to their symptomatic and evolutionary heterogeneity. The genetic-environmental interaction model is the most accepted etiopathogenic model, in which neurobiological processes (genetic factors, connectivity and brain structure) and environmental factors (for example: childhood trauma) are studied. The association between suffering traumatic events in childhood and the subsequent development of a Mental Disorder is of increasing interest.
Objectives
Analyze if a childhood trauma is a modulating factor of psychotic symptoms in patients with Mental Disorder. Analyze the implication of childhood trauma in long-term functionality.
Methods
The sample is made up of 37 patients with psychosis and their healthy brothers. Different sociodemographic, clinical and evolutionary variables were collected in all groups. The sample was evaluated using the semi-structured interview CASH, the WHODAS scale and the self-applied questionnaire CTQ.
Results
We did not find significant differences between the scores of CTQ between patients with psychosis and their healthy brothers. Sexual abuse is significantly correlated with the presence of hallucinations, inappropriate affect, formal thought disorders and catatonic symptoms. Emotional neglect is significantly correlated with the presence of hallucinations, inappropriate affect, affective blunting, and anhedonia. Physical neglect is significantly correlated with flattery and blunt affection. Sexual abuse is correlated with poorer personal care. Emotional neglect is correlated with poorer personal care, poorer family functioning, and worse overall functioning in the last year.
Conclusions
The intensity of traumatic experiences throughout childhood could be considered a modulating factor of psychotic symptoms (positive, negative, disorganized and catatonic) and overall functioning (occupational, family, social and personal care).
Psychopathological symptoms and cognitive impairment are core features of patients with psychotic disorders. Executive dysfunctions are within the most commonly observed deficits and the Wisconsin Card Sorting Test (WCST) is the test most extensively used for their assessment. Yet, the structure of executive deficits remains unclear, as there may be different underlying processes.
Objectives
The study’s aims were to explore and compare the network structure of the WCST measures in psychosis and their unaffected siblings.
Methods
Subjects were 298 patients with a DSM 5 diagnosis of psychotic disorder and 89 of their healthy siblings. The dimensionality and network structure of the 13 WCST measures were examined by means of the Exploratory Graph Analysis (EGA) and centrality parameters.
Results
The WCST network structure comprised 4 dimensions: Perseveration (PER), Inefficient sorting (IS), Failure to maintain set (FMS) and Learning (LNG). Patient and sibling groups showed a similar network structure and in both cases the network structure was reliably estimated.
Conclusions
Perseveration measures reflect the inability to switch sorting rules when necessary. Scores for the IS dimension can occur when the subject ineffectively tries to test different sorting hypotheses, changing at random the response. FMS reflects the subject’s strategy when he/she is able to find out the sorting rule, but is unable to keep applying that rule long enough. LNG comprised conceptual ability and learning items. The lack of significant difference between network structures is in keeping with results from exploratory and confirmatory studies demonstrating an invariant cognitive factor structure between schizophrenia patients and their unaffected siblings.
Cognitive impairments clearly impact the daily functioning of patients with psychosis.
Objectives
To assess cross-sectionally whether there are differences in the cognitive domains assessed with the CAI, for considering the real-world functioning of a sample of patients with psychosis.
Methods
The sample consisted of 76 patients with a DSM-IV psychotic disorder. Patients were assessed with the cognitive assessment interview (CAI), which is an interview-based measure of cognitive functioning that is intermediate between cognitive functioning and daily functioning, and three subscales of the specific levels of functioning (SLOF), an informant-rated measure of functioning. The CAI was used to assess the patient and an informant, and these scores were integrated into a rater composite score. We divided the sample by a median-split procedure for each of the three functional domains, and then applied ANOVAs to compare the two groups (impaired/not impaired) in the six cognitive domains of the CAI: working memory, attention, verbal memory, problem solving, processing speed, and social cognition.
Results
We found significant differences between the impaired vs. non-impaired groups in most of the cognitive domains assessed with the CAI (Fig. 1).
Conclusions
Interview-based assessment of cognition with the CAI allows for the prediction of everyday functioning in patients with psychosis. Impairment in almost all CAI cognitive domains, except for social cognition, was associated with poorer psychosocial functioning.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Parkinsonian motor signs are the most frequent of the genuine motor abnormalities present in drug-naïve patients with schizophrenia, and are also present in patients with a first-episode of psychosis (FEP).
Objective
To study whether there are differences in basal ganglia volumes depending on the presence of Parkinsonism in FEP.
Patients with Parkinsonism showed a trend towards significance to exhibit reduced volumes in the left caudate and right putamen (Fig. 1).
Conclusions
FEP patients who exhibit Parkinsonian signs tend to show reduced left caudate and right putamen volumes in the early phases of psychotic illness, after correcting by gender.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Cognitive impairment is considered the best predictor of functional outcome in psychosis. However, the nature of this relationship still remains to be determined.
Objective
To ascertain the relationship of negative symptoms and cognitive impairment with functional outcome in psychosis.
Methods
Ninety patients with a DSM-IV psychotic disorder diagnosis and 65 healthy controls were included in the study. We assessed the predominant negative symptoms over the course of illness with the Comprehensive Assessment of Symptoms and History (CASH). Functional outcome was assessed with the Specific Levels of Functioning (SLOF). Cognition was assessed with a set of neuropsychological tests, which were normalised to z-scores (regarding controls’ performance). Then, a Global Cognition Index (GCI) was obtained as a mean of the cognitive domains assessed: processing speed, attention, verbal and visual memory, executive functions, working memory and social cognition. We divided the sample in four groups, considering the presence/absence of negative symptoms (cut-off point of 2 in the CASH), and the presence/absence of cognitive impairment (considering a GCI z-score of–1 as cut-off point). We performed a MANOVA to compare the 4 groups’ functional outcome scores.
Results
Fig. 1 shows the significant differences between groups regarding functional outcome.
Conclusions
The combination of negative symptoms and cognitive impairment has deleterious effects over functionality, but negative symptoms alone are related to functional outcome, independently of cognitive impairment.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years.
Methods
The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis.
Results
At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (−10.215 to −0.337) and (−4.731 to −0.605) respectively).
Conclusions
Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.
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