Effect of polygenic risk score, family load of schizophrenia and exposome risk score, and their interactions, on the long-term outcome of first-episode psychosis.

BACKGROUND: 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.

Delusional disorder and schizophrenia: a comparative study across multiple domains.

BACKGROUND: Delusional disorder (DD) is an under-researched condition and its relationship to schizophrenia (SZ) controversial. This study aimed to further characterize DD and to examine multi-domain evidence for the distinction between DD and SZ. METHOD: Using univariate analyses we examined 146 subjects with DD, 114 subjects with paranoid SZ and 244 subjects with non-paranoid SZ on 52 characteristics from several domains including demographics, risk factors, premorbid features, illness characteristics, index episode features, delusional-related features, response to treatment and outcome. In a further step, we searched for independent associations of the examined characteristics with DD v. SZ. RESULTS: Univariate analyses showed that DD differed from either form of SZ in 40 characteristics, the pattern of findings indicated that paranoid SZ was much more similar to non-paranoid SZ than DD. Relative to subjects with SZ, those with DD were more likely to have drug abuse before illness onset, better premorbid sexual adjustment, later age at illness onset, higher levels of affective symptoms and lack of insight, poorer response to antipsychotic medication, better functioning in the domains of personal care, paid work and social functioning; last, subjects with DD had fewer but more severe delusions and higher ratings of conviction of delusional experience than those with SZ. Predominance of jealousy and somatic delusions was confined to subjects with DD. CONCLUSIONS: DD and SZ represent two distinct classes of disorders, the differential features of DD being of nosological, aetiological and therapeutic relevance.

Empirical validity of Leonhard's psychoses: A long-term follow-up study of first-episode psychosis patients.

The validation of nosological diagnoses in psychiatry remains a conundrum. Leonhard's (1979) nosology seems to be one of the few acceptable alternative categorical models to current DSM/ICD systems. We aimed to empirically validate Leonhard's four classes of psychoses: systematic schizophrenia (SSch), unsystematic (USch), cycloid psychosis (Cyclo), and manic-depressive illness (MDI) using a comprehensive set of explanatory validators. 243 patients with first-episode psychosis were followed between 10 and 31 years. A wide-ranging assessment was carried out by collecting data on antecedent, illness-related, concurrent, response to treatment, neuromotor abnormalities, and cognitive impairment variables. Compared with USch, Cyclo, and MDI, SSch displayed a pattern of impairments significantly larger across the seven blocks of explanatory variables. There were no significant differences between Cyclo and MDI in explanatory variables. Except for the majority of illness-onset features, USch displayed more substantial abnormalities in the explanatory variables than Cyclo and MDI. SSch and MDI showed higher percentages of correctly classified patients than USch and Cyclo in linear discriminant analyses. Partial validation of Leonhard's classification was found. SSch showed differences in explanatory variables with respect to Cyclo and MDI. USch showed also significant differences in explanatory variables regarding Cyclo and MDI, although with a lower strength than SSch. There was strong empirical evidence of the separation between both Leonhard's schizophrenia subtypes; however, the distinction between the Cyclo and MDI groups was not empirically supported. A mild to moderate discriminative ability between Leonhard's subtypes on the basis of explanatory blocks of variables was observed.

Cognitive intraindividual variability, cognitive impairment and psychosocial functioning in first-episode psychosis patients.

Cognitive intraindividual variability (IIV) refers to fluctuations in performance across tasks (i.e. dispersion) or in a single task on multiple occasions (i.e. inconsistency). Little is known about IIV in patients with first-episode psychosis (FEP). We aimed to explore the association between IIV and both global cognitive performance and psychosocial functioning in a sample of 103 FEP patients. Patients were recruited at discharge from the PEPsNa program, a FEP follow-up intervention program lasting 24 months. The Social and Occupational Functioning Scale (SOFAS) and the Cognitive Assessment Interview (CAI-Sp) were employed for assessing psychosocial functioning. Cognitive assessments were performed using the MATRICS Cognitive Assessment Battery (MCCB), and the variability in the cognitive functions assessed with the MCCB was used to calculate the IIV. Significant correlations were obtained between IIV and global MCCB scores, the CAI-Sp and the SOFAS. We found significant differences in psychosocial functioning and cognitive performance between patients with high and low IIV. A higher IIV in FEP patients was related both to worse psychosocial functioning and worse global cognitive performance. Unlike global cognitive performance, IIV was not related to clinical characteristics, suggesting that it could be an indicator of cognitive impairment even in the absence of global impairment.

Association and epistatic analysis of white matter related genes across the continuum schizophrenia and autism spectrum disorders: The joint effect of NRG1-ErbB genes.

BACKGROUND: Schizophrenia-spectrum disorders (SSD) and Autism spectrum disorders (ASD) are neurodevelopmental disorders that share clinical, cognitive, and genetic characteristics, as well as particular white matter (WM) abnormalities. In this study, we aimed to investigate the role of a set of oligodendrocyte/myelin-related (OMR) genes and their epistatic effect on the risk for SSD and ASD. METHODS: We examined 108 SNPs in a set of 22 OMR genes in 1749 subjects divided into three independent samples (187 SSD trios, 915 SSD cases/control, and 91 ASD trios). Genetic association and gene-gene interaction analyses were conducted with PLINK and MB-MDR, and permutation procedures were implemented in both. RESULTS: Some OMR genes showed an association trend with SSD, while after correction, the ones that remained significantly associated were MBP, ERBB3, and AKT1. Significant gene-gene interactions were found between (i) NRG1*MBP (perm p-value = 0.002) in the SSD trios sample, (ii) ERBB3*AKT1 (perm p-value = 0.001) in the SSD case-control sample, and (iii) ERBB3*QKI (perm p-value = 0.0006) in the ASD trios sample. DISCUSSION: Our results suggest the implication of OMR genes in the risk for both SSD and ASD and highlight the role of NRG1 and ERBB genes. These findings are in line with the previous evidence and may suggest pathophysiological mechanisms related to NRG1/ERBBs signalling in these disorders.

Neurocognitive correlates of the varied domains of outcomes at 20 year follow-up of first-episode psychosis.

Little is known about long-term outcomes of the first episode of psychosis (FEP) other than in the symptomatic domain. We hypothesised that cognitive impairment is associated with poorer multi-domain outcomes at a long-term follow-up of FEP patients. We followed-up 172 FEP patients for a mean of 20.3 years. Ten outcome dimensions were assessed (symptomatic, functional and personal recovery, social disadvantage, physical health, suicide attempts, number of episodes, current drug use, chlorpromazine equivalent doses (CPZ), and schizophrenia/schizoaffective disorder final diagnosis). Cognition was assessed at follow-up. Processing speed and verbal memory deficits showed significant associations with poor outcomes on symptomatic, social functioning, social disadvantage, higher number of episodes, and higher CPZ. Significant associations were found between visual memory impairments were significantly associated with low symptomatic and functional recovery, between attentional deficits and a final diagnosis of schizophrenia/schizoaffective disorder, and between social cognition deficits and poor personal recovery.Lower cognitive global scores were significantly associated with all outcome dimensions except for drug abuse and physical status. Using multiple outcome dimensions allowed for the inclusion of the patients' perspective and other commonly neglected outcome measures. Taken together, cognitive impairment in FEP patients is strongly related to poor performance on several outcome dimensions beyond symptomatic remission.

Risk factors, pre-morbid functioning and episode correlates of neurological soft signs in drug-naive patients with schizophrenia-spectrum disorders.

BACKGROUND: There is a lack of consistent evidence regarding associations of neurological soft signs (NSS) with illness-related variables in schizophrenia. This study examined NSS in first-episode psychotic patients with respect to their factor structure and associations with risk factors, pre-morbid characteristics, psychopathology and spontaneous extrapyramidal syndromes. METHOD: First-episode, drug-naive patients with schizophrenia-spectrum disorders (n=177) were assessed for NSS using the Neurological Evaluation Scale, and its 26 constituting items were factor analysed. The identified neurological dimensions were then entered into hierarchical regression models as outcome dependent variables of a set of predictors including risk factors (familial loading for schizophrenia, obstetric complications), pre-morbid characteristics (neurodevelopmental delay, symptoms of attention deficit-hyperactivity disorder, pre-morbid functioning), psychopathological domains (reality distortion, disorganization, negative symptoms, mania, depression, catatonia) and spontaneous extrapyramidal syndromes (parkinsonism, dyskinesia, akathisia). RESULTS: Five neurological domains were identified: sequencing, release signs, sensory integration, abnormal movements and coordination. Multivariate analyses showed independent associations (p<0.01) of sequencing with familial liability to schizophrenia, deterioration of pre-morbid adjustment and parkinsonism; release signs with obstetric complications, catatonic symptoms and parkinsonism; sensory integration with familial liability to schizophrenia; abnormal movements with familial liability to schizophrenia, obstetric complications, parkinsonism and dyskinesia; and coordination with neurodevelopmental delay. The empirically derived factors explained additional variance over and above that explained by subscale scores across the examined variables. CONCLUSIONS: Familial liability to schizophrenia, obstetric complications, neurodevelopmental delay, deterioration in pre-morbid functioning and observable motor disorders appear to contribute independently to domains of neurological dysfunction. The findings support a neurodevelopmental model of NSS in schizophrenia.

Epigenetics-by-sex interaction for somatization conferred by methylation at the promoter region of SLC6A4 gene.

BACKGROUND: Depression, anxiety and somatoform disorders are all more prevalent in women than in men. However, specific biological mechanisms contributing to such sex differences remain unknown. Serotonergic pathways are involved in mood and behavior regulation and thus have been suggested to be altered in several psychiatric disorders. The serotonin transporter (SERT), encoded by SLC6A4 gene, has received major attention due to its crucial role in serotonergic transmission. METHODS: 148 monozygotic twin subjects were assessed for (i) lifetime categorical diagnosis of anxious-depressive disorders, following SCID-I-based DSM-IV criteria, and (ii) current psychiatric symptomatology, from a dimensional approach, by means of the Brief Symptom Inventory (BSI). SLC6A4 gene methylation was analyzed by means of Infinium HumanMethylation450 in a subset of the sample. CpG-specific methylation at the promoter region of SLC6A4 gene was further analyzed by means of pyrosequencing technology in the total sample. RESULTS: SLC6A4 methylation was found to be significantly higher in women when compared to men independent of DSM-IV diagnosis. SLC6A4 methylation was further associated with the BSI-derived somatization dimension. CONCLUSIONS: Female hypermethylation of a discrete region located within SLC6A4 promoter region could underlie differential SERT expression in women when compared to men and could be one of the causative mechanisms by which women exhibit increased prevalence of somatic symptoms.

Flea market finds and global exports: Four multistate outbreaks of human Salmonella infections linked to small turtles, United States-2015.

Zoonotic transmission of Salmonella infections causes an estimated 11% of salmonellosis annually in the United States. This report describes the epidemiologic, traceback and laboratory investigations conducted in the United States as part of four multistate outbreaks of Salmonella infections linked to small turtles. Salmonella isolates indistinguishable from the outbreak strains were isolated from a total of 143 ill people in the United States, pet turtles, and pond water samples collected from turtle farm A, as well as ill people from Chile and Luxembourg. Almost half (45%) of infections occurred in children aged <5 years, underscoring the importance of the Centers for Disease Control and Prevention recommendation to keep pet turtles and other reptiles out of homes and childcare settings with young children. Although only 43% of the ill people who reported turtle exposure provided purchase information, most small turtles were purchased from flea markets or street vendors, which made it difficult to locate the vendor, trace the turtles to a farm of origin, provide education and enforce the United States federal ban on the sale and distribution of small turtles. These outbreaks highlight the importance of improving public awareness and education about the risk of Salmonella from small turtles not only in the United States but also worldwide.

Familial aggregation of schizotypy in schizophrenia-spectrum disorders and its relation to clinical and neurodevelopmental characteristics.

INTRODUCTION: This study explored schizotypy as a familial liability marker for schizophrenia-spectrum disorders (SSD) by examining: 1) the aggregation of schizotypy in families with a SSD patient, 2) whether familial resemblance of schizotypy is associated with ridge dissociations (RD), another SSD liability marker, 3) whether schizotypy aggregation patterns influence patients' psychopathology. METHODS: The sample comprised 30 SSD patients and 82 healthy first-degree relatives. Schizotypy was assessed using the Structured Interview for Schizotypy-Revised (SIS-R). Patients' psychopathology was evaluated using the Comprehensive Assessment of Symptoms and History (CASH). RD were identified as anomalies of the dermal ridge junction. Familiality of SIS-R was investigated using a linear mixed model (LMM) and its strength was assessed using an intraclass correlation coefficient (ICC). Another LMM using the absolute differences in SIS-R scores between all possible pairs of relatives as the dependent variable was fitted to obtain an intra-family resemblance score, a family-specific indicator of resemblance of SIS-R scores within each family. RESULTS: 1) Schizotypy was familial (ICC = 0.30); families with high resemblance displayed low schizotypy, whereas families with low resemblance included at least one healthy relative with high schizotypy (p < 0.001). 2) Relatives with RD had higher SIS-R scores (p = 0.018) and belonged to families with discordant schizotypy scores among members (p < 0.001). 3) Patients from high schizotypy families showed more severe disorganized symptoms at the psychotic episode (p = 0.035) and 1 year later (p = 0.011). CONCLUSIONS: Schizotypy is a marker of vulnerability for SSD that runs within a subgroup of families. The schizotypy familial aggregation pattern correlates with RD in relatives and with patients' psychopathology.

Evidence of an epistatic effect between Dysbindin-1 and Neuritin-1 genes on the risk for schizophrenia spectrum disorders.

BACKGROUND: The interest in studying gene-gene interactions is increasing for psychiatric diseases such as schizophrenia-spectrum disorders (SSD), where multiple genes are involved. Dysbindin-1 (DTNBP1) and Neuritin-1 (NRN1) genes have been previously associated with SSD and both are involved in synaptic plasticity. We aimed to study whether these genes show an epistatic effect on the risk for SSD. METHODS: The sample comprised 388 SSD patients and 397 healthy subjects. Interaction was tested between: (i) three DTNBP1 SNPs (rs2619537, rs2743864, rs1047631) related to changes in gene expression; and (ii) an haplotype in NRN1 previously associated with the risk for SSD (rs645649-rs582262: HAP-risk C-C). RESULTS: An interaction between DTNBP1 rs2743864 and NRN1 HAP-risk was detected by using the model based multifactor dimensionality reduction (MB-MDR) approach (P=0.0049, after permutation procedure), meaning that the risk for SSD is significantly higher in those subjects carrying both the A allele of rs2743864 and the HAP-risk C-C. This interaction was confirmed by using a logistic regression model (P=0.033, OR (95%CI)=2.699 (1.08-6.71), R2=0.162). DISCUSSION: Our results suggest that DTNBP1 and NRN1 genes show a joint effect on the risk for SSD. Although the precise mechanism underlying this effect is unclear, the fact that these genes have been involved in synaptic maturation, connectivity and glutamate signalling suggests that our findings could be of value as a link to the schizophrenia aetiology.

[Psychosis associated to megacisterna magna]. / Psicosis asociada a megacisterna magna.

Megacisterna magna is a developmental malformation of the middle-line brain structures, which exists along a continuum with cerebellum hypoplasia (Dandy-Walker variant) and cerebellum agenesia (Dandy-Walker syndrome). Psychotic disorders, and particularly schizophrenia, are now conceptualised as disorders of neurodevelopment. We report on a patient who presented a psychotic disorder (delusional type), and mega cisterna magna. This is the first report of such an association, and it is suggested that both the psychotic disorder and the mega cisterna magna may be the expression of a single underlying neurodevelopment abnormality.

Salud sexual y salud reproductiva en mujeres jóvenes con consumo de sustancias en Chile según datos VIII encuesta nacional de la juventud / Sexual health and reproductive health in young women with substance consumption in Chile according to data VIII national youth survey

OBJETIVOS: Determinar la asociación entre el consumo de sustancias y características de salud sexual y reproductiva de mujeres jóvenes en Chile. MÉTODOS: Estudio transversal analítico en mujeres entre 15 a 24 años. Se formaron 3 grupos: Sin consumo de sustancias (SCS), Consumo no problemático de sustancias (CNPS) y Consumo problemático de sustancias (CPS). Se realizó análisis descriptivo y de asociación entre las variables. Se ajustaron modelos de regresión logística múltiple y ordinal múltiple. RESULTADOS: Muestra de 2.589 jóvenes, el 37,8% correspondió al grupo SCS, 46,3% al grupo CSNP y 15,9% al grupo CPS. En promedio la edad de inicio de actividad sexual fue menor en el grupo CPS (15,9 años p = 0,001) mostrando mayor porcentajes de sexo oral, anal, no uno de condón, relaciones sexuales con parejas menos estables, mayor número de parejas sexuales y violencia en la pareja, (p =0,001). En este grupo se incrementa 5,84 el riesgo de tener la última relación sexual con pareja menos estable (IC95%: 3,90 - 12,01) y 8,35 veces el riesgo de tener 2 o más parejas sexuales (últimos 12 meses) (IC95%: 5,35 - 16,34). En el grupo CNPS se incrementa 1,11 veces el riesgo de tener la última relación sexual con pareja menos estable (IC95%: 1,43 - 3,12), 1,01 veces tener 2 y más parejas sexuales (últimos 12 meses) (IC95%: 1,20 - 3,36). CONCLUSIONES: Reconociéndose que la sexualidad es multifactorial, las mujeres con consumo de sustancias viven situaciones que facilitan riesgos para su salud sexual. El consumo en mujeres jóvenes es un problema de salud pública que presenta desafíos para su abordaje.

OBJECTIVES: To determine the association between substance use and characteristics of sexual and reproductive health of young women in Chile. METHODS: Analytical cross-sectional study in women between 15 and 24 years. Three groups were formed: No substance use (SCS), Non-problematic substance use (CNPS) and Problem substance use (CPS). Descriptive and association analysis was performed between the variables. Multiple logistic regression and multiple ordinal models were adjusted. RESULTS: Sample of 2,589 young people, 37.8% corresponded to the SCS group, 46.3% to the CSNP group and 15.9% to the CPS group. On average the age of onset of sexual activity was lower in the CPS group (15.9 years p = 0.001) showing higher percentages of oral, anal sex, not a condom, sex with less stable partners, greater number of sexual partners and violence in the couple, (p = 0.001). In this group the risk of having the last sexual relationship with a less stable partner is increased 5.84 (95% CI: 3.90 - 12.01) and 8.35 times the risk of having 2 or more sexual partners (last 12 months) (95% CI: 5.35-16.34). In the CNPS group the risk of having the last sexual relationship with a less stable partner is increased 1.11 times (95% CI: 1.43 - 3.12), 1.01 times having 2 and more sexual partners (last 12 months) (95% CI: 1.20-3.36). CONCLUSIONS: Recognizing that sexuality is multifactorial, women with substance use experience situations that facilitate risks to their sexual health. Consumption in young women is a public health problem that presents challenges for its approach.

Factor structure and clinical validity of competing models of positive symptoms in schizophrenia.

BACKGROUND: The factor structure of four competing models of positive symptoms and their clinical validity was studied in a sample of 253 schizophrenia inpatients. METHODS: The following models were tested using confirmatory factor analysis: a one-dimension severity model, a two-dimension model comprising a psychosis factor and a disorganization factor, a four-dimension model based on the Scale for the Assessment of Positive Symptoms (SAPS) structure in subscales, and a five-dimension model derived from the previous one by further differentiating Schneiderian delusions from non-Schneiderian ones. RESULTS: More complex multifactorial models fit the data better than simpler models. The five-dimension model was the best adjusted (goodness of fit index = .844, nonnormed fit index = .812, normed fit index = .728). Whereas the one-dimension model did not display significant association with the clinical variables, multidimensional models were related to age at onset and illness severity. The two-dimension model captured well the clinical correlates of the more complex models. CONCLUSION: None of the tested models showed good fit to the data. The one-dimension model displayed both poor factor validity and poor external validity; therefore, research relying on the SAPS total score may reach misleading conclusions.

An empirical analysis of latent structures underlying schizophrenic symptoms: a four-syndrome model.

Various models of schizophrenia have postulated two syndromes (i.e., positive and negative), although other exploratory factor analyses have suggested a disorganization syndrome. We conducted a confirmatory factor analysis (CFA) on Schedule for the Assessment of Positive Symptoms (SAPS) and Schedule for the Assessment of Negative Symptoms (SANS) items and subscales to assess the latent structure of symptoms reflecting underlying pathological processes. The sample included 253 DSM-IIIR schizophrenic inpatients. Fourteen different models with one, two, three, or four syndromes were compared using CFA for "goodness of fit." The three-syndrome models displayed better fitness than any of the one- or two-syndrome models. All of the three-syndrome models shared the positive and negative dimensions; the third dimension in these three-syndrome models was either the disorganization or Strauss' relational dimensions. In the reported data, a four-syndrome model, including positive, disorganization, negative, and relational dimensions, showed excellent fitness. Despite its limitations, this study suggests the need to explore the validity of a four-syndrome model. The positive-negative model fits poorly with the data.

Factor structure of symptoms in functional psychoses.

Global ratings from the Scale for the Assessment of Positive Symptoms and Scale for the Assessment of Negative Symptoms were subjected to principal-component analysis (PCA) in 80 schizophrenia patients, 76 patients with schizophreniform disorder, 80 patients with schizoaffective and mood disorders, and 78 patients with delusional, brief reactive, and atypical psychoses. The resulting factors were correlated with depressive, manic, and catatonic syndromes, and subjected to a multivariate analysis of variance across DSM-III-R diagnoses. PCAs revealed that psychosis, disorganization, and negative factors were also present in each of the nonschizophrenic groups. The disorganization factor tended to be related to the manic syndrome, and the negative factor to depressive and catatonic syndromes. Overall, the three factors had little diagnostic relevance in functional psychoses, although the negative factor was relatively more characteristic of schizophrenia. The data suggest that positive, negative, and disorganization factors are not specific to schizophrenia; this is consistent with a dimensional view of psychopathology in functional psychoses.

Serum iron in catatonic and noncatatonic psychotic patients.

BACKGROUND: Since low serum iron has been reported in a variety of neuropsychiatric motor disorders, this study was conducted to examine serum iron in patients with a catatonic disorder. METHODS: Forty catatonic and 40 noncatatonic psychotic patients were studied in relation to serum iron levels. The association of serum iron with other clinical variables was also examined. RESULTS: Catatonics had significantly lower mean serum iron than noncatatonics. Ferropenia (serum iron < 50 micrograms/dL) was significantly more prevalent in the catatonic (35%) than in the noncatatonic (7.5%) group. Severity of catatonic symptoms was inversely correlated with level of serum iron, this being due to the negative catatonic symptoms (r = -.34, p = .002). CONCLUSIONS: A subgroup of catatonic patients had ferropenia. Lower serum iron level was associated with both the presence of a categorically defined catatonic syndrome and the severity of the negative catatonic symptoms.

Negative symptoms in schizophrenia: a confirmatory factor analysis of competing models.

OBJECTIVE: The aim of the study was to examine different models of the factor structure of negative symptoms in schizophrenia through the use of a confirmatory factor analysis procedure. METHOD: The cohort comprised 253 inpatients diagnosed with schizophrenia according to DSM-III-R criteria. Negative symptoms were evaluated with the Scale for the Assessment of Negative Symptoms (SANS). Seven alternative models of negative symptoms were compared by means of confirmatory factor analysis. RESULTS: The unidimensional model fit the data modestly. More complex multifactorial models fit the data better than simpler models. Both five-dimension models corresponding to the original SANS structure fit the data quite well; the model excluding inappropriate affect from the SANS was the best adjusted. CONCLUSIONS: Multidimensional models fit the data better than the unidimensional model. The data provide evidence for the factorial validity of the SANS and the characterization of the SANS subscales as true underlying dimensions of observable negative symptoms.

Differentiating primary from secondary negative symptoms in schizophrenia: a study of neuroleptic-naive patients before and after treatment.

OBJECTIVE: The study examined the primary versus secondary character of negative symptoms in a group of first-episode, neuroleptic-naive psychotic patients before and after they started neuroleptic treatment. METHOD: Forty-seven inpatients with a first episode of schizophrenia or related psychotic disorders were examined for the presence of negative symptoms, psychosis, depression, and parkinsonism at admission to an inpatient psychiatric unit, before receiving neuroleptics, and at discharge an average 3.3 weeks later, after starting neuroleptic treatment. RESULTS: Although patients' mean scores on measures of positive, negative, and depressive symptoms decreased significantly over the treatment period, the mean rating of nonakinetic parkinsonism worsened. The mean rating of akinetic parkinsonism did not change significantly over the treatment period. Negative symptoms at admission were not predicted by positive or depressive symptoms at admission. Residual negative symptoms at discharge were mainly predicted by negative symptoms at admission (i.e., primary symptoms) and to a negligible degree by residual positive and depressive symptoms. Change in negative symptoms over the observation period was predicted to a marginal degree by change in depressive symptoms. CONCLUSIONS: Negative symptoms rated during a first psychotic episode before and after starting antipsychotic treatment are mainly primary in character and should be considered as a direct manifestation of the basic dysfunctions of schizophrenia.