Antibodies to infectious agents in individuals at ultra-high risk for psychosis.

BACKGROUND: While there is evidence that some cases of schizophrenia may be associated with microbial infections, the role of microbial agents has not been investigated in people with emerging psychosis. METHODS: Participants were 105 help seeking ultra-high risk individuals. Psychiatric measures included the Brief Psychiatric Rating Scale and the Scale for the Assessment of Negative Symptoms. Serum IgG antibodies against human herpesviruses and Toxoplasma gondii were determined using immunoassay methods. Multiple linear regression with adjustment for age and sex was applied to test associations between serum antibodies and psychiatric measures. RESULTS: Higher levels of serum IgG antibodies against Toxoplasma gondii in Toxoplasma-positive individuals were significantly associated with more severe positive psychotic symptoms. No significant association was observed between antibody levels and psychiatric measures in individuals positive for human herpesviruses. CONCLUSIONS: In some individuals infection with Toxoplasma gondii may be an environmental factor contributing to the manifestation of positive psychotic symptoms.     

The assessment of positive dimension of the psychosis phenotype in college students

The Wisconsin Schizotypy Scales are one of the most used measuring instruments for the assessment of psychometric risk for psychosis. The main goal of the present study was to analyze the reliability of the scores and to provide new sources of validity evidence for the brief version of the Magical Ideation Scale (MIS-B) and the Perceptual Aberration Scale (PAS-B). The final sample was comprised of a total of 1349 university students divided into two subsamples (n1 = 710; M = 19.8 years; n2 = 639; M = 21.2 years). Results show that both measurement instruments have adequate psychometric properties under Classical Test Theory and Item Response Theory. Internal structure analysis of MIS-B and PAS-B, through exploratory and confirmatory factor analysis, yielded an essentially one-dimensional solution. Cronbach’s alpha coefficient for the total score of MIS-B ranged between 0.86 and 0.87, whereas for the PAS-B it ranged between 0.78 and 0.89. A total of 5 items showed a differential functioning for sex. The results indicate that the MIS-B and PAS-B are brief measurement instruments with adequate psychometric properties for the assessment of the positive dimension of the psychosis phenotype and could be used as screening tools in the detection of individuals at risk for psychosis in the general population.     

Antibodies to infectious agents in individuals with recent onset schizophrenia

Abstract. We investigated the levels of antibodies to infectious agents in the serum and cerebral spinal fluids (CSFs) of individuals with recent onset schizophrenia and compared these levels to those of controls without psychiatric disease. We found that untreated individuals with recent onset schizophrenia had significantly increased levels of serum and CSF IgG antibody to cytomegalovirus and Toxoplasma gondii as compared to controls. The levels of serum IgM class antibodies to these agents were not increased. Untreated individuals with recent onset schizophrenia also had significantly lower levels of serum antibody to human herpesvirus type 6 and varicella zoster virus as compared to controls. Levels of antibodies to herpes simplex virus type 1, herpes simplex virus type 2, and Epstein Barr virus, and did not differ from cases and controls.We also found that treatment status had a major effect on the levels of antibodies in this population. Individuals who were receiving treatment had lower levels of antibodies to cytomegalovirus and Toxoplasma gondii, and higher levels of serum antibodies to human herpesvirus type 6 as compared to untreated individuals. The level of antibodies to Toxoplasma and human herpesvirus type 6 measured in treated individuals did not differ from the levels measured in controls. In the case of cytomegalovirus, the levels of CSF antibodies in treated individuals did not differ from those of controls, while the level of serum IgG antibodies to CMV remained slightly greater than controls in this population.Our studies indicate that untreated individuals with recent onset schizophrenia have altered levels of antibodies to cytomegalovirus, Toxoplasma gondii, and human herpesvirus type 6 while the levels of these antibodies in treated individuals with recent onset schizophrenia are similar to those of controls. These findings indicate that infectious agents may play a role in the etiopathogenesis of some cases of schizophrenia.     

P300 asymmetry and positive symptom severity: a study in the early stage of a first episode of psychosis

The amplitude of the P300 event-related potential (ERP) has been reported to be reduced over left compared to right temporal sites in schizophrenia patients. This left temporal P300 reduction has been associated with positive symptom severity and gray matter reduction in the left superior temporal gyrus. We investigated a group of patients with a first episode of schizophrenia spectrum psychosis and a group of normal controls to verify if P300 amplitude asymmetry already exists around the time of presentation for treatment. Relative to normal control subjects, no P300 asymmetry was found in patients. Nevertheless, P300 asymmetry was correlated with the severity of positive symptoms and worse global functioning (GAF), a good predictor of poor outcome.     

A retrospective study of symptom patterns of cannabis-induced psychosis

The aim of this study was to find out whether there are any similarities between cannabis psychosis on the one hand and schizophrenia and mania on the other, and to delineate any consistency in the pattern of clinical symptoms of cannabis psychosis. Relevant data were collected from patient's case-notes depicting biographical information and the frequencies of mental symptoms. Age and duration in hospital agreed between the 3 groups. Although several significant differences were recorded in the distribution of mental symptoms, it was not possible to demonstrate a consistent pattern of symptoms typical of cannabis psychosis.     

Childhood negative experiences and subclinical psychosis in adolescence: a longitudinal general population study

Background: Accumulating evidence suggests that experiences of trauma and victimization during childhood are associated with an increased risk to develop clinical and subclinical psychosis in adulthood. A recent cross‐sectional study showed a significant association between trauma and psychotic experiences in adolescents. The current study aimed to extend these findings by investigating the longitudinal effects of negative life experiences on the risk for subclinical psychotic symptoms 2 years later in an adolescent general community sample. Methods: Data were derived from the standard health screenings of the Youth Health Care Divisions of the Public Health Services, in the South of the Netherlands. A total of 1129 adolescents filled out a self‐report questionnaire at age 13/14 years and 2 years later (15/16 years), assessing psychotic experiences, as well as experiences of being bullied, sexual trauma, and negative life events. Results: Logistic regression analyses revealed that sexual trauma increased the risk for psychotic symptoms 2 years later. Life events contributed to the risk for psychosis over time and psychosis in turn gave rise to new life events. No significant association with bullying was found after controlling for confounders. Conclusion: The results provide further evidence for an association between childhood environment and psychosis in the crucial developmental period of early adolescence. Early and later psychological stress, if severe, may impact on the risk for psychosis in adolescence through mechanisms of person–environment interaction and correlation.     

精神病的跨诊断维度:对精神疾病的分类学与研究的意义（英文）

如果精神病是一种跨诊断的维度,精神病性症状的出现受动态变化的情境和情感因素左右,而后者又是可治疗的,那么目前精神科疾病的分类学和治疗研究的方法可能需要修改。迄今为此,无论在临床工作上还是在疾病概念上,占主导地位的方法是将精神病性症状置于精神分裂症的框架中。然而,终生患病率为1%的精神分裂症只代表了部分预后不佳的精神病谱系障碍,而后者发生更多,终生患病率为3.5%。因此,精神分裂症的研究结果可能反映了预后相关的机制,而非精神病和其他症状维度之间本质上的相关性。同样,常见的非精神病性精神障碍中高达30%的个体有阈下精神病性症状,他们会被归于精神病的跨诊断维度之下,这些精神症状还会影响临床严重程度和治疗有效性。上述发现也同样提示武断区分"精神病性"与"非精神病性"的做法妨碍了临床实践和研究。精神病学诊断手册可以借鉴跨诊断维度(包括精神病的跨诊断维度)的体系。引入跨诊断维度,则既能根据原则进行分类诊断(即疾病分组的特异性),又可结合个体特有的多维度综合评分(即个体特异性)。这样的益处在于促使人们思考在精神病理学中症状之间是如何动态地交互作用的,并思考社会环境是如何影响精神病理症状的。     

The multidimensional measurement of the positive symptoms of psychosis

The measures most frequently used to assess psychotic symptoms fail to reflect important dimensions. The Psychotic Symptom Rating Scale (PSYRATS) aims to capture the multidimensional nature of auditory hallucinations and delusions. Individuals (N = 276) who had recently relapsed with positive symptoms completed the auditory hallucinations and delusions PSYRATS scales. These scores were compared with the relevant items from the SAPS and PANSS, and with measures of current mood. Total scores and distribution of items of the PSYRATS scales are presented and correlated with other measures. Positive symptom items from the SAPS and PANSS reflected the more objective aspects of PSYRATS ratings of auditory hallucinations and delusions (frequency and conviction) but were relatively poor at measuring distress. A major strength of the PSYRATS scales is the specific measurement of the distress dimension of symptoms, which is a key target of psychological intervention. It is advised that the PSYRATS should not be used as a total score alone, whilst further research is needed to clarify the best use of potential subscales.     

分裂样精神病与精神分裂症阴性、阳性症状比较

目的：探讨分裂样精神病与精神分裂症阴性和阳性症状的特点。方法：对49例分裂样精神病与70例精神分裂症患者的阴性和阳性症状作对照研究。结果：两组患者阳性和阴性症状的发生率差异无显著性（P〉0.05）;分裂样精神病组中有妄想症状者明显多于精神分裂症组;而精神分裂症组中情感平淡、思维贫乏等阴性症状者明显多于分裂样精神病（P〈0.01）。结论：分裂样精神病与精神分裂症在阴性、阳性症状方面存在差异。     

The timing of negative symptom exacerbations in relationship to positive symptom exacerbations in the early course of schizophrenia

Although positive and negative symptoms appear to represent independent symptom dimensions of psychopathology when evaluated cross-sectionally among individuals with schizophrenia, it is not known if exacerbations of symptoms on these two dimensions are independent. This prospective longitudinal study examined the temporal relationship between the positive and negative symptom exacerbations among 48 recent-onset schizophrenia or schizoaffective patients who received symptom ratings every 2 weeks on the Brief Psychiatric Rating Scale. Patients were followed for a period of at least 1 year and a mean of 3 years. To examine the temporal relationship between positive and negative symptoms, six time periods were defined in relation to psychotic exacerbation or relapse (e.g., prodromal, concurrent, post-psychotic) and used to compare the timing of positive and negative symptom exacerbations. A substantial proportion of patients had exacerbations of positive symptoms (77%) and negative (42%) symptoms. Negative symptom exacerbations occurred simultaneously with positive symptom exacerbations to a significantly greater extent than expected by chance, and occurred less frequently than expected by chance during the time period most temporally removed from positive symptom exacerbations. Results suggest that the timing of some negative symptom exacerbations is linked to that of positive symptom exacerbations during the early course of schizophrenia.     

A 12-month outcome study of insight and symptom change in first-episode psychosis

Aim: We first aimed to evaluate the progression of insight and psychopathology over the first year of treatment for a psychosis. We hypothesized that improvement in insight would associate with improvement in positive and negative symptoms, and depressive and anxious symptom exacerbation. Secondly, in an exploratory analysis, we aimed to identify quantitatively distinct insight trajectory groups, and to describe the impact of psychopathology over time on the different trajectory groups. Methods: One-hundred and sixty-five patients were administered a comprehensive clinical evaluation, and insight was rated on the Scale for Assessment for Unawareness of Mental Disorder, item 1 (awareness of mental disorder), at admission and after 1, 2, 3, 6, 9 and 12 months. Results: In a generalized estimating equation (GEE) model of change, insight improved concurrently with positive, negative and anxious symptoms between baseline and month 1 in the entire cohort. Latent group-based trajectory analysis revealed five insight groups: good, increasing, decreasing, moderate poor and very poor. GEE modelling revealed that the very poor and moderate poor insight groups displayed greater overall negative symptoms than patients with good and increasing insight trajectories. The good insight group showed significantly greater overall depressive symptoms than the diminished and very poor insight groups. Conclusions: The results suggest that specific longitudinal insight trajectories were driving the observed associations between insight and negative and depressive symptoms in the entire first-episode psychosis cohort. Persistently poor insight may be an important factor in negative symptom maintenance. Good or increasing course of insight may be early clinical indicators of a liability to depression.     

Risk indicators of anxiety throughout adolescence: the TRAILS study

Background: The aim was to identify risk indicators from preadolescence (age period 10–12) that significantly predict unfavorable deviations from normal anxiety development throughout adolescence (age period 10–17 years). Methods: Anxiety symptoms were assessed in a community sample of 2,220 boys and girls at three time‐points across a 5‐year interval. Risk indicators were measured at baseline and include indicators from the child, family, and peer domain. Associations with anxiety were measured with multilevel growth curve analyses. Results: A stable difference in anxiety over adolescence was found between high and low levels of a range of child factors (frustration, effortful control), family factors (emotional warmth received from parents, lifetime parental internalizing problems), and peer factor (victims of bullying) (P<.001). In contrast, the difference in anxiety between high and low levels of factors, such as self‐competence, unfavorable parenting styles, and bully victims, decreased over adolescence (P<.001). For other family factors, associations were weaker (.05Conclusions: Several child, family, and peer factors measured in preadolescence were risk indicators of high levels of anxiety symptoms throughout adolescence. Some factors (such as rejective parenting) were vulnerability indicators for anxiety in early adolescence only, whereas other factors (such as peer victimization) were indicators of long‐term elevated anxiety levels. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

The association of infectious agents and schizophrenia

Abstract

Objectives. The influence of infectious agents on the pathogenesis of psychiatric disorders has been discussed for decades. Pre- and postnatal infections are risk factors for schizophrenia. This may be explained by chronic infections or an altered immune status. However most of the studies have only focused on one single pathogen and not on the impact of different infectious agents. We investigated the association between schizophrenia and various neurotophic infectious agents. Methods. A total of 31 schizophrenic patients and 30 healthy matched individuals were included. Antibody titres of cytomegalovirus, herpes simplex virus, Epstein-Barr virus, mycoplasma, chlamydia and toxoplasma were evaluated. For statistical analysis we used Fisher's exact and Wilcoxon test. Results. Significantly elevated positive antibody titres within schizophrenic patients were found only for Chlamydia trachomatis (P=0.005) and a trend to significance for herpes simplex virus (P=0.055). Combining the different agents, schizophrenics had a significantly higher rate of positive titres to infectious agents as compared to controls (P=0.04). Conclusions. The higher prevalence of antibodies within schizophrenic patients emphasizes a possible role of infectious agents in the pathogenesis of schizophrenia. Our data indicates that not one specific agent might be responsible for schizophrenic symptoms but the resulting immune response in the central nervous system.     

Cognitive endophenotypes of psychosis within dimension and diagnosis

This study sought to characterize the psychosis phenotype, contrasting cognitive features within traditional diagnosis and psychosis dimension in a family sample containing both schizophrenia and psychotic bipolar I disorder. Seventy-six probands with psychosis [44 probands with schizophrenia, 32 probands with psychotic bipolar I disorder] and 55 first-degree relatives [30 relatives of schizophrenia probands, 25 relatives of bipolar probands] were recruited. Standardized clinical and neuropsychological measures were administered. No differences in cognitive performance emerged between probands with schizophrenia and probands with psychotic bipolar disorder, or between relatives of probands with schizophrenia and relatives of probands with bipolar disorder in the domains of working and declarative memory, executive function and attention. Relatives overall showed higher cognitive performance compared to probands, as expected. However, when we segmented the probands and relatives along a psychosis dimension, independent of diagnostic groups, results revealed lower cognitive performance in probands compared to relatives without psychosis spectrum disorders, whereas relatives with psychosis spectrum disorders showed an intermediate level of performance across all cognitive domains. In this study, cognitive performance did not distinguish either probands or their first-degree relatives within traditional diagnostic groups (schizophrenia and psychotic bipolar disorder), but distinguished probands and relatives with and without lifetime psychosis manifestations independent of diagnostic categories. These data support the notion that schizophrenia and psychotic bipolar disorder present a clinical continuum with overlapping cognitive features defining the psychosis phenotype.     

The impact of immigration and visible minority status on psychosis symptom profile

Purpose

Immigrants have heightened risks of psychotic disorders, and it is proposed that migration influences symptom profiles. The purpose of this study was to investigate if either migration experience and/or visible minority status affected symptom profiles, using a cross-culturally validated five-factor model of the Positive and Negative Syndrome Scale (PANSS), in patients with broadly defined psychotic disorders.

Methods

PANSS was assessed in a large catchment area based sample of patients with psychotic disorders verified with the Structured Clinical Interview for DSM-IV (n = 1,081). Symptom profiles based on Wallwork et al. five-factor model were compared for Norwegians (73 %), white immigrants (10.5 %), and visible minority groups (16.5 %).

Results

Visible minorities were significantly younger, had less education, more often a schizophrenia diagnosis and higher PANSS positive, negative and disorganized/concrete factor scores than Norwegians and white immigrants. After controlling for confounders only the items “Delusions” and “Difficulty in abstract thinking” differed between groups. Multivariate analyses indicated that these items were not associated with immigration per se, but rather belonging to a visible minority.

Conclusion

We found mostly similarities in psychotic symptoms between immigrants and Norwegians when using a cross-culturally validated five-factor model of the PANSS. Immigration did not directly influence psychotic symptom profiles but visible minority groups had higher levels of “Delusions” and “Difficulty in abstract thinking”, both symptoms that are partially context dependent.