Multivariate Analysis of Relationship between Childhood Trauma and Psychotic Symptoms in Patients with Schizophrenia

The aim of this study was to examine the relationship between childhood trauma and psychotic symptoms in schizophrenic patients after controlling for the possible confounding factors, such as depression and dissociative symptoms. Ninety-eight schizophrenic inpatients participated. Childhood trauma was examined using the Childhood Trauma Questionnaires (CTQ), which consists of physical abuse (PA), sexual abuse (SA), emotional abuse (EA), physical neglect (PN), and emotional neglect (EN). Positive and Negative Syndrome Scale (PANSS), Dissociative Experience Scale (DES), and Beck''s Depression Inventory (BDI) were also administered. Data were analyzed by partial correlation and general linear model. The total score of CTQ was positively correlated with positive, general, and total scores of PANSS. All five types of childhood trauma were associated with dissociative symptoms. EA and EN were positively correlated with depressive symptoms. Only SA significantly predicted positive symptoms of schizophrenia after controlling for age, sex, BDI, and DES scores, with a dose-response relationship between SA and positive symptoms.     

Psychotic Symptoms and a Diagnosis of Schizophrenia Follow an Initial Diagnosis of Tic Disorder

We report a patient with a tic disorder who later developed psychotic symptoms and was diagnosed with schizophrenia.     

The Impact of Aging,Cognition, and Symptoms on Functional Competence in Individuals With Schizophrenia Across the Lifespan

Objective: Life expectancy in individuals with schizophrenia continues to increase. It is not clear whether cognitive deficits associated with schizophrenia remain as strong predictors of function in older and younger individuals. Thus, we assessed the relationship between cognition and functional competence in individuals with schizophrenia across 7 decades of life. Methods: We analyzed data obtained in 232 community-dwelling participants with schizophrenia (age range: 19–79 years). Cognition was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. Functional competence was assessed using the UCSD Performance-based Skills Assessment, which includes measures of Comprehension and Planning of Recreational Activities Skills, Financial Skills, Communication Skills, Transportation Skills, and Household Management Skills. To assess the effects of Global Cognition on functional competence, we performed hierarchical multivariate linear or logistic regression analyses controlling for age, education, gender, and negative symptoms. Results: Participants’ mean age was 49.1 (SD = 13.2, range = 19–79 years), 161 (69%) were male, and 55 (24%) were aged ≥60. Global Cognition was a predictor of Comprehension and Planning Skills (Exp(β) = 1.048), Financial Skills (Exp(β) = 1.104), Communication Skills (ΔR ² = .31) and Transportation Skills (Exp(β) = 1.066), but not Household Management Skills after adjusting for age, education, gender, and negative symptoms of schizophrenia. Conclusion: Cognition remains a strong predictor of functional competence across the lifespan. These findings suggest that treating cognitive impairment associated with schizophrenia could improve individuals’ function independent of their age.Key words: aging, cognition, functional, competence, lifespan, schizophrenia     

Treating Psychotic Symptoms in Elderly Patients

Research has shown that elderly patients are especially at risk for the development of psychotic symptoms. A combination of factors contributes to the increased risk for psychosis in this patient population. Various DSM-IV diagnostic categories including delirium, schizophrenia, delusional disorder, mood disorders, dementia, substance abuse, and medical-neurologic conditions can be associated with psychotic symptoms. In general, medications are prescribed for specific target symptoms, started at low doses, and titrated gradually. Although buspirone, trazodone, valproic acid, and carbamazepine have been used with some success, antipsychotic medications have been the primary treatment of psychosis in the elderly. Because the atypical antipsychotics offer effective management of psychotic symptoms combined with low liability of extrapyramidal symptoms, these agents may be the current treatment of choice for psychotic symptoms in the elderly when used cautiously.     

Distinguishing Between Schizophrenia and Other Psychotic Disorders

The Diagnostic and Statistical Manual of Mental Disorders (DSM) has provided diagnostic reliability across observers while neglecting biological validity. The current theme issue explores the boundaries between schizophrenia and bipolar disorder, using neuro-cognition, systems neuroscience, and genetics as points of departure to begin consideration of a biologically based reclassification of these illnesses.Key words: schizophrenia, bipolar, validity, classification

“Ce n’est qu’un début, continuons le débat.” (“This is just the beginning, let’s continue the debate.”)French students (May 1968)

In the ongoing debate over where to draw the boundary (if any) between schizophrenia and bipolar disorder, the arguments are familiar, the battle lines clearly drawn, but the scientific observations continue to be updated in important ways that make a reassessment timely. The current issue of the Bulletin features comprehensive overviews from the vantage points of genetics and systems neuroscience that continue to reshape the nature of the debate.Arguments over the discrete vs continuous nature of schizophrenia and bipolar disorder are important because they promise to translate into improved, more patient-specific prognoses and therapies.Disease classifications proceed from some logical beginning: In the absence of both informative biological data and clinical physical signs, clinical phenomenology, family history, and disease course constitute the mandatory starting points on the road to meaningful diagnostic categories. Hence, Kraepelin began in 1893 by defining these 2 entities based on longitudinal course and outcome. He had already begun to backtrack from this dichotomy by 1920 in the final edition of his Lehrbuch.¹ Before that, the follow-up studies from his pupil Zendig² demonstrated favorable outcome in a third of Kraepelin’s own large schizophrenia case series. The boundaries between clinical entities defined by phenomenology appear to be distributed on a continuum and to lack sharp demarcations. Thus, one-third of patients with schizophrenia simultaneously meet criteria for major depression,³ one-third of patients with bipolar illness manifest psychotic symptoms, which in some cases persist between overt episodes of mood disturbance.⁴ Recently, Keshavan⁵ showed no point of symptomatic rarity between schizophrenia, psychotic bipolar disorder, and schizoaffective disorder in the large Bipolar Schizophrenia Network on Intermediate Phenotypes sample. Similarly, the Suffolk County mental health project showed a lack of boundary, defined in terms of functioning, between schizoaffective disorder and schizophrenia,⁶ although there are occasional reports of biological distinctions between them, for example.⁷ Response to medications has not been especially helpful as a guide. The early Northwick Park studies offered some suggestion that patients with psychosis responded to antipsychotics, patients with mood disorders responded to lithium, and patients with features of both syndromes responded to both medicines.⁸ However, antipsychotic medications are now prescribed routinely for schizophrenia, bipolar disorder, and antidepressant treatment–resistant major depression, presumably, in part because they are effective in these conditions. Real-world experience with these patients shows that many are being prescribed polypharmaceutical cocktails of antipsychotic, antidepressant, and mood stabilizer medications. As is frequently pointed out, the one exception to this cross-diagnostic promiscuity seems to be lithium, to which about one-third of nonpsychotic bipolar patients and a much smaller proportion of classic schizophrenia patients respond with symptom remission.⁹ Although both schizophrenia and bipolar disorder are clearly heritable, as Cardno and Owen¹⁰ illustrate in this issue, segregation within families is less clear-cut than believed previously, and these conditions do not decisively “breed true,”¹¹ although psychotic bipolar illness may aggregate familially.⁴ Genome wide–association studies tend to uncover candidate single-nucleotide polymorphisms that confer risk for both disorders, and genes such as DISC-1 are also associated with increased risk for schizophrenia, bipolar illness, major depression, and other conditions.As pointed out by Frangou¹² in this issue, emergent properties such as cognition are an excellent starting point for examining differences between syndromes because they are reliably assessed across centers with standardized tests. Because they demonstrate both heritability and frequent abnormality in unaffected first-degree relatives, they constitute phenotypes, conceptually.¹¹ In this issue, Reilly and Sweeney¹³ point out, “Considerable evidence supports the notion that broadly impaired cognitive functioning is central to the pathophysiology of psychosis, and … [its] magnitude, rather than [its] presence differentiates syndromes within the psychosis spectrum.” They further suggest, “The detection of specific effects … is challenging yet critical if the field is to further advance development of pharmacological treatments targeting cognitive deficits … .” In our search for specificity, we ask if there is any point in the illness course where differences emerge? Frangou¹² notes that important differences are detectable in that premorbid cognitive and social abnormalities appear to be less marked in bipolar illness, although these differences diminish after illness onset. Similarly, copy number variants occurring in central nervous system–relevant genes are significantly commoner in schizophrenia than bipolar disorder, although, as mentioned earlier, genetic differences are not schizophrenia-specific, being found in association with other serious neurodevelopmental disorders, including epilepsy, learning disabilities, and autism spectrum disorders.Where do we go from here? This debate will continue until distinct etiopathologies for schizophrenia and bipolar disorder emerge—parallel events that ultimately ended this type of debate in clinical medicine. Ultimately, though, we are likely to define the new “illnesses” based on regularly co-occurring biological (including genetic) characteristics. One possibility in the short term is that we remain diagnostically uncommitted and code psychosis and mood disorder separately, as suggested by Kotov.¹⁴ Some researchers have argued strongly against this stance.¹⁵ Different associations with indices of neurodevelopmental impairment may be one point of departure as suggested in this issue by Cardno and Owen¹⁰ and Frangou.¹² Frangou suggests that “abnormalities in multiple large-scale neural networks and alterations in local micro-scale circuitry within associative and sensory cortices” caused by environmental insults and genetic variation, “disrupt processes responsible for orderly neuronal configuration” (eg, synaptic integrity, neurotransmission). Identifying such abnormalities then proceeds logically toward a redefinition of major mental illnesses based on systems neuroscience and the defining of “more homogeneous groups of patients.”¹² This strategy may reveal similarities across all putatively developmentally based psychiatric illnesses, including autism and learning disabilities, extending beyond schizophrenia and bipolar disorder. Cardno and Owen¹⁰ suggest we move away from lifetime diagnostic categories toward a system that relies more on “categorical or dimensional syndromes, networks of correlated symptoms, and/or endophenotypes … according to particular research or clinical requirements.”Regarding the genetic underpinnings of these disorders, we ask, “Precisely what is being inherited?” One possibility is that a small number of genes are being passed on that are responsible for multiple clinical manifestations, from mood instability to psychoticism (ie, an instance of pleiotropy). Another possibility is that risk is being inherited for more than one behavioral trait, which happens to commonly co-occur, for a variety of reasons including assortative mating. For example, “psychoticism,” whose pure form is expressed as Kraepelinian schizophrenia, and “mood instability,” whose pure form is expressed as nonpsychotic bipolar illness, may both be passed on, with the possibility of them being mixed together in various combinations to produce, eg, schizoaffective or psychotic bipolar disorder.What might the new disease landscape look like, whether based on neuronal circuit-based endophenotypes or commonalities in risk genes and their associated molecular biological processes? One possibility is that several clinical groupings will emerge that are phenomenologically heterogeneous, containing examples of what we now define clinically as schizophrenia and bipolar disorder, but consistent in their underlying biological markers. This would be analogous to the fate of “dropsy” in medicine. A less satisfactory outcome would be that more knowledge of etiopathology would result in the fissuring of familiar clinical syndromes into unique biological clusters, representing agglomerations defined by differing pathologic processes leading to disruption in final common biological pathways, more along the lines of the manner in which Alzheimer’s disease is now considered. The ultimate hope is to aggregate disorders according to biological mechanisms that underlie clinical phenomena and that point us toward evidence-based treatment targets and interventions. This is consistent with the National Institute of Mental Health’s Research Domain Criteria¹⁶ and the earlier cognitive neuropsychiatric approach.^17–19 This debate began with Kraepelin, is moving forward, but continues.     

Effects of Endurance Training Combined With Cognitive Remediation on Everyday Functioning,Symptoms, and Cognition in Multiepisode Schizophrenia Patients

Aerobic exercise has been shown to improve symptoms in multiepisode schizophrenia, including cognitive impairments, but results are inconsistent. Therefore, we evaluated the effects of an enriched environment paradigm consisting of bicycle ergometer training and add-on computer-assisted cognitive remediation (CACR) training. To our knowledge, this is the first study to evaluate such an enriched environment paradigm in multiepisode schizophrenia. Twenty-two multiepisode schizophrenia patients and 22 age- and gender-matched healthy controls underwent 3 months of endurance training (30min, 3 times/wk); CACR training (30min, 2 times/wk) was added from week 6. Twenty-one additionally recruited schizophrenia patients played table soccer (known as “foosball” in the United States) over the same period and also received the same CACR training. At baseline and after 6 weeks and 3 months, we measured the Global Assessment of Functioning (GAF), Social Adjustment Scale-II (SAS-II), schizophrenia symptoms (Positive and Negative Syndrome Scale), and cognitive domains (Verbal Learning Memory Test [VLMT], Wisconsin Card Sorting Test [WCST], and Trail Making Test). After 3 months, we observed a significant improvement in GAF and in SAS-II social/leisure activities and household functioning adaptation in the endurance training augmented with cognitive remediation, but not in the table soccer augmented with cognitive remediation group. The severity of negative symptoms and performance in the VLMT and WCST improved significantly in the schizophrenia endurance training augmented with cognitive remediation group from week 6 to the end of the 3-month training period. Future studies should investigate longer intervention periods to show whether endurance training induces stable improvements in everyday functioning.Key words: aerobic exercise, endurance training, cognitive remediation, schizophrenia, everyday functioning     

S100B and schizophrenia

The research for peripheral biological markers of schizophrenia, although abundant, has been unfruitful. In the last 2 decades, the S100B protein has made its own room in this area of research. S100B is a calcium‐binding protein that has been proposed as a marker of astrocyte activation and brain dysfunction. Research results on S100B concentrations and schizophrenia clinical diagnosis are very consistent; patients with schizophrenia have higher S100B concentrations than healthy controls. The results regarding schizophrenia subtypes and clinical characteristics are not as conclusive. Age of patients, body mass index, illness duration and age at onset have been found to show no correlation, a positive correlation or a negative correlation with S100B levels. With respect to psychopathology, S100B data are inconclusive. Positive, negative and absence of correlation between S100B concentrations and positive and negative psychopathology have been reported. Methodological biases, such as day/night and seasonal variations, the use of anticoagulants to treat biological samples, the type of analytical technique to measure S100B and the different psychopathological scales to measure schizophrenia symptoms, are some of the factors that should be taken into account when researching into this area in order to reduce the variability of the reported results. The clinical implications of S100B changes in schizophrenia remain to be elucidated.     

Attention and Clinical Symptoms in Schizophrenia

Attentional deficits, long established to characterize patients with schizophrenia spectrum disorders, have traditionally been regarded as part of the disorder's clinical syndrome. In this paper we provide evidence to indicate that: a) impaired attention is a dimension of schizophrenia that is independent of clinical state, and b) that attention does not appear to respond to the medication (i.e. standard neuroleptics) most typically used to treat clinical symptoms. Since intact attention and other cognitive processes appear critical to successful functioning in the community after hospital discharge, these findings have major implications for treatment.     

Racial Differences in S100b Levels in Persons with Schizophrenia

Psychiatric Quarterly - The calcium-binding protein S100b is secreted by glial cells in the brain and is also expressed by melanocytes. In nanomolar concentrations, S100b is considered to be a...     

S100B与缺血性卒中

许多学者已经对血清S100B蛋白作为卒中神经生化学指标进行了广泛的研究,以期帮助临床医师对缺血性卒中做出快速诊断。本文对卒中相关的神经生化学指标,S100B升高机制,S100B应用的局限性,以及S100B发展前景等方面进行了文献回顾和综述。     

Sertraline and Psychotic Symptoms: A Case Series

Sertraline and other SSRIs have a relatively favorable side-effect profile and are widely prescribed. We report the emergence of psychotic symptoms during treatment with sertraline in four patients. Three of these patients had a history of psychotic illness and were on antipsychotic medication, when sertraline was added. The psychotic symptoms emerged within 3 days–7 weeks of starting sertraline and resolved on its discontinuation. We wish to alert clinicians to the possibility that sertraline may provoke or exacerbate positive psychotic symptoms, particularly in patients on neuroleptics, with a previous history of psychosis.