What is schizophrenia?

Summary The psychotic syndrome at the core of schizophrenia appears to be invariable across cultures. The risk of morbidity also seems to vary very little from country to country and over medium periods of time. Moreover, apart from gender differences in first onset, the cumulative lifetime risk is the same in females and males. A similar epidemiological pattern is only found in pathological conditions that are characterized by a precisely defined section of a psychopathological dimension with a continuous distribution in the population, e.g. severe mental retardation being the extreme section of normally distributed IQ values. The interpretation of schizophrenic psychosis as the extreme section of a psychopathological dimension or disposition that is almost evenly distributed in all populations is supported by the fact that milder psychiatric disorders occur more frequently before the onset of the psychosis and in close relatives of schizophrenic patients. The psychopathological heterogeneity of these disorders argues against the assumption of a manifest psychopathological dimension with a continuous transition from the schizophrenic psychosis to the normal schizothymic personality. More probable is a continuously distributed latent vulnerability to schizophrenia — with or without a threshold effect — which in severe degrees disposes to the uniform reaction pattern of the schizophrenia syndrome. Smaller degrees of vulnerability are associated with an increased risk for milder patterns of disturbances, which are also more strongly determined by environment and personality and therefore are rather heterogeneous. These assumptions lead to other epidemiological and genetic models than Kraepelin's early concept of a disease entity does.     

What is schizophrenia?

One of the main questions related to schizophrenia is, naturally enough, what is it? Such a question may seem obvious, naive, impossible, or any combination of these. And certainly it is a bit demanding to expect that anyone could say what schizophrenia is in 1,000 words. On the other hand, we felt that it was worth the effort. We hope that presenting these brief discussions on "what is schizophrenia" by persons who have worked extensively in the field will allow the reader to note areas of overlap and disagreement as well as variations in emphasis. Although no one may yet be able to provide the definitive answer, at least this collection of informed opinions may help clarify the major questions. The essays by John S. Strauss and William T. Carpenter, Jr. are the third in this series. Further collections of these statements will be presented in subsequent issues. Readers' responses and comments are cordially invited.     

What is schizophrenia?

One of the main questions related to schizophrenia is, naturally enough, what is it? Such a question may seem obvious, naive, impossible, or any combination of these. And certainly it is a bit demanding to expect that anyone could say what schizophrenia is in 1,000 words. On the other hand, we felt that it was worth the effort. We hope that presenting these brief discussions on "what is schizophrenia" by persons who have worked extensively in the field will allow the reader to note areas of overlap and disagreement as well as variations in emphasis. Although no one may yet be able to provide the definitive answer, at least this collection of informed opinions may help clarify the major questions. The group of essays by Solomon H. Snyder, Seymour S. Kety, and Michael J. Goldstein is the second in this series. Further collections of these statements will be presented in subsequent issues. Readers' responses and comments are cordially invited.     

What is measured by verbal fluency tests in schizophrenia?

INTRODUCTION: Schizophrenia patients perform below the norm on verbal fluency tests. The causes for this are unknown, but defective memory, executive functioning and psychomotor speed may play a role. METHOD: We examined 50 patients with schizophrenia and related disorders, and 25 healthy controls with a cognitive test battery containing tests for verbal memory, executive functioning and psychomotor speed, and a categorical fluency test. RESULTS: Patients obtained significantly lower test results than the controls on most cognitive measures including the verbal fluency test. During the fluency test, they formed as many clusters, and switched as often between clusters as the controls did, but they generated fewer words per cluster. Interestingly, in the control group, fluency performance was predicted by memory and executive functioning, but not by psychomotor speed. In patients, verbal fluency was predicted by psychomotor speed, but not by memory or executive functioning. DISCUSSION: We conclude that psychomotor speed could be a crucial factor in cognition, and its influence on cognitive test performance should be considered in schizophrenia research. Furthermore, these data illustrate the importance of qualitative analysis of cognitive impairments in schizophrenia patients, as traditional cognitive tests often only provide quantitative information.     

What is the functional significance of hippocampal pathology in schizophrenia?

The hippocampal formation (HF) is one of the brain structures most consistently altered in schizophrenia, yet the contribution of HF pathology to severe mental illness is poorly understood. We present evidence that our current ignorance is attributable to the fact that the anterior HF is heavily involved in schizophrenia but has been inadequately examined by schizophrenia investigators. We propose that the anterior HF in humans, and its counterpart in rodents (ventral HF), constrain diverse responses to psychological stimuli and that disruption of this function contributes to schizophrenia. While current data suggest that hallmark symptoms of schizophrenia most likely result from the role of the anterior HF in the integrated neurocircuit that includes the prefrontal cortex, ventral striatum, and ventral tegmental area, better characterized and phylogenetically preserved neurocircuits may be similarly affected by anterior HF pathology and account for associated findings of the disorder. We propose that focusing on the impact of ventral HF pathology on these simpler circuits and functions in rodents may provide insight into the pathophysiology of severe mental illness in humans. We review several associated findings in schizophrenia to assess the likelihood that each could be a product of this putative anterior HF dysfunction and could therefore be productively studied in rodents by probing ventral HF function.     

What is the value of treating schizophrenia?

OBJECTIVE: Recent generalized cost-effectiveness analyses contrasting schizophrenia with high prevalence mental disorders have noted a need to investigate the mechanisms by which the tensions between equity and efficiency can be reconciled and inform priority setting in resource allocation. This paper explores and illustrates some possible strategies for valuing mental health states, with the broad goal of improving resource allocation decisions. METHOD: Health utility gains derived for current and optimal treatments for schizophrenia, depression and anxiety disorders, potential societal preference weightings, and annual costs per treated case, are used to illustrate the magnitude of the impacts on relative cost-efficiency and societal welfare estimates. These estimates are based on costs per additional quality adjusted life year (QALY) and costs per additional S-QALY (i.e. QALYs adjusted for societal value of health gains) respectively. RESULTS: When broader societal preferences are ignored, current and optimal treatments for depression and anxiety are around 10 times more efficient than those for schizophrenia, but treatments for all three disorders appear to give rise to similar levels of societal welfare when weighting factors reflecting equity concerns are incorporated. CONCLUSIONS: There is manifest inequality in health between individuals with schizophrenia and those with high prevalence mental disorders, even with optimal treatment. Schizophrenia is much more costly to treat but other factors require consideration. Inclusion of societal preferences should lead to more rational decision-making and improved societal welfare. In turn, greater effort needs to be given to the development and validation of appropriate weighting factors reflecting distributive preferences in mental health.     

Computer-assisted cognitive remediation in schizophrenia: What is the active ingredient?

An emerging body of research has shown that computer-assisted cognitive remediation, consisting of training in attention, memory, language and/or problem-solving, produces improvement in neurocognitive function that generalizes to untrained neurocognitive tests and may also impact symptoms and work functioning in patients with schizophrenia. The active ingredient of these interventions, however, remains unknown as control groups in these studies have typically included few, if any, of the elements of these complex behavioral treatments. This study compared the effects of an extended (12-month), standardized, computer-assisted cognitive remediation intervention with those of a computer-skills training control condition that consisted of many of the elements of the experimental intervention, including hours spent on a computer, interaction with a clinician and non-specific cognitive stimulation. Forty-two patients with schizophrenia were randomly assigned to one of two conditions and were assessed with a comprehensive neuropsychological test battery before and after treatment. Results revealed that cognitive-remediation training produced a significant improvement in working memory, relative to the computers-skills training control condition, but that there was overall improvement in both groups on measures of working memory, reasoning/executive-function, verbal and spatial episodic memory, and processing speed. Taken together, these findings suggest that specific practice in neurocognitive exercises targeted at attention, memory and language, produce improvements in neurocognitive function that are not solely attributable to non-specific stimulation associated with working with a computer, interacting with a clinician or cognitive challenge, but that non-specific stimulation has a salutary effect on neurocognition as well.     

Cancer in patients with schizophrenia: What is the next step?

People with schizophrenia, who constitute approximately 0.3–1% of the general population, have a nearly 20% shorter life expectancy than the general population. The incidence of varied types of cancers in patients with schizophrenia is controversial. The majority of previous research has demonstrated that patients who have schizophrenia and cancer have early mortality compared to the general population with cancer. The causes of early mortality in patients with schizophrenia and cancer might be attributed to a lower cancer screening rate and lack of effective treatment, including: (i) patient factors, such as poor lifestyle, passive attitude toward treatment, or comorbidity; (ii) physician factors, such as physician bias, which may decrease the delivery of care for individuals with mental disorders; and (iii) hospital administration factors, such as stigma and discrimination. Additional studies on patients with schizophrenia and cancer are warranted and should include the following: a comprehensive review of previous studies; a focus on differentiating the specific types of cancer; and methods for improvement. To decrease the early mortality of patients with schizophrenia, the following measures are proposed: (i) enhance early detection and early treatment, such as increasing the cancer screening rate for patients with schizophrenia; (ii) provide effective, timely treatment and rehabilitation; (iii) improve patients’ psychiatric symptoms and cognitive impairment; (iv) promote healthy behavior in the general population and emphasize healthy lifestyles in vulnerable populations; and (v) remove the stigma of schizophrenia. To reduce disparities in physical health, public health strategies and welfare policies must continue to focus on this group of patients.     

Visual sensory processing deficits in schizophrenia: is there anything to the magnocellular account?

Visual processing studies have repeatedly shown impairment in patients with schizophrenia compared to healthy controls. Electroencephalography (EEG) and, specifically, visual evoked potential (VEP) studies have identified an early marker of this impairment in the form of a decrement in the P1 component of the VEP in patients and their clinically unaffected first-degree relatives. Much behavioral and neuroimaging research has implicated specific dysfunction of either the subcortical magnocellular pathway or the cortical visual dorsal stream in this impairment. In this study, EEG responses were obtained to the contrast modulation of checkerboard stimuli using the VESPA (Visual Evoked Spread Spectrum Analysis) method. This was done for a high contrast condition and, in order to bias the stimuli towards the magnocellular pathway, a low contrast condition. Standard VEPs were also obtained using high contrast pattern reversing checkerboards. Responses were measured using high-density electrical scalp recordings in 29 individuals meeting DSM-IV criteria for schizophrenia and in 18 control subjects. Replicating previous research, a large (Cohen's d=1.11) reduction in the P1 component of the VEP was seen in patients when compared with controls with no corresponding difference in the VESPA response to high contrast stimuli. In addition, the low-contrast VESPA displayed no difference between patients and controls. Furthermore, no differences were seen between patients and controls for the C1 components of either the VEP or the high-contrast VESPA. Based on the differing acquisition methods between VEP and VESPA, we discuss these results in terms of contrast gain control and the possibility of dysfunction at the cortical level with initial afferent activity into V1 along the magnocellular pathway being intact when processing is biased towards that pathway using low contrast stimuli.     

Auditory sensory dysfunction in schizophrenia: imprecision or distractibility?

BACKGROUND: Schizophrenia is associated with large effect-size deficits in auditory sensory processing, as reflected in impaired delayed-tone matching performance. The deficit may reflect either impaired sensory precision, which would be indicative of neural dysfunction within auditory sensory (temporal) regions, or of increased distractibility, which would be indicative of impaired prefrontal function. The present study evaluates susceptibility of schizophrenic subjects to same-modality distraction to determine whether patients fit a "bitemporal" or "prefrontal" model of sensory dysfunction. METHODS: Tone-matching ability was evaluated in 15 first-episode patients, 18 outpatients with chronic illness, and 21 patients in long-term residential care, relative to 32 nonpsychiatric controls of a similar age. A staircase procedure determined individual thresholds for attaining criterion level correct performance. RESULTS: Tone-matching thresholds in the absence of distractors were significantly elevated in patients in long-term residential care relative to all other groups (P<.001). The effect size (d) of the difference relative to controls was extremely large (SD, 1.95). Schizophrenic patients, even those with elevated tone-matching thresholds, showed no increased susceptibility to auditory distraction (P =.42). Deficits in tone-matching performance in subjects with chronic illness could not be attributed to medication status or level of symptoms. CONCLUSIONS: These findings suggest that sensory processing dysfunction in schizophrenia is particularly severe in a subgroup of patients who can be considered poor-outcome based on their need for long-term residential treatment. Furthermore, the absence of increased auditory distractibility argues against prefrontal dysfunction as an origin for auditory sensory imprecision in schizophrenia. Arch Gen Psychiatry. 2000;57:1149-1155.     

Auditory sensory memory in schizophrenia: inadequate trace formation?

This study explored duration mismatch negativity reductions observed in individuals with schizophrenia, in particular, the relationship to behavioural measures of temporal discrimination and two event-related potential (ERP) components occurring during the first phase of auditory sensory memory. Twenty-two patients with a DSM-IV and ICD-10 diagnosis of schizophrenia and 25 healthy comparison volunteers participated in a behavioural and an ERP testing session. Both groups performed equivalently on behavioural estimates of filled interval duration discrimination and gap detection. In contrast, electrophysiological measures revealed a significant reduction in patients' duration mismatch negativity and a significant difference in patients for the pattern of N100 facilitation over short stimulus onset asynchronies. Whilst behavioural results indicate intact temporal processing of filled intervals and equal temporal resolution limits in schizophrenia, both ERP measures indicated differences in auditory processing that may be traced to activity occurring during the first 250 ms. Results highlight the possibility of abnormalities in the process of auditory trace formation and temporal summation in schizophrenia.     

How stigmatising is schizophrenia in India?

Stigma is a social devaluation of a person because of personal attribute leading to an experience of sense of shame, disgrace and social isolation. The nature of stigma in schizophrenia and its relationship to attribution was studied in one hundred and fifty-nine urban patients of Madras, India who fulfilled DSM-IV criteria for schizophrenia. The response of the primary care givers to fourteen questions on stigma and 14 on what they thought attributed to the illness was elicited. Based on the mean stigma score, the entire sample was divided into two groups- those with high and low stigma. Marriage, fear of rejection by neighbour, and the need to hide the fact from others were some of the more stigmatising aspects. Many care givers reported feelings of depression and sorrow. Discriminant function analysis showed that female sex of the patient and a younger age of both patient and caregiver were related to higher stigma. Among attribution items, having no explanation to offer, and attributions to faulty biological functioning, character of life style, substance abuse and intimate interpersonal relationship discriminated between the two groups. The relevance of stigma in the cultural context is described.     

What perspectives for cognitive remediation in schizophrenia?

Cognitive deficits are routinely evident in schizophrenia, and are of sufficient magnitude to influence functional outcomes in work, social functioning and illness management. Cognitive remediation is an evidenced-based non-pharmacological treatment for the neurocognitive deficits seen in schizophrenia. Narrowly defined, cognitive remediation is a set of cognitive drills or compensatory interventions designed to enhance cognitive functioning, but from the vantage of the psychiatric rehabilitation field, cognitive remediation is a therapy which engages the patient in learning activities that enhance the neurocognitive skills relevant to their chosen recovery goals. Cognitive remediation programs vary in the extent to which they reflect these narrow or broader perspectives but a metaanalytic study reports moderate range effect sizes on cognitive test performance, and daily functioning. Reciprocal interactions between baseline ability level, the type of instructional techniques used, and motivation provide some explanatory power for the heterogeneity in patient response to cognitive remediation. Recent studies indicate that intrinsic motivation mediates the relationship between neurocognition and functional outcomes. Results of these studies suggest that intrinsic motivation should be a viable treatment target in cognitive remediation intervention. In this perspective, NEAR (Neuropsychological Educational Approach to Remediation) program was created to enhance intrinsic motivation by employing more engaging and interesting software packages for cognitive practice, involving consumers in choosing the focus of training and having the NEAR leader serve as a coach to engage the consumers in active guidance of their own treatment program.     

What is new in autism?

PURPOSE OF REVIEW: Autism is now recognized in one out of 150 children. This review highlights the topics within the growing autism literature that are shaping current thinking on autism and advancing research and clinical understanding of autism spectrum disorders. RECENT FINDINGS: The role of single-stranded microdeletions and epigenetic influences on brain development has dramatically altered our understanding of the etiology of the autisms. Recent research has focused on the role of synapse structure and function as central to the development of autism and suggests possible targets of interventions. Brain underconnectivity has been a focus in recent imaging studies and has become a central theme in conceptualizing autism. Despite increased awareness of autism there is no 'epidemic' and no one cause for autism. Data from the sibling studies are identifying early markers of autism and defining the broader autism phenotype. SUMMARY: Larger datasets in genetics, a focus on the early signs of autism, and increased recognition of the importance of defining subgroups of children with autism are leading to a greater understanding of the etiologies of autism. A growing interest in defining the molecular biology of social cognition, which is at the core of autism, will lead to expansion of our presently limited choices of mechanistically based interventions.