Showing papers in "Schizophrenia Bulletin in 1998"

“Cognitive Dysmetria” as an Integrative Theory of Schizophrenia: A Dysfunction in Cortical-Subcortical-Cerebellar Circuitry?

Abstract: Earlier efforts to localize the symptoms of schizophrenia in a single brain region have been replaced by models that postulate a disruption in parallel distributed or dynamic circuits. Based on empirical data derived from both magnetic resonance and positron emission tomography, we have developed a model that implicates connectivity among nodes located in prefrontal regions, the thalamic nuclei, and the cerebellum. A disruption in this circuitry produces "cognitive dysmetria," difficulty in prioritizing, processing, coordinating, and responding to information. This "poor mental coordination" is a fundamental cognitive deficit in schizophrenia and can account for its broad diversity of symptoms.

Translating Research Into Practice: The Schizophrenia Patient Outcomes Research Team (PORT) Treatment Recommendations

Abstract: Beginning in 1992, the Agency for Health Care Policy and Research and the National Institute of Mental Health funded the Schizophrenia Patient Outcomes Research Team (PORT) to develop and disseminate recommendations for the treatment of schizophrenia based on existing scientific evidence. These Treatment Recommendations, presented here in final form for the first time, are based on exhaustive reviews of the treatment outcomes literature (previously published in Schizophrenia Bulletin, Vol. 21, No. 4, 1995) and focus on those treatments for which there is substantial evidence of efficacy. The recommendations address antipsychotic agents, adjunctive pharmacotherapies, electroconvulsive therapy, psychological interventions, family interventions, vocational rehabilitation, and assertive community treatment/intensive case management. Support for each recommendation is referenced to the previous PORT literature reviews, and the recommendations are rated according to the level of supporting evidence. The PORT Treatment Recommendations provide a basis for moving toward "evidence-based" practice for schizophrenia and identify both the strengths and limitations in our current knowledge base.

Models of community care for severe mental illness : A review of research on case management

Abstract: We describe different models of community care for persons with severe mental illness and review the research literature on case management, including the results of 75 studies. Most research has been conducted on the assertive community treatment (ACT) or intensive case management (ICM) models. Controlled research on ACT and ICM indicates that these models reduce time in the hospital and improve housing stability, especially among patients who are high service users. ACT and ICM appear to have moderate effects on improving symptomatology and quality of life. Most studies suggest little effect of ACT and ICM on social functioning, arrests and time spent in jail, or vocational functioning. Studies on reducing or withdrawing ACT or ICM services suggest some deterioration in gains. Research on other models of community care is inconclusive. We discuss the implications of the findings in terms of the need for specialization of ACT or ICM teams to address social and vocational functioning and substance abuse. We suggest directions for future research on models of community care, including evaluating implementation fidelity, exploring patient predictors of improvement, and evaluating the role of the helping alliance in mediating outcome.

Schizophrenia, Sensory Gating, and Nicotinic Receptors

Abstract: A series of human and animal investigations has suggested that altered expression and function of the alpha7-nicotinic cholinergic receptor may be responsible for the auditory sensory gating deficit characterized in schizophrenia patients and their relatives as diminished suppression of an auditory-evoked response (P50) to repeated stimuli. This finding, in conjunction with evidence for familial transmission of this sensory gating deficit, suggests a pathogenic role of the gene for the alpha7-nicotinic receptor in schizophrenia. This article considers the possible effects of this dysfunction in a broader context. Not only is this dysfunction consistent with difficulties in sensory gating, but it might also predispose patients to problems with learning efficiency and accuracy. Such learning problems could underlie schizophrenia patients' delusional thinking, hallucinations, and social dysfunction. In addition, heavy smoking in many schizophrenia patients is consistent with the high concentration of nicotine necessary to activate the receptor and with the receptor's extremely rapid desensitization. Finally, the receptor's possible role in cell growth and differentiation should be considered in connection with developmental deficits and other cellular abnormalities in schizophrenia.

Using an Animal Model of Deficient Sensorimotor Gating to Study the Pathophysiology and New Treatments of Schizophrenia

Abstract: Certain animal models can greatly enhance our understanding of the neurobiology of schizophrenia and can be used to predict the antipsychotic activity of compounds. Prepulse inhibition (PPI), the reduction in startle produced by a prepulse stimulus, is diminished in schizophrenia patients. Theoretically, deficient PPI in schizophrenia patients is a measure of the loss of sensorimotor gating that may lead to sensory flooding and cognitive fragmentation. In rats, PPI is disrupted by systemic administration of dopamine agonists, serotonin agonists, or glutamate antagonists and by a variety of surgical or pharmacological manipulations of neural circuitry linking the limbic cortex, striatum, pallidum, and pontine reticular formation. This article describes several different ways the loss of PPI in rats can be used as a model for studying the pathophysiology and neurobiology of impaired sensorimotor gating in schizophrenia patients and for predicting antipsychotic activity in novel compounds. First, new experimental strategies may be used to distinguish behavioral profiles of "typical" versus "atypical" antipsychotics. Second, this paradigm can be used to study the effects of early developmental insults--including neonatal lesions and isolated rearing--on the adult emergence of deficient sensorimotor gating. Third, using different animal strains and species, as well as gene "knockout" strategies, greatly increases our ability to understand specific genetic or receptor contributions to the regulation of deficient PPI. Each of these uses of the PPI paradigm is enhanced by studies of the basic brain substrates that regulate PPI in rats and by the increasingly sophisticated assessments of PPI and related measures in schizophrenia spectrum patients.

Natural Course of Schizophrenic Disorders: A 15-Year Followup of a Dutch Incidence Cohort

Abstract: Data are presented on the 15-year natural course of schizophrenia and other nonaffective functional psychoses in a cohort of 82 first-contact cases from a circumscribed area in the Netherlands. The subjects were suffering from functional psychosis with International Classification of Diseases-Ninth Revision (ICD-9) diagnoses 295, 297, or 298.3-9 (broad definition of schizophrenia) on entry. Standardized assessments of psychopathology, psychological impairments, negative symptomatology, social disability, and use of mental healthcare were used. The study reveals a pattern of chronicity and relapses with a high risk of suicide: Two-thirds of the subjects had at least one relapse and after each relapse 1 of 6 subjects did not remit from the episode; 1 of 10 committed suicide; and 1 of 7 had at least one episode with affective psychotic symptoms that started on average 6 years after the onset of the schizophrenic disorder. Diagnoses were reclassified in five patients, according to DSM-III-R criteria for a bipolar disorder. The predictive power--in terms of time in psychosis and in partial or full remission--of demographic, illness, and treatment variables at onset of the illness was very limited. Insidious onset and delays in mental health treatment are risk factors that predict a longer duration of first or subsequent episodes. The importance of mental health treatment in regard to outcome is probably subject to change because an early warning and intervention strategy could prevent further damage and deterioration. Our data support the need for an adequate relapse prevention program as a priority for our mental health services.

Review of Integrated Mental Health and Substance Abuse Treatment for Patients With Dual Disorders

Abstract: Patients with severe mental disorders such as schizophrenia and co-occurring substance use disorders traditionally received treatments for their two disorders from two different sets of clinicians in parallel treatment systems. Dissatisfaction with this clinical tradition led to the development of integrated treatment models in which the same clinicians or teams of clinicians provide substance abuse treatment and mental health treatment in a coordinated fashion. We reviewed 36 research studies on the effectiveness of integrated treatment for dually diagnosed patients. Studies of adding dual-disorders groups to traditional services, studies of intensive integrated treatments in controlled settings, and studies of demonstration projects have thus far yielded disappointing results. On the other hand, 10 recent studies of comprehensive, integrated outpatient treatment programs provide encouraging evidence of the programs' potential to engage dually diagnosed patients in services and to help them reduce substance abuse and attain remission. Outcomes related to hospital use, psychiatric symptoms, and other domains are less consistent. Several program features appear to be associated with effectiveness: assertive outreach, case management, and a longitudinal, stage-wise, motivational approach to substance abuse treatment. Given the magnitude and severity of the problem of dual disorders, more controlled research on integrated treatment is needed.

Patterns of usual care for schizophrenia: Initial results from the Schizophrenia Patient Outcomes Research Team (PORT) Client Survey.

Abstract: To examine the conformance of current patterns of usual care for persons with schizophrenia to the Schizophrenia Patient Outcomes Research Team (PORT) Treatment Recommendations, the PORT surveyed a stratified random sample of 719 persons diagnosed with schizophrenia in two States. The types of treatment settings surveyed included acute inpatient programs and continuing outpatient programs in urban and rural locales. Using data from medical record reviews and patient interviews, the PORT assessed the conformance of current care with 12 of the Treatment Recommendations. The rates at which patients' treatment conformed to the recommendations were modest at best, generally below 50 percent. Conformance rates were higher for pharmacological than for psychosocial treatments and in rural areas than in urban ones. Rates of Treatment Recommendation conformance for minority patients were lower than those for Caucasians, and patterns of care varied between the two States. The findings indicate that current usual treatment practices likely fall substantially short of what would be recommended based on the best evidence on treatment efficacy. This disparity underscores the need for greater efforts to ensure that treatment research results are translated into practice.

Facial Expressions of Emotions and Schizophrenia: A Review

Abstract: It is generally agreed that schizophrenia patients show a markedly reduced ability to perceive and express facial emotions. Previous studies have shown, however, that such deficits are emotion-specific in schizophrenia and not generalized. Three kinds of studies were examined: decoding studies dealing with schizophrenia patients' ability to perceive universally recognized facial expressions of emotions, encoding studies dealing with schizophrenia patients' ability to express certain facial emotions, and studies of subjective reactions of patients' sensitivity toward universally recognized facial expressions of emotions. A review of these studies shows that schizophrenia patients, despite a general impairment of perception or expression of facial emotions, are highly sensitive to certain negative emotions of fear and anger. These observations are discussed in the light of hemispheric theory, which accounts for a generalized performance deficit, and social-cognitive theory, which accounts for an emotion-specific deficit in schizophrenia.

A Review of Longitudinal Studies of Cognitive Functions in Schizophrenia Patients

Abstract: Even though the idea that schizophrenia is a neurobehavioral syndrome has become a mainstream position, there is no consensus on the precise nature of the cognitive and neuropsychological impairment. Research on cognitive dysfunctions in schizophrenia has been directed toward discriminating stable dysfunctions (traits) from symptom-linked (state) deficits. A longitudinal study design is the only one that can provide answers to the question of the stability of psychological functions. This article reviews 15 studies with a followup of at least a year. The main conclusion drawn from these studies is that after the onset of schizophrenia, cognitive deficits are relatively stable over long periods. No support for a decline in cognitive functions is found. Thus, schizophrenia does not appear to be a degenerative process, but rather a static encephalopathy. Whether or not the cognitive deficits found in schizophrenia can be remediated is still an open question that needs to be examined.

Anhedonia, Positive and Negative Affect, and Social Functioning in Schizophrenia

Abstract: This study examines the relationship between anhedonia and the trait dimensions of positive affect (PA) and negative affect (NA) in schizophrenia. The relationship between poor social functioning in schizophrenia and these individual differences in affectivity is also examined. Schizophrenia outpatients (n = 37) and normal controls (n = 15) were assessed at a baseline evaluation and again approximately 90 days later. Consistent with the hypothesized decrease in hedonic capacity in schizophrenia, patients reported significantly greater physical and social anhedonia and less PA than controls. However, the schizophrenia group also reported significantly greater NA and social anxiety than did controls. In support of the dispositional view of these individual differences in affectivity, trait measures demonstrated test-retest reliability, and group differences between the schizophrenia group and controls were stable over the 90-day followup period. Within the schizophrenia group, physical and social anhedonia were comparably negatively correlated with trait PA; however, social but not physical anhedonia was significantly positively correlated with NA and social anxiety. Poor social functioning in the schizophrenia group was associated with greater physical and social anhedonia and greater NA and social anxiety. Alternatively, greater trait PA was related to better social functioning. These findings indicate that schizophrenia is characterized by both low PA and elevated NA and that these affective characteristics are a stable feature of the illness. The results also suggest important links between affect and social functioning in schizophrenia.

Psychiatric Illness and Family Stigma

Abstract: Considerable research has documented the stigmatization of people with mental illnesses and its negative consequences. Recently it has been shown that stigma may also seriously affect families of psychiatric patients, but little empirical research has addressed this problem. We examine perceptions of and reactions to stigma among 156 parents and spouses of a population-based sample of first-admission psychiatric patients. While most family members did not perceive themselves as being avoided by others because of their relative's hospitalization, half reported concealing the hospitalization at least to some degree. Both the characteristics of the mental illness (the stigmatizing mark) and the social characteristics of the family were significantly related to levels of family stigma. Family members were more likely to conceal the mental illness if they did not live with their ill relative, if the relative was female, and if the relative had less severe positive symptoms. Family members with more education and whose relative had experienced an episode of illness within the past 6 months reported greater avoidance by others.

Patterns of Current and Lifetime Substance Use in Schizophrenia

Abstract: A structured interview and standardized rating scales were used to assess a sample of 194 outpatients with schizophrenia in a regional Australian mental health service for substance use, abuse, and dependence. Case manager assessments and urine drug screens were also used to determine substance use. Additional measurements included demographic information, history of criminal charges, symptom self-reports, personal hopefulness, and social support. The sample was predominantly male and showed relative instability in accommodations, and almost half had a history of criminal offenses, most frequently drug or alcohol related. The 6-month and lifetime prevalence of substance abuse or dependence was 26.8 and 59.8 percent, respectively, with alcohol, cannabis, and amphetamines being the most commonly abused substances. Current users of alcohol comprised 77.3 percent and current users of other nonprescribed substances (excluding tobacco and caffeine) comprised 29.9 percent of the sample. Rates of tobacco and caffeine consumption were high. There was a moderate degree of concordance between case manager determinations of a substance-use problem and research diagnoses. Subjects with current or lifetime diagnoses of substance abuse/dependence were predominantly young, single males with higher rates of criminal charges; however, there was no evidence of increased rates of suicide attempts, hospital admissions, or daily doses of antipsychotic drugs in these groups compared with subjects with no past or current diagnosis of substance abuse or dependence. Subjects with a current diagnosis of substance use were younger at first treatment and currently more symptomatic than those with no past or current substance use diagnosis. The picture emerging from this study replicates the high rate of substance abuse in persons with schizophrenia reported in North American studies but differs from the latter in finding a slightly different pattern of substances abused (i.e., absence of cocaine), reflecting relative differences in the availability of certain drugs.

Causes and Consequences of the Gender Difference in Age at Onset of Schizophrenia

Abstract: The ABC (age, beginning, course) schizophrenia study was commenced in 1987 to generate and test hypotheses about pathogenic aspects of schizophrenia. One of the main branches of the study focused on how gender influences the age distribution of onset, symptomatology, illness behavior, and early course in schizophrenia. Proceeding from one of the rare, strikingly deviating, consistent findings--the gender difference in age at first admission--we launched a systematic search for explanations by generating and testing hypotheses in a series of substudies. We moved from the epidemiological to the neurobiological and finally to the clinical level. The present article is an attempt to provide a brief overview of the individual stages of the ABC study and the different levels of investigation involved in formulating and testing the estrogen hypothesis in animal experiments and in demonstrating its applicability to human schizophrenia. From these results, three hypotheses were formulated and tested on data from an ABC study sample of 232 first-episode cases of schizophrenia. The analyses described here represent the latest stages of the ABC study.

Family Caregiving in Schizophrenia: Domains and Distress

Abstract: This article focuses on (1) the dimensionality of the caregiving concept; (2) the relation between the identified caregiving dimensions and characteristics of the patient, the caregiver, and their relationship; and (3) the relation between caregiving dimensions and caregiver distress. Findings are based on data from 480 members of the Dutch family organization for patients with schizophrenia/chronic psychosis who completed (1) the Involvement Evaluation Questionnaire (IEQ), which assesses general information (e.g., household characteristics), caregiving, help seeking, coping and distress, and (2) a questionnaire comprising questions on onset and course of the patient's disorder and symptoms characteristic of schizophrenic disorders. Four caregiving domains were found: tension, supervision, worrying, and urging. These domains were strongly related to the patient's symptomatology, contact between the relative and the patient's mental health professional, and the number of hours of mutual contact between the patient and the relative. The connection between patient, caregiver, and relationship variables and the caregivers' distress could be explained substantially by the overall caregiving score. Our findings suggest that caregiving tasks and problems may be diminished and related distress lowered by reducing the patient's symptomatology, increasing relatives' coping capacities, and decreasing the number of contact hours. If distress is reduced, relatives may use less psychotropic medication and may visit their general practitioner less often.

Schizophrenia, Alcohol Abuse, and Violent Behavior: A 26-Year Followup Study of an Unselected Birth Cohort

Abstract: It has been suggested that schizophrenia and alcoholism are associated with violent behavior. But so far there are no published studies from unselected cohorts quantifying the actual risk associated with schizophrenia both with and without comorbid alcoholism. In this study, an unselected birth cohort (n = 11,017) was prospectively followed to the age of 26, and data on psychiatric disorders and crimes were collected from national registers. The odds ratios for violent offenses and recidivism were calculated for each diagnostic group. Men who abused alcohol and were diagnosed with schizophrenia were 25.2 (95% confidence interval (CI) 6.1-97.5) times more likely to commit violent crimes than mentally healthy men. The risk for nonalcoholic patients with schizophrenia was 3.6 (95% CI 0.9-12.3) and for other psychoses, 7.7 (95% CI 2.2-23.9). None of the patients with schizophrenia who did not abuse alcohol were recidivists (> 2 offenses), but the risk for committing more crimes among alcoholic subjects with schizophrenia was 9.5-fold (95% CI 2.7-30.0). This study suggests that to prevent the crimes being committed by people with schizophrenia, it is important that clinicians watch for comorbid alcohol abuse. Language: en

Management of the Adverse Effects of Clozapine

Abstract: Clozapine has been found to be superior to traditional neuroleptics in the treatment of refractory schizophrenia and is increasingly being used to treat schizophrenia, affective disorders, some neurological disorders, and aggression. For many patients, clozapine offers new hope for the successful pharmacological management of a disabling mental disorder. However, up to 17 percent of patients must discontinue treatment with clozapine because of adverse effects, which also limit the rate at which the dose can be increased and the maximum dose that can be tolerated. This article reviews strategies for minimizing and managing the adverse effects of clozapine, including agranulocytosis, seizures, sedation, delirium, obsessive-compulsive symptoms, hypotension, tachycardia, weight gain, sialorrhea, elevated liver enzymes, constipation, nausea, enuresis, fever, and neuromuscular effects. Incidence and morbidity are presented first. Then, the known or hypothesized pathophysiology of the adverse effects are described. Finally, nonpharmacological and pharmacological interventions are reviewed. Under-standing the incidence, pathophysiology, and treatments of adverse effects is essential for a positive therapeutic outcome when prescribing clozapine.

Dysfunctions in Multiple Interrelated Systems as the Neurobiological Bases of Schizophrenic Symptom Clusters

Abstract: The absence of an animal model that accurately approximates schizophrenia limits current research into the pathophysiology of this disorder. Obviously, the cognitive disturbances associated with schizophrenia are difficult to evaluate in laboratory animals. Nonetheless, animal studies have provided insight into the anatomy and physiology of the brain systems that have been implicated in schizophrenia. These studies also suggest how brain systems may be involved in information processing in normal and pathological conditions. Thus, a careful assessment of the properties and functions of the brain regions suggested to be involved in schizophrenic symptoms has been a primary objective in several laboratories. In this review, we discuss the interactions among the brain regions implicated in schizophrenia--the ventral striatum, prefrontal cortex, hippocampus, and dopamine systems--and provide an integrative model linking altered function in these regions with specific clusters of symptoms of schizophrenia.

Effectiveness of Attention Training in Schizophrenia

Abstract: This study assessed the impact of attention training on information processing in schizophrenia. Fifty-four inpatients with chronic schizophrenia were randomly assigned to two groups after baseline assessment with the Continuous Performance Test (CPT). Patients in the experimental group participated in individual sessions of computerized attention remediation, while patients in the control group participated in individual sessions during which they viewed video documentaries. After 18 sessions, reassessment with the CPT showed that patients in the experimental group had made significantly more improvement than the control group, which made no significant change. Brief Psychiatric Rating Scale assessments before and after the study phase indicated that both groups improved on the total score but the experimental group made significantly more improvement. These results suggest that it is feasible to use practice and behavioral learning to remediate a core attention deficit in chronic schizophrenia.

Role of Psychosocial Treatments in Management of Schizophrenia: A Meta-Analytic Review of Controlled Outcome Studies

Abstract: This meta-analytic review sought to answer questions concerning the role of psychosocial treatments in the comprehensive management of patients with schizophrenia. The review focused on the effects of combining psychosocial treatment with somatic treatment. Findings demonstrated the additive and supplementary effects of psychosocial treatments and the durability of these effects. Patients with more chronic illness appeared to be more responsive to psychosocial treatments, as were patients in studies conducted in non-Western countries. Among the Western countries, studies from Scandinavian countries reported the least effectiveness for psychosocial treatments. There was some evidence for differential effect of psychosocial treatments on different dimensions of illness as the measures of disorganized behavior and employment showed little difference in treated and control groups. There was also some evidence for differences between different modalities of treatment as group treatments produced smaller effects. Implications for practice and future research are discussed.

Positron Emission Tomography Studies of Abnormal Glucose Metabolism in Schizophrenia

Abstract: Schizophrenia, a devastating disease characterized by a combination of various types of disturbed behaviors, thoughts, and feelings, may likewise be heterogeneous in etiology. Recent advances in neuroscience and psychopharmacology have suggested a wide array of competing mechanisms that may be involved in schizophrenia, including but not limited to deficits in one or more neurotransmitters and second messenger systems (e.g., dopamine, serotonin, gamma-aminobutyric acid, glutamate, and noradrenaline), neurodevelopmental defects in brain circuitry, and viral infection. Psychiatric genetic studies indicate that schizophrenia is a disorder with multifactorial inheritance. Since cerebral metabolic activity reflects regional brain work for all neurotransmitter systems, imaging metabolism directly with fluorodeoxyglucose and indirectly with blood flow and hemoglobin oxygen saturation can provide information about the functional neuroanatomy of a deficit in individual patients and allow patients to be grouped into more homogeneous subgroups for intensive study. This review summarizes metabolic imaging studies in schizophrenia over the past decade.

Postmortem Studies in Schizophrenia

Abstract: The past decade has seen renewed interest in the neuropathology of schizophrenia. The advent of new postmortem techniques and functional imaging, along with a greater understanding of the neuropsychology of schizophrenia, have provided many new clues to the nature of the underlying brain dysfunction in this disorder. There has also been a greater understanding of the presence of severe cognitive dysfunction among many elderly persons with schizophrenia. In this article, a series of investigations are described that seek to answer basic questions about the neuropathology of schizophrenia, in particular as it pertains to cognitive impairment. The first study describes neuropathological findings in 100 consecutively autopsied persons with schizophrenia, the majority of whom had had detailed antemortem assessments. Results from this first study prompted the conclusion that schizophrenia is not characterized by classical, histologically identifiable neuropathology. Moreover, most cases of dementia in schizophrenia are probably not the result of neuropathologically identifiable dementing illnesses. The next four studies examined chemical markers that are altered in Alzheimer's disease and some other dementing conditions and have also been suggested to be abnormal in schizophrenia: choline acetyltransferase, catecholamines and indolamines, neuropeptides, and synaptic proteins. Schizophrenia cases as a group did not show a cholinergic deficit; nor did they differ from elderly comparison cases with respect to cortical catecholamines and indolamines. Among the schizophrenia cases, however, cognitive impairment was negatively correlated with choline acetyltransferase activity. Those with cognitive impairment showed evidence of cortical noradrenergic and serotonergic deficits. Neuropeptide deficits were also present in schizophrenia, but their pattern differed from that seen in Alzheimer's disease. Increased synaptic protein activity was found in the cingulate cortex of persons with schizophrenia, and this activity was correlated with schizophrenia symptoms. From this second series of studies, it was concluded that some biological measures in schizophrenia may be related to cognitive impairment (e.g., cortical amines), whereas others may be related to diagnosis (e.g., neuropeptide deficits). In addition, synaptic organization may correlate with schizophrenia symptoms.

Predictors of Relapse and Rehospitalization in Schizophrenia and Schizoaffective Disorder

Abstract: In a German multicenter treatment study, 354 patients with schizophrenia and schizoaffective disorder were followed for 2 years. The data collected were taken as a basis for the present predictor study. For the first time, the technique of classification and regression tree (CART) analysis has been employed for this purpose. CART yielded informative data and appeared to be a useful instrument in predictor research. On the outcome variables "relapse" and "rehospitalization," significant predictor variables were found in several areas: neuroleptic treatment, onset and previous course (precipitating factors, first manifestation, hospitalization in the preceding year, suicide attempts), psychopathology (residual type, schizoaffective disorder), social adjustment (marital status, employment, intensity of life, Phillips score), previous life experiences (traumatic experiences and psychiatric or developmental disturbances in childhood), and biology (gender, age). Our investigation confirmed the generally prevalent views regarding the value of neuroleptic treatment, the multifactorial etiology, and the vulnerability stress model of schizophrenia.

Employment, Attitudes Toward Work, and Quality of Life Among People With Schizophrenia in Three Countries

Abstract: This study examines attitudes toward work, work incentives, and the impact of work on quality of life for people with schizophrenia, and investigates whether these findings differ among Western countries We interviewed 24 randomly selected subjects with schizophrenia and schizoaffective disorder (12 employed and 12 unemployed) at each of three sites: Boulder, Colorado, United States; Berlin, Germany; and Berne, Switzerland No significant differences were found in the subjects' attitudes toward work or subjective well-being, although Swiss patients had a higher cost-of-living-adjusted income Unemployed subjects reported a lower subjective reservation (minimum financially worthwhile) wage than employed subjects in Berlin and Berne, whereas the reverse was true in Boulder When subjects from all sites were combined, employed patients displayed less psychopathology and significant advantages in terms of objective and subjective measures of income and well-being: They were also more likely to stress the importance of work The results suggest that work is associated with a markedly better quality of life for people with schizophrenia, but that disability pension programs in the United States might introduce work disincentives

Performance of the Continuous Performance Test Among Community Samples

Abstract: The Continuous Performance Test (CPT) has been modified to be used widely as a potential vulnerability marker of schizophrenia. In genetic analyses of schizophrenia, well-established norms for the CPT are essential in choosing a suitable threshold of CPT for classifying subjects as affected or unaffected. In this study, we investigated the performance of 115 adolescents and 345 adults, randomly sampled from a community, on two sessions of the CPT 1-9 (undegraded and 25% degraded). The results showed that an older age was associated with a decreasing hit rate and sensitivity (d'), while a higher level of education was associated with an increasing hit rate and d' for both sessions of the CPT. Men had higher hit rates and d' than women for the degraded CPT. A practice effect during the second session of the CPT was noted among 20 to 33 percent of the subjects. Poorer CPT performance was associated with schizotypy measured by the Perceptual Aberration Scale and the Schizotypal Personality Questionnaire. Thus, in assessing CPT performance among schizophrenia patients or high-risk populations, we must compare their results to age-, education-, and sex-corresponding norms. The data presented in this report will be valuable in this regard.

Model Generation and Testing to Probe Neural Circuitry in the Cingulate Cortex of Postmortem Schizophrenic Brain

Abstract: In the past decade, there has been increased interest in whether discreet alterations of neural circuitry might play a role in the pathophysiology of schizophrenia. In the absence of a readily identifiable histopathology, a variety of sophisticated neurobiological approaches is being applied to the study of this disorder. In one series of investigations, subtle abnormalities have been detected in the anterior cingulate cortex-layer II (ACCx-II) of schizophrenia patients. One of these studies suggested a reduction of nonpyramidal neurons in schizophrenia patients, and it was postulated that this change could give rise to a relative increase of dopaminergic inputs to the remaining gamma-aminobutyric acid (GABA) cells. Although empiric evidence in support of this hypothesis was obtained, a subsequent post hoc analysis, described in this report, has suggested that this change could have occurred irrespective of whether GABA cells are reduced in number. A shift of cortical dopamine afferents from pyramidal to nonpyramidal neurons in ACCx-II seems to provide a more plausible explanation for such a "miswiring." These findings support critical use of model generation and testing as powerful tools for unraveling the nature of altered neural circuitry in postmortem schizophrenic brain.

Limbic-Cortical Neuronal Damage and the Pathophysiology of Schizophrenia

Abstract: Neurobiological studies of patients with schizophrenia suggest that abnormalities of both anatomy and function occur in limbic-cortical structures. An anatomical circuit links the functioning of the ventral striatum (i.e., nucleus accumbens) with the hippocampus and other limbic-cortical structures where neurobiological abnormalities have been found. In animals, lesions of limbic-cortical neurons cause decreases in glutamatergic input to the nucleus accumbens and are also associated with decreases in presynaptic dopamine release, increases in the density of D2-like dopamine receptors, and insensitivity to the actions of dopamine antagonists such as haloperidol. These experiments suggest a plausible pathophysiology of schizophrenia, in that schizophrenic symptoms may be caused by an abnormal dopaminergic state brought about by a primary limbic-cortical lesion and deficits in glutamatergic inputs to the ventral striatum.

Heterogeneity of the psychoses : Is there a neurodegenerative psychosis?

Abstract: Whereas etiological heterogeneity of the various types of schizophrenia has been repeatedly proposed, relatively few attempts have been made to separate the component diseases. Using a strategy focusing on bimodal distributions within several relevant domains of schizophrenia, we demonstrate that currently available data on schizophrenia patients are consistent with the hypothesis that some of these patients have an ongoing neurodegenerative disease, whereas others do not. We review studies (longitudinal and cross-sectional) documenting progressive increases in ventricular size, accelerated loss of brain tissues, progressive delays in treatment response, and neurochemical (magnetic resonance spectroscopy) and neurophysiological (P300) indices, all of which are consistent with ongoing cerebral degeneration in a significant subgroup of schizophrenia patients. These lines of evidence converge on a conceptualization of schizophrenia as being composed of several etiologically distinct processes, with one subset of psychotic patients evidencing progressive brain degeneration. We conclude with a discussion of possible etiologies for this condition.

Schizophrenia and Delusional Disorder in Older Age: Community Prevalence, Incidence, Comorbidity, and Outcome

Abstract: The opportunity to assess prevalence, incidence, and outcome of schizophrenia and delusional disorder was provided by an age- and sex-stratified random sample of 5,222 persons age 65 years and over. This sample was chosen from general practitioner lists, and interviewed by psychiatric nurses trained to use the Geriatric Mental State (GMS)-AGECAT computerized diagnostic system. GMS-AGECAT ensured the reliability of the selection of cases between the two waves of the study. A subsample was interviewed by a research psychiatrist. The sample was followed up 2 years later using the same method by interviewers blind to the initial findings. The protocols of all nominated cases and subcases of schizophrenia/paranoid disorder diagnosed by AGECAT were reviewed by a clinician and DSM-III-R diagnoses were made. Refusal rate was 13 percent for initial interviews (wave 1) and 15 percent for reinterview 2 years later (wave 2). The prevalence of DSM-III-R schizophrenia was 0.12 percent (95% confidence interval [CI] 0.04-0.25) and delusional disorder 0.04 percent (95% CI 0.00-0.14). The minimum incidence of schizophrenia for new cases was 3.0 (95% CI 0.00 to 110.70); for new and relapsed cases, 45.0 (95% CI 3.54-186.20); and for delusional disorder, 15.6 (95% CI 0.02-135.10) per 100,000 per year. Two of the five cases with schizophrenia were known to have been first diagnosed before age 65. After 2 years, none of the cases of schizophrenia had recovered fully, but none was deluded at followup. Two had developed dementia. The outcome was bad because they remained cases of some type of psychiatric illness but good because of the improvement in their schizophrenia/delusion disorder symptoms.

A Hindi Version of the Diagnostic Interview for Genetic Studies

Abstract: The validity of a Hindi version of the Diagnostic Interview for Genetic Studies (DIGS) was investigated. The original English version was initially translated into Hindi. The Hindi version was then back-translated and compared with the original. Next, a group of psychiatric inpatients and outpatients were interviewed using the Hindi version. The resultant diagnoses were compared with those obtained for the same patients using a Hindi version of the Present State Examination (PSE), and the clinical diagnoses given by the treating psychiatrists. The DIGS diagnoses were significantly correlated with both the PSE diagnoses (Cohen's kappa = 0.80) and the clinical diagnoses (kappa = 0.56). Interrater reliability between three interviewers for diagnoses obtained using the Hindi version of the DIGS varied (kappa = 0.45-1.00). Possible causes for this variability are discussed. The Hindi version of the DIGS fulfills the need for a current comprehensive interview schedule not only for psychiatric genetic research in India, but also for non-genetic research.