Pathogen-mediated NMDA receptor autoimmunity and cellular barrier dysfunction in schizophrenia.

Autoantibodies that bind the N-methyl-D-aspartate receptor (NMDAR) may underlie glutamate receptor hypofunction and related cognitive impairment found in schizophrenia. Exposure to neurotropic pathogens can foster an autoimmune-prone environment and drive systemic inflammation leading to endothelial barrier defects. In mouse model cohorts, we demonstrate that infection with the protozoan parasite, Toxoplasma gondii, caused sustained elevations of IgG class antibodies to the NMDAR in conjunction with compromised blood-gut and blood-brain barriers. In human cohorts, NMDAR IgG and markers of barrier permeability were significantly associated with T. gondii exposure in schizophrenia compared with controls and independently of antipsychotic medication. Combined T. gondii and NMDAR antibody seropositivity in schizophrenia resulted in higher degrees of cognitive impairment as measured by tests of delayed memory. These data underscore the necessity of disentangling the heterogeneous pathophysiology of schizophrenia so that relevant subsets eligible for NMDAR-related treatment can be identified. Our data aid to reconcile conflicting reports regarding a role of pathological NMDAR autoantibodies in this disorder.

Toxoplasma and schizophrenia.

Research on infectious agents as a possible cause of schizophrenia has become prominent in the past decade. Toxoplasma gondii has emerged as a prime candidate for a variety of reasons; (i) many studies have reported that individuals with schizophrenia, compared to controls, have a higher prevalence of antibodies to T. gondii, (ii) some individuals with adult toxoplasmosis develop psychotic symptoms similar to those of schizophrenia, (iii) epidemiologically, there are many similarities between toxoplasmosis and schizophrenia, (iv) antipsychotic drugs known to be effective in schizophrenia also inhibit some parasites, including T. gondii, (v) Toxoplasma has been shown to induce elevated levels of dopamine in experimentally infected animals (elevated dopamine is commonly seen in individuals with schizophrenia) and (vi) studies have shown that individuals with schizophrenia, compared to controls, have had greater exposure to cats in childhood. A number of questions remain concerning a role for Toxoplasma in the aetiology of schizophrenia, including the roles of strain variation, the timing and source of infection, and the role of host genes in determining disease susceptibility. The establishment of a firm association between Toxoplasma and the aetiology of schizophrenia and related disorders would represent a major breakthrough in the understanding of these disorders and would lead to novel methods for their treatment and prevention.

Obesity among individuals with serious mental illness.

OBJECTIVE: To study the distribution and correlates of body mass index (BMI) among individuals with serious mental illness. METHOD: A total of 169 participants were recruited from randomly selected out-patients receiving community-based psychiatric care and were interviewed with items from the National Health and Nutrition Examination Survey (NHANES) III. Their BMI was compared with that of 2404 matched individuals from the NHANES data set. RESULTS: The distribution of BMI in the psychiatric sample significantly differed from that of the comparison group; 50% of women and 41% of men were obese compared with 27% and 20% in the comparison group. Within the psychiatric sample, higher BMI was associated with current hypertension and diabetes, a wish to weigh less, and reduced health-related functioning. CONCLUSION: Obesity is more prevalent among individuals with serious mental illness than in demographically matched individuals from the US general population. Among persons with mental illness, obesity is associated with co-occurring health problems.

Outpatients with schizophrenia and bipolar I disorder: Do they differ in their cognitive and social functioning?

The authors used a battery of cognitive and social functioning measures to evaluate stable outpatients with schizophrenia (n=74) and bipolar I disorder (n=26) who were receiving care at community and rehabilitation programs. The groups did not differ significantly on 36 of 41 measures. For most variables, comparisons between groups yielded effect sizes of <0.5. These results suggest that individuals with bipolar I disorder receiving community and rehabilitation services have many social and cognitive deficits that are as severe as those in schizophrenia.

Cognitive behavioral psychotherapy for schizophrenia: a review of recent empirical studies.

A set of cognitive behavioral psychotherapies (CBT) has been developed for schizophrenia. These interventions have been used for the treatment of both recent onset patients and those with treatment-refractory symptoms. This article reviews clinical trials of CBT for schizophrenia since 1990. The CBT interventions appear to be beneficial in reducing overall symptom levels, especially the severity of delusions. The relative efficacy of CBT is more evident when CBT is compared with routine care than when it is compared with other therapies matched for therapist attention. Further studies are needed to objectively determine the active ingredients of CBT and to better identify the interactions of CBT with concurrent psychosocial and medication treatments.

The relationship among three measures of social functioning in outpatients with schizophrenia.

Deficits in social functioning are a defining characteristic of schizophrenia. Several instruments have been developed to measure social functioning in this population, but there has been little study of the correlation among different instruments. We used the Social Functioning Scale (SFS), the Multnomah Community Ability Scale (MCAS), and the Quality of Life Interview (QOLI) to evaluate 72 stable outpatients with schizophrenia. Results of canonical analyses indicate a significant but limited relationship between each set of measures. The largest overlap was between the QOLI and the SFS (R2c = .597) with less shared variance found between the SFS and the MCAS (R2c = .520) and between the MCAS and the QOLI (R2c = .335). Although the instruments share some common content. the instruments measure different aspects of social functioning. A consensus is needed about how to define and measure social functioning in this population.

Predictors of residential independence among outpatients with schizophrenia.

OBJECTIVE: Many outpatients with schizophrenia receive support or supervision in their place of residence, but the predictors of residential independence are not clearly understood. The purpose of this study was to identify factors that predict the degree of residential independence among outpatients with schizophrenia. METHODS: Seventy-two outpatients with schizophrenia were assigned to three groups based on their degree of residential independence. The three groups were compared on three measures of social functioning, on the Positive and Negative Syndrome Scale, and on a battery of neuropsychological tests. RESULTS: Patients' degree of residential independence was related to their frequency of family contact, hygiene skills, relative absence of negative symptoms, and participation in social activities. In a discriminant function analysis, the residential status of 78 percent of the patients was correctly classified. CONCLUSIONS: Aspects of social functioning are significantly associated with patients' independent living status. Future research is needed to determine how family contact, social activities, and hygiene skills may increase patients' degree of residential independence.

Subjective quality of life in out-patients with schizophrenia: clinical and utilization correlates.

The relationship between subjective quality of life (QOL), clinical measures, and service utilization was measured in out-patients with schizophrenia. A total of 72 subjects completed the Quality of Life Interview and were also assessed by means of the Positive and Negative Syndrome Scale, a battery of neuropsychological tests, and two measures of social functioning. Use of psychiatric services over a 2-year period was ascertained from comprehensive records. Global subjective QOL was lower than patients' satisfaction with specific life domains. There were few significant correlations between satisfaction with, and objective measures of, specific life areas. In a multiple regression, patients' global subjective QOL was inversely related to their scores on the PANSS depression factor, and to the number of psychiatrist out-patient visits.

Assessing clinical outcomes: the community functioning of persons with serious mental illness.

OBJECTIVE: The demand to measure the clinical outcomes of persons with serious mental illness in the community is growing; however, there is no consensus about how to do this task. This paper identifies challenges in measuring the outcomes of persons with serious mental illness and reviews selected instruments that measure the community functioning of this population. METHODS: Papers in peer-reviewed psychiatric journals for the years 1986 to 1996 were reviewed to select instruments that measure two or more domains of community functioning and for which data on reliability and validity have been published. Selected instruments were evaluated, focusing on their format, content, item scoring, length, and original sample population. RESULTS AND CONCLUSIONS: Challenges to measuring the community functioning of persons with serious mental illness include the multiplicity of domains that must be measured, the conflicting interests of various stakeholders involved in care, the limitations of self-report data, and other methodological problems. Nine instruments that met the study criteria were selected from the literature. Three are self-report instruments, and six are based on the report of an informant or independent rater. The instruments vary in length and in their original sample population. The content areas most consistently represented are self-care and social relationships. Life satisfaction, health status, psychiatric symptoms, and work skills are not consistently addressed. Individual instruments have additional limitations, including the absence of behavioral anchors for scale items and the lack of specificity to persons with serious mental illness. Effort should be directed toward sharing data across settings, measuring the effects of treatment interventions, and demonstrating the predictive validity of outcome data.

Lack of insight among outpatients with schizophrenia.

OBJECTIVE: This study investigated the prevalence of lack of insight among outpatients with schizophrenia and the relationship between lack of insight and other variables, including whether patients received professional residential supervision. METHODS: A total of 87 stable outpatients with schizophrenia were drawn from community programs in a public-private mental health system. Subjects' clinical symptoms and insight about their illness were assessed using the Positive and Negative Syndrome Scale, a battery of neuropsychological tests, and the Social Functioning Scale. RESULTS: The illness insight of 43 subjects, or 49.5 percent, was at least moderately impaired. Twenty-one subjects, or 25 percent, had severe insight deficits. In a multiple regression analysis, 40 percent of the variance in lack of insight was predicted by ratings of the severity of delusions, difficulty with abstract thinking, lack of social activities, and absence of anxiety. Patients who received professional residential supervision had more impaired insight than those living independently or with family. CONCLUSIONS: Insight deficits are common among stable outpatients engaged in community-based care. These deficits have implications for patients' use of limited services such as residential supervision.

Neuropsychological deficits in chronic schizophrenics. Relationship with symptoms and behavior.

Thirty-nine hospitalized chronic schizophrenics were administered the Luria-Nebraska Neuropsychological Battery (LNNB) and the Weschler Adult Intelligence Scale-Revised when they were clinically stable. Test variables were related to Brief Psychiatric Rating Scale ratings and two behavioral measures of ward functioning, points and activities. Spearman correlations of test variables with the symptom and behavioral measures were entered into a series of median polish analyses. There was an overall significant relationship between the two sets of variables. Neuropsychological test variables that were most highly correlated with symptom/behavioral measures were LNNB Left Frontal, Memory, and Intellectual Processes scales. The positive symptoms of thought disorder and hallucinations were most consistently related to neuropsychological variables. In contrast with other findings in the literature, negative symptoms were not significantly correlated with neuropsychological performance.