Reduction of plasma glutathione in psychosis associated with schizophrenia and bipolar disorder in translational psychiatry.

The establishment of mechanism-driven peripheral markers is important for translational psychiatry. Many groups, including ours, have addressed molecular alterations in peripheral tissues in association with symptomatic changes in major illnesses. Oxidative stress is implicated in the pathophysiology of schizophrenia (SZ) and bipolar disorder (BP) through studies of patient peripheral tissues and animal models. Although the relationship between peripheral changes and brain pathology remain elusive, oxidative stress may bridge such translational efforts. Nonetheless, the molecular substrates of oxidative stress are not well defined in mental conditions. Glutathione (GSH) is a non-enzymatic antioxidant that eliminates free radicals, and has been suggested to have a role in SZ. We performed a cross-sectional study of 48 healthy controls (CON), 52 SZ patients and 62 BP patients to compare the levels of peripheral GSH by a biochemical enzyme assay. We show a significant reduction of plasma GSH in both SZ and BP patients compared with CON. We evaluated possible influences of clinical characteristics on the level of GSH in SZ and BP. A decrease in GSH level correlated with Positive and Negative Syndrome Scale (PANSS) total and positive scores for SZ and correlated with the PANSS general for BP. Taken together, we provide evidence that SZ and BP display a common molecular signature in the reduction of peripheral GSH in the psychosis dimension.

Reexamining associations between mania, depression, anxiety and substance use disorders: results from a prospective national cohort.

Separate inheritance of mania and depression together with high rates of clinical overlap of mania with anxiety and substance use disorders provide a basis for re-examining the specificity of the prospective association of manic and depression episodes that is a hallmark of bipolar disorder. We analyzed information from 34 653 adults in Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions, a longitudinal nationally representative survey of US adults interviewed 3 years apart. Psychiatric disorders were assessed by a structured interview. We used logistic regression analyses to estimate the strength of associations between Wave 1 manic episodes and Wave 2 depression, anxiety and substance use disorders controlling for background characteristics and lifetime Wave 1 disorders. Corresponding analyses examined associations between Wave 1 major depressive episode with manic episodes and other psychiatric disorders. In multivariable models, Wave 1 manic episodes significantly increased the odds of Wave 2 major depressive episodes (adjusted odds ratio (AOR): 1.7; 95% confidence interval: 1.3-2.2) and any anxiety disorder (AOR: 1.8; 1.4-2.2), although not of substance use disorders (AOR: 1.2; 0.9-1.5). Conversely, Wave 1 major depressive episodes significantly increased risk of Wave 2 manic episodes (AOR: 2.2; 1.7-2.9) and anxiety disorders (AOR: 1.7; 1.5-2.0), although not substance use disorders (AOR: 1.0; 0.9-1.2). Adults with manic episodes have an approximately equivalent relative risk of developing depression episodes and anxiety disorders. Greater research and clinical focus is warranted on connections between manic episodes and anxiety disorders.

Collective levels of stigma and national suicide rates in 25 European countries.

AIMS: There is substantial diversity in national suicide rates, which has mainly been related to socio-economic factors, as well as cultural factors. Stigma is a cultural phenomenon, determining the level of social acceptance or rejection of persons with mental illness in a society. In this study, we explore whether national suicide rates are related to the degree of mental illness stigma in that country. METHODS: We combine the data on country-level social acceptance (Eurobarometer) with the data on suicide rates and socio-economic indicators (Eurostat) for 25 European countries. RESULTS: In a linear regression model controlling for socio-economic indicators, the social acceptance of someone with a significant mental health problem in 2010 was negatively correlated with age standardised national suicide rates in the same year (ß -0.46, p = 0.014). This association also held true when combining national suicide rates with death rates due to events of undetermined intent. CONCLUSIONS: Stigma towards persons with mental health problems may contribute to differences in suicide rates in a country. We hypothesise possible mechanisms explaining this link, including stigma as a stressor and social isolation as a consequence of stigma.

Association between public views of mental illness and self-stigma among individuals with mental illness in 14 European countries.

BACKGROUND: Little is known about how the views of the public are related to self-stigma among people with mental health problems. Despite increasing activity aimed at reducing mental illness stigma, there is little evidence to guide and inform specific anti-stigma campaign development and messages to be used in mass campaigns. A better understanding of the association between public knowledge, attitudes and behaviours and the internalization of stigma among people with mental health problems is needed. METHOD: This study links two large, international datasets to explore the association between public stigma in 14 European countries (Eurobarometer survey) and individual reports of self-stigma, perceived discrimination and empowerment among persons with mental illness (n=1835) residing in those countries [the Global Alliance of Mental Illness Advocacy Networks (GAMIAN) study]. RESULTS: Individuals with mental illness living in countries with less stigmatizing attitudes, higher rates of help-seeking and treatment utilization and better perceived access to information had lower rates of self-stigma and perceived discrimination and those living in countries where the public felt more comfortable talking to people with mental illness had less self-stigma and felt more empowered. CONCLUSIONS: Targeting the general public through mass anti-stigma interventions may lead to a virtuous cycle by disrupting the negative feedback engendered by public stigma, thereby reducing self-stigma among people with mental health problems. A combined approach involving knowledge, attitudes and behaviour is needed; mass interventions that facilitate disclosure and positive social contact may be the most effective. Improving availability of information about mental health issues and facilitating access to care and help-seeking also show promise with regard to stigma.

Barriers to mental health treatment: results from the National Comorbidity Survey Replication.

BACKGROUND: The aim was to examine barriers to initiation and continuation of treatment among individuals with common mental disorders in the US general population. METHOD: Respondents in the National Comorbidity Survey Replication with common 12-month DSM-IV mood, anxiety, substance, impulse control and childhood disorders were asked about perceived need for treatment, structural barriers and attitudinal/evaluative barriers to initiation and continuation of treatment. RESULTS: Low perceived need was reported by 44.8% of respondents with a disorder who did not seek treatment. Desire to handle the problem on one's own was the most common reason among respondents with perceived need both for not seeking treatment (72.6%) and for dropping out of treatment (42.2%). Attitudinal/evaluative factors were much more important than structural barriers both to initiating (97.4% v. 22.2%) and to continuing (81.9% v. 31.8%) of treatment. Reasons for not seeking treatment varied with illness severity. Low perceived need was a more common reason for not seeking treatment among individuals with mild (57.0%) than moderate (39.3%) or severe (25.9%) disorders, whereas structural and attitudinal/evaluative barriers were more common among respondents with more severe conditions. CONCLUSIONS: Low perceived need and attitudinal/evaluative barriers are the major barriers to treatment seeking and staying in treatment among individuals with common mental disorders. Efforts to increase treatment seeking and reduce treatment drop-out need to take these barriers into consideration as well as to recognize that barriers differ as a function of sociodemographic and clinical characteristics.

Use of specialty substance abuse and mental health services in adults with substance use disorders in the community.

AIMS: To examine the patterns and correlates of use of specialty substance abuse and mental health services among adults with alcohol or non-alcohol drug abuse or dependence in the community. METHODS: Analyses focused on 5,568 participants with alcohol or non-alcohol drug abuse or dependence drawn from a large representative cross-sectional survey of the US general population-the 2002 US National Survey on Drug Use and Health (NSDUH). RESULTS: Only 9.7% of adults with substance use disorders used specialty substance abuse services in the past year; 22.4% used mental health services. Severity of substance use disorder and less education were associated with using substance abuse services. Whereas psychological distress and impairment in role functioning due to psychological problems were associated with mental health service use. Male gender, black race/ethnicity, and lack of health insurance acted as barriers to using mental health services but not specialty substance abuse services. Past year use of substance abuse services, but not mental health services, was associated with lower likelihood of continued use of substances in the past month. CONCLUSIONS: Individuals with substance use disorders are more likely to use mental health services than specialty substance abuse services. However, only people who use specialty substance abuse services have a lower risk of continued use of substances. Findings highlight the need for integration of substance abuse treatments in the mental health care system and attention to different barriers to the two types of services.

Height, weight and body mass index (BMI) in psychiatrically ill US Armed Forces personnel.

BACKGROUND: In both psychiatrically ill and psychiatrically healthy adults, the connection between health and individuals' height and weight has long been examined. Specifically, research on the idea that individuals with certain body types were prone to particular psychiatric diseases has been explored sporadically for centuries. The hypothesis that psychiatrically ill individuals were shorter and weighed less than psychiatrically healthy counterparts would correspond with the neurodevelopmental model of psychiatric disease. METHOD: To evaluate possible links between psychiatric illness and physique, the height, weight and BMI of 7514 patients and 85,940 controls were compared. All subjects were part of the National Collaborative Study of Early Psychosis and Suicide (NCSEPS). Patients were US military active duty personnel hospitalized for either bipolar disorder, major depressive disorder, or schizophrenia and controls were psychiatrically-healthy US military active duty personnel matched for date of entry into the service. RESULTS: No consistent differences in height, weight or BMI were found between patients and controls, or between patient groups. Some weak ANOVA differences were found between age at the time of entering active duty and weight, as well as BMI, but not height. CONCLUSIONS: Unlike most previous studies that have looked at the links between height and psychiatric illness, this study of the NCSEPS cohort found that, at entry into the US Armed Forces, there were no consistent decreases in height for patients with bipolar disorder, major depressive disorder or schizophrenia compared with a large control group. Furthermore, there were no consistent differences for weight or BMI.

Residual symptoms and impairment in major depression in the community.

OBJECTIVE: Studies of patients with major depression in treatment settings have found significant residual symptoms and impairment after resolution of the depressive episode. However, only a small proportion of individuals with major depression seek treatment, and little is known about the residual symptoms and impairment associated with major depression in the community. This study used data from the National Comorbidity Survey, which included a nationally representative household sample of respondents in the United States, to assess the course of residual symptoms and impairment after resolution of major depressive episodes in the community. METHOD: National Comorbidity Survey respondents with lifetime major depression who were currently experiencing a major depressive episode and respondents whose last episode had ended more than 1 to 6 months, more than 6 to 12 months, or more than 12 months ago were compared with those without a history of major depression with regard to depressive symptoms and days of impairment in work functioning or other activities in the past 30 days. RESULTS: Respondents whose last episode of major depression had resolved even more than a year ago were still more symptomatic than those without a history of major depression, whereas the number of days of impairment returned to a level indistinguishable from that of respondents without a history of major depression after >6 to 12 months of resolution of the last episode. CONCLUSIONS: Major depression in the community, as in treatment settings, is associated with residual symptoms and impairment. In the community, however, residual impairment may resolve more quickly than residual symptoms.

Impairment in major depression: implications for diagnosis.

A significant change in the criteria for major depressive disorder in the DSM-IV over the earlier editions was the introduction of a criterion of "clinically significant distress and impairment" (criterion C). However, it is not clear that cases of depression which meet this criterion are distinct from cases that do not meet the criterion on characteristics beyond mere severity of illness. This report used data from the National Comorbidity Survey (NCS) to compare the psychiatric and sociodemographic characteristics of cases of DSM-III-R major depression with varying levels of self-rated impairment. The results of the analyses revealed no difference between respondents with different levels of impairment on gender, age of onset, parental history of depression and suicide, duration of illness, and symptom profiles. With regard to the social and psychiatric indicators of severity of illness, on the other hand, there was a gradient for worse outcome among more severely impaired respondents. It is concluded that the less impaired respondents with DSM-III-R major depression cannot be distinguished from the more impaired on illness characteristics that are not related to the severity of illness. Therefore, cases of DSM-III-R major depression with various levels of impairment most probably represent cases of the same illness that vary only in severity.

Mortality and long-term course in schizophrenia with a poor 2-year course: a study in a developing country.

BACKGROUND: The short-term course of schizophrenia is reported to be better in some developing country settings. The long-term course in such settings, however, has rarely been studied. AIMS: To examine the long-term course and mortality of schizophrenia in patients with a poor 2-year course. METHOD: The report is based on two incidence cohorts of first-contact patients in urban and rural Chandigarh, India, originally recruited for the World Health Organization Determinants of Outcome of Severe Mental Disorders study. Patients were assessed using standardised instruments at 2- and 15-year follow-ups. RESULTS: Ninety-two per cent of the patients with a poor 2-year course had a poor long-term course and 47% died - a nine times higher mortality rate than among patients with other 2-year course types. CONCLUSIONS: In this developing country setting, a poor 2-year course was strongly predictive of poor prognosis and high mortality, raising questions about the adequacy of care for such patients.

Duration of remitting psychoses with acute onset. Implications for ICD-10.

BACKGROUND: The acute and transient psychotic disorders (ATPD) in ICD-10 advanced the nosology of remitting psychoses with acute onset. But the proposed criteria for ATPD--especially in regard to duration--are tentative and need to be validated. AIMS: To evaluate: (a) the duration of remitting psychoses with acute onset; (b) the applicability of the ATPD criteria for these cases; and (c) differences in duration and ATPD diagnoses across sociocultural settings. METHOD: Data from the World Health Organization Determinants of Outcome study were used. RESULTS: The 98 cases of remitting psychoses with acute onset had a modal duration of 2-4 months, with 43% falling in this range. Mainly because of this, few met the ATPD criteria. Duration and diagnostic findings were similar across settings. CONCLUSIONS: ATPD criteria need refinement, especially in regard to duration. Further studies aimed at early detection and assessment of onset and duration of these disorders are needed.

Neuropsychological differences between first-admission schizophrenia and psychotic affective disorders.

OBJECTIVE: The study compared the neuropsychological functioning of patients with first-admission schizophrenia with that of patients with first-admission psychotic affective disorders. METHOD: Data came from the Suffolk County Mental Health Project, an epidemiological study of first-admission psychotic disorders. Subjects with a diagnosis of schizophrenia (N=102) and psychotic affective disorders, including bipolar disorder with psychotic features (N=72) and major depressive disorder with psychotic features (N=49), were compared on a battery of neuropsychological tests administered 2 years after the index admission. RESULTS: Subjects with schizophrenia performed worse than those with the psychotic affective disorders, even after adjusting the results for differences in demographic characteristics and general intellectual functioning. The most consistent differences were on tests of attention, concentration, and mental tracking. The two psychotic affective disorder groups were indistinguishable in performance on the neuropsychological tests. CONCLUSIONS: Even early in its course, schizophrenia is distinguishable from psychotic affective disorders by global and specific neuropsychological deficits. These deficits might contribute to the disability and poor outcome associated with schizophrenia in the mid- and long-term course.

Heterogeneity of cycloid psychoses: a latent class analysis.

BACKGROUND: Three hypotheses have been proposed in regard to the origin of cycloid psychoses: (1) they are an independent nosological entity; (2) they are atypical cases of affective disorders; and (3) they are a heterogeneous group of disorders. This study examined the heterogeneity hypothesis by attempting to delineate distinct affective and non-affective subgroups. METHODS: In 60 cases drawn from a classic study of cycloid psychoses by Perris (1974), latent class analysis was used to delineate subgroups. RESULTS: Two classes were identified in the analysis: one characterized by the convergence of affective symptoms and family history of affective disorders and the other by the relative paucity of such features. CONCLUSIONS: Cycloid psychoses are composed of at least two subgroups, distinguishable on the basis of symptoms and family history.

Reliability of the life chart schedule for assessment of the long-term course of schizophrenia.

We report on the inter-rater reliability of the Life Chart Schedule (LCS). The LCS is designed to assess the long-term course of schizophrenia in four key domains (symptoms, treatment, residence, and work) over two time periods (past two years, entire period of illness). The subjects were 27 consecutive admissions to a schizophrenia research unit. The LCS was filled out by pairs of raters, blinded to each others' ratings, using the same data (interview with subject and chart). Reliability was examined for 45 LCS ratings selected from all four domains and both time periods. Selected ratings pertained to the duration of specified experiences, the quality of these experiences, and the long-term time trend. The kappa statistic and the intra-class correlation coefficient (ICC) were used to determine inter-rater reliability for continuous and categorical ratings, respectively. LCS ratings proved reliable in all four key domains and both time periods. The reliability was fair to excellent for ratings of duration of experience (ICC ranged from 0.53 to 0.99), quality of experience (kappa ranged from 0.46 to 0. 92) and long-term time trends (kappa ranged from 0.66 to 0.94). The LCS can be used to obtain reliable ratings of the long-term course of schizophrenia in multiple domains.

Delusion as error: the history of a metaphor.

Error has been the major metaphor for understanding delusions through the past three centuries. Modern definition of delusion as erroneous opinion or belief is evidence of the continuing role of this metaphor to this day. However, through long habituation the metaphorical nature of the association between delusion and error is no longer recognized. In other words, the metaphor has become literal and all but invisible. This paper seeks to shed light on this metaphor by tracing its development from inception in the seventeenth century to the present time. Also, the impact of the metaphor on modern research and therapeutic approaches is briefly discussed. Finally, to put the metaphor of error in perspective, some other metaphors applied to delusion over the years are reviewed.

Duration of illness and structure of symptoms in schizophrenia.

BACKGROUND: Previous research has mainly focused on the cross-sectional structure of symptoms in schizophrenia. This meta-analysis examined the association of duration of illness with the structure of symptoms. METHODS: Using explicit criteria, 22 studies reporting on the correlations of symptoms in 2665 schizophrenic patients were selected. From each study, symptom-pair correlations for negative symptoms as rated by Scale for the Assessment of Negative Symptoms (SANS) and positive symptoms as rated by the Scale for the Assessment of Positive Symptoms (SAPS) were extracted. Variability among symptom-pair correlations across studies was assessed using tests of homogeneity. For symptom-pair correlations which were not found to be homogeneous, the association of average duration of illness with the symptom-pair correlations were examined. RESULTS: There was considerable variability in symptom-pair correlations across studies. Part of this variability was explainable by variations in average duration of illness. Longer duration of illness was associated with lower negative-negative symptom-pair correlations and higher negative-positive symptom-pair correlations. CONCLUSIONS: The findings suggest that the structure of symptoms in schizophrenia evolves over time, following a consistent pattern. In the early stages of illness, negative and positive symptoms form cohesive dimensions. With time, these dimensions become less cohesive and the boundaries between them, less clear.

Fever and acute brief psychosis in urban and rural settings in north India.

BACKGROUND: This case-control study used data from Chandigarh, North India to investigate the association between antecedent fever and acute brief psychosis. AIMS: To assess whether antecedent fever may be a biological correlate of acute brief psychosis, and contribute to the nosology of acute brief psychosis. METHOD: The study was based in an incidence cohort from two catchment areas, an urban and a rural site, that were part of the World Health Organization Determinants of Outcome study. The cases (n = 17) met criteria for acute brief psychosis; controls (n = 40) were patients with other acute and subacute psychoses. The Life Events Schedule was used to determine the presence of antecedent fever. RESULTS: The crude odds ratio for fever as a risk factor for acute brief psychosis was 6.2 (P = 0.004). The odds ratio in a logistic regression analysis--adjusted for site, gender and CATEGO classification--was 11.2 (P = 0.003). CONCLUSIONS: Antecedent fever may be a biological correlate of acute brief psychosis. This finding supports the validity of this entity, and has implications for its aetiology and diagnosis.

Role of psychosocial treatments in management of schizophrenia: a meta-analytic review of controlled outcome studies.

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.

Identifying misidentifications: a phenomenological study.

This study assessed how well the current classification system of the delusional misidentification syndromes (DMSs) represents the full range of misidentification phenomena encountered in self-descriptions of psychotic patients. To this end, a sample of 58 self-descriptions of ex-patients who had suffered from an episode of psychosis were reviewed. Misidentifications fitting the definition of one of the DMSs were identified in only 3 cases, whereas those fitting a general and broad definition were identified in 16 cases. It is argued that the restrictive nature of the currently dominant DMSs classification may have led to the neglect of a wide range of misidentification phenomena which do not fit the descriptions of any one of the classic DMSs. Proper identification, description and classification of these non-DMS misidentification phenomena is needed.