Remission in schizophrenia: analysis in a naturalistic setting

Objective

To investigate the recently defined Positive and Negative Syndrome Scale for Schizophrenia remission criteria in a naturalistic setting of psychotic patients; to identify causal factors that change remission status; and to validate the criteria against global indices of illness, cognitive functions, and social outcome.

Methods

This was a longitudinal naturalistic study of 162 patients, diagnosed with schizophrenia or schizophrenia-related psychotic disorders (mean illness duration, 11 years) and treated with risperidone at study entry. Symptoms, drug treatment, cognitive function, and social outcome were measured at baseline and annually for 5 years. Remission was constructed retrospectively with only indirect data on stability over time.

Results

At study entry, 40% of the patients with schizophrenia were in symptomatic remission, stabilizing between 55% and 60% after a few years. The need for hospitalization became less frequent over time; initially 31%, dropping to 7% by years 4 and 5. Many patients went in and out of remission. Remission was strongly associated with global indices of illness, with intact insight and with social outcome (except work/studies) but not with cognition or medication.

Conclusions

In spite of certain weaknesses of the study, we may conclude that current definition of remission is primarily a symptomatic measure, covering a subset of symptoms, some of which are not schizophrenia-specific. Although the definition may be clinically relevant, we must be aware of the risk that the connotation of the word could induce too much focus on symptom control.     

Response and remission of subjective well-being in patients suffering from schizophrenia spectrum disorders

Background

Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being.

Method

The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome.

Results

Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission.

Conclusions

Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.     

Does personality disorder decrease the likelihood of remission in early-onset chronic depression?

Background

The impact of personality disorders (PD) on the course of depression has been gaining interest among clinical researchers over the past decade. Recent observational studies have found that PD was associated with impaired social functioning and reduced likelihood of depression recovery. Elevated rates of PD have been noted in early-onset and chronic forms subtypes of depression. However, scant data exist regarding the link between PD and outcome for this depression subtype.

Methods

The National Epidemiological Survey on Alcohol and Related Conditions database was analyzed. This survey included 43 093 respondents, 18 years and older, conducted in 2001 through 2002. Logistic regression was used to identify demographic and clinical predictors of remission in early-onset chronic depression.

Results

The absence of PD, having more years of education, and being married considerably improved the likelihood of remission. Paranoid personality disorder and obsessive-compulsive disorder were the only specific PD found to be associated with a reduced probability of remission.

Limitations

Depression remission status may have biased the recollection of PD symptoms. Borderline personality disorder, narcissistic personality disorder, and schizotypal personality disorder were not assessed.

Conclusions

This study suggests that PD are significant predictors of remission in early-onset chronic depression.     

Long-term effects of transference interpretation in dynamic psychotherapy of personality disorders

Background

Only a few treatment studies of personality disorders (PD) patients are on longer-term psychotherapy, general outcome measures are used, and follow-up periods are usually short. More studies of long-term therapies, using outcome measures of core psychopathology, are needed.

Method

This study is a dismantling randomized controlled clinical trial, specifically designed to study long-term effects of transference interpretation. Forty-six patients with mainly cluster C personality disorders were randomly assigned to 1 year of dynamic psychotherapy with or without transference interpretations. The outcome measures were remission from PD, improvement in interpersonal functioning, and use of mental health resources in the 3-year period after treatment termination.

Results

After therapy with transference interpretation PD-patients improved significantly more in core psychopathology and interpersonal functioning, the drop-out rate was reduced to zero, and use of health services was reduced to 50%, compared to therapy without this ingredient. Three years after treatment termination, 73% no longer met diagnostic criteria for any PD in the transference group, compared to 44% in the comparison group.

Conclusions

PD-patients with co-morbid disorders improved in both treatment arms in this study. However, transference interpretation improved outcome substantially more. Long-term psychotherapy that includes transference interpretation is an effective treatment for cluster C personality disorders and milder cluster B personality disorders.     

Prenatal exposure to tobacco and risk for schizophrenia: a retrospective epidemiological study

Introduction

In animal studies, long-term prenatal nicotinic exposure alters the development of dopaminergic neurons. To determine whether prenatal smoking exposure was associated with schizophrenia, using a retrospective design study, we compared the prevalence of tobacco use during pregnancy in mothers of subjects with and without schizophrenia.

Methods

One hundred patients with schizophrenia, 100 nonschizophrenic-matched subjects, and their respective mothers were interviewed. The prevalence of smoking was measured in these individuals as well as in their respective mothers during the pregnancy.

Results

Patients with schizophrenia smoked more often compared with controls (73% vs 57%). In contrast, the prevalence of smoking during pregnancy did not differ between the groups of mothers. Indeed, the amount of tobacco used was significantly lower in mothers of patients with schizophrenia vs mothers of nonpsychotic subjects.

Conclusion

This study did not show any association between prenatal tobacco exposure and further development of schizophrenia.     

Age, sex and first treatment of schizophrenia in a population cohort

Objective

Schizophrenia affects men more than women, but this may not be true at all ages. This study examines the incidence of first hospitalization for treatment of schizophrenia in each sex over different ages.

Methods

We compared the incidence of first admission for treatment in a cohort of 46,388 males and 43,680 females followed from birth until ages 29-41, using life tables and proportional hazards methods.

Results

Life table estimates of cumulative incidence by age 40 were 1.44% in males and 0.86% in females. For over all ages the relative risk (RR) in males was 1.6 (95% confidence limits = 1.4-1.8) compared with females. Before age 17 there was no significant difference between the sexes (RR = 0.86, 0.56-1.3). Excess risk in males was observed only from age 17 (RR = 1.7, 1.4-1.9). There was no evidence of the incidence in females catching up with that in males, during the 30s.

Conclusion

In this population, there was a significant change, over age, in the relative incidence of first hospitalization for schizophrenia between the sexes; the excess incidence in males first developed at age 17.     

Verbal learning contributes to cognitive insight in schizophrenia independently of affective and psychotic symptoms

Objective

Patients with schizophrenia exhibit distorted beliefs and experiences, and their own evaluation of this is labeled cognitive insight. We examined the relationship between cognitive insight and neurocognition, as well as the contribution of neurocognition in explaining cognitive insight.

Method

Clinically characterized patients with schizophrenia (n = 102) were assessed with a measure of cognitive insight, Beck Cognitive Insight Scale (BCIS) and a neuropsychological test battery. The contribution of neurocognition to the explained variance in BCIS components self-reflectiveness (i.e. objectivity and reflectiveness) and self-certainty (i.e. overconfidence in own beliefs) was examined controlling for current affective and psychotic symptoms.

Results

A significant negative correlation was found between self-certainty and verbal learning, whereas no associations were found between self-reflectiveness and any of the neuropsychological tests. Verbal learning was added significantly to the explained variance in self-certainty after controlling for potential confounders.

Conclusion

High self-certainty was associated with poor verbal learning. This suggests that overconfidence in own beliefs is associated with cognitive dysfunction in schizophrenia.     

Effects of placebo interventions on gastric motility and general autonomic activity

Objective

The study aimed to investigate placebo effects on gastric motility and to examine possible autonomic mediating mechanisms.

Methods

Eighteen healthy volunteers received a placebo pill on three occasions together with the verbal suggestion that it would stimulate, relax, or not affect gastric activity. Electrogastrogram, electrocardiogram, and electrodermal activity recordings were conducted for 30 min prior to and following intervention.

Results

Dominant frequency of the gastric slow wave decreased in the stimulant condition, and increased in the relaxant condition, the difference among conditions being significant. No differential effects of the interventions on cardiac interbeat intervals, heart rate variability, and skin conductance levels were observed.

Conclusion

Stomach relaxant and stimulant placebo interventions modulated gastric motility independently from changes in general autonomic activity.     

Psychopathologic, neuropsychological and functional outcome measures during cognitive rehabilitation in schizophrenia: A prospective controlled study in a real-world setting

Background

Cognitive dysfunction has been demonstrated in patients with schizophrenia, and this may affect patients’ functional outcome. The improvement of such dysfunction by means of cognitive remediation interventions has become a relevant target in the care of schizophrenia.

Objective

To assess the effectiveness of the cognitive subprograms of Integrated Psychological Therapy (IPT) on symptomatological, neuropsychological and functional outcome variables and to analyze the relationships between cognitive and functional outcome changes in schizophrenia.

Methods

Thirty-two patients with schizophrenia were assigned to cognitive remediation (IPT-cog) or usual rehabilitative interventions in a naturalistic setting of care. Clinical, neuropsychological and functional outcome variables were assessed at baseline and after 24 weeks of treatment.

Results

The IPT-cog group improved significantly more than the comparison group with respect to psychopathological and functional outcome variables. Moreover, only the IPT-cog group improved significantly in the neuropsychological domains of verbal and working memory, with specific significant correlations between neurocognitive performance and functional outcome changes.

Conclusions

The results of the study confirm the effectiveness of the cognitive remediation component of IPT in schizophrenia, and indicate that some of the changes in functional outcome may be mediated by improvement in specific cognitive domains.     

Correlates of depressive symptoms among women undergoing the menopausal transition

Objective

Studies indicate that approximately 25% of women undergoing the menopausal transition experience depressive symptoms. The purpose of this study was to examine whether menopausal status was associated with the experiencing of depression among midlife women, to assess which demographic and health habit characteristics were associated with depressive symptoms experienced during the menopausal transition, and to analyze the associations between hormone levels and depressive symptoms.

Methods

Data from a community-based sample of 634 women aged 45 to 54 years were analyzed. Each participant completed a questionnaire and provided a blood sample that was used to measure estrogen and androgen concentrations by enzyme-linked immunosorbent assay. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D).

Results

Approximately 25% of the women in the study were experiencing depressive symptoms (CES-D ≥16). The data showed that being a current smoker, having little/no regular physical activity, being in poor health, and reporting a greater number of menopausal symptoms were independently and significantly associated with depressive symptoms. Menopausal status and the measured hormone levels were not significant independent correlates of depressive symptoms.

Conclusions

These findings confirm the relatively high prevalence of depressive symptoms among midlife women and suggest that certain demographic, health habit, and menopausal symptom characteristics may be more important correlates of depressive symptoms in midlife than menopausal status and hormone levels.     

Sexual problems in a sample of the Turkish psychiatric population

Introduction

Sexual functioning has received little attention as an important aspect of patient care for those who have severe mental disorders.

Aim

The aim of this study is to compare sexual difficulties seen in Turkish psychiatric patients and healthy control subjects.

Methods

Study group consisted of outpatients in remission with schizophrenia (n = 84), bipolar affective disorders (n = 90), heroin addiction (n = 88), and healthy control group (n = 98). A sociodemographical data form and the Golombok Rust Inventory of Sexual Satisfaction were applied to all groups (N = 360).

Results

Half of the patient groups and 72.8% of control subjects reported that they had regular sexual life. The patients with heroin addiction complained about more problems in their sexual life than in the other groups. Controls (86.2%) felt more satisfied with their sexual life. Female patients with heroin addiction had statistically significant higher scores in nonsensuality subscale of Golombok Rust Inventory of Sexual Satisfaction. Female patients with schizophrenia and bipolar disorder had statistically significant higher scores in vaginismus subscale than in control group. Between the groups, male patients with bipolar disorder had higher score in most of the items except noncommunication and erectile dysfunction and also had higher total score than in the controls. More men (especially with heroin addiction) thought that their illness and drugs were responsible for their sexual problems, knew the effect of the illness and drugs on their sexual life, and asked questions to their psychiatrists about the problems more than women.

Conclusion

Patients with bipolar disorders and schizophrenia were unaware of effects of their medication on their sexual life. Finally, it was also found that clinicians in our country do not pay sufficient attention to the sexual problems of psychiatric patients.     

The effect of physiologically relevant dynamic shear stress on platelet and endothelial cell activation

Introduction

Blood flow induced shear stress plays an important role in platelet and endothelial cell functions. The goal of this study was to investigate the effect of physiologically relevant dynamic shear stress on platelet and endothelial cells.

Materials and Methods

Pulsatile shear stress waveforms mimicking the flow in a normal left coronary artery (0.1-1 Pa), at a 60% stenosis (0.2 - 6 Pa) and in the recirculation zone (0.01 - 0.5 Pa) behind a stenosis were used to stimulate platelets and endothelial cells in a cone and plate shearing device. Platelet activation was measured by CD62P expression and thrombogenicity. Meanwhile, endothelial cell activation and damage was measured by cell surface ICAM-1 and tissue factor expression using fluorescence microscopy. Endothelial tissue factor activity was measured using a commercial kit.

Results

Results showed that for platelets, a short exposure to elevated shear stress at the stenosis throat did not induce significant increase in platelet activation or thrombogenicity. While the low pulsatile shear stress had a potential for enhanced thrombosis. Both low and high pulsatile shear stress led to a significant increase in ICAM-1 expression on endothelial cell surface, but only low shear stress caused tissue factor over expression and enhanced tissue factor activity.

Conclusion

These results suggest that low pulsatile shear stress may be more atherogenic, compared to elevated shear stress induced by stenosis.     

Impairments in executive functioning in patients with remitted and non-remitted schizophrenia

Objective

Although deficits in executive functioning are prominent in schizophrenia, some patients in remission have shown significantly higher levels of neurocognitive functioning than patients not in remission. However, no consensus on the relationship between neurocognitive functioning and the severity of symptoms has been reached. Additionally, previous studies have mainly examined the primary symptom domains of schizophrenia without considering the influence of anxiety symptoms, which are likely to influence neuropsychological performance. The aim of the present study was to compare the executive functioning of normal controls and with that of patients with schizophrenia in acute and remitted states. We further examined associations between impaired executive functioning in patients and anxiety levels.

Methods

Using a battery of tests assessing executive functioning including subtests of the Cambridge Neuropsychological Automated Test Battery (CANTAB) and the short form of the Korean Wechsler Adult Intelligence Scale (K-WAIS), we assessed 54 patients with schizophrenia and 33 normal controls.

Results

Our results showed that patients with non-remitted schizophrenia obtained significantly lower estimated IQ scores than did normal controls. They also exhibited longer reaction times on the Choice Reaction Time (CRT) test and the Stop Signal Test (SST) subtests of CANTAB and a greater number of total errors and errors that occurred before the extradimensional stage (i.e., pre-ED errors) on the Intradimensional/Extradimensional Shift (IED) subtest of CANTAB. Furthermore, those with schizophrenia in acute states showed significantly slower stop signal reaction times (SSRT) on the SST than did those with remitted schizophrenia and healthy controls. Finally, differences in the pre-ED errors and total adjusted errors on the IED became insignificant when scores on the Beck Anxiety Inventory (BAI) were entered as the covariate, whereas other significant differences remained when these scores were entered.

Conclusion

Differences in executive functioning exist between patients with schizophrenia and healthy controls; these differences can be largely attributed to the relatively poor performance of patients in an active state.     

Impaired secretion of carboxyl-terminal truncated factor VII due to an F7 nonsense mutation associated with FVII deficiency

Introduction

Factor VII (FVII) is a vitamin K-dependent glycoprotein secreted into the blood circulation from hepatic cells. We investigated the molecular basis of the congenital FVII deficiency found in a Japanese patient.

Materials and Methods

We analyzed the F7 gene of the patient, who was diagnosed with a FVII deficiency at pregnancy. We expressed a carboxyl-terminal truncated FVII (Arg462X FVII) corresponding to the identified mutation in CHO-K1 cells. To study roles of the carboxyl-terminus in the secretion of FVII, we also expressed a series of recombinant FVIIs deleted of limited numbers of carboxyl-terminal amino acids (462Arg-466Pro).

Results

We identified a nonsense mutation (c.1384C > T: p.Arg462X) in F7, leading to a lack of five amino acids in the carboxyl-terminus. In expression experiments, Arg462X FVII was undetectable not only by Western blotting, but also by ELISA. A Western blot analysis of the truncated FVIIs revealed that all mutants were expressed in the cells the same as the wild type, but were secreted into the culture medium in lesser amounts than the wild type depending on the length of the deletion, which was confirmed by ELISA. Arg462X FVII did not colocalize with the Golgi on immunofluorescence staining, suggesting that it might be retained in the ER and degraded in the cell.

Conclusion

The carboxyl-terminal amino acids of FVII play an important role in its secretion, and the p.Arg462X mutation was likely to have caused the FVII deficiency in this patient.     

Functional neural substrates of self-reported physical anhedonia in non-clinical individuals and in patients with schizophrenia

Background

Anhedonia is a negative symptom of schizophrenia that has a detrimental impact on functioning and quality of life. Anhedonia also represents a vulnerability marker for schizophrenia when measured in non-clinical individuals. The investigation of the neural correlates of anhedonia in schizophrenia and non-clinical individuals could provide key insights on the pathophysiology of negative symptoms, as well as on the characterization of neural markers of vulnerability.

Methods

Thirty patients with schizophrenia and twenty-six non-clinical individuals were recruited. We used an event-related functional Magnetic Resonance Imaging paradigm involving an emotional picture viewing task. For each group, separately, we correlated the regional BOLD signal changes during hedonic processing with the Chapman Physical Anhedonia Scale scores. An interaction analysis identified the neural correlates of anhedonia specific to schizophrenia.

Results

We found that anhedonia severity in both groups was inversely correlated with the activity of a limited number of emotion-related regions, including the medial prefrontal cortex. The orbitofrontal cortex and putamen/ventral striatum activity was negatively correlated with anhedonia severity in people with schizophrenia only.

Conclusions

The data first suggest that anhedonia severity is linked to a poor modulation of emotional/attentional brain regions during the processing of hedonic information. The link between anhedonia and the activity of the ventral striatum and orbitofrontal cortex found in schizophrenia could reflect the specific impairment of indirect factors, such as reward anticipation deficits, that influence the measurement of anhedonia severity through self-report questionnaires.     

A more proximal impact of dissociation than of trauma and posttraumatic stress disorder on schneiderian symptoms in patients diagnosed with schizophrenia

Background

Dissociation is often related to psychologic trauma and is also commonly correlated with posttraumatic stress disorder (PTSD). Schneiderian symptoms occur in dissociative disorder and PTSD, whereas dissociation and trauma are also frequent in patients with schizophrenia. Dissociation and schneiderian symptoms may reflect posttraumatic symptomatology in some patients diagnosed with schizophrenia who might not develop PTSD.

Method

Seventy-one patients completed an interview assessing symptoms of schizophrenia, depression, dissociative disorder, and PTSD. Data were collected using the Positive and Negative Syndrome Scale, the Montgomery-Asberg Depression Rating Scale, the Arbeitsgemeinschaft Methodik und Dokumentation in der Psychiatrie scale for dissociation, and a Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition-based questionnaire. Multiple analysis of covariance was used to compare psychopathologic measures between groups with or without PTSD criteria A1 and A2, PTSD, and high and low levels of dissociation, controlling for substance abuse.

Result

Trauma and dissociation were associated with more severe symptoms of schizophrenia. Especially high dissociation was associated with an increase in symptom load, whereas criterion A and PTSD had little or no such effect.

Discussion

In the present study, those with more severe schizophrenic and depressive symptoms were also characterized by high dissociation. The possible relation to trauma and schizophrenic diathesis is discussed along with the limitations of the study.     

Exposure to trauma and the clinical presentation of first-episode psychosis in South Africa

Objective

To evaluate the relationship between a history of traumatic experiences and the clinical features of first-episode psychosis (FEP).

Method

We tested associations between trauma variables and duration of untreated psychosis (DUP), age of onset (AO), PANSS-rated positive and negative symptoms and depressive symptoms (Calgary Depression Scale) in a sample of 54 FEP patients.

Results

Mean DUP was 34.4 weeks, while mean AO was 24.7 years. Witnessing a seriously violent assault (49%) was associated with high positive symptoms (p = 0.002), while a significant personal experience of racism and discrimination (39%) was associated with high depressive (p = 0.042) symptoms. Previous sexual assault (44% of females) was associated with high positive (p = 0.028) and negative (p = 0.035) symptoms with a trend association with depressive symptoms (p = 0.092).

Conclusion

Our findings suggest that previous traumatic experience is associated with positive and affective symptoms in FEP.     

Depression and incident diabetic retinopathy: a prospective cohort study

Objective

This study examined whether depression is associated with a higher incidence of diabetic retinopathy among adults with type 2 diabetes after controlling for sociodemographic factors, health risk behaviors and clinical characteristics.

Method

This study included 2359 patients enrolled in Pathways Epidemiologic Follow-Up Study, a prospective cohort study investigating the impact of depression in primary care patients with type 2 diabetes. The predictor of interest was baseline severity of depressive symptoms assessed with the Patient Health Questionnaire-9 (PHQ-9). The outcome was incident diabetic retinopathy. Risk of diabetic retinopathy was assessed using logistic regression, and time to incident diabetic retinopathy was examined using Cox proportional hazard models.

Results

Over a 5-year follow-up period, severity of depression was associated with an increased risk of incident retinopathy [odds ratio =1.026; 95% confidence interval (CI) 1.002-1.051] as well as time to incident retinopathy (hazard ratio=1.025; 95% CI 1.009-1.041). The risk of incident diabetic retinopathy was estimated to increase by up to 15% for every significant increase in depressive symptoms severity (5-point increase on the PHQ-9 score).

Conclusion

Diabetic patients with comorbid depression have a significantly higher risk of developing diabetic retinopathy. Improving depression treatment in patients with diabetes could contribute to diabetic retinopathy prevention.     

A quasi-experimental evaluation of parents as sexual health educators resulting in delayed sexual initiation and increased access to condoms

Objective

To evaluate the effectiveness of an educational intervention for parents of first year high school students in the State of Morelos, Mexico, whose aim was to impact adolescents’ sexual behavior, knowledge and access to contraception.

Material and methods

Quasi-experimental prospective study with eleven control and eleven intervention schools using self-administered questionnaires for parents and adolescents pre- and post-intervention. Parent-child dyads in the control and intervention schools were matched according to parents’ propensity score; the average treatment effect (ATE) was estimated for adolescent’s outcome variables.

Results

At follow-up, we found significant differences for adolescents in the intervention schools: 6.8% delayed initiation of sexual intercourse, 14.4% had correct knowledge about emergency contraception (EC), and 164% reported having received condoms from their parents, when comparing with students in control schools.

Conclusions

Our results suggest that parent-focused interventions could be an innovative and effective strategy to promote adolescents sexual health.     

Five-year follow-up study of disability pension rates in first-onset schizophrenia with special focus on regional differences and mortality

Objective

To evaluate the rate and regional determinants of disability pension in first-admission schizophrenia. In addition, we investigated whether patients with disability pension had increased mortality rates during follow-up.

Method

A nationwide register-based 5-year follow-up study of all patients with onset of schizophrenia between 1998 and 2001 (n=3,875).

Results

A total of 1944 (50.2%) first-onset schizophrenia patients retired on disability pension during the 5-year follow-up. Males retired on pension at an earlier age and more often than females. Regional disability pension rates and retirement times for schizophrenia varied between hospital districts. Patients on disability pension had lower overall and suicide mortality, and they had less physical illness, depression and more psychotropic medication use than patients without disability pension. In regions with a short median time from onset time to retirement, there was significantly higher regional overall mortality and suicide mortality. Disability pension rates were also higher in regions with high involuntary treatment rate.

Conclusion

Half of the schizophrenia patients were pensioned off in 5 years. Lower mortality, especially suicide mortality among disability pensioners, suggests that the decision on a permanent disability pension, indicating for its part the activation of the service system, might be a relief to schizophrenic patients, helping them cope with illness. The retirement process has regional differences, which may be caused by the regional nature of treatment and resources.