Seventeen-year clinical outcome of schizophrenia in Bali

Objective

To examine the 17-year clinical outcome of schizophrenia and its predictors in Bali.

Methods

Subjects were 59 consecutively admitted first-episode schizophrenia patients. Their clinical outcome was evaluated by standardized symptomatic remission criteria based on Positive and Negative Syndrome Scale (PANSS) scores and operational functional remission criteria at 17-year follow-up. The standardized mortality ratio (SMR) over 17 years was also calculated as another index of clinical outcome.

Results

Among these 59 patients, 43 (72.9%) could be followed-up, 15 (25.4%) had died, and one (1.7%) was alive but refused to participate in the study. Combined remission (i.e. symptomatic and functional remission) was achieved in 14 patients (23.7% of original sample). Duration of untreated psychosis (DUP) was a significant baseline predictor of combined remission. Mean age at death of deceased subjects was 35.7, and SMR was 4.85 (95% CI: 2.4-7.3), indicating that deaths were premature. Longer DUP was associated with excess mortality.

Conclusions

The long-term outcome of schizophrenia in Bali was heterogeneous, demonstrating that a quarter achieved combined remission, half were in nonremission, and a quarter had died at 17-year follow-up. DUP was a significant predictor both for combined remission and mortality.     

Association of the ZNF804A gene polymorphism rs1344706 with white matter density changes in Chinese schizophrenia

Background

ZNF804A gene polymorphism rs1344706, the first genetic risk variant to achieve genome wide significance for schizophrenia, has been linked to neural functional connectivity. Dysconnectivity of WM may be the primary pathological mechanism of schizophrenia. Association of this variant with regional WM density has not been investigated in schizophrenic patients.

Methods

69 healthy controls and 80 patients with schizophrenia underwent genotyping of rs1344706 SNPs, and were examined for WM density (T1-weighted MRI). The association of rs1344706 with WM changes in schizophrenia patients and healthy controls was analyzed using a full-factorial 2 × 2 analysis of variance.

Results

1. There was an interaction on WM density in the left prefrontal lobe between the rs1344706 genotype and schizophrenic diagnosis, where the risk T allele carriers presented higher WM density in the schizophrenia patients and lower WM density in healthy controls in comparison with the non-risk allele carriers.2. The risk allele was associated with an increased WM density of the bilateral hippocampus in both the patients and the healthy group.

Limitation

The influence of antipsychotics to the white matter in schizophrenic patients was not fully eliminated.

Conclusions

The ZNF804A variant may confer risk for schizophrenia by exerting its effects on the WM in the left prefrontal lobe together with other risk factors for schizophrenia.     

Prepulse inhibition of the startle reflex in schizophrenia remains stable with short-term quetiapine

Purpose

To study the short-term effect of treatment with quetiapine on prepulse inhibition (PPI) deficits of the startle reflex in schizophrenia patients.

Subjects and methods

Using PPI, we studied a group of 21 schizophrenia patients and 16 controls. Seventeen of the patients were re-tested with PPI after 21 days of treatment with quetiapine.

Results

At baseline, an almost significant decrease in PPI was found in the patients as compared to the controls. PPI measurements did not change in the patients after 21 days of treatment with quetiapine, despite their clinical improvement.

Conclusion

Our results suggest that short-term quetiapine treatment may not modify PPI measures in schizophrenia patients.     

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.     

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.     

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.     

Is COPD associated with suicide behavior?

Background

The goal of this study is to examine the relationship between chronic obstructive pulmonary disease (COPD) and suicidal ideation and suicide attempt among adults in the United States.

Methods

Data were drawn from the National Comorbidity Study-Replication (NCS-R), a household probability sample of adults ages 18 and older in the United States.

Results

COPD is associated with significantly increased odds of suicidal ideation and suicide attempt, compared with those without COPD. The association between COPD and suicide attempt remained statistically significant after adjusting for demographics, depression, panic disorder, substance use and nicotine dependence. The association between COPD and suicidal ideation was no longer significant after adjusting for nicotine dependence.

Conclusions

Our findings provide initial evidence that there is a relationship between COPD and suicidal behavior among adults in the community. Future studies that can examine the relationship between COPD and completed suicide, as well as replication of these results, would improve our understanding of whether and to what degree COPD confers an increased vulnerability for suicide behavior.     

Affect recognition as an independent social function determinant in schizophrenia

Introduction

Facial affect recognition deficits may represent specific deficits and contribute to social dysfunction in patients with schizophrenia. Whether their impacts on social dysfunction are independent to those caused by deficits in basic neurocognition and clinical symptoms needs to be further delineated.

Method

Association patterns between affect recognition and basic neurocognitive abilities in 40 acute and 33 stable patients with schizophrenia were compared to explore whether their interrelationships changed across clinical stages. The independent contribution of affect recognition deficits to social dysfunction was explored by multivariate models controlling for general intellectual ability, basic neurocognition, and clinical symptoms.

Results

Affect recognition deficits were associated with social role performances, self-care, and contributed independently to global social functioning in stable patients but not in acute patients. Conversely, affect recognition deficits were associated with impaired basic neurocognitions in acute patients but not in stable patients.

Conclusion

In stabilized community patients with schizophrenia, affect recognition deficits were relatively independent to basic neurocognition and had significant social functional consequences.     

Progressive alterations of the auditory association areas in young non-psychotic offspring of schizophrenia patients

Background

Schizophrenia may involve progressive alterations of structure and hemispheric lateralization of auditory association areas (AAA) within the superior temporal gyrus. These alterations may be greater in male patients. It is unclear if these deficits are state-dependent or whether they predate illness onset and reflect familial diathesis.

Aims

We sought to compare AAA cortical thickness, surface area and lateralization across adolescent and young adult non-psychotic offspring of schizophrenia patients (OS) and healthy controls at baseline and one year follow-up. We also assessed the moderating effect of gender on these measures.

Methods

Fifty-six OS and thirty-six control subjects were assessed at baseline and at follow-up on AAA surface area and thickness using FreeSurfer to process T1-MRI-images. We used repeated measures ANCOVAs, controlling intra cranial volume and age with assessment-time and side as within-subject factors and gender and study group as between-subject factors.

Results

Surface area deficit in OS was greater on the left than on the right, as reflected in a lower surface area laterality-index (left-right/left + right  × 100) in OS compared to controls. Left, but not right surface area and surface area laterality-index showed a longitudinal decline in OS compared to controls. Male OS declined more than controls on surface area and thickness.

Conclusions

Left AAA surface area may progressively decline in young non-psychotic offspring at familial diathesis for schizophrenia causing a continuing reversal of the leftward AAA lateralization. Progressive surface area reduction and thinning of AAA may be more prominent in young non-psychotic male offspring at risk for schizophrenia.     

The prevalence of self-harm behaviors among a sample of gastric surgery candidates

Objective

The surgical treatment of obesity is becoming increasingly popular; yet, little is known about the self-harm characteristics and adjunctive self-regulation difficulties of those seeking such surgery. In the literature, one study has explored presurgery suicide attempts and several studies have explored the prevalence of postsurgical completed suicides. However, beyond suicide attempts and completions, little is known about the broader self-harm/self-regulation profiles of these patients. In this study, we examined the prevalence of 22 such behaviors among a sample of gastric surgery candidates.

Method

Using a cross-sectional approach, we examined 121 surgical candidates for 22 self-reported self-harm and self-regulatory behaviors.

Results

The studied behaviors with the highest prevalence rates in this cohort were sexual promiscuity (22.3%), torturing oneself with self-defeating thoughts (20.7%), alcohol abuse (19.0%), and engaging in emotionally abusive relationships (16.5%). With regard to suicide attempts, 9.1% of participants acknowledged a history and 9.1% reported past overdoses.

Conclusions

These data suggest that (a) adjunctive self-regulatory difficulties may affect a substantial minority of individuals who are seeking gastric surgery for obesity (e.g., promiscuity and alcohol abuse), and (b) the anticipated prevalence rate for past suicide attempts in this population appears to be approximately 10%.     

Depression and cognitive deficits in geriatric schizophrenia

Objective

Past reports have found patients with comorbid depression and schizophrenia spectrum disorders exhibit greater deficits in memory and attention compared to schizophrenia spectrum disorder patients without depressive symptoms. However, in contrast to younger schizophrenia patients, the few past studies using cognitive screens to examine the relationship between depression and cognition in inpatient geriatric schizophrenia have found that depressive symptomatology was associated with relatively enhanced cognitive performance. In the current study we examined the relationship between depressive symptoms and cognitive deficits in geriatric schizophrenia spectrum disorder patients (n = 71; mean age = 63.7) on an acute psychiatric inpatient service.

Method

Patients completed a battery of cognitive tests assessing memory, attention and global cognition. Symptom severity was assessed via the PANSS and Calgary Depression Scale for Schizophrenia.

Results

Results revealed that geriatric patients' depression severity predicted enhancement of their attentional and verbal memory performance. Patients' global cognitive functioning and adaptive functioning were not associated with their depression severity.

Conclusion

Contrary to patterns typically seen in younger patients and non-patient groups, increasing depression severity is associated with enhancement of memory and attention in geriatric schizophrenia spectrum disorder patients. Also, diverging from younger samples, depression severity was unassociated with patients adaptive and global cognitive functioning.     

Winter birth excess in schizophrenia and in non-schizophrenic psychosis: sex and birth-cohort differences

Objective

Despite the fact that association between winter birth excess and schizophrenia in the northern Hemisphere is well established, possible sex or birth-cohort differences in this winter birth excess remain unclear. We aimed to evaluate sex and birth-cohort differences in the seasonal birth distribution of patients with schizophrenia or non-schizophrenic psychosis.

Method

The sample included 321 ICD-10 schizophrenia and 294 non-schizophrenic psychosis patients consecutively admitted into a psychiatric hospitalization unit in Granada, southern Spain, during a nine-year period (1998-2006). The distribution of births among the general population born over the same period as the patients was calculated.

Results

Among schizophrenia males (n = 258), it was possible to demonstrate that the observed proportion of winter birth (December, January or February) was significantly higher than expected. Among schizophrenia females (n = 63), although proportions were as in males and the effect size of the difference between observed and expected winter births was not lower than for men, only a statistical trend could be demonstrated. Among patients with non-schizophrenic psychosis, the observed proportion of winter birth was significantly higher than expected in women, but not in men. The sex-adjusted proportion of winter birth among schizophrenia patients born in the 1940's (a time period characterized by poor economy and widespread food restrictions because of the Spanish post-civil-war period) was significantly higher than among those born later; a difference that does not occur among patients with a non-schizophrenic psychosis.

Conclusions

Among schizophrenia patients born in winter there appear to be slight sex-differences and strong birth-cohort differences, possibly due to epidemiological factors such as poverty or maternal nutritional deprivation. Epidemiological findings related to winter birth excess among patients with schizophrenia must be identified in longitudinal studies.     

The base rates and factors associated with reported access to firearms in psychiatric inpatients

Objective

The aim of this study was to define whether specific patient demographic groups, diagnoses or other factors are associated with psychiatric inpatients reporting firearms access.

Methods

A retrospective medical records review study was conducted using information on access to firearms from electronic medical records for all patients 16 years and older admitted between July 2007 and May 2008 at the Mayo Clinic Psychiatric Hospital in Rochester, MN. Data were obtained only on patients providing authorization for record review. Data were analyzed using univariate and multivariate logistic regression analyses accounting for gender, diagnostic groups, comorbid substance use, history of suicide attempts and family history of suicide/suicide attempts.

Results

Seventy-four percent (1169/1580) of patients provided research authorization. The ratio of men to women was identical in both research and nonresearch authorization groups. There were 14.6% of inpatients who reported firearms access. In univariate analysis, men were more likely (P<.0001) to report access than women, and a history of previous suicide attempt(s) was associated with decreased access (P=.02). Multiple logistic regression analyses controlling for other factors found females and patients with history of previous suicide attempt(s) less likely to report access, while patients with a family history of suicide or suicide attempts reported increased firearms access. Diagnostic groups were not associated with access on univariate or multiple logistic regression analyses.

Conclusions

Men and inpatients with a family history of suicide/suicide attempts were more likely to report firearms access. Clinicians should develop standardized systems of identification of firearms access and provide guidance on removal.     

Alterations of the early auditory evoked gamma-band response in first-degree relatives of patients with schizophrenia: hints to a new intermediate phenotype

Background

There is growing evidence of abnormalities of high-frequency oscillations in the gamma-range of the electroencephalography in schizophrenia. The generation of neural activity in the gamma-band was shown to be critically related to a glutamatergic and GABAergic microcircuit which is also known to be involved in the pathophysiology of schizophrenia. Recently, a reduction of the early auditory evoked gamma-band response (eGBR) in schizophrenic patients was reported. In order to investigate the possible applicability of this neurophysiological marker as an intermediate phenotype for schizophrenia, this is the main question of our investigation: Is the early eGBR decreased regarding evoked power and phase locking in first-degree relatives of patients with schizophrenia?

Methods

We investigated the early eGBR in 17 unaffected first-degree relatives of patients with schizophrenia and in age-, gender- and education-matched groups of schizophrenic patients and healthy controls using an auditory reaction task.

Results

First-degree relatives of patients with schizophrenia and schizophrenic patients showed a significant reduction of evoked power and phase locking of the early eGBR compared to healthy controls.

Conclusion

This study shows significantly reduced evoked power and phase locking of the early auditory eGBR in first-degree relatives of patients with schizophrenia pointing to the applicability of this marker as a heritable intermediate phenotype for schizophrenia. The findings are in line with the hypothesis of a disturbed GABAergic interneural modulation of pyramidal cells in schizophrenia and findings of different schizophrenia risk genes associated with transmission at glutamatergic and GABAergic synapses.     

Differential brain activation during facial emotion discrimination in first-episode schizophrenia

Background

Aberrant brain activation during facial emotion discrimination has been described in chronic schizophrenia, while little is known about early stages of the illness. The aim of the current study was to investigate valence-specific brain activation of emotion discrimination in first-episode schizophrenia. These patients provide the advantage of lacking the effects of long-term medication and chronic illness course and can hence further enhance the understanding of underlying psychopathological mechanisms.

Methods

Using event-related fMRI, we investigated 18 first-episode schizophrenia patients and 18 matched healthy subjects during an explicit emotion discrimination task presenting happy, sad and neutral monochromatic facial expressions. A repeated measure analysis of variance (ANOVA) with the factors Group (patients, healthy subjects), Gender and Emotion (happy, sad, neutral) was performed on behavioural and functional data.

Results

Behavioural performance did not differ between groups. Valence-independent hypoactivations in patients were observed for the anterior cingulate and orbitofrontal cortex while hyperactivations emerged in the posterior cingulate and the precuneus. Emotion-specific group differences were revealed in inferior parietal and orbitofrontal brain areas and the hippocampus.

Conclusions

First-episode schizophrenia already affects areas involved in processing of both, emotions and primary facial information. Our study underlines the role of dysfunctional neural networks as the basis of disturbed social interactions in early schizophrenia.     

Early retirement from work among employees with a diagnosis of personality disorder compared to anxiety and depressive disorders

Objective

Risk of retirement from work before statutory retirement age among employees with personality disorders is unknown.

Method

We used diagnoses of awarded medical rehabilitations and hospitalisations to select two clinical cohorts from a population of 151,618 employees: participants in rehabilitation (total N = 1942, 233 personality disorder, 419 anxiety disorder and 1290 depression cases) and hospitalised patients (N = 1333, 354, 126 and 853, respectively). Early retirement from work was tracked through national registers during a period of 5 years. Cox proportional hazard models were used to examine the association of diagnostic groups with risk of early retirement.

Results

In models adjusted for age, sex and socioeconomic position, the relative risk of early retirement for patients with personality disorders was 3.5-fold (95% CI 2.1 to 5.8) in the rehabilitation cohort and 2.3-fold (95% CI 1.6 to 3.5) in the hospital cohort compared with anxiety disorders. The corresponding hazard ratios of early retirement for personality disorders compared with depressive disorders were 1.1 (95% CI 0.8-1.5) and 1.7 (95% CI 1.4-2.1), respectively.

Conclusions

Personality disorders increase the risk of early retirement at least to an equal extent as depression and more than twice that of anxiety disorders.     

L’enfance des schizophrènes : revue de la littérature

Introduction

Pre-morbid antecedents in schizophrenia have been studied for some time now more particularly as potential markers of vulnerability. What are the tell-tale signs in some of the patient's childhood? The authors suggest a non-exhaustive review of the literature on this subject.

Method

The authors reviewed the literature (English and French) of prospective and retrospective studies.

Results

Many fields appear to be impaired during the childhood of some schizophrenic patients, fields such as: developmental abnormalities, speech impairments, social interactions, behaviour, cognitive functioning. The authors also noticed the presence of neurological soft signs and para-clinical abnormalities.

Discussion

The authors suggest a critical and synthetic review of existing data: what can be retained of this data? The authors also discuss the evolution of these signs and their interaction with the evolution of the disease itself.

Conclusion

Many of these signs were noticed in several children who later developed schizophrenia. For many authors, the more important these signs are, the more severe the disease will be. These pre-morbid antecedents give rise to theoretical questions and open perspectives concerning an early diagnosis of schizophrenia.     

Autonomic modulation in healthy first-degree relatives of patients with major depressive disorder

Background

Cardiac mortality is known to be increased in patients with major depression. Several studies have reported an imbalance within the autonomic nervous system (ANS) of patients with major depressive disorder (MDD) as one putative cause. Since a heritability of autonomic modulation was demonstrated in healthy subjects, we aimed to investigate autonomic modulation in first-degree relatives of patients with MDD to find potential autonomic imbalances.

Methods

We included 30 patients with MDD, 30 of their first-degree relatives (siblings or offspring) and 30 matched healthy controls in our study. We obtained a high resolution electrocardiogram and beat to beat blood pressure measurements for 30 min at rest. Linear and nonlinear parameters of heart rate variability (HRV) and baroreflex sensitivity (BRS) were calculated.

Results

Parameters of HRV and BRS did not differ significantly between relatives and controls. We found significant differences between patients and controls for some HRV and BRS parameters confirming results of previous studies.

Discussion

Findings of our study suggest that an imbalance of autonomic function is related to patients with depression and not to first-degree relatives. Thus, a genetic background for autonomic dysfunction is rather unlikely.     

Depressive symptoms predict long-term mortality after liver transplantation

Objective

Depressive symptoms are common after liver transplantation (LT). We studied whether depressive symptoms affect long-term survival after LT.

Methods

In a prospective cohort study, 134 liver transplant patients were assessed for depressive symptoms using the Beck Depression Inventory—short form (BDI), focusing on the 3 months post-LT score and on the score change from the waiting list period. They were followed up for long-term survival. The median duration of the follow-up period was 43 months post-LT. None of the 134 patients was lost to follow-up for survival.

Results

A total of 33.6% of the LT patients had mild to moderate depressive symptoms 3 months post-LT. Eighteen (13.4%) patients died during the follow-up. Using Cox proportional hazards analysis, depressive symptoms were significantly associated with mortality (hazard ratio [HR] 1.22, 95% confidence interval (CI) 1.07-1.40, P<.003), one more point in the BDI score being associated with a 17% increase in mortality risk. Other predictive factors of mortality were older age and hepatitis C virus with recurrence 3 months post-LT. Similarly, an increase in depressive symptoms between the waiting list and 3 months post-LT periods predicted mortality (HR 1.18, 95% CI 1.01-1.38, P=.03), especially for patients without depressive symptoms on waiting list (HR 1.56, 95% CI 1.16-2.12, P=.004).

Conclusion

Depressive symptoms after LT and an increase in depressive symptoms between the waiting list and post-LT are associated with an increased risk of long-term mortality. Interventions that could reduce depressive symptoms could potentially decrease long-term mortality after LT.     

Factors associated with referral to mental health services among suicide attempters visiting emergency centers of general hospitals in Korea: does history of suicide attempts predict referral?

Objective

This study examined whether a history of past suicide attempts was a critical factor for referral to mental health services among suicide attempters visiting emergency centers of general hospitals in Korea.

Method

In this cross-sectional study, a resident of emergency medicine at each emergency center interviewed 310 suicide attempters visiting five tertiary general hospitals located in Seoul, using standardized questionnaires, during 7 months in 2007. We examined associations between suicide attempt history and referral to mental health services via multiple logistic regressions.

Results

Subjects' rate of referral to mental health services was 47.3%. When we controlled for participant age, time of arrival at the emergency center, psychiatric treatment history, use of alcohol, suicide attempt lethality and subjective expectation to suicide attempts, past suicide attempts did not predict referral to mental health services (odds ratio=1.74; 95% confidence interval .88-3.43).

Conclusion

Psychiatric interventions for suicide reattempters visiting emergency centers are important for preventing suicide, but providers have not considered suicide attempt history as a critical factor for referral to mental health services. Therefore, we suggest that more effort is needed to systemize psychiatric interventions for suicide reattempters at emergency centers in Korea.