Abnormal prediction error is associated with negative and depressive symptoms in schizophrenia

Prediction error in learning is where learning occurs to the degree to which an outcome consequent to a stimulus is surprising. It has been suggested that abnormal use of prediction error in schizophrenia may underlie the formation of inappropriate associations giving rise to psychotic symptoms. Kamin blocking is a phenomenon that demonstrates prediction error. Kamin blocking is shown where prior learning about a stimulus A paired with an outcome retards learning about a stimulus B when presented subsequently as part of a stimulus compound AB paired with the same outcome. Prior studies have indicated reduced Kamin blocking in schizophrenia specifically in non-paranoid patients. It is however unclear how reduced Kamin blocking is associated with specific symptoms in schizophrenia. The present study examined Kamin blocking performance in a high functioning community-based sample of 34 people with schizophrenia and 48 controls closely matched for pre-morbid IQ. In these patients we measured Kamin blocking and symptoms using positive and negative symptom scales (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) and Scale for the Assessment of Positive Symptoms (SAPS). Results confirmed that people with schizophrenia had significantly reduced Kamin blocking. Kamin blocking performance was associated with negative and depressive symptoms. These associations with symptoms were crucially not found with baseline associative learning or unblocking measures, confirming specificity to the Kamin blocking effect. These data demonstrate first that abnormal prediction error as assessed in the Kamin blocking task is associated with negative and depressive symptoms rather than positive symptoms in high functioning schizophrenia patients. Second this strongly suggests that reduced Kamin blocking may be useful as an animal model of specific relevance to negative and depressive symptoms in schizophrenia.     

Oxidative-antioxidative systems and their relation with serum S100 B levels in patients with schizophrenia: effects of short term antipsychotic treatment

Oxidative stress may be a contributing factor in the etiopathophysiology of schizophrenia, which may be exacerbated by the treatment with antipsychotics with pro-oxidant properties. Increased levels of S100 B are associated with neurodegenerative disorders, including schizophrenia. The aim of the present study was to investigate the role of oxidative cell damage in the pathogenesis of schizophrenia. Forty patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia and 35 healthy control subjects were included in the study. Serum S100 B level was determined to investigate brain damage. Plasma malondialdehyde (MDA) levels and susceptibility of red blood cell (RBC) to oxidation were determined to investigate the oxidative status and plasma vitamin E, vitamin C, serum total carotenoid levels and total antioxidant capacity and RBC superoxide dismutase (SOD) and whole blood glutathione peroxidase activities were measured to investigate the antioxidative defence before and after 6 weeks of antipsychotic treatment. Plasma MDA and serum S100 B levels and RBC-SOD activity were significantly higher in the schizophrenia group than those of the control group. Treatment did not modify any of the oxidative-antioxidative system parameters or serum S100 B levels. S100 B level was significantly higher in patients with negative symptoms than the patients with positive symptoms and the control subjects. S100 B levels were significantly reduced after 6 weeks of treatment in patients with negative symptoms. The results of the present study might support the oxidative cell injury hypothesis of the schizophrenia. Furthermore, the underlying mechanisms of the subgroups of schizophrenia might be different as suggested by the increased S100 B levels and its decrement after treatment in patients with negative symptoms.     

Mirtazapine augmentation enhances cognitive and reduces negative symptoms in schizophrenia patients treated with risperidone: a randomized controlled trial

This preliminary study aimed to determine if adding mirtazapine to risperidone might improve negative and cognitive symptoms in schizophrenia. In an 8-week, double-blind clinical trial, we randomly assigned 21 stabilized outpatients with schizophrenia undergoing risperidone treatment to adjunctive treatment with either mirtazapine or a placebo. The mirtazapine group exhibited a statistically significant improvement in cognitive function, including vocabulary and immediate memory, and negative symptoms (as measured by negative symptom scales) and showed an adverse effect of 5.83 kg mean weight gain. This study suggests augmenting risperidone with mirtazapine can effectively improve both negative and some cognitive symptoms of schizophrenia.

Research highlights

? Mirtazapine enhances some cognitive symptoms of schizophrenia. ? Mirtazapine reduces negative symptoms of schizophrenia.     

Longitudinal volume changes of the pituitary gland in patients with schizotypal disorder and first-episode schizophrenia

An enlarged volume of the pituitary gland has been reported in the schizophrenia spectrum, possibly reflecting the hypothalamic-pituitary-adrenal (HPA) hyperactivity. However, it remains largely unknown whether the pituitary size longitudinally changes in the course of the spectrum disorders. In the present study, longitudinal magnetic resonance imaging (MRI) data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The pituitary volume was measured at baseline and follow-up (mean, 2.7 years) scans and was compared across groups. The pituitary volume was larger in the schizophrenia patients than controls at baseline, and both patient groups had significantly larger pituitary volume than controls at follow-up. In a longitudinal comparison, both schizophrenia (3.6%/year) and schizotypal (2.7%/year) patients showed significant pituitary enlargement compared with controls (− 1.8%/year). In the schizophrenia patients, greater pituitary enlargement over time was associated with less improvement of delusions and higher scores for thought disorders at the follow-up. These findings suggest that the pituitary gland exhibits ongoing volume changes during the early course of the schizophrenia spectrum as a possible marker of state-related impairments.     

A follow-up MRI study of the fusiform gyrus and middle and inferior temporal gyri in schizophrenia spectrum

While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the superior temporal gyrus (STG) during the early phases of schizophrenia, it remains largely unknown whether other temporal lobe structures also exhibit similar progressive changes and whether these changes, if present, are specific to schizophrenia among the spectrum disorders. In this longitudinal MRI study, the gray matter volumes of the fusiform, middle temporal, and inferior temporal gyri were measured at baseline and follow-up scans (mean inter-scan interval = 2.7 years) in 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. Both schizophrenia and schizotypal patients had a smaller fusiform gyrus than controls bilaterally at both time points, whereas no group difference was found in the middle and inferior temporal gyri. In the longitudinal comparison, the schizophrenia patients showed significant fusiform gyrus reduction (left, − 2.6%/year; right, − 2.3%/year) compared with schizotypal patients (left: − 0.4%/year; right: − 0.2%/year) and controls (left: 0.1%/year; right: 0.0%/year). However, the middle and inferior temporal gyri did not exhibit significant progressive gray matter change in all diagnostic groups. In the schizophrenia patients, a higher cumulative dose of antipsychotics during follow-up was significantly correlated with less severe gray matter reduction in the left fusiform gyrus. The annual gray matter loss of the fusiform gyrus did not correlate with that of the STG previously reported in the same subjects. Our findings suggest regional specificity of the progressive gray matter reduction in the temporal lobe structures, which might be specific to overt schizophrenia within the schizophrenia spectrum.     

The association of genotypic combination of the DRD3 and BDNF polymorphisms on the adhesio interthalamica and medial temporal lobe structures

Abnormal neurodevelopment in midline structures such as the adhesio interthalamica (AI), as well as in the medial temporal lobe structures has been implicated in schizophrenia, while its genetic mechanism is unknown. This magnetic resonance imaging study investigated the effect of the genotypic combination of the dopamine D3 receptor (DRD3) Ser9Gly and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms on the AI length and volumetric measures of the medial temporal lobe structures (amygdala, hippocampus, and parahippocampal gyrus) in 33 schizophrenia patients and 29 healthy controls. The subjects with a combination of the Ser/Ser genotype of DRD3 and Met-containing genotypes of BDNF (high-risk combination) had a shorter AI than those without it in the healthy controls, but not in the schizophrenia patients. The subjects carrying the high-risk combination had a smaller posterior hippocampus than those without it for both diagnostic groups. These genotypic combination effects on brain morphology were not explained by the independent effect of each polymorphism. These findings suggest the effect of gene-gene interaction between the DRD3 and BDNF variations on brain morphology in midline and medial temporal lobe structures, but do not support its specific role in the pathogenesis of schizophrenia.     

Relapse and therapeutic interventions in a 1-year observational cohort study of nonadherent outpatients with schizophrenia

Objectives

To evaluate the incidence rate of relapse, the clinical profiles, and the therapeutic interventions employed for patients with schizophrenia deemed as likely nonadherers to oral antipsychotic drugs.

Methods

A cohort of 597 outpatients whose therapy was modified because of a psychiatrist-perceived risk of nonadherence was followed for 12 months in an observational study. Baseline correlates of subsequent relapse were analyzed with Cox regression.

Results

At baseline, patients' mean (SD) age and time since diagnosis were 40.1 (11.1) and 15.2 (10.0) years, respectively; 63.7% were males. The Clinical Global Impression scale-Severity (CGI-S) score was ≥ 4 in 87.3% of the patients. Antipsychotic drugs were modified in 506 patients (84.8%); nonpharmacologic therapies were modified in 190 patients (31.8%). In both cases, the primary reason for the modifications was insufficient efficacy of current therapeutic regimen. The proportion of patients in oral antipsychotic monopharmacy decreased from 83.8% to 57.6%; 15.4% started long-acting (depot) formulations. Over the 12-month observation period, 90 patients (15.1%) relapsed. The hazard rate of relapse was higher in patients with substance use disorder or familial psychiatric antecedents and lower in patients who underwent modifications of nonpharmacological therapies or with negative attitude toward antipsychotic medication at baseline.

Conclusions

Effective interventions to prevent relapse in patients with long-standing schizophrenia involving therapeutic challenges related to nonadherence are feasible. Rationale for the baseline correlates, and cues for clinical prevention of relapse in these patients are provided.     

The relationship between symptom severity and regional cortical and grey matter volumes in schizophrenia

Objective

To investigate the relationship between symptom severity and cortical and grey matter volumes in schizophrenia.

Method

Fifty-three outpatients with schizophrenia were assessed by the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. Symptoms were grouped into five factors (negative, relational, inattention, disorganization, and reality distortion). Cortical and lobar grey matter volumes within all regions of the brain were obtained from magnetic resonance images using two independent software tools. The relationships between brain volumes and symptom factors were analyzed by partial correlations controlling for age, gender, dose and type of antipsychotic medication, and intracranial volume.

Results

Negative symptoms were generally associated with larger cortical volumes in all regions of the brain, and the relational and inattention factors were associated with larger frontal grey matter volumes. The reality distortion factor was associated with smaller cortical volumes throughout the brain and with smaller frontal and temporal grey matter volumes.

Conclusion

Differential contribution of positive and negative symptoms to variation in cortical and grey matter volumes indicates separate neurobiological mechanisms underlying the two major symptom domains in schizophrenia.     

Acute and chronic effects of electroconvulsive treatment on oxidative parameters in schizophrenia patients

Electroconvulsive therapy (ECT) is an effective treatment alternative for schizophrenia. Previous studies have already indicated the possible effects of oxidative stress in this disorder. However, there have been no previous studies evaluating the effects of ECT on the oxidative stress in these patients. We therefore aimed to investigate the acute and chronic effects of ECT on serum levels of oxidant and antioxidant molecules in schizophrenia patients (n = 28). The serum MDA and CAT levels of the patients with schizophrenia were higher than that of the controls before ECT (n = 20) but there was no significant difference in the serum NO and GSH levels of the patient groups compared to the controls. We found that the NO levels of the patients were higher than the controls in the group experiencing their first episode but not in the chronic group. There was a significant clinical improvement in the patients in terms of BPRS, SANS and SAPS reduction after the 9th ECT, but not the 1st ECT. Serum MDA levels were significantly reduced compared to the baseline after the 9th ECT session although there was no significant difference after the 1st session. Separate evaluation of the patient groups revealed that the significant MDA decrease following ECT was in the patients experiencing their first episode and not in the chronic group. No significant difference was noted in the serum levels of other oxidant and antioxidant molecules after either the 1st or 9th ECT session. These results suggest that ECT does not produce any negative effect on oxidative stress in patients with schizophrenia.     

Adhesio interthalamica alterations in schizophrenia spectrum disorders: A systematic review and meta-analysis

Magnetic resonance imaging (MRI) studies have reported a variety of brain abnormalities in association with schizophrenia. These include a higher prevalence of an absent adhesio interthalamica (AI; also known massa intermedia), a gray matter junction that is present between the two thalami in approximately 80% of healthy subjects. In this meta-analytic review, we describe and discuss the main AI MRI findings in schizophrenia spectrum disorders (SSDs) to date. The MEDLINE and ISI Web of Knowledge^SM databases were searched up to December 2010, for studies that used MRI to assess AI in patients with SSD and controls. From fourteen potential reports, eleven were eligible to be part of the current review. These studies included 822 patients with SSD and 718 healthy volunteers. There was a large degree of variability in the MRI methods they employed. Patients with SSD had a higher prevalence of absent AI than healthy volunteers (odds ratio = 1.98; 95% confidence interval 1.33-2.94; p = 0.0008). This association was evident in both male and female SSD subjects, and there was no evidence that the prevalence was related to age or duration of illness. The significance of the absence of an AI for SSD may be clarified by studies in large, longitudinal community-based samples using standardized methods.     

Disrupted regional homogeneity in treatment-resistant depression: a resting-state fMRI study

Background

Using a newly developed regional homogeneity (ReHo) approach, we were to explore the features of brain activity in patients with treatment-resistant depression (TRD) in resting state, and further to examine the relationship between abnormal brain activity in TRD patients and specific symptom factors derived from ratings on the Hamilton Rating Scale for Depression (HRSD).

Methods

24 patients with TRD and 19 gender-, age-, and education-matched healthy subjects participated in the fMRI scans.

Results

1.

Compared with healthy controls, decreased ReHo were found in TRD patients in the left insula, superior temporal gyrus, inferior frontal gyrus, lingual gyrus and cerebellum anterior lobe (culmen) (p < 0.05, corrected).

2.

Compared with healthy controls, increased ReHo were found in the left superior temporal gyrus, cerebellum posterior lobe (tuber), cerebellum anterior lobe (culmen), the right cerebellar tonsil and bilateral fusiform gyrus (p < 0.05, corrected).

3.

There was no correlation between the ReHo values in any brain region detected in our study and the patients' age, years of education, illness duration, HRSD total score and its symptom factors.

Limitation

The influence of antidepressants to the brain activity in TRD patients was not fully eliminated.

Conclusions

The pathogenesis of TRD may be attributed to abnormal neural activity in multiple brain regions.     

Cavum septum pellucidum in subjects at ultra-high risk for psychosis: compared with first-degree relatives of patients with schizophrenia and healthy volunteers

OBJECTIVE: The cavum septum pellucidum (CSP) is a space between the two leaflets of the septum pellucidum, and is a putative marker of disturbance in early brain development. We examined whether CSP was present more frequently in subjects at ultra-high risk (UHR) for psychosis compared to first-degree relatives of patients with schizophrenia (genetic high risk, GHR) and healthy controls (HC). METHODS: We evaluated CSP in 87 subjects (30 UHR, 23 GHR, and 34 HC) according to a published grading system using high-resolution magnetic resonance imaging (MRI) with 0.45-mm slice thickness. We also assessed two other criteria: presence of CSP on at least one MRI slice, and abnormally large CSP (i.e., > or =6 mm in length). Correlational analysis between CSP measures and clinical symptoms was also examined. RESULTS: Based on the grading scale, the UHR group exhibited a significantly higher incidence of abnormal CSP (grades 2, 3, and 4) compared to the HC group, but there were no significant differences in the incidence of abnormal CSP between the UHR and GHR or the GHR and HC groups. There were no significant differences among the groups in the presence of CSP on at least one MRI slice or abnormally large CSP based on the length of CSP. In addition, no significant correlations between CSP measures and clinical symptoms were found. CONCLUSION: These findings suggest that abnormal CSP might be associated with susceptibility to psychosis, although the CSP itself might be a normal anatomical variant. Further studies using a larger sample are needed to clarify issues on neurodevelopmental perspective in subjects at high risk for psychosis.     

Facial emotion perception in Chinese patients with schizophrenia and non-psychotic first-degree relatives

Although there is a consensus that patients with schizophrenia have certain deficits in perceiving and expressing facial emotions, previous studies of facial emotion perception in schizophrenia do not present consistent results. The objective of this study was to explore facial emotion perception deficits in Chinese patients with schizophrenia and their non-psychotic first-degree relatives. Sixty-nine patients with schizophrenia, 56 of their first-degree relatives (33 parents and 23 siblings), and 92 healthy controls (67 younger healthy controls matched to the patients and siblings, and 25 older healthy controls matched to the parents) completed a set of facial emotion perception tasks, including facial emotion discrimination, identification, intensity, valence, and corresponding face identification tasks. The results demonstrated that patients with schizophrenia performed significantly worse than their siblings and younger healthy controls in accuracy in a variety of facial emotion perception tasks, whereas the siblings of the patients performed as well as the corresponding younger healthy controls in all of the facial emotion perception tasks. Patients with schizophrenia also showed significantly reduced speed than younger healthy controls, while siblings of patients did not demonstrate significant differences with both patients and younger healthy controls in speed. Meanwhile, we also found that parents of the schizophrenia patients performed significantly worse than the corresponding older healthy controls in accuracy in terms of facial emotion identification, valence, and the composite index of the facial discrimination, identification, intensity and valence tasks. Moreover, no significant differences were found between the parents of patients and older healthy controls in speed after controlling the years of education and IQ. Taken together, the results suggest that facial emotion perception deficits may serve as potential endophenotypes for schizophrenia.     

Alterations of the amplitude of low-frequency fluctuations in treatment-resistant and treatment-response depression: A resting-state fMRI study

Background

Patients with treatment-resistant depression (TRD) and those with treatment-response depression (TSD) respond to antidepressants differently and previous studies have commonly reported different brain networks in resistant and nonresistant patients. Using the amplitude of low-frequency fluctuations (ALFF) approach, we explored ALFF values of the brain regions in TRD and TSD patients at resting state to test the hypothesis of the different brain networks in TRD and TSD patients.

Methods

Eighteen TRD patients, 17 TSD patients and 17 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans.

Results

There are widespread differences in ALFF values among TRD patients, TSD patients and healthy subjects throughout the cerebellum, the visual recognition circuit (middle temporal gyrus, middle/inferior occipital gyrus and fusiform), the hate circuit (putamen), the default circuit (ACC and medial frontal gyrus) and the risk/action circuit (inferior frontal gyrus). The differences in brain circuits between the TRD and TSD patients are mainly in the cerebellum, the visual recognition circuit and the default circuit.

Conclusions

The affected brain circuits of TRD patients might be partly different from those of TSD patients.     

Improvements in both psychosis and motor signs in Parkinson's disease, and changes in regional cerebral blood flow after electroconvulsive therapy

Purpose

Psychotic symptoms in Parkinson's disease (PD) are relatively common and, in addition to creating a disturbance in patients' daily lives, have consistently been shown to be associated with poor outcome. The use of anti-PD medications has been the most widely identified risk factor for PD psychosis (PDP). However, the pathophysiology of PDP remains unclear. Although the efficacy of electroconvulsive therapy (ECT) for PD had been pointed out, only one study has demonstrated the effectiveness of ECT on both psychotic symptoms and motor symptoms. The aim of this study was to examine the acute effectiveness of ECT on PD and to identify the brain areas associated with PDP.

Methods

The study was conducted at Juntendo University Hospital in Tokyo. Eight patients with L-DOPA- or dopamine (DA) agonist-induced PDP, who were resistant to quetiapine treatment, were enrolled. Severity of PD was evaluated using the Hoehn and Yahr stage. Psychotic symptoms were evaluated using multiple measures from the Scale for the Assessment of Positive Symptoms (SAPS). Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (99mTc ECD SPECT) was used to assess regional cerebral blood flow (rCBF) before and after a course of ECT. A voxel-by-voxel group analysis was performed using Statistical Parametric Mapping (SPM5).

Results

Our study clearly demonstrated that PDP was significantly less severe after ECT than before ECT, as indicated by change in mean SAPS total domain score (t = 7.2, P = 0.0002). Furthermore, the patients showed significant improvement in Hoehn and Yahr stage after ECT (t = 11.7, P < 0.0001). A further notable observation was significant increase in rCBF in the right middle frontal gyrus after ECT.

Conclusion

We conclude that a course of ECT produced notable improvements not only in PDP but also in the severity of PD. The findings of change in rCBF suggest implications for dysfunction in the middle frontal region for patients with PDP.     

Association of MB-COMT polymorphisms with schizophrenia-susceptibility and symptom severity in an African cohort

The catechol-O-methyltransferase (COMT) gene is an attractive schizophrenia candidate gene, encoding a catabolic dopamine enzyme. The enzyme exists as two distinct isoforms, with the membrane bound enzyme (i.e. MB-COMT) being predominantly expressed in the brain. Since African populations remain underrepresented in genetic/genomic research, we performed an association study to determine whether MB-COMT genetic variants are associated with schizophrenia-susceptibility and symptom severity in the South African Xhosa population. Fourteen candidate polymorphisms were selected by means of a literature search and in silico analyses and were subsequently genotyped in a cohort of 238 Xhosa schizophrenia patients and 240 healthy Xhosa controls. Genetic association was tested with schizophrenia-susceptibility as well as symptom severity within the patient group. Polymorphisms of interest were also analysed using functional assays. Two SNPs, rs2020917 (OR=0.54, 95% CI 0.37-0.79; P=0.0011) and rs737865 (OR=0.52, 95% CI 0.36-0.74; P=0.0002), in the P2 promoter region were significantly associated with schizophrenia as well as an increase (increase=11.2%, 95% CI 3.7%-19.2%; P=0.0031) in reporter gene expression. The minor alleles of these SNPs were underrepresented in the schizophrenia cohort, indicating a possible protective effect. The P2 region also formed part of a haplotype found to be associated with the severity of the negative symptoms of the disorder. The data generated by this study indicate that genetic variation of MB-COMT could be associated with schizophrenia and negative symptom severity in the Xhosa population and may therefore be one of the genomic loci contributing towards the disorder in the South African community. Future large-scale studies in other African schizophrenia populations are required to further elucidate the significance of these findings.     

The kynurenine pathway in adolescent depression: Preliminary findings from a proton MR spectroscopy study

Background

Cytokine induction of the enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in the development of major depressive disorder (MDD). IDO metabolizes tryptophan (TRP) into kynurenine (KYN), thereby decreasing TRP availability to the brain. KYN is further metabolized into several neurotoxins. The aims of this pilot were to examine possible relationships between plasma TRP, KYN, and 3-hydroxyanthranilic acid (3-HAA, neurotoxic metabolite) and striatal total choline (tCho, cell membrane turnover biomarker) in adolescents with MDD. We hypothesized that MDD adolescents would exhibit: i) positive correlations between KYN and 3-HAA and striatal tCho and a negative correlation between TRP and striatal tCho; and, ii) the anticipated correlations would be more pronounced in the melancholic subtype group.

Methods

Fourteen adolescents with MDD (seven with melancholic features) and six healthy controls were enrolled. Minimums of 6 weeks MDD duration and a severity score of 40 on the Children's Depression Rating Scale-Revised were required. All were scanned at 3 T with MRI, multi-voxel 3-dimensional, high, 0.75 cm³, spatial resolution proton magnetic resonance spectroscopic imaging. Striatal tCho concentrations were assessed using phantom replacement. Spearman correlation coefficients were Bonferroni-corrected.

Results

Positive correlations were found only in the melancholic group, between KYN and 3-HAA and tCho in the right caudate (r = 0.93, p = 0.03) and the left putamen (r = 0.96, p = .006), respectively.

Conclusions

These preliminary findings suggest a possible role of the KYN pathway in adolescent melancholic MDD. Larger studies should follow.     

Association between the MnSOD Ala-9Val polymorphism and development of schizophrenia and abnormal involuntary movements in the Xhosa population

Reactive oxygen species (ROS)-mediated damage has been hypothesized to play a role in the development and poor outcome of schizophrenia, as well as the development of neuroleptic-induced abnormal involuntary movements. Recently, the functional polymorphism (Ala-9Val) in the manganese superoxide dismutase (MnSOD) gene (part of the antioxidant defense mechanism) was found to be associated with schizophrenia in a Turkish population. This study was aimed at replicating this finding in a Xhosa population. In addition, the role of Ala-9Val in abnormal involuntary movement and tardive dyskinesia development in the Xhosa population was also investigated. The schizophrenic patient group (n=286) and a healthy control group (n=243) were genotyped for the Ala-9Val polymorphism using heteroduplex-single stranded conformational polymorphism (HEX-SSCP) analysis. No significant difference in genotype or allele frequency could be observed between the schizophrenia and control group (P=0.294 and P=0.528 respectively). In addition no association could be found between the polymorphism and symptom severity (SANS and SAPS). The Xhosa schizophrenia patient group with abnormal involuntary movements (n=54) and a subgroup with tardive dyskinesia (n=30) was found to significantly differ in Ala-9Val genotype frequency (P=0.008 and P=0.011 respectively) compared to the Xhosa schizophrenia patient group without abnormal involuntary movements (n=204). However, no significant difference was found for the allele frequencies (P=0.955 and P=0.161). Further, using ANCOVA no association was found between AIMS score and genotype in the group with abnormal involuntary movements (P=0.1234). However, in the patient group with tardive dyskinesia an association was observed between genotype and AIMS score (P=0.0365). These results do not support a major role of the MnSOD Ala-9Val polymorphism in the development of schizophrenia or symptom severity in the Xhosa population. Yet it seems to be involved in the development of abnormal involuntary movements and tardive dyskinesia and may even modulate the severity of tardive dyskinesia.     

Social jetlag and sleep deprivation are associated with altered activity in the reward-related brain areas: an exploratory resting-state fMRI study

ObjectiveThe aim of this research was to assess the effect of social jetlag (SJL) and its interaction with partial sleep deprivation on resting-state brain activity using the fractional amplitude of low-frequency fluctuation (fALFF) during free-living conditions.MethodsA total of 28 normal weight healthy subjects were enrolled in four study groups (with SJL [with sleep deprivation and without sleep deprivation] and without SJL [with sleep deprivation and without sleep deprivation]), matched 1:1:1:1 for age, gender, and body mass index (BMI). Resting-state functional magnetic resonance imaging (fMRI) scans were collected with SIEMENS 3T scanner while subjects were in a fasting state.ResultsParticipants with SJL had significantly higher fALFF values in right lingual gyrus and right putamen and significantly lower fALFF values in left and right inferior parietal lobe in comparison with participants without SJL and without sleep deprivation. Subjects with sleep deprivation had significantly higher fALFF in the thalamus and left superior frontal gyrus. In those with both SJL and sleep deprivation, we observed higher fALFF values in right Brodmann Area (BA)18 and lower values in left and right parietal inferior lobe. Subjects with SJL alone had significantly lower fALFF values in left frontal mid gyrus (BA6) than those with sleep deprivation alone.ConclusionsSJL was associated with altered resting-state brain activity in regions that have been shown to be involved in hedonic feeding. The effect of SJL was independent of effects induced by short sleep duration. These alterations might represent the substrate for the increased risk of obesity observed in those with SJL.