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.     

Gender-specific associations of depression with positive and negative symptoms in acute schizophrenia

This clinical study analyzed gender-specific relationships of depression with other psychopathological and clinical variables in hospitalized patients with schizophrenia. During clinical routine treatment 119 inpatients with acute schizophrenia (DSM-IV) were investigated with the Calgary Depression Rating Scale for Schizophrenia (CDSS), the Clinical Global Impressions (CGI), and the Positive and Negative Syndrome Scale (PANSS). Depression scores of 77 male and 42 female patients (mean age 31.6+/-10.3 years) were related to background variables and to positive and negative symptom scores. Mean CDSS (5.8+/-5.6) and PANSS scores (total 76.9+/-22.1, positive symptoms 17.6+/-7.6, negative symptoms 20.5+/-7.8) were not significantly different between males and females. In females, depression was independently associated with higher negative symptom scores (P<0.01) and younger age (P<0.05) whereas in males positive symptoms (P<0.05) and short hospitalization (P<0.05) were the main factors associated with depression. The study revealed gender-specific differences in the relationship of depression with negative and positive symptoms.     

Left orbitofrontal and superior temporal gyrus structural changes associated to suicidal behavior in patients with schizophrenia

Suicidal attempts are relatively frequent and clinically relevant in patients with schizophrenia. Recent studies have found gray matter differences in suicidal and non-suicidal depressive patients. However, no previous neuroimaging study has investigated possible structural abnormalities associated to suicidal behaviors in patients with schizophrenia. A whole-brain magnetic resonance voxel-based morphometric examination was performed on 37 male patients meeting the DSM-IV criteria for schizophrenia. Thirteen (35.14%) patients had attempted suicide. A non-parametric permutation test was computed to perform the comparability between groups. An analysis of covariance (AnCova) model was constructed with a statistical threshold of p<0.05 corrected for multiple comparisons. After controlling for age and severity of illness, results showed significant gray matter density reduction in left superior temporal lobe (p=0.03) and left orbitofrontal cortex (p=0.04) in patients who had attempted suicide when comparing with non-suicidal patients. Although sample size limitations and potential clinical heterogeneity preclude definitive conclusions, these data point to structural differences in key cerebral areas. Neuroimaging studies are necessary to expand our knowledge of biological mechanisms underlying suicide in schizophrenia.     

Schizophrenia with auditory hallucinations: a voxel-based morphometry study

Many studies have shown widespread but subtle pathological changes in gray matter in patients with schizophrenia. Some of these studies have related specific alterations to the genesis of auditory hallucinations, particularly in the left superior temporal gyrus, but none has analysed the relationship between morphometric data and a specific scale for auditory hallucinations. The present study aims to define the presence and characteristics of structural abnormalities in relation with the intensity and phenomenology of auditory hallucinations by means of magnetic resonance voxel-based morphometry (MR-VBM) method applied on a highly homogeneous group of 18 persistent hallucinatory patients meeting DSM-IV criteria for schizophrenia compared to 19 healthy matched controls. Patients were evaluated using the PSYRATS scale for auditory hallucinations. Reductions of gray matter concentration in patients to controls were observed in bilateral insula, bilateral superior temporal gyri and left amygdala. In addition, specific relationships between left inferior frontal and right postcentral gyri reductions and the severity of auditory hallucinations were observed. All these areas might be implicated in the genesis and/or persistence of auditory hallucinations through specific mechanisms. Precise morphological abnormalities may help to define reliable MR-VBM biomarkers for the genesis and persistence of auditory hallucinations.     

Auditory and visual P300 reflecting cognitive improvement in patients with schizophrenia with quetiapine: A pilot study

We recorded event-related potentials (ERPs) in patients with schizophrenia before and after treatment with quetiapine, to investigate this drug's effects on cognitive function. Auditory and visual oddball stimulus discrimination paradigms were presented to patients with schizophrenia (N = 20) before and after 3 months' treatment with quetiapine. The 2-stimulus auditory oddball paradigm used a standard tone (1000 Hz, 75 dB, 80%) and a target tone (2000 Hz, 75 dB, 20%). The 2-stimulus visual oddball paradigm used a standard stimulus (small circle, 80%) and a target stimulus (large circle, 20%). Patients' severity of psychopathology was initially evaluated with the Positive and Negative Syndrome Scale (PANSS) and was likewise re-evaluated after treatment. After treatment with quetiapine, patients' P300 amplitudes increased over baseline for both tasks (auditory stimuli, P < 0.01; visual stimuli, P < 0.01) and their P300 latencies for both target stimuli decreased significantly (auditory stimuli, P < 0.001; visual stimuli, P < 0.01). Visual P300 amplitude was negatively correlated with the severity of positive symptoms at the Fz electrode before the treatment (r = − 0.45, P < 0.05). After treatment with quetiapine, there were no significant correlations between severity of positive or negative symptoms and visual P300 amplitudes for midline electrodes. These findings suggest that the reduced and delayed P300 may be a state marker for schizophrenia, which may in turn be modulated by positive symptoms, and also suggest that the amplitude and latency for both auditory and visual tasks may be decreased by quetiapine treatment. Based on these results, we suggest that the atypical antipsychotic quetiapine may improve some aspects of cognitive domains in patients with schizophrenia.     

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.     

Differential clinical, structural and P300 parameters in schizophrenia patients resistant to conventional neuroleptics

Schizophrenia is a heterogeneous clinical condition that may reflect a variety of biological processes. In particular, treatment-resistant (TR) schizophrenia may have a distinct neurobiological substrate. Within the context of clinical data, a simultaneous study with different imaging techniques could help to elucidate differences in cerebral substrates among schizophrenia patients with different responses to treatment. In the present work we used a set of biological data (basal and longitudinal volumetry, and P300 event-related potential measurements) to compare TR and treatment-responsive chronic schizophrenia patients with healthy controls. The TR patients showed higher baseline clinical scores, a more severe basal profile of brain alterations, as well as a different outcome as regards to volume deficits. These data support the notion that biological substrates vary among groups of different psychotic patients, even when they have the same diagnosis, and that those substrates may be related to the response to treatment.     

Working memory and attention deficits in adolescent offspring of schizophrenia or bipolar patients: comparing vulnerability markers

Background

Working memory deficits abound in schizophrenia and attention deficits have been documented in schizophrenia and bipolar disorder. Adolescent offspring of patients may inherit vulnerabilities in brain circuits that subserve these cognitive domains. Here we assess impairments in offspring of schizophrenia (SCZ-Offspring) or bipolar (BP-Offspring) patients compared to controls (HC) with no family history of mood or psychotic disorders to the second degree.

Methods

Three groups (n = 100 subjects; range: 10-20 yrs) of HC, SCZ-Offspring and BP-Offspring gave informed consent. Working memory was assessed using a delayed spatial memory paradigm with two levels of delay (2 s & 12 s); sustained attention processing was assessed using the Continuous Performance Task—Identical Pairs version.

Results

SCZ-Offspring (but not BP-Offspring) showed impairments in working memory (relative to HC) at the longer memory delay indicating a unique deficit. Both groups showed reduced sensitivity during attention but only BP-Offspring significantly differed from controls.

Conclusions

These results suggest unique (working memory/dorsal frontal cortex) and potentially overlapping (attention/fronto-striatal cortex) vulnerability pathways in adolescent offspring of patients with schizophrenia and bipolar disorder. Working memory and attention assessments in these offspring may assist in the clinical characterization of the adolescents vulnerable to SCZ or BP.     

Gray matter volume deficits are associated with motor and attentional impairments in adolescents with schizophrenia

Cognitive deficits have been well described in adolescents with schizophrenia, but little is known about the neuroanatomical basis of these abnormalities. The authors examined whether neuropsychological deficits observed in adolescents with schizophrenia were associated with cortical gray matter volume deficits. Volumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous MR images and automatically segmented into gray and white matter in 52 patients and 48 healthy volunteers. Subjects received a comprehensive neuropsychological test battery, assessing five different functional domains: executive, attention, verbal memory, motor and sensory motor. Children and adolescents with schizophrenia were found to have lower total cortical and lower superior frontal gyrus gray matter volumes and lower test scores across all functional domains compared to healthy volunteers. Among patients, the lower total cortical gray matter volume was associated with worse functioning on the attention and motor domains. Our findings point to widespread, perhaps multifocal, pathology as contributing to cognitive dysfunction in adolescents with schizophrenia.     

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.     

Overflow movements and white matter abnormalities in ADHD

Multiple motor abnormalities have been identified in some children with Attention Deficit/Hyperactivity Disorder (ADHD). These include persistence of overflow movements, impaired timing of motor responses and deficits in fine motor abilities. Motor overflow is defined as co-movement of body parts not specifically needed to efficiently complete a task. The presence of age-inappropriate overflow may reflect immaturity of the cortical systems involved in automatic motor inhibition. Theories on overflow movements consistently implicate impairments in white matter (WM) tracts, including the corpus callosum. WM connections might be altered selectively in brain networks and thus influence motor behaviours. We reviewed the scientific contributions on overflow movements and WM abnormalities in ADHD. They suggest that WM abnormalities in motor/premotor circuits, which are important for motor response inhibition, might be responsible for overflow movements in patients with ADHD.     

A double-blind study of paliperidone palmitate and risperidone long-acting injectable in adults with schizophrenia

This 13-week double-blind study was designed to assess noninferiority of the recently approved (in the U.S.) injectable atypical antipsychotic paliperidone palmitate (PP) versus risperidone long-acting injectable (RIS-LAI) in adult patients with schizophrenia. Patients (N = 1220) were randomized (1:1) to either a) PP: deltoid injections on day 1 (150 mg eq.), day 8 (100 mg eq.), and once-monthly flexible dosing as deltoid or gluteal injections on day 36 (50 mg eq. or 100 mg eq.) and day 64 (50 mg eq. or 100 mg eq. or 150 mg eq.) or b) RIS-LAI: gluteal injections days 8 and 22 (25 mg), days 36, 50 (25 or 37.5 mg) and days 64, 78 (25, 37.5 or 50 mg). RIS-LAI-treated patients received oral supplementation with RIS 1-6 mg/day (days 1 to 28), and PP-treated patients received oral placebo. The safety analysis set (n = 1214) included 58% men, 78% white, with mean (SD) baseline PANSS total score: PP, 84.1 (12.09); and RIS-LAI, 83.6 (11.28). Mean (SD) change from baseline to endpoint in PANSS total score decreased similarly in both groups; PP (−18.6 [15.45]) and RIS-LAI (−17.9 [14.24]). PP treatment was noninferior to RIS-LAI (point estimate [95% CI]: 0.4 [−1.62;2.38], per-protocol analysis set [primary analysis]). The tolerability and safety of PP was generally similar to RIS-LAI with no new safety or tolerability findings.     

Cognitive dysfunctions in patients with obsessive-compulsive disorder compared to the patients with schizophrenia patients: relation to overvalued ideas

OBJECTIVE: The clinical overlaps between schizophrenia and obsessive-compulsive disorder (OCD) seem to be related to thought disorders involving obsessions, overvalued ideas, and delusions. Overvalued ideas are beliefs falling in between obsessions and delusions and are stronger than obsessions but weaker than delusions. The goal of the present study was to compare patients with OCD to those with schizophrenia in terms of cognitive functions and to relate cognition and overvalued ideas in OCD. METHODS: Twenty three patients with OCD (free of depression), 24 patients with schizophrenia, and 22 healthy subjects matched to patients in age, gender, education, and hand dominance were included in the study. All subjects were administered neurocognitive tests assessing verbal learning-memory, executive functions, verbal fluency, attention and verbal working memory. RESULTS: Patients with schizophrenia showed worse performance on cognitive tests than the OCD and control groups. The severity of overvalued ideas was significantly correlated to cognitive functions in the OCD group. There were no significant differences in cognitive functions between schizophrenia group and the OCD patients who had higher scores on the Overvalued Ideas Scale (OVIS). CONCLUSION: Overvalued ideas in OCD may be related to cognitive dysfunctions in OCD and this subtype of OCD may have similar characteristics to schizophrenia in terms of cognition.     

Voxel based morphometric and diffusion tensor imaging analysis in male bipolar patients with first-episode mania

Objectives

Structural abnormality of both gray and white matter has been detected in patients with bipolar disorder (BD). But results were greatly inconsistent across studies which were most likely attributed to heterogeneous populations as well as processing techniques. The present study aimed to investigate brain structural and microstructural alterations in a relative homogenous sample of bipolar mania.

Methods

3D T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were conducted in 18 patients with BD and 27 healthy volunteers. Gray matter (GM) and white matter (WM) differences were evaluated using voxel-based morphometry (VBM) and voxel-based analysis of fractional anisotropy (FA) maps derived from DTI, respectively.

Results

Patients with BD had a larger volume of GM in the left thalamus and bilateral basal ganglia, including the bilateral putamen and extending to the left claustrum, as well as reduced FA values in the left posterior corona radiata.

Conclusions

By combined analysis, alterations in subcortical GM areas and part of the corresponding association fiber area were detected. Compared with observations in homogeneous samples, our findings indicate that disruption of the limbic network may be intrinsic to BD.     

A voxel-based morphometric MRI study of stabilized obsessive-compulsive adolescent patients

Background

The aim of this study was to determine whether treated stabilized adolescents with obsessive-compulsive disorder (OCD) present brain structure differences in comparison with healthy control subjects.

Methods

Twenty-seven adolescents with already-treated OCD and 27 healthy controls matched by age, sex and estimated intellectual level were assessed by means of psychopathological scales and magnetic resonance imaging (MRI). Axial three-dimensional T1-weighted images were obtained in a 1.5 T scanner and analyzed using optimized voxel-based morphometry (VBM).

Results

Compared with controls, stabilized patients with OCD did not present any statistical differences in the whole brain. However, a small volume correction analysis yielded significant results that survived correction for multiple comparisons, showing decreased white matter (WM) volume in a small area of the parietal cortex (t = 3.39, p = 0.045 FWE (family wise error)-corrected) of OCD patients in comparison with healthy controls. There was no significant correlation between decreased WM volume in the parietal cortex and obsessive-compulsive symptomatology.

Conclusion

There were no global significant differences in either gray matter (GM) or WM. Small differences were found between adolescent patients with stabilized OCD and healthy controls as regards in WM volume in right parietal areas. The parietal lobe may play a role in the pathophysiology of OCD, even in clinically stabilized patients.     

Error-related negativity abnormalities in generalized anxiety disorder and obsessive-compulsive disorder

Enhanced error-related negativity (ERN) has been associated with anxiety among both non-clinical and clinical populations. However, whether it is abnormal among adult patients with generalized anxiety disorder (GAD) is still unknown. The present study investigated it across GAD and obsessive-compulsive disorder (OCD). Event related brain potentials (ERPs) were recorded from a group of 27 GAD patients, 25 OCD patients and 27 healthy control participants during a modified Erikson Flankers task. ERP difference waveforms were obtained by subtracting ERP to correct response (CRN) from ERP to error response (ERN). The Ne component of ERPs at medial frontal electrodes were analyzed and reported. The Ne component of ERP difference waveform was enhanced only in OCD patients, but not in GAD patients, as compared to the healthy controls. An exploratory analysis also revealed higher Ne amplitude of error trial waveforms in both GAD and OCD patients than in healthy controls, and an insignificant group difference in Ne component of correct trial waveforms. The Ne amplitude of error trial waveforms also correlated with Hamilton Anxiety Rating Scale (HAMA) scores and with Hamilton Depression Rating Scale (HAMD) scores across the three subject groups. The main findings of the present study suggest that error processing is altered in OCD but not in GAD, and that ERN abnormalities in GAD are possibly associated with an overactive response checking process or excessive response monitoring.     

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.