Brain cell membrane motion-restricted phospholipids in patients with schizophrenia who have seriously and dangerously violently offended

This study directly assessed, for the first time, whether there was a change in brain cell motion-restricted membrane phospholipids in vivo in male forensic patients with schizophrenia who had seriously and violently offended (homicide, attempted murder, or wounding with intent to cause grievous bodily harm) while psychotic, by quantification of the broadband resonance signal from 31-phosphorus neurospectroscopy scans. Cerebral 31-phosphorus magnetic resonance spectroscopy was carried out in 15 such patients, who suffered from positive symptoms of schizophrenia, and in 12 age- and sex-matched normal control subjects. Spectra were obtained from 70 x 70 x 70 mm(3) voxels using an image-selected in vivo spectroscopy pulse sequence. There was no significant difference in the broad resonances between the two groups, with the mean (standard error) percentage broadband signal for the patients being 57.8 (5.6) and that for the control subjects 57.7 (6.0). The phosphomonoesters and phosphodiesters narrow signals also did not differ between the groups. These results suggest that patients with schizophrenia who have predominantly positive symptoms may not show neuroimaging-based signs compatible with the membrane phospholipid hypothesis of schizophrenia.     

Cerebral spectroscopic and oxidative stress studies in patients with schizophrenia who have dangerously violently offended

Background

The aim of this study was to bring together all the results of in vivo studies of ethane excretion and cerebral spectroscopy in patients with schizophrenia who have dangerously seriously violently offended in order to determine the extent to which they shed light on the degree to which the membrane phospholipid hypothesis and the actions of free radicals and other reactive species are associated with cerebral pathophysiological mechanisms in this group of patients.

Methods

The patients investigated were inpatients from a medium secure unit with a DSM-IV-TR diagnosis of schizophrenia. There was no history of alcohol dependency or any other comorbid psychoactive substance misuse disorder. Expert psychiatric opinion, accepted in court, was that all these patients had violently offended directly as a result of schizophrenia prior to admission. These offences consisted of homicide, attempted murder or wounding with intent to cause grievous bodily harm. Excreted ethane was analyzed and quantified by gas chromatography and mass spectrometry (m/z = 30). 31-phosphorus magnetic resonance spectroscopy data were obtained at a magnetic field strength of 1.5 T using an image-selected in vivo spectroscopy sequence (TR = 10 s; 64 signal averages localized on a 70 × 70 × 70 mm³ voxel).

Results

Compared with age- and sex-matched controls, in the patient group the mean alveolar ethane level was higher (p < 0.0005), the mean cerebral beta-nucleotide triphosphate was lower (p < 0.04) and the mean gamma-nucleotide triphosphate was higher (p < 0.04). There was no significant difference between the two groups in respect of phosphomonoesters, phosphodiesters or broad resonances.

Conclusion

Our results are not necessarily inconsistent with the membrane phospholipid hypothesis, given that the patients studied suffered predominantly from positive symptoms of schizophrenia. The results suggest that there is increased cerebral mitochondrial oxidative phosphorylation in patients with schizophrenia who have dangerously and seriously violently offended, with an associated increase in oxygen flux and subsequent electron 'leakage' from the electron transport chain leading to the formation of superoxide radicals and other reactive oxygen species. In turn, these reactive species might cause increased lipid peroxidation in neuroglial membranes, thereby accounting for the observation of increased ethane excretion.

     

Altered white matter/gray matter proportions in the striatum of patients with schizophrenia: a volumetric MRI study

OBJECTIVE: Anatomical structures of the striatum were studied in 58 patients with schizophrenia and 56 healthy comparison subjects of both genders matched for age and handedness. METHOD: Magnetic resonance imaging scans were used to measure gray matter, white matter, and CSF volumes of the caudate, putamen, and nucleus accumbens in the left and the right hemispheres. RESULTS: White matter/gray matter ratios of the striatal structures were significantly lower in patients than in healthy subjects. In patients, relative white matter volumes in the caudate and nucleus accumbens were reduced, whereas gray matter in the putamen was increased. The total accumbens volume did not differ by diagnosis, but left side accumbens was larger than right in the healthy subjects. The proportion of white matter was greater in women in both the patient and healthy comparison groups. Total caudate and putamen volumes demonstrated no differences due to diagnosis or laterality, but a negative correlation was found in patients between white matter volumes and increasing age. There were no significant correlations among total striatal volumes, white matter/gray matter ratios, age at onset of illness, or illness duration. An estimate of lifetime neuroleptic consumption was positively correlated with right gray matter volume of the putamen in male schizophrenia patients who received typical neuroleptics. CONCLUSIONS: The proportion of white matter to gray matter tissue volumes of the caudate, putamen, and nucleus accumbens is altered in medicated chronic schizophrenia patients, but the total volumes are unchanged.     

Regional changes in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI

This study examined regional structural changes in the whole brain in 45 medicated patients with schizophrenia (23 males and 22 females), comparing with 42 age- and sex-matched healthy volunteers (22 males and 20 females). Automated voxel-based analysis on three-dimensional magnetic resonance imaging (MRI) was conducted using statistical parametric mapping (SPM). Compared with the controls, relative gray matter in the patients was significantly reduced in the left superior temporal, left middle and inferior frontal, right inferior frontal, and bilateral anterior cingulate and medial temporal areas. Gray matter reductions in the left superior temporal and prefrontal areas were found predominantly in the male patients, while the anterior cingulate gray mater reduction was more striking in the female patients. On the contrary, significant gray matter increases in the patients were found in the parietal areas and the cerebellum. In the white matter, significant reduction was found in the bilateral anterior limbs of the internal capsule and the superior occipitofrontal fasciculus, whereas the bilateral parietal white matter showed significant increases. These results suggest that a pathological process in schizophrenia predominantly affects the fronto-temporolimbic-paralimbic regions. Reduced white matter in the connecting bundles, which was first found in this study, may imply morphological substrates for abnormalities in the fronto-thalamic and fronto-temporolimbic connectivity in schizophrenia.     

Men with schizophrenia who behave violently: the usefulness of an early- versus late-start offender typology

Persons who develop schizophrenia are more likely than nondisordered persons to commit crimes. It is important to investigate those who offend, in order to develop treatment programs that effectively prevent recidivism, and eventually, early childhood violence prevention programs. Recent studies have shown that among offenders with major mental disorders, there are two groups: early starters, who begin their criminal careers in adolescence; and late starters, who first offend as adults. The present study examined 272 violent male offenders with schizophrenia in Sweden who underwent a pretrial psychiatric assessment between 1988 and 1995. Early- and late-start offenders were found to present differences in behavior, comorbid disorders, personality traits, and referrals for treatment in childhood, adolescence, and adulthood. Their parents also differed. The findings have implications for treatment and management of offenders with schizophrenia, for risk assessment, and for prevention.     

首发精神分裂症患者的脑灰质减少

目的 采用基于体素的形态学(VBM)分析方法对高分辨磁共振图像进行分析,研究首发精神分裂症患者大脑灰质变化,探讨患者脑灰质改变与临床症状之间的关系.方法 对符合CCMD-3诊断标准的首发精神分裂症患者以及健康志愿者各16例进行脑结构核磁共振扫描,并应用VBM进行脑灰质体积分析.所有患者均完成阳性与阴性症状量表(PANSS)评估.结果 与健康对照相比,患者组灰质密度降低的脑区有右侧小脑(t=5.17,P＜0.001)、右侧顶上回(t=5.01,P＜0.001)、左侧颞上回至岛叶被盖(t=4.79,P＜0.001)、左侧额中回(t=4.71,P＜ 0.001)、左侧额下回(t=4.70,P＜0.001)、右侧舌回(t=4.62,P＜ 0.001)、左侧海马杏仁体(t=4.11,P＜0.001).患者组左侧Heschl's回的灰质密度与PANSS量表总分(r=-0.509,P=0.044)以及PANSS阳性症状量表得分(r=-0.554,P=0.026)呈显著负相关.结论 首发精神分裂症患者的脑灰质减少以左侧额、颞叶为主,其中左侧Heschl's回灰质变化与患者的精神病性症状有相关性.     

Bilateral volume reduction of the insular cortex in patients with schizophrenia: a volumetric MRI study

The morphologic changes of the insular cortex have been described in schizophrenia, but with inconsistencies between reports. We investigated the insular cortex volume by magnetic resonance imaging in 59 schizophrenia patients (31 males, 28 females) and 62 age- and gender-matched healthy controls (31 males, 31 females). The insular cortex volume was measured on consecutive coronal 1-mm slices. Volumes of the left and right insular cortex were significantly reduced in schizophrenia patients compared with control subjects. There were no effects of gender on the insular cortex volume in the patient group or control subjects. Bilateral insular cortex volumes were correlated negatively with illness duration in the patient group. The findings of this study suggest that there is a possible progressive loss of the gray matter volume of the bilateral insular cortices subsequent to the onset of schizophrenia.     

精神分裂症患者脑结构异常的MRI研究

目的　探讨脑结构的改变 (尤其是第Ⅲ脑室 )特点及其与精神分裂症症状产生及疗效的关系。方法　选用我院住院的首发精神分裂症患者 ,共 51例 ,正常对照组为 2 3例健康志愿者。对入组后的患者于治疗前和治疗后 2个月进行PANSS(阳性与阴性症状量表 )评定 ,以PANSS减分率作为疗效指标。磁共振成像扫描采用SiemensMagnetomP8型永磁性磁共振机 ,磁场强度 0 2T。测量包括第Ⅲ脑室横径等在内的 1 7条径线。结果　病例组第Ⅲ脑室横径、双侧外侧裂宽度明显增宽 ,胼胝体厚度明显减少 ,病例组与对照组之间存在显著差异。PANSS阴性分量表、思维解体因子减分率与左侧海马横径均呈负相关。PANSS其他分量表及因子减分率与MRI各参数均无显著相关。结论　精神分裂症患者存在的脑结构异常可能构成了精神分裂症的神经生物学基础。脑结构异常与疗效的关系有待进一步研究     

Gender differences in temporal lobe structures of patients with schizophrenia: a volumetric MRI study

OBJECTIVE: The temporal lobe and associated structures have been previously implicated in the neuroanatomy of schizophrenia. This study was designed to assess the potential influence of gender on the morphology of temporal lobe structures, including the superior temporal gyrus and the amygdala/hippocampal complex, in patients with schizophrenia and to examine whether schizophrenic patients differ morphologically in these structures from comparison subjects. METHOD: Magnetic resonance imaging was used to measure the volume of temporal lobe structures, including the superior temporal gyrus, the amygdala/hippocampal complex, and the temporal lobe (excluding the volumes of the superior temporal gyrus and amygdala/hippocampal complex), and two comparison areas--the prefrontal cortex and caudate--in 36 male and 23 female patients with schizophrenia and 19 male and 18 female comparison subjects. RESULTS: There was a significant main effect of diagnosis in the superior temporal gyrus and the amygdala/hippocampal complex, with smaller volumes in patients than in comparison subjects. There was a significant gender-by-diagnosis-by-hemisphere interaction for temporal lobe volume. Temporal lobe volume on the left was significantly smaller in male patients than in male comparison subjects. Female patients and female comparison subjects demonstrated no significant difference in temporal lobe volume. There were no statistically significant gender interactions for the superior temporal gyrus, the amygdala/hippocampal complex, or the comparison regions. CONCLUSIONS: These findings suggest that there may be a unique interaction between gender and the pathophysiologic processes that lead to altered temporal lobe volume in patients with schizophrenia.     

Mapping brain structure in attention deficit-hyperactivity disorder: a voxel-based MRI study of regional grey and white matter volume

The neuroanatomical basis of attention deficit-hyperactivity disorder (ADHD) is postulated to involve brain circuitry responsible for attention and executive function. Relatively new automated methods of MRI analysis allow rapid examination of each volume element (voxel) of whole brain, therefore we planned a comprehensive quantitative examination of brain anatomy in children with ADHD using voxel-based methods. We aimed to quantify whole brain, global tissue class and regional grey and white matter volume differences in 28 male children with ADHD and 31 closely matched controls. Since ADHD is often complicated by comorbid oppositional defiant disorder (ODD) and conduct disorder (CD), we also conducted post-hoc analyses of subgroups of children with ADHD with and without these comorbidities. Significant regional deficits in ADHD were observed within a predominantly right-sided frontal-pallidal-parietal grey matter network and bilateral white matter tracts. Post-hoc comparisons suggested that comorbid ODD or CD did not greatly alter the extent of regional pathology in ADHD. The exceptions being cerebellar and striatal volume deficits which were significantly greater in children with ADHD plus comorbidities, but not those with ADHD alone, compared to controls. Overall, restricted structural brain abnormalities caused by ADHD were localized to brain systems known to be necessary for attention and executive function.     

A volumetric MRI and magnetization transfer imaging follow-up study of patients with first-episode schizophrenia

Conventional MRI studies have not provided definitive evidence of progressive loss of brain volume in the early stages of schizophrenia, although more subtle changes may have gone undetected. We have looked for such subtle changes using volumetric MRI and magnetization transfer imaging (MTI), an advanced MRI technique sensitive to subtle neuropathological abnormalities. Magnetization transfer images and high-resolution volumetric T1-weighted images were acquired from 16 patients with first-episode schizophrenia at the start of the study and 3.7 years later. A group of 12 healthy controls were also scanned on two occasions. Images were processed using a voxel-based approach that allows whole-brain analysis. There was a group difference with a significant volume loss in the patients' white matter adjacent to the lateral ventricles in the right and left temporal lobes, in medial temporal gyrus, and in the white matter in and around the right middle frontal gyrus. No cortical differences were detected between the groups using MTI or volumetric MRI. The absence of any time-by-group interaction suggests that these abnormalities do not progress in the early stages of the disease. The results of the study need to be interpreted in the light of the small sample size and of the limitations of current image analysis methods.     

有无冲动攻击行为首发精神分裂症脑灰质体积的比较

目的 比较有无冲动攻击行为精神分裂症脑灰质结构的不同.方法 收集16例有冲动攻击行为和24例无冲动攻击行为的首发未用药的精神分裂症患者,以三维快速扰相梯度回波序列获得其脑部磁共振成像.所得图像以统计参数图软件包进行预处理,然后两组脑局部灰质体积进行t检验.结果 有冲动攻击行为组右侧中央前回、中央后回区(MNI:x=44,y=-4,z=58;体素集合数=851)和右侧眶额回区(MNI:x=20,y=34,z:-24,体素集合数=108)脑灰质体积小于无冲动攻击行为组,差异有统计学意义(t=-3.72,P<0.001;t:3.17,P<0.001).未发现冲动攻击行为组存在灰质体积大于无冲动攻击行为组的脑区.结论 右侧中央前回、中央后回和眶额回灰质异常与精神分裂症的冲动攻击行为可能有关.     

Bilateral volume reduction of the insular cortex in patients with schizophrenia: a volumetric MRI Study

The morphologic changes of the insular cortex have been described in schizophrenia, but with inconsistencies between reports. We investigated the insular cortex volume by magnetic resonance imaging in 59 schizophrenia patients (31 males, 28 females) and 62 age- and gender-matched healthy controls (31 males, 31 females). The insular cortex volume was measured on consecutive coronal 1-mm slices. Volumes of the left and right insular cortex were significantly reduced in schizophrenia patients compared with control subjects. There were no effects of gender on the insular cortex volume in the patient group or control subjects. Bilateral insular cortex volumes were correlated negatively with illness duration in the patient group. The findings of this study suggest that there is a possible progressive loss of the gray matter volume of the bilateral insular cortices subsequent to the onset of schizophrenia.     

Occipital lobe gray matter volume in male patients with chronic schizophrenia: A quantitative MRI study

Schizophrenia is characterized by deficits in cognition as well as visual perception. There have, however, been few magnetic resonance imaging (MRI) studies of the occipital lobe as an anatomically defined region of interest in schizophrenia. To examine whether or not patients with chronic schizophrenia show occipital lobe volume abnormalities, we measured gray matter volumes for both the primary visual area (PVA) and the visual association areas (VAA) using MRI based neuroanatomical landmarks and three-dimensional information. PVA and VAA gray matter volumes were measured using high-spatial resolution MRI in 25 male patients diagnosed with chronic schizophrenia and in 28 male normal controls. Chronic schizophrenia patients showed reduced bilateral VAA gray matter volume (11%), compared with normal controls, whereas patients showed no group difference in PVA gray matter volume. These results suggest that reduced bilateral VAA may be a neurobiological substrate of some of the deficits observed in early visual processing in schizophrenia.     

Olanzapine increases grey and white matter volumes in the caudate nucleus of patients with schizophrenia

There are inconsistent reports regarding the caudate nucleus volume in patients with schizophrenia compared with healthy subjects. The reason for this is that neuroleptic medication may affect the volume of the caudate nucleus in schizophrenic patients. To clarify which antipsychotic medication changes the volume of the caudate nucleus in patients with schizophrenia, we measured the volumes of grey and white matter in the caudate nucleus of schizophrenic patients. Ten patients with schizophrenia were examined twice by magnetic resonance imaging (MRI) to measure the grey and white matter volumes in the caudate nucleus. After the first MRI examination, all the patients were treated with olanzapine. The clinical responses were evaluated by the positive and negative rating scale. When the symptoms improved, the patients were examined by a second MRI scan. Ten healthy control subjects also underwent MRI. The schizophrenic patients had reduced volumes of grey and white matter in the caudate nucleus compared to the healthy control subjects. The volumes of grey and white matter in the caudate nucleus of the schizophrenic patients increased after treatment with olanzapine. These findings suggest that treatment with olanzapine may increase the grey and white matter volumes in the caudate nucleus in patients with schizophrenia.     

Visual feature conjunction in patients with schizophrenia: an event-related brain potential study

The neural mechanisms supporting performance during single feature and feature conjunction detection were investigated in patients with schizophrenia and age-matched controls using event-related brain potentials. In different blocks of trials, participants responded to visual targets defined by one of two colors, one of two orientations, or both color and orientation. All participants were faster and more accurate in detecting targets defined by a single feature than for targets defined by a conjunction of features. Relative to controls, patients made more errors and were slower in detecting targets defined by a combination of features. Patients also generated a smaller N2 wave to single and conjunctive targets, and showed greater P3b reduction over the right hemisphere for conjunctive targets than for targets defined by color only. In addition, target stimuli generated an increased negativity at the occipital sites that varied in scalp distribution with the attended features in controls but not in patients. Both behavioral and electrophysiological data provide converging evidence for deficits in integrating visual features in schizophrenia and suggest that processing features of visual objects in schizophrenia are partly supported by distinct functional networks.     

Neuropsychologic functioning and structural MRI of the brain in patients with schizophrenia

The first episode of schizophrenia represents a transition from a premorbid to a morbid state. Studying the first episode of schizophrenia is useful since it is devoid of the confounds of chronicity and long-term medication. It is also likely to direct us to the core deficits of the illness. Studies on first-episode schizophrenia suggest a generalized neuropsychologic impairment, but that memory, attention and executive function are more severely impaired. Support for a neurodevelopmental model of neuropsychologic impairment in schizophrenia is derived from the findings that much of the neuropsychologic impairment is present by illness onset, that neuropsychologic impairment remains stable over time and that there is a weak relation between duration of untreated psychosis and neuropsychologic impairment. However, neuropsychologic impairment is moderated by neuroleptic treatment, with some evidence that atypical antipsychotics may have some beneficial effects over conventional antipsychotics. The causal mechanisms of brain abnormality in the temporal and frontal lobes appear to be different to that of neuropsychologic impairment in schizophrenia. The observation that there is a brain volume decrement over time and that the rate of change is higher during the first 5 years would be consistent with a neurodegenerative model of schizophrenia. At the same time, the basal ganglia are vulnerable to volumetric increase secondary to neuroleptic medication. Understanding the roles of the neurodevelopmental and neurodegenerative models of schizophrenia is important in deciding intervention strategies.