Differential fractional anisotropy abnormalities in adolescents with ADHD or schizophrenia

Schizophrenia and Attention-Deficit/Hyperactivity Disorder (ADHD) are associated with similar deficits in working memory, attention, and inhibition. Both disorders also involve abnormalities of white matter integrity, possibly reflecting neural communication disruptions. There are likely some regional white matter abnormalities that underlie the common cognitive impairment, though also some regional abnormalities unique to each disorder. We used diffusion tensor imaging (DTI) to compare white matter integrity, as indicated by fractional anisotropy (FA), in adolescents with schizophrenia (n = 15) or ADHD (n = 14) and healthy controls (n = 26). Schizophrenia patients had uniquely low FA, relative to the other two groups, in bilateral cerebral peduncles, anterior and posterior corpus callosum, right anterior corona radiata, and right superior longitudinal fasciculus. ADHD patients had uniquely high FA in left inferior and right superior frontal regions. Both clinical groups had lower FA than controls in left posterior fornix. The two disorders generally demonstrated distinct patterns of abnormal connectivity suggesting that common cognitive and behavioral deficits derive from distinct sources, though the posterior fornix may be involved in both disorders. Schizophrenia was associated with abnormally low FA in widespread circuitry indicative of general connectivity disruptions, whereas ADHD was associated with abnormally high FA in frontal networks that may indicate impaired branching of fibers.     

Temporal lobe abnormalities in first-episode psychosis

OBJECTIVE: The nature and time course of temporal lobe abnormalities in psychotic illness remain controversial. Confounds include disease chronicity, gender, and handedness. The present study investigated temporal substructures in right-handed male patients experiencing their first episode of psychotic illness. METHOD: Magnetic resonance imaging scans were obtained for 25 minimally treated patients experiencing their first psychotic episode and 16 healthy comparison subjects. Group differences in volumes of the hippocampus, amygdala, planum temporale, and Heschl's gyrus were tested. RESULTS: The patients had smaller bilateral hippocampal and left planum temporale volumes than the comparison subjects. Paranoid and nonparanoid patients differed in left amygdala volume. CONCLUSIONS: The authors conclude that bilateral hippocampal and left planum temporale abnormalities are present near the onset of psychosis.     

Genetically mediated brain abnormalities in schizophrenia

Schizophrenia is a highly heritable, neurobehavioral disorder; however, the mode of inheritance is complex, and linkage findings have been difficult to replicate. Some consistent linkage findings have emerged on chromosomes 1, 6, 8, 11, 13, 15, and 22. New methods are being developed for candidate gene identification, including the use of neurobiologic phenotypes observed in relatives of persons with schizophrenia. Neuroimaging studies of relatives implicate abnormal hippocampal structure and inefficient prefrontal network functioning, probably representing mild variants of the abnormalities observed in schizophrenia. These characteristics may represent stable markers of vulnerability to schizophrenia, because they are not confounded by effects of antipsychotic drugs or psychosis. Recent studies provide evidence for a small role of the catechol-O-methyltransferase gene on 22q, and the serotonin receptor transporter gene on 17q11–q12 in the development of schizophrenia. Linking genes and brain regions or networks is an important step in identification of the pathophysiology of schizophrenia.     

Familial abnormalities of endocannabinoid signaling in schizophrenia

Objectives: Epidemiological and experimental evidence suggests that the endocannabinoid system plays a pathophysiological role in schizophrenia. This is reflected by elevated cerebrospinal levels of the endocannabinoid anandamide in schizophrenia and its initial prodromal states.

Methods: We analyzed plasma concentrations of anandamide, 2-arachidonoyl-sn-glycerol, palmitoylethanolamide and oleoylethanolamide from 25 twin pairs discordant for schizophrenia, six discordant for bipolar disorder and eight healthy twin pairs to determine hereditary traits.

Results: Twin pairs discordant for schizophrenia or bipolar disorder had significantly higher levels of anandamide and palmitoylethanolamide compared to healthy twins (both P?P?=?0.042) and 2-arachidonoyl-sn-glycerol levels (P?=?0.049) than twins who remained healthy.

Conclusions: We suggest that the protective upregulation of endocannabinoid signalling reflects either a hereditary trait or mirrors a modulating response to genetically influenced cerebral function involving, e.g., other neurotransmitters or energy metabolism.     

MRI study of white matter diffusion anisotropy in schizophrenia

Diffusion tensor imaging (DTI) can provide information about brain white matter integrity. The results of DTI studies in schizophrenia are somewhat variable and could benefit from standardized image processing methods. Fourteen patients with schizophrenia or schizoaffective disorder and 14 healthy volunteers underwent DTI. Scans were analyzed using a rigorous voxelwise approach. The key dependent variable, fractional anisotropy, was lower for patients in the corpus callosum, left superior temporal gyrus, parahippocampal gyri, middle temporal gyri, inferior parietal gyri, medial occipital lobe, and the deep frontal perigenual region. Regions showing reduced white matter fractional anisotropy are known to be abnormal in schizophrenia. The voxelwise method used in the current study can provide the basis for hypothesis-driven research.     

精神分裂症不同症状的MRI对照研究

选择４０例住院精神分裂症病人（其中阳性症状组３０例，阴性症状组１０例），和正常对照组２０例检测头颅ＭＲＩ。结果：精神分裂症脑结构异常率为３２．５％，其中脑软化７．５％，海马回梗塞１７．５％，脑白质变性１５％，额颞皮层萎缩２５％，阴性症状组病人的两侧脑室前角，三角区间距，三脑室宽径，大脑纵裂前半间距，左、右侧裂池宽距比正常对照组明显扩大，阳性症状组病人的两侧脑室三角区间距，三脑室宽径亦比正常对照组明     

Evidence for white matter abnormalities in schizophrenia

PURPOSE OF REVIEW: The purpose of this review is to highlight important recent imaging, histological, and genetic findings relevant to white matter abnormalities in schizophrenia. It is cast within the context of research findings conducted over the last 5 years, where we analyze their importance in understanding schizophrenia, as well as discuss future directions for research. RECENT FINDINGS: White matter abnormalities have long been hypothesized in schizophrenia, although only recently has it become possible to investigate them more closely. This has come about as a result of advances in neuroimaging, including new imaging techniques sensitive to white matter structure, as well as advances in computer science, with new analysis techniques making it possible to evaluate several interconnected brain regions at a time. Postmortem studies, with advances such as fluoroscopy and electron microscopy, have also led to quantifying populations of different brain cells, including myelin-forming oligodendrocytes. Moreover, molecular studies enable examination of immunoreactivity of proteins that are responsible for building myelin sheaths. Additionally, microarray genetic studies allow us to investigate myelin-related genes in schizophrenia. Taken together, these technological advances bring us closer to understanding white matter pathology in schizophrenia. SUMMARY: Advances in new imaging techniques likely account for the renewed interest in investigating white matter abnormalities in schizophrenia, with over 30 new articles published on this topic in the last 12 months, compared with 11 the year before. We review recent imaging, histological, and genetic findings that suggest white matter abnormalities in schizophrenia.     

Temporal evolution of electroencephalographic abnormalities in Creutzfeldt-Jakob disease

Summary Frequent serial EEG investigations of three patients with neuropathologically confirmed Creutzfeldt-Jakob disease lasting 13, 24 and 68 weeks revealed typical periodic activity of short duration with stereotyped bilateral sharp waves at the 7th, 8th, and 12th week, respectively, after the onset of symptoms. During the later stages, there were several deviations from this typical pattern. However, periodic activity was preceded between the 3rd and 9th week by intermittent localized or lateralized delta rhythms, which gradually changed into periodic activity. This early temporal evolution of EEG abnormalities may be helpful in the early diagnosis of Creutzfeldt-Jakob disease when accompanied by other investigations to exclude other causes of intermittent delta rhythms.     

Reduced left uncinate fasciculus fractional anisotropy in deficit schizophrenia but not in non-deficit schizophrenia

Aims: Schizophrenia is a psychiatric disorder manifesting with heterogeneous symptom clusters and clinical presentations. The deficit syndrome is the condition defined by the existence of primarily negative symptoms, and patients with the deficit syndrome differ from non‐deficit patients on measures of brain structure and function. In the current study, by using diffusion tensor imaging (DTI), we investigated the frontotemporal connectivity that is hypothesized to differ between deficit and non‐deficit schizophrenia. Methods: Twenty‐nine patients and 17 healthy controls were included in the study. The patients had deficit (n = 11) or non‐deficit (n = 18) schizophrenia and they were evaluated clinically with the Schedule for Deficit Syndrome (SDS) and Positive and Negative Syndrome Scale (PANSS). Diffusion‐based images were obtained with a 1.5T Siemens Magnetic Resonance Imaging machine and analyses were carried out with Functional Magnetic Resonance Imaging of the Brain Library Software – Diffusion tool box software. Results: The fractional anisotropy values in the left uncinate fasciculus of schizophrenia patients with the deficit syndrome were lower than those of non‐deficit patients and the controls. There were no differences between non‐deficit schizophrenia patients and controls. Conclusion: These findings provide evidence of left uncinate fasciculus damage resulting in disrupted communication between orbitofrontal prefrontal areas and temporal areas in deficit schizophrenia patients.     

Premorbid abnormalities in mania,schizomania, acute schizophrenia and chronic schizophrenia

The aim of this study was to examine the hypothesis that differences in outcome among affective and non-affective psychoses are associated with differences in the degree of developmental deviance. We conducted a retrospective survey of first contact cases treated over a 20-year period in a psychiatric hospital serving a catchment area in South London. All patients with non-depressive functional psychoses residing in the catchment area who received their first psychiatric treatment between 1965 and 1984 were included in the study. Cases were classified according to the relative chronicity of their illness into four non-overlapping groups: mania, schizomania, acute schizophrenia and chronic schizophrenia. There was a linear trend in the association between illness chronicity and proxy measures of developmental deviance, such as premorbid unemployment, single status and poor academic achievement. Compared to individuals with mania, schizophrenic patients had a 3–6 times increased risk of premorbid abnormality. For patients with schizomania and acute schizophrenia, the risk was 1.5–3 times greater than for manic subjects. We conclude that the prevalence of premorbid abnormalities is highest among chronic schizophrenia, but similar disturbances also occur, to a lesser degree, in less disabling affective and non-affective psychotic disorders.MRC Social Psychiatry Unit, Institute of Psychiatry     

Cortical structural abnormalities in deficit versus nondeficit schizophrenia

Schizophrenia has been associated to a distorted time clock. By subtracting contact duration from Inter Response Interval, we report evidence for preserved internal clock in schizophrenia, with normal spontaneous tapping tempo. Contact durations were however increased in patients suggesting a specific problem in the fast integration of incoming haptic feedback with outgoing motor efferences. This integration deficit would emerge at an early phase, since Ultra High Risk patients also revealed abnormal tapping stability. Tactile screens revealed to be a simple and low cost apparatus that may constitute a suitable measuring kit for the characterisation of sensory motor deficits in clinical settings.     

Gyrification abnormalities in childhood- and adolescent-onset schizophrenia.

BACKGROUND: Gyrification is an important index of brain development. We used magnetic resonance scanning technology to compare brain surface morphology and measures of gyrification in children and adolescents with a schizophrenia spectrum disorder and in age-equivalent healthy controls. METHODS: Magnetic resonance scans were obtained from 42 patients and 24 healthy controls, mean age 17.7 years for both groups. We employed novel quantitative measures of brain morphology, including cortical thickness and a variety of indices of sulcal and gyral curvature. We examined these measures in the whole brain and in the frontal, temporal, parietal, and occipital lobes. RESULTS: There were significant decreases in cortical thickness in the patients. This was most pronounced in the cortical tissue that underlies the sulci. The patient group had significantly more flattened curvature in the sulci and more steeped or peaked curvature in the gyri. CONCLUSIONS: This study quantitatively examines cortical thickness and surface morphology in children and adolescents with schizophrenia. Patients with schizophrenia demonstrated patterns of brain morphology that were distinctly different from healthy controls. In light of current theories of the formation of gyri and sulci, these changes may reflect aberrations in cerebral and subcortical connectivity.     

Glutathione peroxidase and CT scan abnormalities in schizophrenia

The search for morphological clues to the etiology of schizophrenia has led to widespread application of computed tomography (CT) scans in the examination of patients. These investigations have resulted in numerous reports over the past several years of brain atrophy and increased ventricle-brain ratios (VBR), suggestive of neuronal tissue damage, associated with the disorder. Altered activity of cellular antioxidant systems have been implicated in the neuronal cell loss that is associated with degenerative diseases of the central nervous system (CNS), but this phenomenon has not been investigated with respect to functional disorders like schizophrenia. A search for such a relationship in schizophrenics with evidence of brain atrophy has been initiated by measuring the activity of the important antioxidant enzyme glutathione peroxidase (GPx) in blood samples from a population of chronic schizophrenics and age- and sex-matched nonschizophrenic mental patients as controls. A strong negative correlation has been found between GPx activity in both isolated platelets and erythrocytes and CT scan measures of brain atrophy and VBR in the schizophrenics, but not in the control population, which exhibited comparable CT scan abnormalities. These observations suggest a unique relationship of GPx to the mechanism of tissue damage in the schizophrenics.     

EEG alpha photic driving abnormalities in chronic schizophrenia

Periodic photic stimuli across the entire electroencephalographic (EEG) frequency range were used in an attempt to assess EEG functional differences between chronic schizophrenic patients and control subjects. The EEG responses to these photic stimuli were significantly attenuated in the schizophrenic patients, specifically at the frequencies within the EEG alpha range. The schizophrenic patients also showed an alpha range attenuation in the “no stimulus” EEG alpha measure, such that there was a significant correlation across subjects between the “stimulus” and “no stimulus” EEG alpha range abnormalities. These abnormalities are discussed with reference to possible dysfunctional thalamic mechanisms involved in the pacing of EEG alpha activity and the gating of information through the cerebral cortex.     

Gamma frequency-range abnormalities to auditory stimulation in schizophrenia

BACKGROUND: Basic science studies at the neuronal systems level have indicated that gamma-range (30-50 Hz) neural synchronization may be a key mechanism of information processing in neural networks, reflecting integration of various features of an object. Furthermore, gamma-range synchronization is thought to depend on the glutamatergically mediated interplay between excitatory projection neurons and inhibitory neurons utilizing gamma-aminobutyric acid (GABA), which postmortem studies suggest may be abnormal in schizophrenia. We therefore tested whether auditory neural networks in patients with schizophrenia could support gamma-range synchronization. METHODS: Synchronization of the electroencephalogram (EEG) to different rates (20-40 Hz) of auditory stimulation was recorded from 15 patients with schizophrenia and 15 sex-, age-, and handedness-matched control subjects. The EEG power at each stimulation frequency was compared between groups. The time course of the phase relationship between each stimulus and EEG peak was also evaluated for gamma-range (40 Hz) stimulation. RESULTS: Schizophrenic patients showed reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. In addition, schizophrenic patients showed delayed onset of phase synchronization and delayed desynchronization to the click train. CONCLUSIONS: These data provide new information on selective deficits in early-stage sensory processing in schizophrenia, a failure to support the entrainment of intrinsic gamma-frequency oscillators. The reduced EEG power at 40 Hz in schizophrenic patients may reflect a dysfunction of the recurrent inhibitory drive on auditory neural networks.