N1 and P300 abnormalities in patients with schizophrenia, epilepsy, and epilepsy with schizophrenialike features.

BACKGROUND: The scalp-recorded N1 and P300 components of the event-related brain potential (ERP) are commonly reduced in patients with schizophrenia but not in patients with epilepsy. Epilepsy patients with interictal chronic schizophrenialike features (EPI-SZ) provide a comparison group for determining whether the ERP amplitude abnormalities seen in schizophrenic patients are associated with shared clinical features of EPI-SZ and schizophrenic patients or overlapping pathophysiologies, or are specific to a distinct schizophrenia etiology. METHODS: Patients with schizophrenia (n = 24) were compared with normal control subjects (n = 32) and patients with epilepsy syndromes on visual and auditory oddball ERP paradigms. Epilepsy patients included those with chronic interictal schizophrenialike features (n = 6) and those without (n = 16). RESULTS: Auditory P300 amplitude was reduced in both schizophrenic and EPI-SZ patients, whose positive or negative symptoms did not differ. In contrast, N1 amplitude was reduced only in schizophrenic patients. Delays in both N1 and P300 were associated with epilepsy patients and EPI-SZ but not schizophrenic patients. CONCLUSIONS: The schizophrenialike symptoms in epilepsy probably represent a phenocopy of schizophrenia with common clinical features and some common pathophysiologies but distinct etiologies. P300 amplitude appears to be sensitive to schizophrenialike features, regardless of whether they occur in the context of schizophrenia or epilepsy. N1 amplitude reduction appears to be specific to schizophrenia, suggesting its sensitivity to the distinct etiology of schizophrenia.     

Hypofrontality in schizophrenia: a review of the evidence

This paper reviews the possible role of frontal lobe dysfunction in the pathophysiology of schizophrenia. Pathological, computerized axial tomography (CAT) scan and magnetic resonance imaging (MRI) studies have indicated that a substantial number of schizophrenic patients show structural abnormalities in the frontal lobe areas and other parts of the brain. In some cases, these changes can be correlated with negative symptoms. Attempts to study frontal lobe function with neuropsychological tests, topographic EEG, cerebral blood flow (CBF) and positron emission tomography (PET) scans have also indicated that a substantial number of schizophrenics show abnormalities compared to normal controls. However, these abnormalities can be seen to some degree in other conditions. As well, patients early in the course of their illness tend not to show frontal lobe functional abnormalities. The implications of these findings for current theories of schizophrenia are discussed.     

Mitochondrial encephalomyopathy: clinical aspects, CT morphology and neuropathology

Basing on the example of two cases, the clinical and morphological variability of mitochondrial encephalomyopathies is demonstrated. Both patients were of short build, and the clinical signs and symptoms were dementia, ataxia, epilepsy and hardness of hearing, whereas signs of myopathy were very mild or absent. Computed tomography showed infratentorial pronounced atrophy of the brain and basal ganglia calcifications, in one case additionally ischemic infarctions, as can be seen in "mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome" (MELAS). A CT follow-up over 8 years with a progression of the abnormalities parallel to the progressive clinical course is demonstrated. Besides typical "ragged red fibres-myopathy" different abnormalities of mitochondria were seen by the electron microscope. One of the patients died; he had exceptional pathological-anatomical findings with mitochondrial cardiomyopathy, angioma and necrotising encephalopathy of Leigh's type. The two case reports show that in patients with such multisystemic neurological signs and CT-findings mitochondrial encephalomyopathy should be considered and a muscle biopsy should be performed.     

Prefrontal abnormalities in patients with simple schizophrenia: structural and functional brain-imaging studies in five cases

Simple schizophrenia is an uncommon disorder with unknown pathophysiology, and its position in the current diagnostic system is ambiguous. Brain-imaging studies may help to elucidate its pathophysiology. Five patients fulfilling both ICD-10 criteria for simple schizophrenia and DSM-IV criteria for simple deteriorative disorder underwent computed tomography, magnetic resonance imaging, and single photon emission computed tomography. These scans were assessed individually by visual inspection as well as automatically by comparison with scans in normal controls or other schizophrenia subtype patients using voxel-based image analyses. Three of the five simple schizophrenia patients had findings of atrophy and reduced cerebral perfusion in the frontal areas. Voxel-based analyses also showed prefrontal grey matter deficits and hypoperfusion in simple schizophrenia patients compared with the controls. Although this study is limited by the small number of patients with simple schizophrenia, the results suggest that simple schizophrenia, or at least this subpopulation, may have rather homogeneous morphological and functional deficits in the prefrontal cortex. It is also suggested that simple schizophrenia may occupy an extreme position of the schizophrenic continuum where the prefrontal deficits and negative symptoms are most purely manifested.     

Tripartite relationship among P300, clinical features and brain structure in neuroleptic-naive schizophrenia

Auditory P300 abnormalities in schizophrenia patients have been repeatedly reported by many studies. However, reported relationships among P300 abnormalities, clinical features and other biological variables, such as abnormalities in structural brain imaging, are notably discrepant. This is partially due to the inclusion of patients who have had long-term administration of neuroleptics and those from whom this treatment has been withdrawn. The present study measures event-related potentials in 13 neuroleptic-naive schizophrenia patients using an auditory oddball paradigm to clarify the relationships among P300 amplitude, clinical features and brain structure. All patients underwent computed tomography to estimate the area of the right and left frontal cortical sulci and Sylvian fissures. Clinical symptoms were assessed using the Positive And Negative Syndrome Scale. The high correlation coefficients were obtained between P300 amplitude and the anxiety/depression factor score (r = -0.77), the positive factor score (r = -0.58) and between P300 amplitude and the area ratios of the fronto-temporal region (r = -0.66). These findings show that fronto-temporal region and P300 amplitude are closely related to the earliest stage of illness even in neuroleptic-naive patients.     

Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia.

BACKGROUND: Structural magnetic resonance imaging (MRI) of the brain in patients with schizophrenia has consistently demonstrated several abnormalities. These are thought to be neurodevelopmental in origin, as they have also been described in first episode cases, although there may be a progressive component. It is not known at which point in development these abnormalities are evident, nor to what extent they are genetically or environmentally mediated. METHODS: One hundred forty-seven high-risk subjects (with at least two affected first or second degree relatives), 34 patients in their first episode, and 36 healthy control subjects received an MRI scan covering the whole brain. After inhomogeneity correction, regions of interest were traced by three group-blind raters with good inter-rater reliability. Regional brain volumes were related to measures of genetic liability to schizophrenia and to psychotic symptoms elicited at structured psychiatric interviews. RESULTS: High-risk subjects had statistically significantly reduced mean volumes of the left and right amygdalo-hippocampus and thalamus, as compared to healthy control subjects. They also had bilaterally larger amygdalo-hippocampi and bilaterally smaller lenticular nuclei than the schizophrenics. High-risk subjects with symptoms had smaller brains than those without. The volumes of the prefrontal lobes and the thalamus were the only consistent associates of genetic liability. CONCLUSIONS: Subjects at high risk of developing schizophrenia have abnormalities of brain structure similar to but not identical to those found in schizophrenia. Our results suggest that some structural abnormalities are genetic trait or vulnerability markers, others are environmentally mediated, and that the development of symptoms is associated with a third overlapping group of structural changes. Particular risk factors for schizophrenia may interact at discrete time points of neurodevelopment with different effects on specific brain regions and may represent relatively distinct disease processes.     

Proton magnetic resonance spectroscopy of lenticular nuclei in simple schizophrenia

1. The lenticula nuclei have been suggested to be the site of structural and functional abnormalities in schizophrenia. 2. Recently, several studies involving proton magnetic resonance spectroscopy (1H MRS) showed that the ratio of N-acetyl-aspartate (NAA) to choline-containing compounds (Cho) was significantly reduced in the basal ganglia region in patients with schizophrenia. 3. Simple schizophrenia is characterized by social withdrawal and affective flattening, but not by prominent catatonic, hebephrenic or paranoid features. 4. We studied, using 1H MRS, the lenticula nuclei of 10 patients with simple schizophrenia, and 10 age- and sex-matched healthy controls. 5. No differences between the patients and the controls were found in any of the measured ratios, i.e. Cho/Cr, NAA/Cr and NAA/Cho. 6. Our results suggest the normal viability of neuronal cells, as found on quantification of NAA, Cr and Cho, in the lenticular nuclei of patients with simple schizophrenia. 7. The pathophysiology of simple schizophrenia may be different from those of other types of schizophrenia.     

Functional imaging of memory retrieval in deficit vs nondeficit schizophrenia

BACKGROUND: Neuroimaging studies have provided evidence of abnormal frontal and temporal lobe function in schizophrenia. Frontal cortex abnormalities have been associated with negative symptoms and temporal lobe abnormalities with positive symptoms. The deficit and nondeficit forms of schizophrenia were predicted to differ in prefrontal cortical activity, but not in medial temporal lobe activity. METHODS: Regional cerebral blood flow was studied using oxygen 15 positron emission tomography during 3 different memory retrieval conditions in 8 control subjects, 8 patients with the deficit syndrome, and 8 patients without the deficit syndrome. Behavioral and positron emission tomography data were analyzed using a mixed-effects model to test for population differences. RESULTS: In all memory conditions, frontal cortex activity was higher in patients without the deficit syndrome than in patients with the deficit syndrome. During the attempt to retrieve poorly encoded words, patients without the deficit syndrome recruited the left frontal cortex to a significantly greater degree than did patients with the deficit syndrome. The 2 schizophrenia subtypes did not differ in the activity or recruitment of the hippocampus during memory retrieval. CONCLUSION: Frontal cortex function during memory retrieval is differentially impaired in deficit and nondeficit schizophrenia, whereas hippocampal recruitment deficits are not significantly different between the 2 schizophrenia groups.     

Frontal lobe psychopathology: mania, depression, confabulation, catatonia, perseveration, obsessive compulsions, and schizophrenia

The frontal lobes can be subdivided into major functional neuroanatomical domains, which, when injured, surgically destroyed, or reduced in activity or volume, give rise to signature pathological and psychiatric symptomology. A review of case reports and over 50 years of research, including magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography scans, indicates that apathy, "blunted" schizophrenia, major depression, and aphasic-perseverative disturbance of speech and thought are associated with left lateral as well as bilateral frontal (and striatal) abnormalities. Impulsiveness, confabulatory verbosity, grandiosity, increased sexuality, and mania are associated with right frontal (as well as bilateral) disturbances. Gegenhalten, catatonia, and disturbances of "will" are indicative of medial frontal injuries. Disinhibitory states and obsessive-compulsive perseverative abnormalities are more frequently observed with orbital frontal lobe dysfunction, including frontal-striatal disturbances. These associations, however, are not always clear-cut as patients with the same diagnosis may demonstrate different symptoms that may be due to an additional abnormality in a different region of the brain. Moreover, as the frontal subdivisions are richly interconnected, and as frontal lobe abnormalities are not always discrete or well localized, a wide array of seemingly divergent waxing and waning symptoms may be manifest, sometimes simultaneously, including manic depression and what has been referred to as the "frontal lobe personality."     

精神分裂症的强迫症状临床分析

对符合ＣＣＭＤ－２诊断标准的３９例伴有强迫症状的精神分裂症患者同不伴有强迫症状的精神分裂症患者进行对照分析，发现伴有强迫症状者其疗效和预后优于不伴发者。精神分裂症所伴发的强迫症状其内容荒谬、空洞，而且这些患者缺乏自知力及相应的情感体验。本研究结果还表朋强迫症状多发生在精神分裂症的疾病进展期，和以往的国内外报道不一致。     

Eating Disorder and Schizophrenia

Abstract: Five cases with eating disorders (one case with anorexia nervosa alone, 4 cases with anorexia nervosa and bulimia nervosa) complicated with schizophrenia and 3 cases of bulimia nervosa complicated with schizophrenia were reported. The eating disorders and schizophrenia were diagnosed according to the diagnostic criteria of DSM-III-R. As to the type of schizophrenia, 4 patients were of an undifferentiated type and 4 cases were of a disorganized type. Regarding the prepsychotic personality, 6 of the 8 cases showed schizothyme personality traits. All the patients showed depressive symptoms which are relatively common in eating disorders. In all the patients, significant social or school life difflculties persisted and a resumption of premorbid functioning was not seen. The possibility of an afflnity between anorexia nervosa and schizophrenia was discussed.     

Clinical significance of sleep EEG abnormalities in chronic schizophrenia

This study aimed to investigate the relationship between measures of clinical symptom severity and sleep EEG parameters in a relatively diagnostically homogeneous group of patients with schizophrenia. We obtained sleep EEG data in 15 drug-free inpatients who met DSM-IV-R criteria for schizophrenia, undifferentiated type, with 15 age- and sex-matched normal controls over two consecutive night polysomnographic recordings. Clinical symptoms were assessed by the Positive and Negative Symptom Scale (PANSS) and Hamilton Rating Scale for Depression. Characteristic features of sleep disturbance were seen in patients with schizophrenia: profound difficulties in sleep initiation and maintenance, poor sleep efficiency, a slow wave sleep (SWS) deficit, and an increased REM density. SWS was inversely correlated with cognitive symptoms. REM density was inversely correlated with positive, cognitive, and emotional discomfort symptoms as well as PANSS total score. Our data demonstrate that drug-free patients with chronic undifferentiated type schizophrenia suffer from profound disturbances in sleep continuity and sleep architecture. Both the SWS deficit and cognitive impairment found in schizophrenics in this study may relate to similar underlying structural brain abnormalities.     

'Simple schizophrenia': a controlled MRI and clinical/neuropsychological study

The present study explored the frequency of neuromorphological, neurological and neuropsychological abnormalities in 13 patients with an ICD-8/9 diagnosis of simple schizophrenia, also fulfilling DSM-IV criteria for 'simple deteriorative disorder', and in 13 matched patients with an ICD-8/9 diagnosis of a subtype of schizophrenia other than simple schizophrenia, fulfilling DSM-IV criteria for schizophrenia. The frequency of neuromorphological abnormalities in the two patient groups was also compared with that observed in 13 neurological control subjects. Both patients with simple schizophrenia and those with other schizophrenia subtypes showed a higher frequency of brain developmental abnormalities and greater ventricular and subarachnoid space volumes than controls. There was no significant difference between the two groups of patients with respect to neuromorphological variables. Two patients with simple schizophrenia (vs. none of those with other schizophrenia subtypes) had gross brain abnormalities; they were the most deteriorated subjects in the whole sample. Patients with simple schizophrenia, as compared to those with other schizophrenia subtypes, presented a higher frequency of soft neurological signs and a greater impairment of social relationships.     

Leukocyte elastase and autoantibodies to nerve growth factor in the acute phase of schizophrenia and their relationship to symptomatology.

Many investigations suggest that abnormalities of the immune system are involved in the pathophysiology of schizophrenia. We recently found increased activity of leukocyte elastase (LE) and elevated levels of autoantibodies to neurospecific protein - nerve growth factor (Aab to NGF) - products of the innate and adaptive arms of the immune system in the serum of patients with acute stage schizophrenia. The aim of this study is to elucidate whether or not the changes of LE activity and Aab to NGF level are related to prominent features of schizophrenia. Patients (n=71) corresponding to ICD-10 criteria for relapse-remitting schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS). Patients with predominantly positive symptoms showed significantly elevated serum levels of Aab to NGF compared to patients with predominantly negative symptoms, who were more likely to exhibit the high LE activity. Moreover, progression of positive symptoms was coupled with gradual increase of Aab to NGF level and reduction of LE activity. Based on these findings we conclude that the high levels of Aab to NGF relate to a clinical picture characterised mainly by positive symptoms of schizophrenia, whereas high LE-activities relate to a clinical picture with mainly negative symptoms of schizophrenia.     

Biological studies in schizophrenia

The question of whether schizophrenia is associated with structural or functional abnormalities of the nervous system, or both, has become the principal focus of biological studies of schizophrenia. Computed tomography studies have revealed ventricular enlargement and cortical atrophy in a subgroup of schizophrenic patients. While present from the early stages of the illness, they appear to be most severe in patients with negative symptoms and poor outcome. Quantitative neuropathological studies have tentatively demonstrated decreased volume of specific brain areas, neuronal loss, and other changes in the limbic system, basal ganglia, and frontal cortex. Dopamine (DA) remains the neurotransmitter most likely to be involved in schizophrenia, although there is also evidence for disturbances of serotonin and norepinephrine. Post-mortem and positron emission tomographic studies suggest an increased number of D2 DA receptors in some schizophrenics. Neuroendocrine studies reinforce the role of DA in schizophrenics. Viral infections and autoimmune disturbances may be responsible for some types of schizophrenia, but there is no firm experimental evidence to support either hypothesis. The possibility that mixtures of structural abnormalities and functional changes involving DA occur in the same patients rather than independently as part of two syndromes (Type I, II) seems attractive. Future studies should identify subtypes of schizophrenia based on biological criteria and contribute to identification of specific genetic abnormalities which increase vulnerability to manifest the schizophrenic phenotype.     

Single photon emission computed tomography and serial MRI in preterm infants with kernicterus

Single photon emission computed tomography was performed in three preterm infants with athetoid cerebral palsy due to kernicterus. No clinical signs and symptoms of kernicterus, or ultrasonographic abnormalities were seen during the neonatal period in any patients. Although MRI during infancy revealed high intensity areas in bilateral globi pallidi in all of them, MRI abnormalities were mild in two of them. On later MRI, subtle high intensity areas in the globi pallidi were recognized in only one of them. Single photon emission computed tomography demonstrated hypoperfusion in the basal ganglia regions in all patients. Regions of interest analyses showed decreased blood flow in the basal ganglia related to the cortical areas. Single photon emission computed tomography will be useful for the diagnosis of kernicterus, whereas MRI abnormalities become less clear beyond infancy.     

A contribution to the differential diagnosis of the "group of schizophrenias": structural abnormality of chromosome 4.

A structural abnormality of chromosome 4 [inv 4 (p15.2; q21.3)] is reported in a male presenting with DSM-III-R schizophrenia, undifferentiated type (295.94) and in his mother, who displayed symptoms associated with schizotypal personality disorder (DSM-III-R 301.22). The proband had a performance IQ of 91, poor motor coordination, stature in the lowest quartile and an impaired sense of time. There were no diagnostic physical or neurological abnormalities. Mild ventricular enlargement and prominent sulci were found on computed tomography. Both he and his chromosomally normal father had strabismus which required surgical correction. This case joins the long list of chromosomal abnormalities previously reported to confer an increased risk of mental illness and emphasizes the importance of a sophisticated differential diagnosis in evaluating patients who present with symptoms of schizophrenia. The implications for recent initiatives which attempt to localize genes conferring susceptibility to schizophrenia and other major mental illnesses are discussed.     

家族性与散发性精神分裂症的临床特征对照研究

目的 探讨家族性与散发性精神分裂症临床特征的异同，方法 对６４例家族性精神分裂症，１５３例散发性精神分裂症的临床资料进行对比分析，结果 与散发性精神分裂症相比，家族性精神分裂症以阴性症状为主，疗效相对较差，易复发。结论家族性与散发性精神分裂症的临床特征存在明显差异，家族史的研究对分析精神分裂症的症状，采用治疗方法，判断预后及探讨精神分裂症新的分类方法具有重要价值。     

Dementia as a complication of schizophrenia

OBJECTIVES: Cognitive impairment is known to occur in schizophrenia, and may be marked in institutionalised patients. The aim of this study was to determine whether it ever warrants an additional diagnosis of dementia. METHODS: A population of chronic schizophrenic patients who were aged 65 or younger and showed no organic risk factors for dementia were screened for presence of disorientation. Any showing this underwent neuropsychological testing, physical investigations, and structural and functional neuroimaging. Information about day to day cognitive function was also obtained from carers. RESULTS: Eight patients aged 28 to 64 were identified who showed disorientation; in all cases this was accompanied by general intellectual impairment and objective evidence of a dementia syndrome. The patients' schizophrenic symptoms were unexceptional and did not seem sufficient to account for their cognitive impairment. Neuropsychological testing disclosed relative sparing of visual and visuospatial function and language syntax, but pervasive deficits in memory and executive function. Brain CT demonstrated only minor abnormalities but most of the patients showed frontal or temporal hypoperfusion on SPECT. CONCLUSIONS: Dementia in schizophrenia seems to be a real entity with a neuropsychological signature similar to that of frontotemporal dementia. Functional but not structural imaging abnormalities may also be characteristic.     

Neurophysiologic studies in Morvan syndrome.

This study was conducted to clarify the clinical and neurophysiologic characteristics of patients with Morvan syndrome, and to compare and contrast this syndrome with other forms of autoimmune encephalitis. A retrospective chart review of the clinical features and neurophysiologic studies of two cases of Morvan syndrome seen at the Mayo Clinic was performed. Neurophysiologic studies included polysomnography, comprehensive autonomic testing, MRI, positron emission tomography, EEG, and single-photon emission computed tomography. In two cases of Morvan syndrome, the clinical features, electrophysiologic findings, and immunologic studies (high levels of voltage-gated potassium channel antibodies) were consistent with previously reported findings. Several novel observations were made. Autonomic testing demonstrated peripheral autonomic neuropathy in addition to autonomic hyperactivity. Polysomnography showed complete absence of sleep. Neuroimaging study findings were largely normal. Morvan syndrome is an autoimmune disorder affecting both the peripheral and central nervous system. Neurophysiologic studies demonstrate hyperexcitability of peripheral nerves, autonomic dysfunction, and severe insomnia. The absence of abnormalities on imaging studies suggests that central nervous system symptoms are related to functional rather than structural disruption of neural networks.