A controlled magnetic resonance imaging study of corpus callosum thickness in schizophrenia

Two previous postmortem studies reported an increased thickness of the corpus callosum in schizophrenic patients compared to psychiatric controls. We report an in vivo study of the corpus callosum in schizophrenic patients (n = 38) and healthy controls (n = 41) using magnetic resonance (MR) brain imaging. A significant increase in mean callosal thickness was found in the middle and anterior, but not the posterior, parts of the callosal body. However, when the patients and controls were compared by gender and handedness, schizophrenic men were found not to differ from control men in callosal thickness, regardless of handedness, whereas schizophrenic women were found to have a highly significant increase in callosal middle and anterior thickness compared to control women. The data suggest that increased callosal thickness in schizophrenia is gender related, a factor that is not considered by postmortem studies. The implications of increased callosal dimensions in female schizophrenics are discussed.     

Left-handed first-episode, neuroleptic-naive schizophrenic patients have a higher prevalence of autoantibodies.

Using standard immunological techniques, sera from first-episode, neuroleptic-naive schizophrenic patients (n = 51) and age, race and sex matched healthy controls (n = 51) were screened for seven common autoantibodies. Significantly more left-handed (67%) than right-handed (23%) schizophrenic patients had autoantibodies (p = 0.011). Left-handed schizophrenic patients were six times more likely than right-handed patients or controls and four times more likely than left-handed controls to test positive for autoantibodies (p = 0.012). These data suggest that disease and sinistrality contribute to the excess of autoantibodies in schizophrenia.     

The size and fiber composition of the anterior commissure with respect to gender and schizophrenia.

BACKGROUND: In light of evidence for deviations in asymmetry and alterations in the anatomy of the corpus callosum in schizophrenia, this study examined the anterior commissure in post mortem brains (n = 14 female control patients, 15 male control patients, 11 female schizophrenic patients, 15 male schizophrenic patients). METHODS: Measures were made of the cross-sectional area of the anterior commissure in the midsagittal plane. In addition, the fiber density and fiber number were measured in a subset of cases (n = 10 female control subjects, 10 male control subjects, 8 female schizophrenic patients, 9 male schizophrenic patients), using the Palmgren silver stain and stereological methods. RESULTS: In control subjects, fiber numbers were greater (p = .024) in women than men. In schizophrenia, the cross-sectional area was unaffected, but for fiber density there was a significant gender x diagnosis interaction (p = .026), corresponding to a reduction in female, but not male patients with schizophrenia. CONCLUSIONS: The reduction in density of fibers in the anterior commissure is consistent with an alteration of interhemispheric connectivity in schizophrenia, but the restriction of the finding to women emphasizes the relevance of gender to understanding the nature of the hemispheric interaction.     

Prevalence of sleep-related respiratory disorders in 101 schizophrenic inpatients

Abstract We studied the prevalence of sleep-related respiratory disorders (SRRD) in 101 schizophrenic inpatients (64 men and 37 women) and in 48 healthy volunteers (control group:22 men and 26 women) using ambulatory pulse-oximetric devices. Those with a desaturation index (DI) 5 were classified as having SRRD. The prevalence of SRRD in the schizophrenic patients (men 21.9%, women 13.5%) was not higher than that in the control group (men 30.7%, women 13.6%). Gender difference in the prevalence of SRRD was not observed in schizophrenic group. This was probably because the schizophrenic women took an increased amount of sleeping pills. Neuroleptics were shown to be least effected on SRRD.     

Sex differences, season of birth and platelet 5-HT levels in schizophrenic patients

Summary. Similar occurrence of schizophrenia was observed in men and women independent of their season of birth. Platelet 5-HT concentration was determined in 116 healthy control subjects (61 male and 55 female) and 152 patients with schizophrenia (96 male and 56 female). Platelet 5-HT concentration was significantly higher in male than in female healthy persons and schizophrenic patients. Male and female healthy subjects born in different seasons had similar platelet 5-HT concentrations, whereas schizophrenic patients with different birth-seasons had significantly different platelet 5-HT concentrations. The highest platelet 5-HT levels were observed in both male and female schizophrenic patients born in winter when compared to matched healthy controls. Male schizophrenic patients born in winter had higher platelet 5-HT levels than schizophrenic men born in spring and summer. Female schizophrenic patients born in winter had higher platelet 5-HT than schizophrenic women born in all other seasons. These results indicated sex differences in platelet 5-HT levels in healthy persons and schizophrenic patients. The relationship between season of the birth and platelet 5-HT concentration observed only in schizophrenic patients added further support to the presumption that schizophrenia is connected with a disturbance in the central serotoninergic system. Received January 26, 1998; accepted September 18, 1998     

Serum amino acids, central monoamines, and hormones in drug-naive, drug-free, and neuroleptic-treated schizophrenic patients and healthy subjects

Basal serum amino acids (including central monoamine precursors), central monoamines, and hormones were studied in schizophrenic patients (drug-naive; n = 20; drug-withdrawn for 3 or more days, n = 67; neuroleptic-treated, n = 23) and healthy subjects (n = 90) to answer the following questions: (1) Do neuroleptic-withdrawn and neuroleptic-naive patients differ on these serum measures? (2) What are the effects of neuroleptic treatment on these measures? (3) On which variables do drug-free and neuroleptic-treated patients differ? Because serum amino acid, central monoamine, and hormone levels were similar in drug-naive and drug-withdrawn patients, data from these groups ("drug-free") were combined and compared to those of healthy subjects and neuroleptic-treated patients. Asparagine, citrulline, phenylalanine, and cysteine were higher, while tyrosine, tryptophan, and the ratio of tryptophan to competing amino acids were significantly lower in drug-free schizophrenic patients than in healthy subjects. Dopamine was increased, and melatonin and thyroid hormones were decreased in drug-free schizophrenic patients compared to healthy subjects. Norepinephrine, epinephrine, and prolactin were higher in neuroleptic-treated men compared to drug-free male patients or healthy men. These results are consistent with the hypothesis of dopaminergic overactivity in schizophrenia, which might be caused by altered amino acid precursor availability and could be related to the decrease in melatonin and reduction in thyroid hormone levels.     

Sinistrality in schizophrenia

Sinistrality characterized by an excess of non-right handedness has been reported in schizophrenic patients. Two factors, sex and kind of evaluation of handedness have contributed to major discrepancies across studies.AIM: The hypothesis tested was that schizophrenic patients show a sinistral shift in handedness compared to controls taking into account the sex and using a continuum scoring system for evaluating handedness.METHODS: Seventy-three (73.1% males) schizophrenic patients (DSMIV) and 81 (64.2% males) controls were evaluated with the Edinburgh Handedness Inventory (EHI [Neuropsychologia, 9 (1971) 97]).RESULTS: The EHI score mean difference between patients with schizophrenia and control group was not significant when sex was taken into account.CONCLUSION: Schizophrenic patients taken as a whole did not show a sinistral shift in handedness even if the sex and the continuum score for handedness were considered.     

Non-right-handedness and obstetrical complications in paranoid hallucinatory schizophrenics.

In previous studies a link between pregnancy complications, minor physical anomalies and non-right-handedness was described in schizophrenic patients. There is evidence of an anomaly in the lateralization process in schizophrenia. Many studies of handedness and schizophrenia have found that schizophrenic patients have an increased rate of non-right-handedness compared with normal subjects. The contemporary neurodevelopmental hypothesis of schizophrenia emerged from pathobiological findings. In addition there is evidence for early brain lesions and malformations in fetal brain development. Especially pregnancy and birth complications have been found to be a risk factor for the later development of schizophrenia. In this study we set out to test the possible association between diagnosis and handedness, diagnosis and risk factors, as well as gender and handedness for 60 patients (30 men, 30 women) and 60 controls. The percentage of non-right-handedness was significantly elevated in the patient group (p = 0.0025). In a gender-specific analysis this result could be confirmed only for male patients. Peri- and postnatal developmental risk factors were significantly elevated in schizophrenics compared with controls. The percentage of all risk factors in the male group of schizophrenic non-right-handers was significantly elevated compared with right-handed male schizophrenics.     

Detection of facial expressions of emotions in schizophrenia

The aim of the present study was to examine spatial processing of facial emotion in schizophrenic patients suffering from affective symptoms. A face-in-the-crowd task using schematic stimuli was administered to schizophrenic patients with flat affect (n=30), schizophrenic patients suffering from anhedonia (n=30), schizophrenic patients not suffering from anhedonia or flat affect (n=28), and a group of healthy controls (n=30). Participants searched displays of neutral schematic faces for a face with a positive or negative mouth expression. Schizophrenic patients manifested a general slowing of response speed compared to normal subjects. All patient groups as well as normal subjects found negative faces more quickly than positive faces amongst neutral faces. Unexpectedly, with increasing anhedonia as assessed by psychiatric rating, a more efficient spatial detection of positive facial expression was observed. For flat-affect patients only, efficiency of search for negative facial expression did not differ from that in the neutral face control condition. This response pattern indicates that, in flat-affect schizophrenic patients, spatial search of negative facial expression might be slowed after the initial engagement of search processes. Potential explanations of the face processing effects found in anhedonia are discussed.     

Perseveration and over-switching in schizophrenia

Perseveration and switching in positive and negative schizophrenic patients are usually seen as manifestations of attention disorders. They may be closely related to each other, but have not been investigated in an integrated fashion. Such integrated investigation could contribute to the neurophysiological understanding of the relationship between the regional and the pharmacological deficit in schizophrenia. This study has developed a new tool-the Combined Attention Test (CAT)-for the simultaneous measuring of perseveration and switching. Forty-one unmedicated schizophrenic patients were tested. Using the Positive and Negative Sorting Scale (PANSS), subjects were classified into the two experimental groups: positive and negative schizophrenics. The control group consisted of 24 healthy subjects. Schizophrenic patients with positive symptoms tended to switch more than schizophrenic patients with negative symptoms and normal subjects; schizophrenic patients with negative symptoms tended to perseverate more than schizophrenic patients with positive symptoms and normal subjects. Over-switching is discussed as a specific symptom related to positive schizophrenia.     

Maximum phonation time as a tool of screening respiratory muscle weakness in myopathic patients]

We examined the relation of maximum phonation time (MPT) and vital capacity (VC) and reviewed the usefulness of MPT as a respiratory function screening. SUBJECTS: 18 healthy adult subjects (8 men and 10 women), and 32 myopathic patients (24 men and 8 women). METHODS: MPT and VC were measured in sitting position. Six patients were tested with and without air stacking by glossopharyngeal respiration. RESULTS: In healthy subjects, MPT was 29.9 +/- 11.8 seconds in men and 21.7 +/- 7.8 seconds in women. Second trials showed good reproducibility. The healthy group had no correlation between MPT and VC. The patient group showed a significant positive correlation between MPT and VC (r2= 0.25, p=0.003). All patients with MPT less than 15 seconds showed VC less than 1.5 l and %VC less than 50%. Air-stacking by glossopharyngeal respiration significantly increased the MPT. CONCLUSIONS: MPT is a useful screening test for respiratory muscle weakness. The patients are easily aware of the effect of air-stacking by glossopharyngeal respiration.     

Elevated Cellular Immune Response to Human Heat-Shock Protein-60 in Schizophrenic Patients

Heat shock protein-60 (HSP60) is implicated in several autoimmune diseases as a triggering antigen. Based on the autoimmune hypothesis of schizophrenia, we examined cellular and humoral responses against HSP60 and a series of its peptide fragments with peripheral blood samples of schizophrenic patients and healthy subjects each of group size between 12 to 32 participants. The average stimulation indices of peripheral blood mononuclear cells (PBMC) to HSP60 were 3.17 ± 0.36 (mean ± SE) for schizophrenic patients and 2.23 ± 0.24 (mean ± SE) for healthy subjects, with a significant difference between the groups (P = 0.0457). In parallel, 38 synthetic peptide fragments of HSP60, each of 18–21 amino acids, were tested for in vitro sensitization of PBMC. With one peptide (p32) the average stimulation index of PBMC from schizophrenic patients was significantly higher than that obtained for PBMC of control subjects (P = 0.0006). Comparing the cellular immune response to p32 between patients who were distinctive responders (n = 10) or non-responders (n = 10) to neuroleptic treatment indicated a similar elevation of cellular response in these groups. Antibodies against HSP60 were screened by dot-blot and ELISA in the sera of the above blood samples. Titers of IgG and IgM against HSP60 were found to be of similar magnitude in schizophrenic patients and in controls. Titers of IgA against HSP60 were somewhat higher in the sera of schizophrenic patients in comparison to sera of control subjects (P = 0.0605). Received: 26 November 1998 / Accepted: 10 July 1999     

Functional brain asymmetry and attentional modulation in young and stabilised schizophrenic patients: a dichotic listening study

Impaired functional brain asymmetry has been shown in schizophrenic patients, in addition to attentional deficits related to this laterality impairment. However, it has usually been shown in older patients with frequent positive symptoms. This is a matter of concern because previous studies have suggested that such deficits interact with subgroup characteristics, especially positive symptoms like hallucinations and age/duration of the illness. Thus, in this study, we tested a homogeneous group of young and stabilised schizophrenic patients. We used a verbal dichotic listening test with consonant-vowel syllables to study brain asymmetry and attentional modulation. Nineteen patients were compared with healthy subjects with the same age, handedness and gender distribution. All subjects were tested during a divided and two focused attention conditions. The patient and reference group showed the same performance pattern. This indicates that young and stabilised patients show normal functional brain asymmetry and normal ability to modulate attention. It is suggested that impairments in functional asymmetry and attentional modulation may follow a continuum related to symptomatology and age/duration of illness.     

Schizophrenic patients treated with clozapine or olanzapine perform better on theory of mind tasks than those treated with risperidone or typical antipsychotic medications

Theory of mind (ToM), the ability to attribute mental states to others, is associated with medial prefrontal cortical (mPFC) activity and is impaired in schizophrenia. Olanzapine or clozapine but not typical antipsychotics or risperidone preferentially affect c-fos expression in mPFC in animals. We tested the hypothesis that schizophrenic patients treated with different antipsychotics would perform differently on ToM tasks. Groups receiving Typicals (n=23), Clozapine (n=18), Olanzapine (n=20) or Risperidone (n=23) and a Control group of healthy volunteers (n=24) were matched for age, gender, handedness and education. ToM functioning was assessed with picture sequence, second-order belief and faux-pas tests. Schizophrenic groups performed similarly to controls on non-ToM conditions. The Olanzapine and Clozapine groups performed similarly to Controls on ToM tasks. The Typicals and Risperidone groups performed worse than the other groups on ToM tasks. We concluded that ToM performance of schizophrenic patients is influenced by the antipsychotic they are taking. Our results suggest that olanzapine or clozapine but not typicals or risperidone may improve or protect ToM ability.     

Smaller cerebellar vermis but not hemisphere volumes in patients with chronic schizophrenia

OBJECTIVE: The authors previously reported that men with chronic schizophrenia had a smaller vermian subregion than did healthy men. In this study, they tested whether posterior superior vermis reduction would be seen in a larger group of schizophrenia patients, both male and female. METHOD: Brain volumetric analyses were performed with magnetic resonance imaging (MRI) in 59 male and female patients with chronic schizophrenia and 57 male and female healthy comparison subjects. RESULTS: The men as well as the women with schizophrenia had significantly smaller total vermis volume and smaller vermian subregions than did the healthy subjects. Total intracranial volume and cerebellar hemisphere volumes did not differ between schizophrenic and healthy subjects. CONCLUSIONS: The findings support the previous finding that in patients with chronic schizophrenia, there is a selective volume reduction of the cerebellar vermis within the cerebellum.     

Urinary 3-methoxy-4-hydroxyphenylglycol and psychiatric diagnosis

The authors examined the quantities of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the urine of 11 schizophrenic female patients, 14 primary affective disorder (depressed type) female patients, and 10 healthy comparison women. The primary affective disorder patients had significantly less MHPG in their urine than did the comparison subjects. The schizophrenic patients when compared with the healthy subjects or the depressed patients did not excrete significantly different amounts of MHPG in urine. The variance in MHPG in schizophrenic patients was quite large; some had very low urinary MHPG. There was a significant positive correlation between agitation and urinary MHPG for schizophrenic but not depressed patients. The authors discuss theoretical and practical implications of these findings.     

精神分裂症患者7种自身抗体测定与分析

目的 观察精神分裂症患者种类自身抗体水平,从而探讨本病的发病与自身免疫的关系。方法 抗核抗体（ANA）、抗双链DNA抗体（A－dsDNA)测定用间接荧光抗体法;抗心磷脂抗体（ACA）、抗辛环孢素抗体（CyPAb)、抗钙调素抗体（CaM-Ab)、抗甲状腺球蛋白抗体（TG－Ab)、抗脑抗体（ABAb)测定用间接ELISA法。结果 52例精神分裂症患者的血清中,有多种自身抗体的阳性率偏高,总阳性率为38．5％,明显高于正常对照组。阳性结果与病程的长短及阴阳性症状之间无明显相关关系。结论 尚不能从本组研究结果得出精神分裂症的发病与自身免疫因素有关;自身抗体的产生可能是本病的后果,在病的病情的发展中可能起重要作用。     

Blood serotonin levels in suicidal schizophrenic patients

A decrease in central serotonin metabolism has been found in suicidal patients. In schizophrenic patients suicidality is predominantly observed as a transient phenomenon being most pronounced during an acute psychotic episode. We investigated blood serotonin levels as a paradigm for serotonin metabolism in suicidal schizophrenic women who were psychotic and compared their data with those of nonsuicidal psychotic schizophrenic women and healthy controls. Blood serotonin was lower in suicidal female schizophrenic patients (0.44 +/- 0.05 mumol/l, n = 17) than in nonsuicidal female schizophrenic patients (0.94 +/- 0.07 mumol/l, n = 17; P less than 0.001) or in healthy women (0.90 +/- 0.02 mumol/l, n = 26; P less than 0.001). These findings support the hypothesis that decreased serotonin metabolism may be associated with suicidal behavior in schizophrenic women.     

Abnormal functional brain asymmetry in depression: evidence of biologic commonality between major depression and dysthymia

Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having "pure" dysthymia show the same abnormality of perceptual asymmetry as MDD. It also examined gender differences in lateralization, and the extent to which abnormalities of perceptual asymmetry in depressed patients are dependent on gender. Unmedicated patients having either a MDD (n=96) or "pure" dysthymic disorder (n=42) and healthy controls (n=114) were tested on dichotic fused-words and complex-tone tests. Patient and control groups differed in right hemisphere advantage for complex tones, but not left hemisphere advantage for words. Reduced right hemisphere advantage for tones was equally present in MDD and dysthymia, but was more evident among depressed men than depressed women. Also, healthy men had greater hemispheric asymmetry than healthy women for both words and tones, whereas this gender difference was not seen for depressed patients. Dysthymia and MDD share a common abnormality of hemispheric asymmetry for dichotic listening.     

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study.

The present study measured prefrontal cortical gray and white matter volume in chronic, male schizophrenic subjects who were characterized by a higher proportion of mixed or negative symptoms than previous patients that we have evaluated. Seventeen chronic male schizophrenic subjects and 17 male control subjects were matched on age and handedness. Regions of interest (ROI) were measured using high-resolution magnetic resonance (MR) acquisitions consisting of contiguous 1.5-mm slices of the entire brain. No significant differences were found between schizophrenic and control subjects in mean values for prefrontal gray matter volume in either hemisphere. However, right prefrontal white matter was significantly reduced in the schizophrenic group. In addition, right prefrontal gray matter volume was significantly correlated with right hippocampal volume in the schizophrenic, but not in the control group. Furthermore, an analysis in which the current data were combined with those from a previous study showed that schizophrenic subjects with high negative symptom scores had significantly smaller bilateral white matter volumes than those with low negative symptom scores. White matter was significantly reduced in the right hemisphere in this group of schizophrenic subjects. Prefrontal volumes were also associated with negative symptom severity and with volumes of medial-temporal lobe regions - two results that were also found previously in schizophrenic subjects with mostly positive symptoms. These results underscore the importance of temporal-prefrontal pathways in the symptomatology of schizophrenia, and they suggest an association between prefrontal abnormalities and negative symptoms.