Abnormalities In Schizophrenic Patients Research Articles

Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models.

Schizophrenia is a grave neuropsychiatric disease which frequently onsets between the end of adolescence and the beginning of adulthood. It is characterized by a variety of neuropsychiatric abnormalities which are categorized into positive, negative and cognitive symptoms. Most therapeutical strategies address the positive symptoms by antagonizing D2-dopamine-receptors (DR). However, negative and cognitive symptoms persist and highly impair the life quality of patients due to their disabling effects. Interestingly, hippocampal deviations are a hallmark of schizophrenia and can be observed in early as well as advanced phases of the disease progression. These alterations are commonly accompanied by a rise in neuronal activity. Therefore, hippocampal formation plays an important role in the manifestation of schizophrenia. Furthermore, studies with animal models revealed a link between environmental risk factors and morphological as well as electrophysiological abnormalities in the hippocampus. Here, we review recent findings on structural and functional hippocampal abnormalities in schizophrenic patients and in schizophrenia animal models, and we give an overview on current experimental approaches that especially target the hippocampus. A better understanding of hippocampal aberrations in schizophrenia might clarify their impact on the manifestation and on the outcome of this severe disease.

Interference of commissural connections through the genu of the corpus callosum specifically impairs sensorimotor gating

White matter abnormalities in schizophrenic patients are characterized as regional tract-specific. Myelin loss at the genu of the corpus callosum (GCC) is one of the most consistent findings in schizophrenic patients across the different populations. We characterized the axons that pass through the GCC by stereotactically injecting an anterograde axonal tracing viral vector into the forceps minor of the corpus callosum in one hemisphere, and identified the homotopic brain structures that have commissural connections in the two hemispheres of the prefrontal cortex, including the anterior cingulate area, the prelimbic area, the secondary motor area, and the dorsal part of the agranular insular area, along with commissural connections with the primary motor area, caudoputamen, and claustrum. To investigate whether dysmyelination in these commissural connections is critical for the development of schizophrenia symptoms, we generated a mouse model with focal demyelination at the GCC by stereotactically injecting demyelinating agent lysolecithin into this site, and tested these mice in a battery of behavioral tasks that are used to model the schizophrenia-like symptom domains. We found that demyelination at the GCC influenced neither the social interest or mood state, nor the locomotive activity or motor coordination. Nevertheless, it specifically reduced the prepulse inhibition of acoustic startle that is a well-known measure of sensorimotor gating. This study advances our understanding of the pathophysiological contributions of the GCC-specific white matter lesion to the related disease, and demonstrates an indispensable role of interhemispheric communication between the frontal cortices for the top-down regulation of the sensorimotor gating.

Deficits of Tactile Passive Perception Acuity in Patients With Schizophrenia.

Background: Scarce literature has yet to characterize the tactile discrimination capability as well as the underlying mechanism of tactile deficits in psychotic disorder. In particular, very little is known regarding the tactile perception acuity in schizophrenia.Methods: A total of 131 clinically stable patients with schizophrenia (SCZ) and 79 healthy control (HC) volunteers were enrolled in the study. All the participants were tested on a tactile stimulus device which could quantify the tactile discrimination capability with right index finger scanned over the angles via the passive finger-movement apparatus. The MATRICS Consensus Cognitive Battery (MCCB) was adapted to assess the neurocognition of the participants. Correlation analysis and multivariate linear regression analysis were performed to investigate the relationship between tactile perception performance and neurocognitive function.Results: It was discovered that there existed a significant deficits in the tactile passive perception acuity (i.e., tactile angle discrimination threshold) in patients with schizophrenia compared with their healthy controls (F (3, 206) = 11.458, P = 0.001,partial η2 = 0.053). The MCCB total score and its six domains were significantly lower in SCZ patients than those in HCs (all p < 0.001). In the SCZ group, the composite score of the MCCB (r = −0.312, P < 0.001) and domains of neurocognition including speed of processing (r = −0.191, P = 0.031), attention/vigilance (r = −0.177, P = 0.047), working memory (r = −0.316, P < 0.001), verbal learning (r = − 0.332, P < 0.001), visual learning (r = −0.260, P = 0.004), and reasoning and problem solving (r = −0.209, P = 0.018) showed significant negative correlations with the tactile angle discrimination threshold. Multivariate linear regression analysis revealed that neurocognition impairment, especially the decline of working memory (B = −0.312, P < 0.001),underpin the tactile perception discrimination deficits in patients with SCZ.Conclusion: To the best of our knowledge, this is the first study to unravel the deficits of tactile passive perception acuity and its underlying neurocognition basis in patients with SCZ. This finding adds novel evidence to the subtle variation in haptic discrimination skills in schizophrenia which contributes to a more comprehensive understanding of the sensory profiles of this disorder.

A study on haloperidol and risperidone induced metabolic derangements in patients with newly diagnosed schizophrenia

Background: The occurrence of metabolic abnormalities in schizophrenic patients has been increased with the rampant use of second-generation antipsychotics. The aim and objective of this study is to compare the metabolic derangements induced by a typical antipsychotic: haloperidol and an atypical antipsychotic, risperidone in patients with newly diagnosed schizophrenia in a tertiary care hospital.Methods: Out of 60 newly diagnosed schizophrenic patients, 30 patients received tablet haloperidol and the remaining 30 patients received tablet risperidone orally. The anthropometric measurements like height, weight, waist circumference was measured and blood investigations like fasting blood glucose level and fasting lipid profile were taken at baseline and at the end of 3 and 6 months of drug therapy. The metabolic derangements induced by the two antipsychotics were compared and analyzed at end of 3rd and 6th month using SPSS software version 16.Results: At the end of 6th month statistically significant differences (p&lt;0.05) were observed in weight, waist circumference, fasting blood sugar, fasting triglyceride and high-density lipoprotein level between the haloperidol and risperidone group on following the International Diabetic Federation (IDF) criteria of metabolic syndrome. Risperidone caused metabolic abnormalities in 13.3%, 4 patients whereas none of the patients in haloperidol group developed metabolic syndrome.Conclusions: Hence it is concluded that the atypical antipsychotic risperidone has been associated with an increased risk of causing metabolic abnormalities than the typical antipsychotic haloperidol. Regular and periodic monitoring of the anthropometric and metabolic parameters in schizophrenic patients on antipsychotics especially the atypical antipsychotics is mandatory to prevent further complications.

Objective and quantitative equilibriometric evaluation of individual locomotor behaviour in schizophrenia: Translational and clinical implications.

Psychiatry is the only medical specialty that lacks clinically applicable biomarkers for objective evaluation of the existing pathology at a single-patient level. On the basis of an original translational equilibriometric method for evaluation of movement patterns, we have introduced in the everyday clinical practice of psychiatry an easy-to-perform computerized objective quantification of the individual locomotor behaviour during execution of the Unterberger stepping test. For the last 20years, we have gradually collected a large database of more than 1000 schizophrenic patients, their relatives, and matched psychiatric, neurological, and healthy controls via cross-sectional and longitudinal investigations. Comparative analyses revealed transdiagnostic locomotor similarities among schizophrenic patients, high-risk schizotaxic individuals, and neurological patients with multiple sclerosis and cerebellar ataxia, thus suggesting common underlying brain mechanisms. In parallel, intradiagnostic dissimilarities were revealed, which allow to separate out subclinical locomotor subgroups within the diagnostic categories. Prototypical qualitative (dysmetric and ataxic) locomotor abnormalities in schizophrenic patients were differentiated from 2 atypical quantitative ones, manifested as either hypolocomotion or hyperlocomotion. Theoretical analyses suggested that these 3 subtypes of locomotor abnormalities could be conceived as objectively measurable biomarkers of 3 schizophrenic subgroups with dissimilar brain mechanisms, which require different treatment strategies. Analogies with the prominent role of locomotor measures in some well-known animal models of mental disorders advocate for a promising objective translational research in the so far over-subjective field of psychiatry. Distinctions among prototypical, atypical, and diagnostic biomarkers, as well as between neuromotor and psychomotor locomotor abnormalities, are discussed. Conclusions are drawn about the translational and clinical implications of the new approach and its future perspectives.

Protective Effects of Quetiapine on Metabolic and Inflammatory Abnormalities in Schizophrenic Patients during Exacerbated Stage.

Inflammation has been considered important in the pathogenesis of schizophrenia. Increasing evidence reveals that patients with schizophrenia have abnormal expression of cytokines, which are related to development of metabolic abnormalities. Metabolic abnormality has become a critical issue, though its longitudinal relationship with the disorder, such as the antipsychotics influence, is unclear. We aimed to investigate whether abnormalities of metabolic parameters and cytokine levels in acute exacerbated schizophrenic patients existed, and whether intervention of antipsychotic could help. The present study analyzed peripheral cytokines and metabolic/hemodynamic parameters in healthy controls and acute exacerbated schizophrenic patients hospitalized for three weeks under the unique treatment of quetiapine, a well-known second-generation antipsychotic. Our results showed that patients with schizophrenia were predisposed to metabolic abnormalities in acute exacerbation, including body mass index (BMI) and waist circumference (WC). The patients were also prone to dysglycemia, lower high-density lipoprotein cholesterol (HDL-c) levels, and higher blood pressure with concomitant of elevation of interleukin (IL)-2, IL-6 and IL-10 in which IL-6 was associated with BMI. After quetiapine treatment, IL-2, IL-6 and IL-10 remained higher than the controls, but IL-10 was significantly decreased in follow-up comparison. Glycemic-related indexes, HDL-c and IL-10 levels were significantly changed by variance analysis. Results of the present study imply that acute exacerbated schizophrenic patients with metabolism abnormalities may involve disruption of expression of cytokines, and that quetiapine may have therapeutic effects. Nonetheless, metabolism parameters of patients undergoing treatment with quetiapine should be closely monitored.

Intranasal desmopressin as an adjunct to risperidone for negative symptoms of schizophrenia: A randomized, double-blind, placebo-controlled, clinical trial

Considering the role of neurohypophyseal peptides in normal development and function of higher cortical processes along with their proven abnormalities in schizophrenic patients, these pathways have recently attracted greater attention as treatment targets for schizophrenia. Desmopressin (DDAVP) is a synthetic analog of vasopressin. This study aimed to evaluate the efficacy and safety of DDAVP nasal spray as an adjunct to risperidone in improving negative symptoms of schizophrenia. In this randomized double-blind placebo-controlled clinical trial, forty patients aged 18–50 years with a DSM IV-TR diagnosis of chronic schizophrenia and a minimum score of 60 on positive and negative syndrome scale (PANSS) were equally randomized to receive DDAVP nasal spray (20mcg/day) or placebo in addition to risperidone for 8 weeks. Patients were partially stabilized and treated with a stable dose of risperidone (5 or 6mg/day) for at least four weeks prior to entry. Participants were rated by PANSS every two weeks and decrease in the PANSS negative subscale score was considered as our primary outcome. By the study endpoint, DDAVP-treated patients showed significantly greater improvement in the negative symptoms (P=0.001) as well as the PANSS total and general psychopathology subscale scores (P=0.005 and P=0.003; respectively) compared to the placebo group. Treatment group was the strongest predictor of changes in negative symptoms (β=−0.48, t=−3.67, P=001). No serious adverse event or fluid/electrolyte imbalance was reported in this trial. In conclusion, DDAVP nasal spray showed to be an effective and safe medication for improving negative symptoms in patients with chronic schizophrenia.

Metabolic issues in schizophrenic patients receiving antipsychotic treatment.

Schizophrenia is a psychotic disorder with a complex pathophysiology and requires treatment that includes long term administration of antipsychotics that is said to be associated with metabolic syndrome. This study was designed to evaluate the impact of seven different antipsychotics prescribed to schizophrenic patients, on development of metabolic syndrome in the patients. A total of 210 patients with schizophrenia (30 patients in each drug therapy group) were recruited according to ICD-10 criteria and were assigned to receive the drug for 16weeks. Measurement of anthropometric (body weight, waist circumference, blood pressure) and biochemical parameters (glucose, insulin, HOMA-IR, triglycerides, LDL, HDL) was done and the patients were subjected to ATP-III defined criteria for metabolic syndrome. Patients undergoing treatment with olanzapine were more prone to metabolic syndrome as the drug induces weight gain after 16weeks of treatment. It also induces dyslipidemia (P<0.001) and hyperglycemia (P<0.01). Clozapine was found to be second most potent drug in inducing metabolic syndrome as the weight in clozapine treated patients increased after 16weeks, along with a significant increase in glycemic (P<0.001) and lipid parameters (P<0.01). Aripriazole and amisulphride are comparatively safer drugs as their role in inducing metabolic abnormalities in schizophrenic patients was insignificant, although the impact of long term administration of these drugs needs to be explored. It is clear from the study that antipsychotic treatment induces metabolic syndrome so, it becomes important that the metabolic and cardiovascular risk factors should be surveillance regularly in schizophrenic patients undergoing antipsychotic treatment.

S21-4. Neuropathological hypothesis of sleep dysfunction in Schizophrenia

The purpose of this lecture is to review the polysomnographic non-rapid eye movement sleep abnormalities in schizophrenic patients and to present evidence for possible pathophysiologic mechanisms. Deficits of delta wave sleep are commonly reported sleep architecture abnormalities in schizophrenia. In the1960’s, Feinberg described this abnormality and about twenty years later, he first proposed that a decline in synaptic density resulting from abnormal reorganization of brain structure during early adolescence might cause the decline in delta wave amplitude and the onset of schizophrenia. Recent neuropathological studies of schizophrenia revealed that the dendritic spine density was particularly reduced in layer three of the neocortex. And excessive spine pruning is now considered a potential factor underlying reduced cortical gray matter volume in schizophrenia. Aberrant neuronal pruning is also believed to contribute to compromise the thalamocortical circuitry. Several recent studies have reported markedly reduced sleep spindle activity mediated by thalamocortical circuits in schizophrenia. Animal studies have reported sleep spindles have been linked to synaptic plasticity and memory consolidation. Thus, aberrant pruning can result in structural brain abnormalities and deficits of two distinct rhythms during sleep. Furthermore, each of these impairments appears to be associated with both cognitive deficits and symptoms of schizophrenia.

Effects of pioglitazone on metabolic abnormalities, psychopathology, and cognitive function in schizophrenic patients treated with antipsychotic medication: A randomized double-blind study

BackgroundSchizophrenic patients treated with antipsychotic drugs (AP) have an increased frequency of glucose–lipid metabolic abnormalities and diabetes. Pioglitazone has been shown to be effective in the treatment of glucose and lipid abnormalities in diabetes and decreasing longer-term conversion of impaired glucose tolerance to frank diabetes. Some studies also suggest possible pro-cognitive and antidepressant effects of pioglitazone. We studied the effects of pioglitazone on potential metabolic, symptomatic and cognitive benefits in schizophrenic patients treated with AP. Methods54 schizophrenic patients with at least both a)impaired glucose and b) triglycerides≥120mg/dL and/or low HDL levels, participated in a double-blind placebo controlled study of 3month treatment with Pioglitazone (30–45mg/day) or matched placebo, at 5 sites (4 U.S., 1 China). Fasting glucose and lipid parameters, and psychopathology (PANSS scale) were assessed monthly, and patients had a glucose tolerance test and cognitive testing (RBANS and CPT) at baseline and at the end of study. Statistical analysis used mixed model repeated measures analysis, supplemented by completer and LOCF analysis. ResultsIn the total sample there was an overall effect (P's<.05 to <.01) of pioglitazone on preventing deterioration in fasting glucose and improving HDL and PANSS depression scores; in the pioglitazone group comparison of baseline vs 3month values also showed significant (P<.05) decreases in fasting insulin, 2h glucose in GTT and insulin resistance (HOMA-IR). However there were marked differences between the responses of patients in the U.S. sites vs the China site. In the U.S. sample, patients treated with pioglitazone, when compared to placebo treated patents, had significantly lower fasting glucose (F=3.99, P=0.02), improved insulin sensitivity (lower H0MA-IR, F=6.24, P=.002), lower triglycerides (F=2.68, P=.06) and increased HDL (F=6.50, P=.001). By the end of the study 52% of the pioglitazone treated patients compared to 15% of the placebo patients had fasting glucose in the normal range (Fisher's exact test P=.02). Pioglitazone also significantly improved PANSS depression factor scores (F=2.82, P=0.05). It did not improve cognitive performance on the RBANS or CPT tasks. Pioglitazone did not increase weight or produce any other significant side-effects. In the small mainland China site sample, pioglitazone treatment, as compared to placebo, did not show greater improvement in metabolic parameters or psychopathology ratings. ConclusionsIn the sample of patients from the U.S., pioglitazone was an efficacious and safe treatment for glucose and lipid metabolic abnormalities in schizophrenic patients treated with AP, and it may also have beneficial effects on depressive symptoms. It may be particularly useful in patients whose weight gain effects from antipsychotics have plateaued and where weight loss is not the primary goal. The risk vs. benefits of longer term treatment with pioglitazone has to be carefully evaluated for individual patients.

Convergent Evidence from Multimodal Imaging Reveals Amygdala Abnormalities in Schizophrenic Patients and Their First-Degree Relatives

BackgroundShared neuropathological features between schizophrenic patients and their first-degree relatives have potential as indicators of genetic vulnerability to schizophrenia. We sought to explore genetic influences on brain morphology and function in schizophrenic patients and their relatives.MethodsUsing a multimodal imaging strategy, we studied 33 schizophrenic patients, 55 of their unaffected parents, 30 healthy controls for patients, and 29 healthy controls for parents with voxel-based morphometry of structural MRI scans and functional connectivity analysis of resting-state functional MRI data.ResultsSchizophrenic patients showed widespread gray matter reductions in the bilateral frontal cortices, bilateral insulae, bilateral occipital cortices, left amygdala and right thalamus, whereas their parents showed more localized reductions in the left amygdala, left thalamus and right orbitofrontal cortex. Patients and their parents shared gray matter loss in the left amygdala. Further investigation of the resting-state functional connectivity of the amygdala in the patients showed abnormal functional connectivity with the bilateral orbitofrontal cortices, bilateral precunei, bilateral dorsolateral frontal cortices and right insula. Their parents showed slightly less, but similar changes in the pattern in the amygdala connectivity. Co-occurrences of abnormal connectivity of the left amygdala with the left orbitofrontal cortex, right dorsolateral frontal cortex and right precuneus were observed in schizophrenic patients and their parents.ConclusionsOur findings suggest a potential genetic influence on structural and functional abnormalities of the amygdala in schizophrenia. Such information could help future efforts to identify the endophenotypes that characterize the complex disorder of schizophrenia.

Neuropsychological correlates of eye movement abnormalities in schizophrenic patients and their unaffected relatives

Impairments on neuropsychological and eye movement tasks have been demonstrated in schizophrenic patients and also reported in their unaffected relatives. However, it is not clear to what extent these phenotypes overlap. This study examined the relationship between specific eye movement and neuropsychological measures. The relationship between performance on eye movement and neuropsychological tasks was measured in 79 schizophrenic patients (63% from multiply affected families), 129 of their healthy first-degree relatives, and 72 normal controls. Antisaccade scores were correlated with most measures of neurocognitive functioning, and this correlation was strongest in schizophrenic patients in all cases. In the schizophrenic patients, but not their relatives or controls, the antisaccade distractibility error (ADE) score correlated significantly with current intelligence, verbal memory (immediate and delayed recall), and associative learning. In the case of crystallised IQ and delayed verbal memory, smaller correlations were present in unaffected relatives, although neither survived Bonferroni correction. Smooth pursuit performance was unrelated to any neuropsychological measure. Our study suggests that antisaccade errors are likely to represent part of a generalized neuropsychological deficit in schizophrenia.

Memory-guided saccade abnormalities in schizophrenic patients and their healthy, full biological siblings

Ocular-motor inhibition errors and saccadic hypometria occur at elevated rates in biological relatives of schizophrenic patients. The memory-guided saccade (MS) paradigm requires a subject to inhibit reflexive saccades (RSs) and to programme a delayed saccade towards a remembered target. MS, RS, and central fixation (CF) tasks were administered to 16 patients who met the criteria for DSM-IV schizophrenia, 19 of their psychiatrically healthy siblings, and 18 controls. Patients and siblings showed elevated MS error rates reflecting a failure to inhibit RSs to a visible target, as required by the task. In contrast to controls, prior errors did not improve MS accuracy in patients and siblings. The specific characteristics of the elevated MS error rate help to clarify the nature of the disinhibition impairment found in schizophrenics and their healthy siblings. Failure to inhibit premature saccades and to improve the accuracy of subsequent volitional saccades implicates a deficit in spatial working-memory integration, mental representation and/or motor learning processes in schizophrenia.

Metabolic syndrome in Thai schizophrenic patients: a naturalistic one-year follow-up study

BackgroundNot only the prevalence, but also the progress of metabolic abnormalities in schizophrenic patients is of importance for treatment planning and policy making. However, there have been very few prospective studies of metabolic disturbance in schizophrenic patients. This study aimed to assess the progress of metabolic abnormalities in Thai individuals with schizophrenia by estimating their one-year incidence rate of metabolic syndrome (MetS).MethodsWe screened all schizophrenic patients who visited our psychiatric clinic. After the exclusion of participants with MetS at baseline, each subject was reassessed at 6 and 12 months to determine the occurrence of MetS. The definition of MetS, as proposed by the International Diabetes Federation (IDF), was applied.ResultsFifty-seven participants (24 males and 33 females) had a mean of age and duration of antipsychotic treatment of 37.5 years old and 8.4 years, respectively. At baseline, 13 subjects met the MetS definition. Of 44 subjects who had no MetS at baseline, 35 could be followed up. Seven of these 35 subjects (20.0%) had developed MetS at the 6- or 12-month visit, after already having 2 MetS components at baseline. The demographic data and characteristics of those developing and not developing MetS were not different in any respect.ConclusionThai schizophrenic patients are likely to develop MetS. Their metabolic abnormalities may progress rapidly and fulfill the MetS definition within a year of follow-up. These findings support the importance of assessing and monitoring metabolic syndrome in schizophrenic patients.

Troubles métaboliques associés aux antipsychotiques atypiques : consensus belge sur la conduite à tenir

The current literature supports that schizophrenia (and bipolar disorders) appear to be associated with a higher prevalence of type 2 diabetes. Because of the silent nature of diabetes mellitus, and the fact that schizophrenic patients are not screened comprehensively for the disease, the true prevalence of hyperglycemia and diabetes may be substantially underestimated. Notably, it has been suggested that schizophrenia as such carries an increased risk, as certain characteristics of schizophrenic patients such as unhealthy life style promote the diabetes risk. This risk may be increased by antipsychotic drug treatment, as was already suggested for first-generation antipsychotics (FGA). The amount of literature on the association of SGA and metabolic disorders is much larger however, although well-controlled prospective data are sparse. Reports comprise abnormal glucose regulation, exacerbation of existing type 1 and 2 diabetes, new-onset pseudo-type 1 or type 2 diabetes, diabetic ketoacidosis, coma and death. In large-scale studies (mostly retrospective), reviews and meta-analyses, the association was not found for all drugs. According to recent reviews, the risk of developing diabetes was highest for clozapine and olanzapine, followed by quetiapine and risperidone. The hierarchy of liability of weight gain, or differential effects on insulin resistance was also in the described order. Apart from disturbances in glucose metabolism, further frequent metabolic abnormalities in schizophrenic patients on SGA include features of the metabolic syndrome. Antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, while agents such as haloperidol, risperidone and ziprasidone were associated with reductions in plasma triglycerides. Amisulpride, aripiprazole and ziprasidone seem to carry the lowest risk for weight gain, diabetes and effects on insulin resistance. As a consequence, there is a shift in attention toward physical health monitoring in patients with mental health disorders. The APA and ADA as well a British working group have recently published the findings on SGA and metabolic abnormalities in a joint statement (table I).

Neurogenic Actions of Atypical Antipsychotic Drugs and Therapeutic Implications

Brain imaging and postmortem studies have reported a reduction in the volume of discrete brain regions, as well as cellular abnormalities in schizophrenic patients. In addition, basic research studies have demonstrated effects of antipsychotic drugs on cell morphology and number. Of particular interest is adult neurogenesis, which has been linked to cognitive and memory improvements, and is also associated with the behavioural actions of antidepressants. While the action of antidepressant treatment is restricted mainly to the hippocampus, long-term administration of antipsychotics is reported to increase neurogenesis in the subventricular zone (SVZ), as well as the subgranular zone (SGZ) of the hippocampus. In addition, antipsychotic drugs increase the proliferation of non-neuronal cell types in the prefrontal cortex and could thereby influence the function of this brain region. Typical and atypical antipsychotic drugs differentially regulate neurogenesis in the SVZ and SGZ. Although the therapeutic relevance remains speculative, the results are consistent with the hypothesis that the actions of antipsychotic agents could be mediated, in part, by increased proliferation of neuronal as well as glial cells. Additional animal studies and postmortem analyses are required to further test this possibility and to investigate the relevance of this work in the pathophysiology and treatment of schizophrenia.

Deformable model with surface registration for hippocampal shape deformity analysis in schizophrenia

Changes to the hippocampal structure have been reported as consistent structural abnormalities in schizophrenic patients and have been related to the learning and memory deficits in such patients. Although many magnetic resonance (MR) imaging studies have focused on the hippocampal volume, local structural changes were difficult to discriminate from normal neuroanatomical variations. 3D shape deformation analysis of the brain structure may reflect localized schizophrenic abnormalities. A deformable model, evolved from the ellipsoid to hippocampal surface, with 2562 vertexes, was developed to analyze the left and right hippocampus shapes in 22 schizophrenic patients and 22 healthy age and gender matched controls. One of the most critical issues in the shape analysis is the determination of homologous points between two objects. To determine more accurate corresponding points, an alignment procedure, consisting of coarse and fine steps, following a deformation process, was applied. The performance of the alignment process was tested using artificial data, to get the alignment error to within 3° for each angle. A volume analysis indicated the hippocampal volume to be bilaterally reduced in schizophrenic patients compared to the normal controls, with a shape analysis showing a deformity pattern of the hippocampal surface. Bilateral inward deformities in the anterior and posterior hippocampus and a unilateral outward deformity in the right anterior hippocampus were observed, respectively.

Deformable model with surface registration for hippocampal shape deformity analysis in schizophrenia

Changes to the hippocampal structure have been reported as consistent structural abnormalities in schizophrenic patients and have been related to the learning and memory deficits in such patients. Although many magnetic resonance (MR) imaging studies have focused on the hippocampal volume, local structural changes were difficult to discriminate from normal neuroanatomical variations. 3D shape deformation analysis of the brain structure may reflect localized schizophrenic abnormalities. A deformable model, evolved from the ellipsoid to hippocampal surface, with 2562 vertexes, was developed to analyze the left and right hippocampus shapes in 22 schizophrenic patients and 22 healthy age and gender matched controls. One of the most critical issues in the shape analysis is the determination of homologous points between two objects. To determine more accurate corresponding points, an alignment procedure, consisting of coarse and fine steps, following a deformation process, was applied. The performance of the alignment process was tested using artificial data, to get the alignment error to within 3° for each angle. A volume analysis indicated the hippocampal volume to be bilaterally reduced in schizophrenic patients compared to the normal controls, with a shape analysis showing a deformity pattern of the hippocampal surface. Bilateral inward deformities in the anterior and posterior hippocampus and a unilateral outward deformity in the right anterior hippocampus were observed, respectively.

Smaller frontal gray matter volume in postmortem schizophrenic brains.

The prefrontal cortex exhibits prominent functional, biochemical, and anatomic abnormalities in schizophrenic patients. However, smaller than normal volume of the frontal lobe has not been found in previous postmortem studies of schizophrenic subjects, and magnetic resonance imaging (MRI) scans of schizophrenic subjects have not consistently revealed frontal volumetric deficits. The variability in MRI findings may be related partly to difficulty in defining the posterior border of the frontal lobe. In this study, precise measurements of frontal lobe volume from postmortem brains were derived by defining the posterior border according to the brain atlas of Talairach and Tournoux and by applying stereologic methods to estimate gray and white matter volumes. Whole, or nearly whole, formalin-fixed left hemispheres from 14 schizophrenic and 19 normal comparison subjects were analyzed. Total cortical gray and white matter volumes, as well as frontal cortical gray and white matter volumes, were measured by using the Cavalieri method. Only frontal gray matter volume was significantly smaller in the schizophrenic subjects than in the comparison subjects (12% difference). The differences between groups in total gray and white matter volumes and frontal white matter volume (6%-8% smaller in the schizophrenic subjects than in the comparison subjects) did not reach statistical significance. The smaller frontal gray matter volume observed in schizophrenic brains suggests that pathology of the frontal lobe may be more severe than that of the three posterior lobes and may account for the prominence of prefrontal dysfunction associated with schizophrenia.

Psychiatrie im Wandel: neuronale Netzwerkstörungen lassen sich mit moderner Kernspintomographie sichtbar machen

Over the last 20 years major advances in mathematics and computing opened up remarkable opportunities for studying the function, biochemistry and microstructure of the human brain. Magnetic resonance imaging (MRI) in neuroscience describes the functional organisation of the brain at the level of large neuronal groupings, networks and systems. By relating these to normal and disturbed information processing and behaviour in humans, means for the systematic analysis of the spatio-temporal functional architecture of the human brain along with the plasticity of that architecture are provided. At the same time, the focus of psychiatric research is increasingly moving from the differential description of phenomenology and disease course to an understanding of the biological basis of mental disorders. This also becomes evident when considering the spectrum of schizophrenia where investigators have consistently tried to identify the neurobiological substrate of information-processing deficits that seem characteristic for schizophrenic patients. Widespread abnormalities in different stages of information processing seem to lead to a cascade of downstream effects on higher cortical functions such as working memory or concept formation. In recent studies, the phenotypic characterisation of basic information processes as well as cognitive abnormalities in schizophrenic patients have been elaborated with new MRI methods. In both neuroleptic naive first episode and chronically ill schizophrenic patients in remission functional MRI demonstrated a dysfunction of the first relay station of the thalamus and in the prefrontal cortex as compared to normal controls. Furthermore, this technique revealed significant differences in prefrontal function between patients with typical and atypical antipsychotics. Using MR-spectroscopy in accordance with these functional data patients receiving typical neuroleptic medication showed a significantly lower mean NAA (marker for neuronal viability) in the anterior cingulate gyrus in comparison to the group of patients receiving atypical antipsychotic drugs, and had significantly more perseveration errors in the WCST. No significant group differences were found in either the creatine and phosphocreatine signal or the signal from choline-containing compounds. However, there was a clear association between the age-corrected NAA signal in the cingulate gyrus and the perseveration errors as well as the length of atypical treatment. In addition to differences between patients and healthy subjects these findings also showed differences within the patient group depending on treatment. These results support the hypothesis of a dysfunction in prefronto-temporo-limbic and early visual information-processing networks in schizophrenia. Furthermore, there was a specific relationship between neuronal and neuropsychological functioning. In keeping with animal data these results also indicate that chronic treatment with antipsychotics has regionally specific effects on the prefrontal cortex. Based on functional and metabolic MRI, circuit dysfunctions have been demonstrated within prefrontal and thalamic areas. In future, the non-invasive monitoring of therapeutic interventions with modern imaging methods in a multimodal approach may help to improve treatment by allowing approaches to be tailored for the individual patient.