Schizophrenic Subgroups Research Articles

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.

Convergence and Divergence of Brain Network Dysfunction in Deficit and Non-deficit Schizophrenia.

Deficit schizophrenia (DS), characterized by primary and enduring negative symptoms, has been considered as a pathophysiologically distinct schizophrenic subgroup. Neuroimaging characteristics of DS, especially functional brain network architecture, remain largely unknown. Resting-state functional magnetic resonance imaging and graph theory approaches were employed to investigate the topological organization of whole-brain functional networks of 114 male participants including 33 DS, 41 non-deficit schizophrenia (NDS) and 40 healthy controls (HCs). At the whole-brain level, both the NDS and DS group exhibited lower local efficiency (Eloc) than the HC group, implying the reduction of local specialization of brain information processing (reduced functional segregation). The DS, but not NDS group, exhibited enhanced parallel information transfer (enhanced functional integration) as determined by smaller characteristic path length (Lp) and higher global efficiency (Eglob). The Lp and Eglob presented significant correlations with Brief Psychiatric Rating Scale (BPRS) total score in the DS group. At the nodal level, both the NDS and DS groups showed higher functional connectivity in the inferior frontal gyrus and hippocampus, and lower connectivity in the visual areas and striatum than the controls. The DS group exhibited higher nodal connectivity in the right inferior temporal gyrus than the NDS and HC group. The diminished expression of Scale for the Assessment of Negative Symptoms (SANS) subfactors negatively correlated with nodal connectivity of right putamen, while asociality/amotivation positively correlated with right hippocampus across whole patients. We highlighted the convergence and divergence of brain functional network dysfunctions in patients with DS and NDS, which provides crucial insights into pathophysiological mechanisms of the 2 schizophrenic subtypes.

P.3.d.065 - Depot antipsychotic medication like a protective factor in readmission in a mental health hospitalization unit. A descriptive study in a subgroup of schizophrenics

P.3.d.065 - Depot antipsychotic medication like a protective factor in readmission in a mental health hospitalization unit. A descriptive study in a subgroup of schizophrenics

Carbonyl stress and schizophrenia.

Appropriate biological treatment and psychosocial support are essential to achieve and maintain recovery for patients with schizophrenia. Despite extensive efforts to clarify the underlying disease mechanisms, the main cause and pathophysiology of schizophrenia remain unclear. This is due in large part to disease heterogeneity, which results in biochemical differences within a single disease entity. Other factors include variability across clinical symptoms and disease course, along with varied risk factors and treatment responses. Although schizophrenia's positive symptoms are largely managed through treatment with atypical antipsychotics, new classes of drugs are needed to address the unmet medical need for improving cognitive dysfunction and promoting recovery of negative symptoms in these patients. Accumulation of toxic reactive dicarbonyls, such as methylglyoxal, are typical indicators of carbonyl stress, and result in the modification of proteins and the formation of advanced glycation end products, such as pentosidine. In June 2010, we reported on idiopathic carbonyl stress in a subpopulation of schizophrenia patients, leading to a failure of metabolic systems with plasma pentosidine accumulation and serum pyridoxal depletion. Our findings suggest two markers, pentosidine and pyridoxal, as beneficial for distinguishing a specific subgroup of schizophrenics. We believe that this information, derived from in vitro and in vivo studies, is beneficial in the search for personalized and hopefully more effective treatment regimens in schizophrenia. Here, we define a subtype of schizophrenia based on carbonyl stress and the potential for using carbonyl stress as a biomarker in the challenge of overcoming heterogeneity in schizophrenia treatment.

Ultrastructural abnormalities of astrocytes in the hippocampus in schizophrenia and duration of illness: A postortem morphometric study

There is a lot of evidence of astrocytic dysfunction in schizophrenia. We performed an electron microscopic morphometric study of astrocytes in the CA3 hippocampal region in 19 cases of schizophrenia and 16 normal controls. No significant group differences were found in cell size, volume fraction (Vv) and area density (Na) of mitochondria and lipofuscin granules. Young control subjects (<50 years old) had significantly lower area of cell, nucleus and cytoplasm and higher Vv and Na of mitochondria than old controls (>50 years old), and young and old schizophrenic cases. No significant differences between young and old schizophrenic subgroups were found. Vv and Na of mitochondria correlated negatively (r=−0.66, r=−0.72, P<0.01) and Vv of lipofuscin granules correlated positively (r=0.72, P=0.001) with duration of illness. These parameters did not correlate with age in controls and in schizophrenic subjects. Both Vv and Na of mitochondria were significantly lower in the subgroup of cases with duration of disease of>21 years. than in the control group and in the subgroup of cases with duration of illness of<21 years (P<0.01). The data suggest progressive disturbances of astrocyte function due to the deficit of mitochondria in schizophrenia.

Differences in hippocampal volume between major depression and schizophrenia: a comparative neuroimaging study

Several studies have demonstrated that structural brain change is detectable in the hippocampus in both patients, with schizophrenia and major depression. Only few studies, however, compared both clinical disease entities directly and no larger study has tried to take different disease stages into account. The objectives of this study are to investigate whether hippocampal volumes are reduced in patients with schizophrenia and those with major depression with the same duration of illness compared to healthy controls and to assess further changes at different disease stages. A total of 319 inpatients and healthy controls were enrolled and investigated with magnetic resonance imaging (MRI). Hippocampal volumes were measured using the segmentation software BRAINS. Bilateral hippocampal volume reductions were detected in both schizophrenic and depressed patients compared to healthy control (HC) subjects. Although younger, schizophrenic (SZ) patients showed in their MRI scans significant bilaterally reduced hippocampal volumes compared to patients with major depression. Although the hippocampal reductions were similar at the onset of symptomatic manifestation of both diseases, there was a further significant reduction of the left hippocampus in the recurrently ill SZ subgroup. The data suggest rather dynamic structural brain alterations in schizophrenia compared to major depression. Here, the presented application of the comparative neuroscience approach, by the use of large neuroimaging MRI databases, seems highly valuable. In the field of psychiatry, with its still controversial operationalized descriptive diagnostic entities, the cross-nosological approach provides a helpful tool to better elucidate the still unknown brain pathologies and their underlying molecular mechanisms beyond a single nosological entity.

Ultrastructural abnormalities of astrocytes in the hippocampus in schizophrenia and duration of illness: A postortem morphometric study

There is a lot of evidence of astrocytic dysfunction in schizophrenia. We performed an electron microscopic morphometric study of astrocytes in the CA3 hippocampal region in 19 cases of schizophrenia and 16 normal controls. No significant group differences were found in cell size, volume fraction (Vv) and area density (Na) of mitochondria and lipofuscin granules. Young control subjects (<50 years old) had significantly lower area of cell, nucleus and cytoplasm and higher Vv and Na of mitochondria than old controls (>50 years old), and young and old schizophrenic cases. No significant differences between young and old schizophrenic subgroups were found. Vv and Na of mitochondria correlated negatively (r=-0.66, r=-0.72, P<0.01) and Vv of lipofuscin granules correlated positively (r=0.72, P=0.001) with duration of illness. These parameters did not correlate with age in controls and in schizophrenic subjects. Both Vv and Na of mitochondria were significantly lower in the subgroup of cases with duration of disease of>21 years. than in the control group and in the subgroup of cases with duration of illness of<21 years (P<0.01). The data suggest progressive disturbances of astrocyte function due to the deficit of mitochondria in schizophrenia.

Proton magnetic resonance spectroscopy of the frontal, cingulate and perirolandic cortices and its relationship to skin conductance in patients with schizophrenia

The aim of the present study was to determine whether specific subgroups of schizophrenic patients, grouped according to electrodermal characteristics, show differences in the N-acetylaspartate/creatine plus choline (NAA / (Cr + Cho)) ratios in the frontal, cingulate and perirolandic cortices. Skin conductance levels (SCL) and skin conductance responses to auditory stimulation were measured in 38 patients with schizophrenia and in the same number of matched healthy volunteers (control). All subjects were submitted to multivoxel proton magnetic resonance spectroscopic imaging. When compared to the control group, patients presented significantly lower NAA / (Cr + Cho) ratios in the right dorsolateral prefrontal cortex (schizophrenia = 0.95 +/- 0.03; control = 1.12 +/- 0.04) and in the right (schizophrenia = 0.88 +/- 0.02; control = 0.94 +/- 0.03) and left (schizophrenia = 0.84 +/- 0.03; control = 0.94 +/- 0.03) cingulates. These ratios did not differ between electrodermally responsive and non-responsive patients. When patients were divided into two groups: lower SCL (less than the mean SCL of the control group minus two standard deviations) and normal SCL (similar to the control group), the subgroup with a lower level of SCL showed a lower NAA / (Cr + Cho) ratio in the left cingulate (0.78 +/- 0.05) than the controls (0.95 +/- 0.02, P < 0.05) and the subgroup with normal SCL (0.88 +/- 0.03, P < 0.05). There was a negative correlation between the NAA / (Cr + Cho) ratio in the left cingulate of patients with schizophrenia and the duration of the disease and years under medication. These data suggest the existence of a schizophrenic subgroup characterized by low SCL that could be a consequence of the lower neuronal viability observed in the left cingulate of these patients.

Sexualdelinquenz bei Schizophrenie – eine Vergleichsstudie

Studies suggest a complex relationship between schizophrenia and sexually offensive behaviour. The mental disorder itself, antisocial personality traits, drug abuse and adverse childhood experiences are suggested to have an impact on sexual offending in mentally disordered offenders. Similarities in psychosexual variables for schizophrenic and sexual offenders in general are found. This study aimed to preserve first findings of sex offence features and behaviours exhibited by psychotic men in Germany. Furthermore a typology of the schizophrenic offenders was developed. Records of 64-male restricted hospital order in-patients (32 patients with and 32 patients without an ICD-10 psychotic disorder) examined at the Institute for Forensic Psychiatry or resident in the Department of Psychiatry and Psychotherapy of the prisons in Berlin from 1980 - 2006 with an index conviction for a contact sex offence against a woman provided the material for research. A comparative trial design was used to differentiate the psychotic and non psychotic offender group. A check list which based on the method of a content analysis containing items related to the offender and the index offence was developed and applied to the records of men. A similar extent of social isolation, psychosexual variables and adverse childhood experiences are found for schizophrenic and non schizophrenic offenders. Negative symptoms of schizophrenia as well as antisocial traits had a great impact on schizophrenic sexual offending. Solely the occurrence of bizarre behaviour was influenced by positive symptoms. Different offence characteristics appeared in the four outlined schizophrenic subgroups such as bizarre behaviour of the psychotic, assaultive behaviour of the dissocial, chaotic behaviour of the substance abusive and negative childhood experiences of the sadistic schizophrenic offenders. The partly controversial findings underline the need for further studies to understand sexual offending in the heterogeneous group of schizophrenic men.

Lack of association between dopamine D3 receptor Ser9Gly polymorphism and schizophrenia in Han Chinese population.

The Ser9Gly polymorphism in dopamine D3 receptor gene (DRD3) was considered an important factor in the pathogenesis of schizophrenia. Allele and genotype frequencies of this polymorphism were studied in different ethnic groups of schizophrenic patients. However, the results have been inconclusive. To determine whether the DRD3 Ser9Gly polymorphism is associated with schizophrenia or influences its psychopathological symptoms in Han Chinese population. We recruited 256 schizophrenic patients and 285 normal controls matched for gender, age and ethnicity. Pretreatment psychotic symptoms were evaluated with the Positive and Negative Symptom Scale (PANSS) in 128 acutely exacerbated schizophrenic in-patients. Genotyping of Ser9Gly polymorphism was performed with a polymerase chain reaction restriction fragment length polymorphism method and reconfirmed by a direct sequencing technique. No significant difference was found between either patients with schizophrenia or with more homogeneous schizophrenic subgroups and healthy controls in genotype distributions and allele frequencies for the DRD3 Ser9Gly polymorphism. Similarly, DRD3 Ser9Gly genotype differences failed to reach significance in PANSS global, positive, negative and general symptoms scores. There is a trend (P = 0.064) towards higher PANSS positive symptoms scores in subjects carrying the Gly/Gly genotype. This study does not support the role of DRD3 Ser9Gly polymorphism in increasing genetic risk for schizophrenia in Han Chinese population. Still, there is a possibility that the DRD3 Ser9Gly variant may reflect genetic variation of severity of positive symptoms in acutely exacerbated schizophrenia. Further studies are warranted to investigate the effect of the DRD3 Ser9Gly polymorphism in relation to longer time course of schizophrenia, including treatment response to antipsychotics.

Decreased numerical density of CA3 hippocampal mossy fiber synapses in schizophrenia

The CA3 region of the hippocampus is unique in its connectivity, its role in cognitive maintenance, and its great vulnerability in schizophrenia. The down regulation of the expression and binding activity of glutamate receptors was revealed in the CA3 hippocampal region and may be attributed to cognitive disturbances in schizophrenia. Our previous study demonstrated that only schizophrenics with predominantly positive (but not predominantly negative) symptoms had smaller-sized branched spines (thorny excrescences) of CA3 pyramidal neurons and fewer synaptic contacts formed by dentate mossy fiber terminals (MFT-synapses). In the present study, we used an unbiased stereological physical dissector method to verify whether the numerical density of MFT-synapses is altered in schizophrenia. A morphometric study was performed in 10 normal controls and eight age-matched cases with chronic schizophrenia, including five cases with predominantly positive and three with predominantly negative symptoms. Schizophrenic cases had a significantly reduced numerical density of MFT-synapses (-25%, P < 0.01) compared with the control group. The decrease was similar in schizophrenic subgroups with predominantly positive and predominantly negative symptoms. No effects of postmortem delay, age, duration of disease, and neuroleptic exposure were found. Taken together with our previous results, the data suggest that the decrease of numerical density of MFT-synapses may be the result of different mechanisms in schizophrenics with predominantly positive and predominantly negative symptoms.

Characteristics of early psychosis

There is little research on characteristics related to course and prognosis of early-onset psychosis. The present article aims to advance our knowledge of this disorder for the purpose of proper diagnosis and treatment. It focuses on premorbid and prodromal characteristics, treatment history, symptoms and classifications, and differences between subgroups with affective and schizophrenic psychosis. A chart review was constructed to study a group of 129 subjects (12-18 years) with psychotic symptoms referred to the University Medical Center in Utrecht. The group was characterized by early—but nonspecific—treatment, developmental problems (mostly social), and clear prodromal symptoms. Drug abuse, depressive symptoms, and suicidal behavior were also frequent. Male sex, a relatively long prodromal phase, school problems, and drug abuse were more indicative of the schizophrenic subgroup. Introversion was characteristic for boys with schizophrenia. Classifications, however, were not stable. These findings suggest that early recognition of psychosis can be enhanced in health and youth care facilities. Careful examination of the prodromal phase seems helpful to differentiate between schizophrenic and affective psychosis.

P50 inhibitory gating deficit is correlated with the negative symptomatology of schizophrenia

Abnormal sensory gating in schizophrenia has frequently been reported. The strength of central inhibitory pathways was measured using the P50 component of the auditory evoked potential in a conditioning–testing paradigm. The relationships between a relative decrease in P50 amplitude to repeated auditory stimuli and clinical symptoms remain controversial. Using the Positive and Negative Syndrome Scale, we studied the P50 auditory conditioning–testing paradigm in 81 schizophrenic subjects, categorized into subgroups with and without prominent negative symptoms, in comparison with 88 control subjects. We found increased ratios of testing stimuli to conditioning stimuli in both schizophrenic subgroups relative to findings in the control group. In addition, we found significantly increased mean latencies of the P50 responses to conditioning (C) and testing (T) stimuli and significantly increased T/C ratios in the subgroup with negative symptoms compared with the subgroup with non-negative symptoms.

The Poor General Health of the Severely Mentally Ill: Impact of Schizophrenic Diagnosis

This study focused on poor health among the severely mentally ill and additional risks associated with schizophrenia. Records of 781 clients in short-term residential treatment programs provided data. The schizophrenic subgroup was compared to others in bivariate analyses, with significant findings included in logistic regression. Those with schizophrenia were more likely to be male, unemployed, and insured by MediCal/Medicare. Most health problems occurred at similar rates across diagnoses, reflecting common environmental risk factors. Those with schizophrenia had less substance abuse and fewer liver conditions, but more diabetes and chronic respiratory problems. Implications for providers and for research are discussed.

P.3.024 Skin conductance levels identify two subgroups of schizophrenics with different conentration of N-acetylaspartate in the left cingulated gyrus

P.3.024 Skin conductance levels identify two subgroups of schizophrenics with different conentration of N-acetylaspartate in the left cingulated gyrus

A Tc-99m HMPAO SPECT study of regional cerebral blood flow in drug-free schizophrenic patients with deficit and non-deficit syndrome

Twenty-nine patients with DSM-IV diagnoses of schizophrenia were categorized into deficit syndrome ( n=14) and non-deficit syndrome ( n=15) subgroups on the basis of the Schedule for the Deficit Syndrome. The patients, who had all been free of antipsychotic medication for at least 3 weeks, and 17 sex- and age-matched normal controls were studied with single-photon emission computed tomography with Tc-99m HMPAO. Age at onset, Brief Psychiatric Rating Scale (BPRS) total scores, BPRS positive symptom subscores and duration of illness were similar between the two schizophrenic subgroups. As expected, the deficit patients had more negative symptoms than the non-deficit patients. There were no statistically significant correlations between clinical parameters and regional cerebral blood flow (rCBF) values. The deficit syndrome subgroup showed diminished rCBF in the frontal regions bilaterally, right parietal regions and right superior temporal region compared with the control groups. Deficit patients showed significantly lower rCBF perfusion ratios in the right superior and inferior frontal cortex than did the non-deficit patients. No differences were detected between the controls and the non-deficit schizophrenic patients in terms of rCBF perfusion indices. The results of the present study confirm previous reports of different patterns of rCBF in deficit vs. non-deficit schizophrenic subgroups.

Correlation of neurodevelopmental disorders in schizophrenia

Contemporary aetiopathogenetic considerations, based on neuro-imaging, genetic and developmental neurobiology studies, suggest neurodevelopmental origin of schizophrenia. Several lines of evidence including structural abnormalities on in vivo brain imaging, the excess of prenatal and obstetric complications and the association of congenital and minor physical anomalies with schizophrenia, strongly indicate the neurodevelopmental pathogenesis of schizophrenia. On the other hand, controversial concept of psychotic continuum suggests schizophrenia and depression sharing the same genetic contribution to the pathogenesis. If this would be the case, depression could also be considered as neurodevelopmental disorder. The aims of the study were to investigate the association between: a) pregnancy and birth complications (PBC), and b) minor physical anomalies (MPA) and schizophrenia or depression. Experimental groups consisted of 60 schizophrenic, 28 major depression patients and 30 healthy controls. All patients were diagnosed according to DSM-IV. Schizophrenic group was divided with regard to PANSS score into positive (n = 32) and negative form (n = 28) subgroups. PBC informations were gathered from maternal recall while MPA were examined by using Waldrop scale for adults. The results showed that negative and positive schizophrenic subgroups had significantly more PBC than depressive group (p < 0.05), as well than controls (p < 0.001; p < 0.05; respectively). There was nonsignificant trend for more PBC in negative than in positive subgroup. All schizophrenic patients had higher rates of MPA than depressives (p < 0.05). This trend for more MPA was not significant in comparison with healthy controls. These findings suggest that schizophrenia, especially its negative forms, could be considered as a member of the spectrum of neurodevelopmental disorders, which does not seem to be the case with depression. PBC and MPA could also be valuable in evaluation of risks for schizophrenia and possible predictive indicators of its development.

Body image, symptoms and insight in chronic schizophrenia.

Historically, schizophrenics' body image problems were regarded as related particularly to delusions and hallucinations. However, during the 1980s, the predominant view of the phenomenology of the disorder broadened to include negative symptoms; deviations in schizophrenics' body image underlie various behaviors or allegations concerning the body and should be refocused. The present study attempted to detect body image deviations in chronic schizophrenia using the Body Image Questionnaire (BIQ), which comprises three hypothetical components (anatomical, functional and other psychological components), and to clarify their related clinical characteristics in symptoms and insight. The BIQ was administered to 93 chronic schizophrenics (diagnosed according to DSM IV; 44 men and 49 women) and 177 normals (78 men and 99 women) adults. The combined data of the three BIQ components in schizophrenic and normal subjects were factor-analyzed separately, and factor scores obtained were compared between schizophrenic and normal groups. The factor scores that differentiated groups were further compared between schizophrenic subgroups, determined by high or low scores for positive symptoms assessed by Scale for the Assessment of Positive Symptoms, negative symptoms by Scale for the Assessment of Negative Symptoms and insight by the Schedule for Assessing Insight. Significant differences between diagnostic groups were found in five of nine factor scores. Dullness in movement, powerlessness, unusually strong gastrointestinal function, lifelessness and fragility proved to be the deviated body images in chronic schizophrenic patients. Powerlessness and lifelessness proved to be related to positive and negative symptoms, and unusually strong gastrointestinal function and fragility to insight.

Patterns of recovery of autonomic dysfunctions and neurocognitive deficits in schizophrenics after acute psychotic episodes.

In this study, the authors aimed to identify patterns of autonomic dysfunction and neurocognitive deficit recovery. The authors performed laboratory assessments on 66 patients with schizophrenia immediately after an acute psychotic episode and 6, 12, and 18 months later. Shortly after the psychotic episode, the patients displayed cardiovascular hyperarousal at rest, cardiovascular and electrodermal hyporeactivity during 2 Continuous Performance Tasks (CPTs) and deficits in 2 behavioral CPT measures (i.e., reaction time and omission error rate) compared with 29 normal controls. In the subsequent postpsychotic course, changes indicative of a process of recovery occurred in all measurement areas, although with regard to autonomic hyporeactivity amelioration was limited to a subgroup of schizophrenics with complete and persistent symptomatic remission. Neurocognitive improvement in CPTs did not appear to depend on unimpaired autonomic reactivity mechanisms.

Abnormal phospholipid metabolism in schizophrenia: evidence from epidemiological findings, clinical observations, and preliminary clinical trials.

Both epidemiological findings and clinical observations and have shaped our thinking as regards to the neuropathology of schizophrenia. Epidemiological findings implicating environmental risk factors, including maternal dietary deficiency and urban birth place, suggest schizophrenia is a developmental disorder, whereas clinical observations gave rise to the "dopamine hypothesis." Epidemiological findings lead to complex multifactorial models, while clinical observations lead to more readily to testable, but not necessarily generalizable, hypotheses. Points where findings from these different approaches converge may provide us with new insights and points of departure. In this paper, clinical observations and epidemiological findings are presented which suggests that a subgroup of schizophrenics have abnormalities in phospholipid metabolism. Preliminary clinical trials involving administration of omega-3 fatty acids thus far appear to support this hypothesis.