Clinical Neuroscience

[Investigation of the dopamine dysregulation hypothesis of schizophrenia with neuroimaging techniques]

SZEKERES György, PÁVICS László, JANKA Zoltán

AUGUST 20, 2002

Clinical Neuroscience - 2002;55(07-08)

[The most elaborated biochemical concept of schizophrenia is the dopamine hypothesis. However, this classical theory is based on indirect observations. It has recently become possible to study this theory directly by means of advanced functional neuroimaging techniques, the development of specific radioligands and study protocols that are eligible to monitor dynamic changes in the neurotransmitter systems. According to the early concept, the essence of schizophrenia is the hyperactivity of the dopamine system. Nevertheless, this idea has gone through many modifications. In accordance with the modified dopamine hypothesis, the cognitive deficit and negative symptoms are related to the hypoactivity of the dorsolateral prefrontal cortex while the acute phasis of the disease associates with hyperactivity of the ventral striatal elements of the dopaminergic system. Between these dysfunctions there is causality via their exuberant connections. Beyond that, the interactions between the prefrontal and striatal anomalies implicate the involvement of other neurotransmitters than dopamine. Observations from model psychosis induced by N-methyl-D-aspartate antagonists and in vivo neuroimaging investigations in humans support primarily the role of glutamatergic system. Our developing knowledge about the neurochemical mechanism of schizophrenia can significantly affect therapeutic strategies as well.]



Further articles in this publication

Clinical Neuroscience

[The molecular genetic control of bony developmental malformations affecting the craniocervical junction and the cervical spine]


[In this review a new interpretation of the origin of bony developmental malformations affecting the craniocervical junction and the cervical spine is presented based on recent advances in the understanding of embryonic development of the spine and its molecular genetic control. Radiographs, CT and MRI scans or CT myelograms of patients with Klippel-Feil syndrome were used for demonstration. Detailed clinical and radiologial analysis of these patients was published earlier [David KM, Stevens JM, Thorogood P, Crockard HA. The dysmorphic cervical spine in Klippel-Feil syndrome: interpretations from developmental biology. Neurosurg Focus 1999;6(6):1.]. Homeotic transformation due to mutations or disturbed expression of Hox genes is a possible mechanism responsible for C1 assimilation. Notochordal defects and/or signalling problems, that result in reduced or impaired Pax-1 gene expression, may underlie vertebral fusions. This, together with asymmetrical distribution of paraxial mesoderm cells and a possible lack of communication across the embryonic mid-line, could cause the asymmetrical fusion patterns. The wide and flattened shape of the fused vertebral bodies, their resemblance to the embryonic cartilaginous vertebrae and the process of progressive bony fusion with age suggest that the fusions occur before or, at the latest, during chondrification of vertebrae. The authors suggest that the aforementioned mechanisms are likely to be, at least in part, responsible for the origin of the bony developmental malformations affecting the craniocervical junction and the cervical spine.]

Clinical Neuroscience

[Application of kinematic parameters for the assessment of impairments due to central motoneuron damage]

FAZEKAS Gábor, FEHÉR Miklós, KOCSIS László, STEFANIK Györgyi, BOROS Zsuzsanna, JURÁK Mihály

[Evidence based medicine requires objective methods for the assessment of status of the patients. The method described by the authors makes it possible to assess motoric impairment of patients in an objective way. It is based on three-dimensional motion analysis. Authors present the case history of two patients with spastic hemiparesis due to central nervous system damage. Changes in motoric impairment were followed by three-dimensional motion analysis. This method can be adapted for the assessment of motor impairment arising from other reasons as well.]

Clinical Neuroscience

[The evolution of psychoneuroimmunology]


Clinical Neuroscience

[Percutaneous procedure for treatment of diseased vertebral bodies with different etiology: vertebroplasty]


[Percutaneous vertebroplasty is a radiologically guided invasive technique consisting of the injection of surgical cement into the diseased vertebral body. The procedure results in immediate pain relief and strengthening of the bone due to the polymerization process of the filling material hardening the vertebral body and preventing further collapse. This method is suitable for the treatment of osteoporotic vertebral fractures and of osteolytic vertebral body metastases without neurological signs, in multiple appearance as well. Authors present technical details of the procedure performed by bi-directional fluoroscopy and combined CT-fluoroscopy control as well as short-term experience obtained by treatment of 17 patients.]

Clinical Neuroscience


All articles in the issue

Related contents

Clinical Neuroscience

TLR4 (Toll-like receptor-4) expression and frontal-cingulate volumes in schizophrenia

LI Hua, KÉRI Szabolcs

Evidence suggests that pathogen-associated pattern recognition receptors (Toll-like receptors, TLRs) are implicated in the pathophysiology of schizophrenia. TLRs are important in both peripheral immune responses and neuronal plasticity. However, the relationship between peripheral TLR expression and regional brain volumes is unknown in schizophrenia. We therefore assessed 30 drug-naïve, first-episode patients with schizophrenia. TLR4+/TLR1+ monocytes were measured using flow-cytometry. High resolution magnetic resonance images (T1 MRI) were obtained and analyzed with FreeSurfer. Results revealed significant negative correlations between the percentage of TLR4+ monocytes, mean fluorescent intensities, and brain volumes in frontal and anterior cingulate regions. The measures of TLR1+ monocytes did not show significant relationships with regional brain volumes. These results raise the possibility that abnormal TLR-activation is associated with decreased brain volumes in schizophrenia.

Clinical Neuroscience

Symptom profiles and parental bonding in homicidal versus non-violent male schizophrenia patients

HALMAI Tamás, TÉNYI Tamás, GONDA Xénia

Objective - To compare the intensity and the profile of psychotic symptoms and the characteristics of parental bonding of male schizophrenia patients with a history of homicide and those without a history of violent behaviour. Clinical question - We hypothesized more intense psychotic symptoms, especially positive symptoms as signs of a more severe psychopathology in the background of homicidal behaviour. We also hypothesized a more negatively perceived pattern (less Care more Overprotection) of parental bonding in the case of homicidal schizophrenia patients than in non-violent patients and non-violent healthy controls. Method and subjects - Symptom severity and symptom profiles were assessed with the Positive and Negative Syndrome Scale in a group of male schizophrenia patients (n=22) with the history of committed or attempted homicide, and another group (n=19) of male schizophrenia patients without a history of violent behaviour. Care- and Overprotection were assessed using the Parental Bonding Instrument (PBI) in a third group of non-violent healthy controls (n=20), too. Results - Positive, negative and general psychopathology symptoms in the homicidal schizophrenia group were significantly (p<0.005) more severe than in the non-violent schizophrenia group. Non-violent schizophrenia patients scored lower on Care and higher on Overprotection than violent patients and healthy controls. Homicidal schizophrenia patients showed a pattern similar to the one in the healthy control group. Conclusions - It seems imperative to register intense positive psychotic symptoms as predictive markers for later violent behaviour. In the subgroup of male homicidal schizophrenia patients negatively experienced parental bonding does not appear to be major contributing factor to later homicidal behaviour.

Clinical Neuroscience

[The application of RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) in neurocognitive testing of patients suffering from schizophrenia and dementia]

JUHÁSZ Levente Zsolt, KEMÉNY Katalin, LINKA Emese, SÁNTHA Judit, BARTKÓ György

[Introduction - The purpose of our study was to find out whether the Hungarian adaptation of the RBANS (Repeatable Battery for the Assessment of Neuropsychological Status), a brief neurocognitive screening test, is appropriate for the differentation of healthy and non-healthy subject groups, or for the detection of differences between the cognitive performance of patient groups. Patients and method - The test battery was administrated to 38 healthy subjects, 69 schizophrenic patients, and 18 patients suffering from dementia (10 probable Alzheimer-type and eight vascular dementia). Results - There was a significant decrease of performance in all patient groups compared to the healthy group. In the schizophrenic group, the test indicated a deterioration of functioning in all cognitive areas. The patient group with Alzheimer-type dementia performed only slightly better than the schizophrenic group, because the fall of performance was not significant only one of the cognitive areas (in the visuo-spatial tasks) when compared to the healthy group. There was no difference between the performance of patients with vascular dementia and that of healthy subjects in direct memory, verbal and visuo-spatial tasks. The test results indicated an even deterioration of cognitive areas in patients with Alzheimer-type dementia. As for the vascular dementia group, the most vulnerable area proved to be that of attention, while their verbal functions were relatively spared. The deterioration in other cognitive functions shown by schizophrenic subjects was more moderate, but still significant. A comparison of the RBANS scores of the schizophrenic patients in our study and the result of an American study was also carried out. The global indeces showed no difference; only the pattern of the sub-scales was a little different. Conclusion - The Hungarian version of the RBANS seems appropriate for the differentiation of healthy and deteriorated cognitive performance in a Hungarian patient population.]

Lege Artis Medicinae

[Clozapine - the last resort antipsychotic for treatment resistant schizophrenia ]


[More than 60 years old is the first antipschychotic drug that is operating atypically as well. With its multifarious history it gained the golden standard title of all therapy resistent schisophrenic cases for the last three decades. In this article we place clozapine on the map of psychopharmacology and review its history’s most important chapters. In the third part we discuss some of the most relevant effects and side effects of clozapine in the light of latest research and practical considerations touching the problem of the optimal start timing. ]

Clinical Neuroscience

[Relationship between the efficacy of atypical antipsychotics and polymorphism of dopamine D3 receptor in schizophrenia]

SZEKERES György, JUHÁSZ Anna, KÉRI Szabolcs, RIMANÓCZY Ágnes, SZENDI István, SZABÓ Zoltán, JANKA Zoltán

[Object - Numerous relevant variants of dopamine receptors have been identified in schizophrenia. The Ser9Gly gene polymorphism of dopamine D3 receptor is known as a susceptibility factor for the disease. In addition, it has a role in the modification of therapeutic effect of antipsychotics. In this naturalistic study the authors investigated the relationship between this polymorphism and the therapeutic response to atypical antipsychotics. Method - 75 patients with schizophrenia according to DSM-IV and 45 healthy controlls were recruited. The patients were divided to responder and nonresponder subgroups, cut-off: >20 point improvement in Global Assessment of Functioning. By polymerase chain reaction the genotype of dopamine D3 receptor of every participant was determined. Results - The Ser9Ser genotype of dopamine D3 receptor was more frequent in the nonresponder subgroup (64%, p=0.0018). The Ser9 allele was overrepresented among nonresponder patients (82%, p=0.0172). Conclusion - Based on our results, the worse therapeutic response to atypical antipsychotics is associated with Ser9 variant of dopamine D3 receptor.]