Clinical Neuroscience

[Psychosis as a process - New implications of staging models of schizophrenia]


NOVEMBER 30, 2013

Clinical Neuroscience - 2013;66(11-12)

[The article discusses contributing factors in the pathogenesis of schizophrenia. In the last fifteen years, the emphasis has shifted from curative to prodromal and premorbid characteristics of later schizophrenia patients. Nevertheless, most studies are limited to the area of early detection and intervention of schizophrenia with much fewer focusing on actual prevention. A more general preventive approach not limited to psychotic condition is clearly underestimated. Following a review of current literature on prodromal approaches and identified premorbid markers of schizophrenia, the article outlines a possible trajectory of later psychotic condition with detectable, distinct stages from birth on. Based on this extended staging model involving neurotoxic impact and early prefrontal-limbic dysfunction, it argues for a refined, phase-specific treatment protocol including preventive interventions. Accepting a model of schizophrenia as an illness with detectable, phase-specific signs and symptoms from infancy on leads to the need to implement preventive interventions. Through this approach, we could, in the optimal case, be able to identify early signs of neuromotoric and cognitive dysfunction not specific for psychosis. Furthermore, it would be useful to lay greater emphasis on the detection of these early signs in the training of health care professionals. This approach calls for a close cooperation between psychologists, psychiatrists, neuropsychologists and special education experts and a change in the way we view psychotic illness.]



Further articles in this publication

Clinical Neuroscience

[Reversible hepatocerebral degeneration-like syndrome due to portovenous shunts]


[Ataxia and tremor are rare manifestations of hepatocerebral degeneration due to portovenous shunts. Ammonia is a neurotoxin that plays a significant role in the pathogenesis of hepatic encephalopathy. A 58-year old male patient was assessed with the complaints of gait disturbance, hand tremor, and impairment of speech. His neurological examination revealed dysarthric speech and ataxic gait. Bilateral kinetic tremor was noted, and deep tendon reflexes of the patient were hyperactive. Serum ammonia level was found to be 156.9 μg/dL. Cranial magnetic resonance (MR) imaging revealed increased signal intensity in bilateral globus pallidus on T1-weighted axial sections, and bilateral prominent hyperintense lesions in the middle cerebellar peduncles on T2-weighted axial sections. On his abdominal MR portography, multiple portohepatic venous collaterals were noted in the right and left lobes of liver parenchyma in 2D FIESTA axial MR sections. To our knowledge, we reported the first case of acquired hepatocerebral degeneration presenting with cerebral symptoms without any hepatic findings in which clinical improvement was noted, and hyperammonemia disappeared following medical treatment.]

Clinical Neuroscience

[Status epilepticus and its treatment - Update 2013]

GYIMESI Csilla, JUHOS Vera, HORVÁTH Réka, BÓNÉ Beáta, TÓTH Márton, FOGARASI András, KOMOLY Sámuel, JANSZKY József

[Our study provides an overview of the results and guidelines published on the treatment of status epilepticus in the last five years. In recent years, as a result of scientific observations and collected data, the definition of and treatment approach to status epilepticus have been refined and novel therapeutic methods have been developed. The updated guidelines provide guidance in everyday medical practice. However, only a relatively small number of randomized studies are available on status epilepticus, especially in second-line treatment and third-line treatment, thus it is difficult to transfer the newest methods into clinical practice and into updates to treatment protocols. Due to the nature and epidemiology of the disease, the treatment of status epilepticus remains a daily challenge for healthcare providers. The key points of an effective treatment are: expeditiously initiating appropriate therapy, concurrent causal treatment and anticonvulsant therapy, early detection of nonconvulsive status epilepticus, as well as avoiding "overtreatment" and side effects.]

Clinical Neuroscience

[Comparative efficacy of different muscle relaxants in the rehabilitation of post-stroke patients with spasticity]


Clinical Neuroscience

[Diffusion MRI measured white matter microstructure as a biomarker of neurodegeneration in preclinical Huntington’s disease]

KINCSES Tamás Zsigmond, SZABÓ Nikoletta, TÓTH Eszter, ZÁDORI Dénes, FARAGÓ Péter, NÉMETH Dezsõ, JANACSEK Karolina, BABOS Magor, KLIVÉNYI Péter, VÉCSEI László

[Background - Huntington’s disease is a progressive neurodegenerative disease, genetically determined by CAG trinucleotide expansions in the IT15 gene. The onset of the symptoms is related to the number of CAG triplets. Because the patients are asymptomatic in the early phase of the disease, in vivo biomarkers are needed to follow up the neurodegeneration and to test putative neuroprotective approaches. One such promising biomarker is the diffusion MRI measured microstructural alteration of the white matter. Methods - Seven presymtomatic, mutation carriers and ten age-matched healthy controls were included in the study. Diffusion parameters were compared between groups and correlated with measures describing neurodegeneration. In order to reduce the possible misregistration bias due to atrophy the analysis was restricted to the core of each fibre bundles as defined by maximal fractional anisotropy (Tract- Based Spatial Statistics). Results - Decreased fractional anisotropy, along with increased mean, parallel and perpendicular diffusivity was found in white matter tracts, mainly in the corpus callosum. An inverse correlation was detected between the fractional anisotropy and neurodegeneration score (derived from the number of CAG triplets and the patient age) from the areas of the left precentral gyrus, frontal lobe, corpus callosum and the capsula extrema. Altered diffusion parameters are promising biomarkers of the neurodegeneration in Huntington’s disease.]

Clinical Neuroscience


All articles in the issue

Related contents

Clinical Neuroscience

Alexithymia is associated with cognitive impairment in patients with Parkinson’s disease

SENGUL Yildizhan, KOCAK Müge, CORAKCI Zeynep, SENGUL Serdar Hakan, USTUN Ismet

Cognitive dysfunction (CD) is a common non-motor symptom of Parkinson’s disease (PD). Alexithy­mia is a still poorly understood neuropsychiatric feature of PD. Cognitive impairment (especially visuospatial dysfunction and executive dysfunction) and alexithymia share com­mon pathology of neuroanatomical structures. We hypo­thesized that there must be a correlation between CD and alexithymia levels considering this relationship of neuroanatomy. Objective – The aim of this study was to evaluate the association between alexithymia and neurocognitive function in patients with PD. Thirty-five patients with PD were included in this study. The Toronto Alexithymia Scale–20 (TAS-20), Geriatric Depression Inventory (GDI) and a detailed neuropsychological evaluation were performed. Higher TAS-20 scores were negatively correlated with Wechsler Adult Intelligence Scale (WAIS) similarities test score (r =-0.71, p value 0.02), clock drawing test (CDT) scores (r=-0.72, p=0.02) and verbal fluency (VF) (r=-0.77, p<0.01). Difficulty identifying feelings subscale score was negatively correlated with CDT scores (r=-0.74, p=0.02), VF scores (r=-0.66, p=0.04), visual memory immediate recall (r=-0.74, p=0.01). VF scores were also correlated with difficulty describing feelings (DDF) scores (r=-0.66, p=0.04). There was a reverse relationship bet­ween WAIS similarities and DDF scores (r=-0.70, p=0.02), and externally oriented-thinking (r=-0.77,p<0.01). Executive function Z score was correlated with the mean TAS-20 score (r=-62, p=0.03) and DDF subscale score (r=-0.70, p=0.01) Alexithymia was found to be associated with poorer performance on visuospatial and executive function test results. We also found that alexithymia was significantly correlated with depressive symptoms. Presence of alexithymia should therefore warn the clinicians for co-existing CD.

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

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

SZEKERES György, PÁVICS László, JANKA Zoltán

[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.]

Lege Artis Medicinae

[How many cardiovascular events can be avoided by a lipid lowering therapy based on preventive guidelines?]

MÁRK László

[The lipid lowering therapy became one of the most important elements in the cardiovascular prevention, yet it is not appropriately evaluated neither by the doctors, nor by the patients. The lipid goal attainment should to be improved according to Hungarian and international data. Using a recommendation guided lipid lowering therapy the most benefit can be expected in the patients at very high risk who alrea­dy had a cardiovascular event, where the LDL-cholesterol goal is 1.8 mmol/L. Calculating upon the data of 170000 patients of Cholesterol Treatment Trialists’ Collaboration a decrease of LDL-cholesterol level from 2.5 mmol/L to 1.8 in 100 patients in 10 years would avoid 3 myocardial infarctions, strokes or death, lowering that from 3.5 mmol/L to the goal would prevent these 3 events within 5 years. Using the traditional LDL-cholesterol lowering medication, high dose statin and ezetimibe, if the attitude of doctors and the compliance of patients would be ideal, the 1.8 mmol/L goal attainment rate would be over 80%. Unfortunately, up to now the reimbursed administration of ezetimibe in Hungary is still bound to a specialist’s recommendation, adding it to any dose of any statin an additional 20% LDL-cholesterol can be expected. The reimbursed administration of PCSK9-inhibitors is possible only based on a special request to National Health Insurance Fund. To achieve a better national cardiovascular morbidity and mortality the attitude of the doctors and the adherence of the patients to the lipid lowering therapy should be improved (it’s the goal of the present paper as well).]