Károly  Mirnics and Péter Gaszner


The diagnosis and therapy of schizophrenia is one of the major problems for the clinical psychiatrist,
while research within this field is a continuing challenge for its researchers, and the answer to the
questions encountered is not always clear and convincing. To face these challenges, Karoly Mirnics and
his research team met several schizophrenia research experts on 11 October, 2011 at the Department
of Clinical and Theoretical Mental Health, Semmelweis University, Budapest, to discuss this topic in
the form of a brainstorming session.
The scientific papers of the ”Schizophrenia: biology, diagnostics and therapy” workshop are
now published in Neuropsychopharmacologia Hungarica as short communications. In the workshop,
schizophrenia as a separate disorder; its genetic background; the contributing environmental factors
and their relevance and importance; related brain anomalies (as causative factors); treatment options;
etiological models; diagnostic requirements; pharmaco-, socio- and psychotherapeutic approaches,
and forensic and legal issues were discussed and debated, and were sometimes left without a clear
and straightforward answer.
Besides neuropsychopharmacologic issues, in the previous one and a half decades Neuropsychopharmacologia Hungarica always provided opportunity for the publication of various other psychiatric
and research topics. It is our honour to publish the most recent research results of renowned Hungarian
and foreign professionals in the much-debated field of schizophrenia research.

Origins and perspectives of the schizophrenia research

Gabor Faludi, Peter Dome and Judit Lazary


Schizophrenia is a complex psychiatric disorder with a heterogeneous clinical phenotype. Ancient paradigms focused on clinical experiences and hypotheses mostly without validated measurements but in the modern neuroscientific era the trend has turned oppositely; although an expanding body of evidence is available in association with the neurobiological background of schizophrenia, it seems that development of phenotypic description has been missing from the focus. However, now it is clear that a relevant and sophisticated diagnostic system is also essential for the appropriate interpretation of comprehensive molecular studies. Besides a brief review of most important data on schizophrenia research, the authors call attention to a complex diagnostic system (Composite Diagnostic Evaluation, CODE) which can be a valuable clinical partner of currently accepted models of schizophrenia, such as the neurodevelopmental hypothesis.

(Neuropsychopharmacol Hung 2011; 13(4): 185-192)

Keywords: schizophrenia, epidemiology, etiology, pathomechanism



The diagnosis of schizophrenia has undergone substantial change during the last 100 years
since its first descriptions by Kraepelin and Bleuler, this process is still continuing at present.
The never ending changes of the diagnosis are partially attributable to the symptomatologic
heterogeneity seen in schizophrenia and the complex etiology understood only to a small
extent. On the other hand, the evolution of the diagnostic systems reflects the standpoints,
priorities, and possibilities in the treatment of the disorder in the given period of time.
The original accounts of Kraepelin and Bleuler grasped distinct features of schizophrenia,
these works still influence our understanding and concepts about the disorder. To resolve
the problem of phenotypic heterogeneity there have been two conceptual approaches
appearing throughout the history of schizophrenia diagnostics. The categorical approach
has defined subgroups within the disorder, whereas dimensional thinking puts emphasis
on the severity of different symptom clusters. The present revision of the DSM is characterized by the strengthening of the dimensional approach. Ongoing and future research about
pathophysiologically determined biomarkers will have a major impact on the diagnostic
system of schizophrenia. The overall aim of these changes is to improve our understanding
and indirectly the treatment possibilities of patients suffering from this complex disorder. 

(Neuropsychopharmacol Hung 2011; 13(4): 193-203)

Keywords: schizophrenia, diagnosis, Kraepelin, Bleuler, categorical, dimensional, DSM-V, biomarker


Schizophrenia is a complex, devastating brain disorder with clear genetic and environmental contributions to the emergence of the disease. In the last several decades of research hundreds of millions of dollars were spent of the elusive search for schizophrenia susceptibility genes, but the results have been meager. Researchers have identified a number of genetic variants that predispose the brain to developing the disease, yet alone they can explain only a very small number of the schizophrenia occurrence. Vulnerability in DISC1, NRG1, DTNBP1, RGS4, KCNH2, COMT, AKT1 and other putative schizophrenia genes, together with copy number variants, leave unexplained the vast majority of diseased cases. Furthermore, most of the uncovered disease-associated genetic variants have been inconsistently replicated across multiple cohorts and do not lead to altered protein structure. In summary, we argue that large-scale genetic studies will not provide us with the answers we seek: we have to accept that there are no schizophrenia-predisposing genes with large effect sizes, and due to the diversity of findings, genetics-based novel therapies of schizophrenia are not realistic. The new treatments will have to come from functional studies of intracellular pathways and understanding the confluence of environmental influences and genetic predisposition, and their combined effects on developmental mechanisms and intracellular cascades.

(Neuropsychopharmacol Hung 2011; 13(4): 205-210)

Keywords: schizophrenia, genetic predisposition, susceptibility genes, copy number variation, genome-wide association studies

Schizophrenia, environment and epigenetics

Must Anita, Janka Zoltán and Horváth Szatmár


Psychotic, cognitive and affective symptoms defining schizophrenia may, though much less
severe, manifest themselves in up to 10 to 20% of the general population. What explains the
fact that in certain cases the symptoms require even constant medical supervision, while
others are capable of living a normal life within social conventions? Which factors lead to
the transition of mild, subclinical manifestations and vulnerability indicators towards the
outburst of one of the most severe and depriving mental disorders? Genetic susceptibility is
undoubtedly crucial. More recent research findings emphasize the modifying effect of specific
environmental factors on gene expression. The gene-environment interplay may induce socalled epigenetic alterations which may manifest themselves over several generations. Future
integrative, multi-dimensional and flexible schizophrenia research approaches focusing on
the identification of neurobiological and cognitive outcomes are much needed to understand
disease vulnerability, susceptibility mechanisms, periods and interactions. Research methods
may differ, but our aim is common – establishing more effective diagnostic and therapeutic

 (Neuropsychopharmacol Hung 2011; 13(4): 211-217)

Keywords: schizophrenia, environmental factors, epigenetics, vulnerability


In this study morphological knowledge about schizophrenia including different levels from
macroscopic to molecular changes is summarized. We have had data on the schizophrenic
brain for more than 100 years. Cortical and subcortical regional grey matter volume and density
decreases, as well white matter lesions are well-known phenomena. They induce disconnectivity which is a significant element in the pathology of schizophrenia. The most important
detectable macroscopic changes are volume reductions in the temporal lobe, prefrontal
cortex, superior temporalis gyrus, anterior cingulate gyrus and planum temporale. The later
is also important in terms of the hemispheric asymmetry reduction, which is considered to
be a relevant feature of the disease. Recently several macroscopic changes, mainly neuropil
alterations, axonal and dendritic changes, and extensive functional and structural alterations
of the synapses have been revealed. Although numerous mechanisms (aberrated migration,
altered pruning and neuroplasticity) have already been identified in the background, a full
picture has not yet emerged. Remarkable results have been collected concerning the energy
metabolism in the brain, lipid metabolism, and proteomic results. At present there are controversial data concerning the association between the development of the above-mentioned
alterations and antipsychotic medication.

 (Neuropsychopharmacol Hung 2011; 13(4): 219-227)

Keywords: schizophrenia, postmortem, morphology, synapse, pruning, liquor


The neurodevelopmental hypothesis of schizophrenia suggests that subtle anomalous brain development occurs in utero which reveals itself symptomatically, years later, as the heterogeneous symptoms of schizophrenia. This paper shortly reviews data on the presence of minor physical anomalies in those affected by schizophrenia and also summarizes a few results from structural brain imaging studies, which promote the neurodevelopmental hypothesis of the disease.

(Neuropsychopharmacol Hung 2011; 13(4): 229-232)

Keywords: neurodevelopment, minor physical anomalies, structural brain imaging, schizophrenia

Non-pharmacological biological therapies in schizophrenia

Gabor Gazdag and Gabor S. Ungvari


Non-pharmacological biological therapies of schizophrenia have dramatically developed over the last eight decades. Starting from a historical perspective authors aim to give an overview about the development of convulsive therapy. Recommendations of the most influential guidelines and the controversies in the worldwide clinical practice are discussed and clinical conditions responsive to electroconvulsive therapy are reviewed. Finally, the place of the new neurostimulation techniques, particularly TMS is outlined.

(Neuropsychopharmacol Hung 2011; 13(4): 233-238)

Keywords: electroconvulsive therapy, transcranial magnetic stimulation, schizophrenia, 
catatonia, post-partum psychosis


Schizophrenia is a disorder of the brain with multicausality, chronicity, and various symptom
manifestations within its course. The therapeutic interventions are determined by the actual
psychiatric condition characterized by the three main syndromes (positive, negative and
cognitive symptoms). Antipsychotics are essential drugs in the therapy of schizophrenia and
anxiolytics, antidepressants, antiepileptics are only adjuvants with temporary use. The previous
studies show no results in the therapy of the cognitive symptoms, and the new antipsychotics improve the negative symptoms moderately. The reduction and prevention of positive
symptoms is practicable with the established selection of antipsychotics. The antipsychotics
are the basis therapy of schizophrenia so the knowledge of their pharmacology and clinical
effects are essential for the clinicians. The typical-atypical classification is an outworn concept
because there are pharmacological differences not only between the two groups but within
the groups too. There are no significant differences among the antipsychotics with respect to
efficiency but their side effect profiles are very different. The choice of a drug is influenced by
the actual psychic and somatic conditions, comorbidity on one hand, and on the other hand
by the pharmacodynamic and pharmacokinetic characteristics of the drugs. For example an
antipsychotic with high affinity to dopamine receptors would be the good choice to eliminate
the psychotic syndrome, but another one with low risk to cause extrapyramidal side effects
would be the right choice for long term therapy. The next important question is the adjustment
of the dose which is determined by the patient’s somatic conditions and pharmacological
factors, such as absorption, activity of metabolizing enzymes, function of the blood-brain
barrier. In the lack of this property the clinicians can optimalize the dose only with the evaluation of the clinical response. The switch of a drug is required if it is ineffective or causes side
effects. In these cases the clinicians have to be familiar with the pharmacological features of
the two drugs and the condition of the patient. In the course of schizophrenia you can experience depressive, anxious, aggressive states that can be treated with adjuvants, but the risk/
benefit ratio of these therapies should be considered. In addition to the drug administration
the patients need psychological intervention and/or social therapy, however that cannot
work without effectively tailored pharmacotherapy. Important viewpoints are the patient’s
well-being and the level of his functionality, that also depends on the right drug therapy. The
aim of the author was to help the clinicians in their decision making.

 (Neuropsychopharmacol Hung 2011; 13(4): 239-247)

Keywords: schizophrenia, pharmacotherapy, antipsychotics



Referring to the scientific literature the authors analyze the correlation between criminal
offense and psychiatric disorders. Frequency of violent behaviour in schizophrenia together
with the risk factors are reviewed. The issue of violent offense is separately discussed. Impact
of deinstitutionalization on offense is also analyzed. Results regarding the genetic correlations are also reviewed. Finally the question of re-offending is discussed. In summary the
importance of this issue in stigmatization and in the development of the mental health care
system is highlighted.

 (Neuropsychopharmacol Hung 2011; 13(4): 257-261)

Keywords: schizophrenia, violent offense, substance abuse, sociodemographic variables, stigmatization


The development of new therapeutic approaches is considered to be a major contributor to
the re-evaluation of therapeutic outcomes in schizophrenia. The present review accentuates
the recent dimensional concept of improvement, including the integration of social and
clinical aspects of different treatment approaches together with the culture-specific pragmatic
concept of the therapeutic success. The outpatient status of the patient in itself is no longer
recognised as a final success of the therapy, if the very basic aspects of self-management
and performance, education and employment of the schizophrenic patients are not properly
resolved. Thus the symptomatic therapy alone, without the amelioration of social skills, can
no longer be recognised as a satisfying therapeutic target. Novel sensitive possibilities of the
measurement of functional improvement were recently introduced in order to facilitate both
the development of a personalized, efficient treatment and the evaluation of therapeutic
efficacy in schizophrenia.

 (Neuropsychopharmacol Hung 2011; 13(4): 249-256)

Keywords: Schizophrenia, improvement, social skills, dimensional approach, outcome measures