Schizophrenia: From the brain to peripheral markers. A consensus paper of the WFSBP task force on biological markers

Abstract

Objective. The phenotypic complexity, together with the multifarious nature of the so-called ''schizophrenic psychoses'', limits our ability to form a simple and logical biologically based hypothesis for the disease group. Biological markers are defined as biochemical, physiological or anatomical traits that are specific to particular conditions. An important aim of biomarker discovery is the detection of disease correlates that can be used as diagnostic tools. Method. A selective review of the WFSBP Task Force on Biological Markers in schizophrenia is provided from the central nervous system to phenotypes, functional brain systems, chromosomal loci with potential genetic markers to the peripheral systems. Results. A number of biological measures have been proposed to be correlated with schizophrenia. At present, not a single biological trait in schizophrenia is available which achieves sufficient specificity, selectivity and is based on causal pathology and predictive validity to be recommended as diagnostic marker. Conclusions. With the emergence of new technologies and rigorous phenotypic subclassification the identification of genetic bases and assessment of dynamic disease related alterations will hopefully come to a new stage in the complex field of psychiatric research.

Schizophrenia and cytokines

“…Poznato je da u shizofreniji postoji dopaminergičko-glutamatergička disfunkcija, čija je neuroanatomska osnova kortiko-strijato-talamusno-kortikalni krug [18]. Brojna istraživanja na animalnm modelima potvrdjuju predpostavku da citokini utiču na neurotransmitersku aktivnost [19]. Simplifikovano, pojedini citokini koji se frekventno dovode u korelaciju sa shizofrenijom dovode do neurohemijskih promena u ovom oboljenju npr.-IL-6 stimuliše povećavanje serotonina i dovodi do mezokortikalne dopaminske aktivnosti u hipokampusu i prefrontalnom korteksu [20], TNF-a ima stimulatorni efekat na kateholamine u slučaju akutnog oslobadjanja, dok hronično utiče na inaktivaciju kateholaminske sekrecije [21], IL-2 stimuliše dopaminsku neurotransmisiju sa jedne strane, akutno administriran utiče i na povečanje noradrenalina na funkcionalno značajnim mestima, a sa druge strane utiče i na inhibiciju oslobadjanja acetilholina u hipokampusu i prefrontalnom korteksu [22,23].…”

Psychosis in Neurosyphilis - Clinical Aspects and Implications

“…The so-called positive symptoms are hypothesized to arise from hyperactive mesolimbic dopamine neurons. Negative symptoms, cognitive deficits, and affective symptoms are considered a result of underactivity of mesocortical dopamine neurons and their projections to the prefrontal cortex [13,19]. These structures may be involved in parenchymatous destruction by T. pallidum, but as far as we know, there are no specific regional findings published.…”

“…Some studies suggest that GABA biosynthesis might be a central component in the pathophysiology of psychosis. However, disturbances on the transmitter level may reflect secondary changes to primary dysfunctions [13,19]. As far as we know, there is no literature concerning T. pallidum and dopamine that focuses on NMDA or GABA pathways.…”

“…Described and observed pathophysiological changes have been correlated with changes in homocysteine metabolism, oxidative stress, excitotoxicity and altered tryptophan catabolism [21]. Lymphocyte and protein abnormalities, autoantibodies and cytokines are also implicated in immune system dysfunction in psychosis [13,22]. Further studies focused on mechanisms including the immunological balance between type 1 and type 2 immune activation, which have an influence on the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase in the CNS, leading to an altered availability of serotonin and tryptophan.…”

“…In the 1970s interest in this research area increased again, and the World Health Organization held a symposium in 1983 entitled ‘Research on the viral hypothesis of mental disorders'. Since that time, scientific interest in the area has continuously increased [11,12,13,14]. …”