Towards a Comprehensive Pathophysiology

of Schizophrenia Based on Impaired

Glial-Neuronal Interactions - Part II


By Dr. Bernhard J. Mitterauer

Professor of Forensic Neuropsychiatry

Salzburg, Austria



Editor’s Note: Presented here is Part II of a two-part paper. Part I was featured in the previous January-February 2013 issue of this Journal.



Pathophysiological model of schizophrenia

The core symptoms of schizophrenia can be divided into positive and negative symptoms, with the former including hallucinations, delusions, and disorganization, and the latter including anergia, flattening of affect, and poverty of thought content accompanied by significant disturbances in cognitive function (Meltzer, 2003). Hypotheses concerning the etiology of schizophrenia comprise biological, psychological and sociological approaches (Carpenter and Buchanan, 1995; Shastry, 2002; Kapur and Lecrubier, 2003; Lenzenweger et al., 2007). Generally one can explain delusions and hallucinations in terms of a “loss of ego- or self-boundaries in the sense of an inner/outer confusion” (Fisher and Cleveland, 1968; Sims, 1991; Mitterauer, 2003).


Non-functional astrocytic receptors cause astrocytic domain decomposition

Let me attempt to show how it may be possible to deduce the main schizophrenic symptoms from an unbalanced tripartite synapse. If the glial receptors are totally non-functional and therefore cannot be occupied by neurotransmitters, the system is unbalanced. As in Fig. 6 depicted, the glial receptors (glR) are non-functional (crosses) and cannot be occupied by neurotransmitters (NT), so that the activation of the gliotransmitters (GT) is impossible. Hence, they cannot negatively feedback to the receptors on the presynapse (prR) and are unable to depolarize the postsynaptic neuron. As a consequence, the glia lose their inhibitory or boundary-setting function and the neural transmitter flux is unconstrained, as the flux of thought on the phenomenological level.


Non-functional glial receptors (glR), depicted by crosses, cannot be occupied by neurotransmitters (NT). Since the activation and production of gliotransmitters (GT) is not possible, glia do not negatively feed back to the presynaptic receptors (prR) and cannot depolarize the postsynaptic neuron. This severe synaptic disturbance leads to an unconstrained neurotransmission (fat arrows).


Four astrocytes (Ac1...Ac4) are interconnected via gap junctions (g.j.) building a glial network. Four neurons (N1...N4) are interconnected via axons (Ax) building a neuronal network (dendrites not shown). The synaptic interactions between the glial and neuronal networks are interrupted, since the astrocytic receptors (AcR) are nonfunctional (crosses).


As already described, synaptic glial-neuronal interactions are organized into astrocyte domains. Non-functional astrocytic receptors decompose the glial network from the neuronal one causing a gap between the two. Thus, the term schizophrenia is correct in view of this pathophysiological model. Fig. 7 represents a simple diagram of this network decomposition. Four astrocytes (Ac1…Ac4) are interconnected by gap junctions (g.j.) building a glial network (syncytium). Four neurons (N1…N4) are also interconnected via axons (Ax) generating a neuronal network. Since the astrocytic receptors (AcR) are non-functional, synaptic glial-neuronal interactions are disrupted (crosses).


Because the astrocyte domain organization may be significant for qualitative information structuring in the brain (Mitterauer, 2010), its decomposition leads to a generalization of information processing in the neuronal networks. Thus, schizophrenics cannot recognize qualitatively different features of subjects and objects but instead they must think in general cases. This cognitive incapability may cause a misinterpretation of a given reality in the sense of delusions and hallucinations. One may argue that a glial determination of neuronal networks into functional units is not necessary because the neuronal system is compartmentalized  per se (Rall, 1995). However, according to my view, there is a qualitative difference between the purely neuronal compartments and the glia-determined domains. Neuronal compartments may be merely functional for information processing, whereas glial-neuronal compartments may in addition have an information-structuring potency that we need for recognizing the qualitative differences between objects and individuals in our environment. That capacity may be lost in schizophrenic patients. Therefore, one can also speak of a loss of conceptual boundaries in schizophrenia. Let me now deduce the main symptoms of schizophrenia from unbalanced tripartite synapses caused by non-functional glial receptors. Table 1 shows the basic schizophrenic symptoms (American Psychiatric Association, 1998) that may be caused by a loss of conceptual boundaries. This disorder can affect cognitive processes such as thinking. If a schizophrenic patient is unable to delimit conceptual boundaries among words, thoughts, or ideas with different meanings, then meaningless word constructs (neologisms) or disorganized speech are the typical phenomenological manifestations, called “thought disorder”.


Table 1.  Interpretation of basic schizophrenic symptoms

Loss of boundaries



Thought disorder






Catatonic symptoms


Affective flattening


If the loss of boundaries concerns concepts, a thought disorder results. In the case of a loss of ontological boundaries among the Self and the others (Non-Selves), delusions occur. This loss of ontological boundaries can also affect the perception system in the sense of hallucinations. The loss of boundaries among motor modules shows up in catatonic phenomena. If the boundaries between emotional qualities are lost, affective flattening is the typical symptom. (Mitterauer, 2003)


From an ontological point of view, delusions are the consequence of the loss of boundaries between the self and the others (nonselves). Here, the self is defined as a living system capable of self-observation (Mitterauer and Pritz, 1978). One could also say that our brain embodies a distinct ontological locus of self-observation. Everything taking place in the brains of schizophrenic patients is reality because they cannot differentiate between their inner world and the outer world. Therefore, they cannot see ontological differences between the selves and the nonselves. This loss of ontological boundaries may lead to a delusional misinterpretation of reality.


Hallucinations may be caused by the same disorder. However, the perception systems are phenomenologically affected. A schizophrenic who hears the voice of a person in his head is absolutely convinced that this person is really speaking to him. The loss of ontological boundaries or inner/outer confusion shows its phenomenological manifestation in the auditory system. Such a disorder can also occur in other sensory systems.


If the loss of boundaries affects the motor system in the brain, the symptomatology is called catatonia. A state of catatonic agitation in which a disinhibited discharge of nearly all motor systems occurs is an expression of motor generalization with raging and screaming as behavioral components. One could also say that the brain’s inability to constrain information processing among motor modules appears in catatonic phenomena. Hence, the catatonic type of schizophrenia represents a serious disorder of motor behavior. Typical symptoms are excessive motor activity and motoric immobility (stupor). Both phenomena appear to be purposeless and not influenced by external stimuli. In such a catatonic state, a patient is unable to communicate. He or she cannot see the other. Everything that happens takes place in the brain of the patient.


Affective flattening is regarded as a negative schizophrenic symptom (Arajärvi et al., 2006). This symptom can also be explained as a loss of boundary setting. The different affective or emotional qualities cannot be produced within the brain, and the communication of feelings is disturbed as a result (Holden, 2003).


Some genetic considerations

There is growing evidence of disease-related altered astrocyte gene expression. These findings suggest an imbalance of glutamate-glutamine cycle in the communication of neurons and astrocytes (Hashimoto et al., 2005). There is also evidence for a broad involvement of astrocytes in other aspects of the pathophysiology in schizophrenia (Bernstein et al., 2009). However, if we focus on nonfunctional receptor proteins on astrocytes, an aberrant splicing may represent a genetic candidate mechanism. Aberrant or non-splicing causes truncated or chimeric proteins such that receptor occupancy is not possible. What the mechanisms of aberrant splicing concerns, significant findings have been reported (Faa et al., 2010). Nonsense, missense, and even synonymous mutations can induce aberrant skipping of the mutant exon, producing nonfunctional proteins. If the exchange of nucleotides generates a synonymous codon that represents the same aminoacid as the original triplet, one speaks of a silent mutation. These mutations have erroneously been classified as nonpathogenic, but are now recognized as affecting the splicing machinery resulting in defective proteins. Aberrant splicing may play a decisive role in the pathophysiology of various diseases (Wang and Cooper, 2007). Why not in schizophrenia, as I hypothesized nearly a decade ago?

Recently, gene losses in the human genome have been identified (Quintana-Murci, 2012). These loss-of-function variants are located in human protein-coding genes. Since the first comprehensive, genome-wide catalogue of variants likely to disrupt protein-coding genes is now available; this genetic approach could also be promising for the identification of nonfunctional receptors on astrocytes in brains with schizophrenia. Moreover, epigenetic factors may also play an important role. Epigenetics broadly refers to heritable changes in phenotype or gene expression caused by mechanisms other than changes in the underlying primary DNA sequence. Several major types of epigenetic mechanisms are DNA methylation, genomic imprinting, histone modifications, and expression control by noncoding RNA. Recent data suggest the influence of these epigenetic alterations in schizophrenia (Deng et al., 2010).


Unconstrained neurotransmission may cause demyelination

Generally, in pathological conditions neurotransmitters can be released excessively, damaging the cells they normally act on. Since oligodendrocytes have receptors for the various transmitters, neurotransmitter excess can cause demyelination (Káradóttir and Attwell, 2007). Already in 1977 a study was published documenting severe breakdown of myelin in dogs injected with myelin (Saakov et al, 1977). In the grey matter of the brain the death of neurons in pathological conditions is often caused by a rise of extracellular glutamate concentration activating NMDA receptors and causing an excessive rise of Ca2+. Glutamate can also damage white matter oligodendrocytes. Concentrations of glutamate which alone are not toxic sensitize oligodendrocytes to subsequent complementary attack that inserts membrane attack complexes into the oligodendrocyte, allowing a toxic Ca2+ influx to occur (Alberdi et al, 2006).


In line with the presented synaptic model of the pathophysiology of schizophrenia, an unconstrained flux of neurotransmitters occurs. This may hold for all the various neurotransmitter types. This unconstrained flux of neurotransmitters may affect oligodendrocytes either by flooding of their cognate receptors on oligodendrocytes, exerting a toxic Ca2+ influx, or via a hyperactivation of axons with an excess of axonic ATP production and a consequent toxic effect on oligodendrocytes (Mitterauer and Kofler-Westergren, 2011) (Fig. 8). In addition, ATP released from axons cannot activate astrocytic receptors, since they do not function. Therefore, a stimulation of myelination by mature oligodendrocytes is not possible. These pathological mechanisms may cause demyelination, as observed in brains with schizophrenia (Skelly et al, 2008; Takahashi et al, 2010). Note, although decreased expression of oligodendrocyte-related genes has been identified (Höstad et al, 2009), it seems implausible that genetics alone could account for demyelination in schizophrenia (Fields, 2009).



A synaptic neurotransmitter (NT) excess hyperexcites the axon and floods the cognate receptors (R) on the oligodendrocyte (Oc). In parallel, a non-synaptic ATP excess occurs, also flooding R. This flooding of NT and ATP exerts a toxic effect on the Oc, leading to its decay. These mechanisms may be responsible for the decomposition of oligodendrocyte-axonic interactions and the disconnection of neuronal networks.


Moreover, the permanent hyperactivation of axons may also impair them so that neuronal networks disconnect. This may represent a possible mechanism that could at least in part be responsible for the disconnection of neuronal networks identified in brains with schizophrenia (Höstad et al, 2009).


Loss of Oligodendrocytes May Cause a Decay of Gap Junctions in the Panglial Syncytium Responsible for Memory Impairment

Since gap junctions between astrocytes and oligodendrocytes are heterotypic, composed of special astrocytic connexins and different oligodendrocytic connexins, a loss of oligodendrocytes disrupts astrocyte-oligodendrocytic gap junctions in the panglial syncytium, leading to a “leaky” syncytium (Fig. 9). Gap junctions form plaques that may embody memory structures (Robertson, 2002). Therefore, a loss of gap junctions may impair memory. In addition, genetic or (and) exogenous disorders can affect gap junctional plaque formation which may be the case in schizophrenia. In this context one could speak of a syncytiopathy in schizophrenia (Mitterauer, 2009). However, memory impairment may also be caused by a disorganization of neuronal networks (Wolf et al, 2008).





On the left, a panglial syncytium composed of astrocytes (Ac) and oligodendrocytes (Oc) interconnected via gap junctions (g.j.). A loss of Oc may cause a decay of Oc-Ac gap junctions (crosses). Such a “leaky” panglial syncytium may be responsible for memory impairment.


Schizophrenic dysintentionality based on a severe disorder of glial-neuronal interactions

According to Frith (1992), schizophrenia can be explained by a failure to integrate the intention to act with the perceptual registration of the consequences of that action. At a neurobiological level this integrative abnormality might correspond to a failure to integrate signals from the (intentional) prefrontal regions and the (perceptual) temporal cortices. However, this is a pure neuronal view excluding the glial cell system. In further elaborating my theory of glial-neuronal interaction, I have hypothesized that the intentional or action programs of the brain may be generated in the panglial syncytium (Mitterauer, 2007). Based on a formal model it can be shown how glial syncytia compute in a highly combinatorial manner cycles of various lengths via gap junctions. These cycles are transferred in tripartite synapses to the neuronal system (Mitterauer, 2011). The neuronal system tests these intentional programs with regard to their feasibility in the environment. In feeding back the feasibility of intentional programs to the glial syncytium, learning processes can occur.

For the clinically experienced psychiatrist it is evident that patients with schizophrenia are unable both to test their delusional programs and to realize these unrealistic intentions in the environment. I have named this disorder “schizophrenic dysintentionality” (Mitterauer, 2005). But let us consider the elementary pathophysiological mechanisms of schizophrenia as proposed. First of all, there is a break of information processing between the glial system and the neuronal system in tripartite synapses and also in the “orthogonal” oligodendrocyte-axonic interaction. In this view, the term schizophrenia (split of consciousness) is appropriate. In other words: a patient with schizophrenia is permanently stressed by a world of intentions that cannot be mediated via tripartite synapses to the neuronal system for reality testing. Such considerations could be explanatory with concern to recent findings of abnormalities in the white matter of the brain (Markis et al., 2010). Supposing that a patient is under permanent pressure to realize his/her intentional programs generated in the panglial syncytium, then the normal apoptosis could be accelerated or mutations in astrocytes and in the oligodendrocyte-myelin system could be activated. The effect is a decrease in white matter. Considering the loss of oligodendrocytes which are normally interconnected with astrocytes via gap junctions, the decay of oligodendrocytes must also destruct the panglial syncytium in the sense of an increasing loss of gap junctions. This loss of gap junctions may again destruct the capacity of the panglial syncytium to generate intentional programs.


Many patients with schizophrenia become increasingly psychobiologically exhausted in the chronic course of their illness, which is called schizophrenic residuum. Of course, the frequently observed disorders in neuronal networks may also play a role, but the destruction of the panglial syncytium leading to a dysintentionality per se, may be basically responsible for the negative view of life, as typically seen in the schizophrenic residuum. Most impressively, if the prefrontal cortex is severely affected, these patients are incapable of planning. Therefore, what they want is merely the satisfaction of simple biological needs (eating, drinking, smoking, getting money to buy something, etc.). One could also say that with the destruction of the panglial syncytium all kinds of destiny are broken down as well.

How could astrocytes react to this disaster? Reactive astrocytosis may be a compensatory attempt. Reactive astrocytosis occurs prominently in response to all forms of CNS injury or disease. Recent studies point to the role of reactive astrocytes in helping to limit tissue degeneration and preserve function after CNS injury (Sofroniew, 2005). So why not in schizophrenia? If one interprets the degeneration of the panglial syncytium caused by stress as a functional brain injury, then reactive astrocytosis may here exert the same mechanism. However, in schizophrenia astrocytosis may not only react to injuries of the neuronal system, but also attempt to generate a new astrocytic syncytium in reaction to the degeneration of the panglial syncytium. In this way the patient can generate intentional programs and keep a “touch of destiny” alive.  This conjecture is experimentally testable, if one compares the degree of dysintentionality – defined as the ability to produce intentions or plans – of schizophrenic patients with and without reactive astrocytosis.


Finally, reactive astrocytosis can be seen in the light of the Astrocentric Hypothesis (Robertson, 2002). According to this hypothesis, astrocytes represent the core cells in the brain that not only control the glial-neuronal interaction, but also determine the functions within the panglial syncytium. Therefore, astrocytes may be capable – at least – to attempt repairing dysfunctions in the panglial syncytium, as may be the case in schizophrenia. Admittedly, the pertinent findings in brains with schizophrenia are contradictory. However, astrocytosis (astrogliosis) may not occur widespread in the brain (Bernstein et al., 2008), but it could represent a local phenomenon.





Pathophysiology of non-schizophrenic delusions

The pathophysiological mechanism of non-schizophrenic delusions may significantly differ from schizophrenic delusions. Let us focus on the extrasynaptic fluid, especially Ca2+ ions, in information transmission. Astrocytes sense a decrease of Ca2+ in the extrasynaptic space via Cx43 hemichannels and produce ATP that activates inhibitory interneurons, which negatively feed back to the presynapse. I hypothesize that if Ca2+ is totally exhausted (e.g. by stress), the negative feedback mechanism cannot be generated. The exhaustion of Ca2+ may be caused by hyperexcitable neurons flooding the synaptic neurotransmission. Importantly, the astrocytic receptors are normally expressed, but they cannot cope with the synaptic neurotransmitter flooding without an extrasynaptically generated negative feedback. Thus, in non-schizophrenic delusions an unconstrained information flux may also occur, but astrocytes per se may not be affected. Here, the brain operates in a holistic and not schizophrenic way. This pathophysiological mechanism could explain why patients with paranoid psychoses can mostly be successfully treated with antipsychotic drugs. Their blockade of postsynaptic receptors constrains neurotransmission such that astrocytes can work normally again. Although the neurons may remain hyperexcited, the Ca2+ depletion is sufficient to activate the negative feedback mechanism described. In parallel, the astrocytic receptors are again able to modulate synaptic information processing, since they can cope with the amount of neurotransmitters and temporarily turn off synaptic information processing based on a negative feedback mechanism.


Do glia play a comparable role in dream states and schizophrenic delusions?

One of my schizophrenic patients spontaneously told me: “schizophrenia is dreaming, that’s all”. Here, I will shortly attempt a “gliocentric” explanation that this patient could be right. Despite progress in biological sleep or dream research, up to now it is based on an exclusively neuronal approach (Hobson, 2005). However, the current hypotheses on glial-neuronal interactions (Robertson, 2002; Mitterauer, 2007; Mitterauer and Kopp, 2003) could be explanatory what the alteration of consciousness in dreams concerns. Let me focus on strange dream contents and scenarios. Strange dreams are defined as dream contents that are unfeasible in wake conscious states. These are often compared to the main schizophrenic symptoms of delusions and hallucinations. I hypothesize that the same mechanism may be at work in the generation of both strange dreams and schizophrenic delusions. It is experimentally verified that in tripartite synapses astrocytes produce transmitters that occupy receptors on the presynapse temporarily interrupting synaptic information transmission in the sense of a negative feedback. In other words: astrocytes have a temporal boundary-setting function (Mitterauer, 1998). The elementary mechanism may exert an information structuring function determining the compartmental organization of neuronal networks.

In schizophrenia, this astrocytic information structuring function may be lost, since astrocytes do not produce transmitters or express non-functional receptors because of pertinent mutations. The effect is an unconstrained information flux in synapses leading to compartmentless neuronal networks in the sense of a generalization of neuronal information processing. I call this “loss of self-boundaries in schizophrenia” (Mitterauer, 2003).


Therefore, a patient with schizophrenia is incapable of testing the reality of his (her) delusional ideas. The phenomenological difference is that the dreaming person upon awakening is fully able to test the reality. In contrast, the schizophrenic patient is not. Supposing that our intentional programs are permanently generated in the glial syncytia (Mitterauer, 2007), then their realization in the neuronal networks via perception and motion is decisive. In dreams we have the chance to play our intentions in various scenarios independent of their feasibility, since the perception systems are turned off.

Now, it is typical for strange dream scenarios that objects or individuals of the environmental realities confuse and design uncanny figures and pictures in the sense of a loss of boundaries. The same glial mechanism could be responsible as in schizophrenic delusions. However, whereas schizophrenia represents a chronic pathological process (mutations), dream states occur as a circadian physiological behavior that gives us the chance of acting out our hidden intentions without the pressure of their feasibility. Based on these considerations the elementary function of glia in dream states could be described as follows: astrocytes temporarily (according to the hypothalamic circadian rhythms) turn off their interactions with the neuronal system in tripartite synapses. This mechanism is comparable to that proposed for schizophrenia. In addition, the generation of intentional programs in the glial syncytia not only continues, but even dominates the consciousness as dreams states.



My model of impaired glial-neuronal interactions in schizophrenia is based on the core hypothesis that nonfunctional astrocytic receptors may cause an unconstrained synaptic information flux such that glia lose their modulatory function in tripartite synapses. This may lead to a generalization of information processing in the neuronal networks responsible for delusions and hallucinations on the behavioral level. In this acute paranoid stage of schizophrenia, nonfunctional astrocytic receptors or their loss decompose the astrocyte domain organization with the effect that a gap between the neuronal and the glial networks arises. If the illness progresses, the permanent synaptic neurotransmitter flux may additionally impair the oligodendrocyte-axonic interactions, accompanied by a “creeping” decay of oligodendroglia, axons, and glial gap junctions responsible for severe cognitive impairments. Here we may deal with after-effects caused by the basic fault of information processing in tripartite synapses. Importantly, the same may hold true what the neuroinflammatory hypothesis (Brown, 2008) concerns. The activation of microglia observed in brains with schizophrenia could represent a reaction to the decay of nervous tissue described and not a primary pathophysiological mechanism of schizophrenia.


Currently, post mortem brains with schizophrenia are investigated with Storm microscopy, a method that achieves resolution below the optical diffraction limit (University of Applied Sciences, Linz, Austria). Whereas in the prefrontal cortex of normal brains big amounts of receptors located on the processes of astrocytes are found, in brains with schizophrenia astrocytic receptors cannot be identified in this region. Since these preliminary results concern only serotonergic receptors in the prefrontal cortex, further investigations of other receptor types on astrocytes in pertinent brain regions is necessary. Should it be possible to verify the central role of astrocytic receptors in the pathophysiology of schizophrenia, then a diagnostic marker would be available, if an in vivo identification is possible as well.




This paper is dedicated to my friend and great neuroscientist Gerhard Werner (†), University of Austin, Texas. I am also grateful to Birgitta Kofler-Westergren for preparing the final version of this paper.



Alberdi, E., Sanchez-Gomez, M.V., Torre, I., Domercq, M., Perez-Samatin, A.,

        Pérez-Cerdá, F., Matute, C., 2006. Activation of kainate receptors sensitizes

        oligodendrocytes to complement attack. J Neurosci. 26, 3220-3228.

American Psychiatric Association, 1998. Diagnostic and statistical manual of

        mental disorders. American Psychiatric Association, Washington.

Arajärvi, R., Varilo, T., Haukka, J., Suvissari, J., Suokas, J., Juvonen, H., Muhonen, M.,

        Lönnquist, J., 2006. Affective flattening and alogia associate

        with familial form of schizophrenia. Psychiatry Res. 141, 161-172.

Araque, A., Parpura, V., Sanzgiri, R.P., Haydon, P.G., 1999. Tripartite synapses:

        glia, the unacknowledged partner. Trends Neurosci. 22, 208-215.

Auld, D.S., Robitaille, R., 2003. Glial cells and neurotransmission: an inclusive

        view of synaptic function. Neuron 40, 389-400.

Berge, S., Koenig, T., 2008. „Cerebral disconnectivity: an early event in schizophrenia.”

        Neuroscientist 14, 19-45.

Bernstein, H.G., Steiner, J., Bogerts, B., 2009. „Glial cells in schizophrenia:

        pathophysiological significance and possible consequences for therapy.” Expert Rev.

        Neurother. 9, 1059-1071.

Brown, A.S., 2008. The risk for schizophrenia from childhood and adulthood infections.

        Am. J. Psychiatry 165, 7-10.

Carpenter, W.T., Buchanan, R.W., 1995. Schizophrenia: introduction and overview,

        In: Kaplan, H.J., Sadock, B.J. (Eds.), Comprehensive Textbook of Psychiatry, 

        Williams and Wilkins, Baltimore, pp. 899-902.

De-Miguel, F.F., Fuxe, K., 2012. Extrasynaptic neurotransmission as a way of modulating

        neuronal functions. Front. Physiol. doi:10.3389/fphys2012.00016.

Deng, Z., Sobell, J.L., Knowles, J.A., 2010. Epigenetic alterations in schizophrenia.

        Focus 8, 358-365.

Dermietzel, R., Spray, D.C., 1998. From neuroglue to glia: a prologue. Glia 24, 1-7.

Di, X., Chan, R.C., Gong, Q., 2009. White matter reduction in patients with

       schizophrenia as revealed by voxel-based morphometry: an activation likelihood

       estimation meta-analysis. Prog. Neuropsychopharmacol. Biol.

       Psychiatry 33, 1390-94.

Erdi, P., Flaugher, B., Jones, T., Ujfalussy, B., Zalanyi, L., Diwadkar, V.A., 2007.

       “Computational approach to schizophrenia. Disconnection syndrome and dynamical

        pharmacology.” AIP Conference Proceedings 1028, 65-87.

Faa, V., Cobana, A., Incani, F., Constantino, L., Cao. A., Rosatelli, M.C., 2010.

        A synchronous mutation in the CFTR gene causes aberrant splicing in an italian

        patient affected by a mild form of cystic fibrosis. J. Mol. Diagnostics 12, 380-383.

Fields, R.D., 2009. The other brain, Simon and Schuster, New York.

Fields, R.D., 2010. Change in the brain’s white matter. Science 330, 768-769.

Fields, R.D., Ni, Y., 2010. Nonsynaptic communication through ATP release

       from volume-activated anion channels in axons. Sci. Signal. 3, ra 73.

Fisher, S., Cleveland, S.E., 1968. Body image and personality. Dover, New York.

Friston, K.J., 1998. “The disconnection hypothesis. Schiz. Res. 30, 115-125.

Frith, C.D., 1992. The cognitive neuropsychology of schizophrenia. Psychology

        Press, East Sussex, UK.

Halassa, M.M., Fellin, T., Haydon, P.G., 2009. Tripartite synapses: roles for

        astrocytic purins in the control of synaptic physiology and behavior.

        Neuropharm. 57, 343-346.

Halassa, M.M., Haydon, P.G., 2010. Integrated Brain Circuits: Astrocytic

       Networks Modulate Neuronal Activity and Behavior, Ann. Rev. Physiol.

       72, 335-355.

Hashimoto, K., Engberg, G., Shimizu, E., Nordin, C., Lindstrom, L.H., Iyo, M.,

        2005. Elevated glutamine/glutamate ratio in cerebrospinal fluid of first episode

        and drug naive schizophrenic patients. BMC Psychiatry 5, 6.

Hobson, J.A., 2005. Sleep is of the brain, by the brain and for the brain. Nature 437,


Höstad, M.N, Segal, D., Takahashi, N., et al., 2009. Linking white and grey matter

        in schizophrenia: oligodendrocyte and neuron pathology in the prefrontal

        cortex. Front. Neuroanat. 3:9. doi;10.3389/neuro.05.009.2009.

Ishibashi, T., Dakin, K.A., Stevens, B., Lee, P.R., Kozlov, S.V., Stewart, C.L.,

        Fields, R.D., 2006. Astrocytes promote myelination in response to

        electrical impulses. Neuron 49, 823-832.

Kapur, S., Lecrubier, Y., 2003. Dopamine in the pathophysiology and treatment

        of schizophrenia. Martin Dunitz, London.

Káradóttir, R., Attwell, D., 2007. Neurotransmitter receptors in the life and death

       of oligodendrocytes. Neuroscience 145, 1426-38.

Kettenmann, H., Ransom, B.R., 2005. Neuroglia. Oxford University Press, Oxford.

Kettenmann, H. and Steinhäuser, C. (2005). „Receptors for neurotransmitters and

        Hormones”, in: Kettenmann, H., Ransom, B.R. (Eds.), Neuroglia, Oxford

        University Press, Oxford, pp. 131-145.

Kyriakopoulos, M., Perez-Iglesias, R., Woolley, J.B., Kamaan, R.A., Vyas, N.S.,

        Barker, G.J., Frangou, S., McGuire, P.K., 2009. Effect of age at onset

        of schizophrenia on white matter abnormalities. Br. J. Psychiatry 195, 346-353.

Lenzenweger, M.F., McLachlan, G., Rubin, D.B., 2007. Resolving the latent structure

        of schizophrenia endophenotypes using expectation-maximization-based finite

        mixture modeling. J. Abn. Psychology 116, 16-29.

Markis, N., Seidman, L.J., Ahern, T., Kennedy, D.N., Caviness, V.S., Tsuang, M.T.,

        Goldstein, J.M., 2010. White matter volume abnormalities and association

        with symptomatology in schizophrenia. Psychiatry Res. 183, 21-29.

Meltzer, H., 2003. „Multiple neurotransmitters involved in antipsychotic drug action”,

        In: Kapur, S., Lecrubier, Y. (Eds.), Dopamine in the pathophysiology and treatment

        of schizophrenia, Martin Dunitz, London, pp. 177-205.

Mitterauer, B., 1998. An interdisciplinary approach towards a theory of

       consciousness. BioSystems 45, 99-121.

Mitterauer, B., 2003. The loss of self-boundaries: towards a neuromolecular theory

        of schizophrenia. BioSystems 72, 209-215.

Mitterauer, B., 2005. Nonfunctional glial proteins in tripartite synapses:

        a pathophysiological model of schizophrenia.  Neuroscientist 11, 192-198.  

Mitterauer, B., 2007. Where and how could intentional programs be generated in

       the brain?  A hypothetical model based on glial-neuronal interactions.

       BioSystems 88, 101-112.

Mitterauer, B., 2009. Loss of function of glial gap junctions may cause severe

        cognitive impairments in schizophrenia. Med. Hypotheses 73, 393-397.

Mitterauer, B., 2010. Significance of the astrocyte domain organization for

        qualitative information structuring in the brain. Adv. Biosci. Biotechnol. 1, 391-397.

Mitterauer, B., 2011. Qualitative information processing in tripartite synapses: a

        hypothetical model. Cogn. Comput. DOI 10.1007/s12559-011-9115-2.

Mitterauer, B., Kofler-Westergren, B., 2011. Possible effects of synaptic imbalances

        on oligodendrocyte-axonic interactions in schizophrenia: a hypothetical model.

        Front. Psychiatry 2, doi: 10.3389/fpsyt.2011.00015.

Mitterauer, B., Kopp, C., 2003. The self-composing brain: towards a glial-neuronal

       brain theory. Brain and Cognition 51, 357-367.

Mitterauer, B., Pritz, W.F., 1978. The concept of the self: a theory of

        self-observation. Int. Rev. Psychoanal. 5, 179-188.

Newman, E.A., 2005. “Glia and Synaptic Transmission”, in: Kettenmann, H.,

        Ransom, B.R. (Eds.), Neuroglia, Oxford University Press, Oxford, pp. 355-366.

Oberheim, N.A., Wang, X., Goldman, S., Nedergaard, M., 2006. Astrocytic

        complexity distinguishes the human brain, Trends Neurosci. 29, 547-553.

Pereira, A., Furlan, F.A., 2010. Astrocytes and human cognition: modeling

        information integration and modulation of neuronal activity. Prog.

        Neurobiol. 92, 405-420.

Quintana-Murci, L., 2012. Gene losses in the human genome. Science 335, 806-807.

Ransom, B.R., Ye, Z., 2005. Gap junctions and hemichannels, in: Kettenmann, H.,

        Ransom, B.R. (Eds.), Neuroglia, Oxford University Press, Oxford, pp. 177-189.

Robertson, J.M., 2002.The Astrocentric Hypothesis: proposed role of astrocytes

        in consciousness and memory formation. J. Phys. (Paris) 96, 251-255.

Rusakov, D.A., 2012. Depletion of extracellular Ca2+ prompts astroglia to modulate

        synaptic network activity. Sci. Signal. 5, pe 4.

Saakov, B.A., Khoruzhaya, T.A., Bardakhchyan, E.A., 1977. Ultrastructural

        mechanisms of serotonin demyelination. Bulleten Eksperimental noi Biologii I

        Meditsiny 83, 606-610.

Santello, M., Volterra, A., 2010. Astrocytes as aide-mémoires, Nature 463, 169-170.

Shastry, B.S., 2002. Schizophrenia: a genetic perspective. Int. J. Mol. Med. 9, 207-212.

Sims, A., 1991. An overview of the psychopathology of perception; first rank symptoms

        as a localizing sign in schizophrenia, Psychopathology 24, 369-374.

Skelly, L.R., Calhoun, V., Meda, S.A., et al., 2008. Diffusion tensor imaging

        in schizophrenia: relationship to symptoms. Schizophr. Res. 98, 157-162.

Steffek, A.E., 2007. „The role of astrocytes in the pathophysiology of schizophrenia.”

        Dissertation, University of Michigan, 159 pages, 3276299.

Stellwagen, D., Malenka, R.C., 2006. Synaptic scaling mediated by glial

        TNF-alpha. Nature 440, 1054-1059.

Stevens, B., Porta, S., Haak, L.L., Gallo, V., Fields, R.D., 2002. Adenosine, a

        neuron-glial transmitter promoting myelination in the CNS in response to

        action potentials. Neuron 36, 855-868.

Stevens, B., Tanner, S., Fields, R.D., 1998. Control of myelination by specific patterns

       of neural impulses. J. Neurosci.18, 9303-11.

Takahashi, N., Sakurai, T., Davis, K.L., Buxbaum, J.D., 2010. Linking

        oligodendrocyte and myelin dysfunction to neurocircuitry abnormalities in

        schizophrenia. Prog. Neurobiol. 93, 13-24.

Torres, A., Wang, F., Xu, Q., Fujita, T., Dobrowolski, R., Willecke, K., Takano, T.,

        Nedergaard, M., 2012. Extracellular Ca2+ acts as a mediator of

        communication from neurons to glia. Sci. Sign. 208 ra8.

Wang, G., Cooper, T.A., 2007. Splicing in disease: disruption of the splicing code

        and the decoding machinery. Nature Rev. Gen. 8, 749-761.

Wolf, R.C., Höse, A., Frasch, K., Walter, H.,Vasic, N., 2008. Volumetric

        abnormalities with cognitive deficits in patients with schizophrenia.

        Eur. Psychiatry 23, 541-548.



Dr. Bernhard Josef Mitterauer graduated with an M.D. from the University of Graz. Eight years later he received his academic degree in europsychiatry and Psychoanalysis. Between 1976 and 1984 Dr Mitterauer studied Philosophy with Gotthard Günther, the famous

Philosopher of Cybernetics, in Hamburg. He developed  close friendship and intensive scientific collaboration with Günther, whose philosophy has influenced Dr. Mitterauer’s work up to this day. In 1984 Dr. Mitterauer was appointed a Professor of Neuropsychiatry at the University of Graz. He has been serving as a Professor and Head of Forensic Neuropsychiatry at the University of Salzburg since 1989. He has been married to Gertraud Laimböck since 1970, and they have a daughter and a son.


Concurrently with his practical work as a Neuropsychiatrist, Dr. Mitterauer has been involved in interdisciplinary research in Biocybernetics since the beginning of his professional career. In the 1970’s he published basic research studies on emotion, depression, narcissism and self-observation. Notably, in 1981 he earned the Eiselberg Award for his already internationally acknowledged research on suicide. During the 1980’s he published numerous studies dealing with a new “dialectic” psychopathology. His book Architectonics, Metaphysics of Feasibility deals with a future-oriented interpretation of technical activities, especially the development of robots. An important result of Dr. Mitterauer ’s basic research is the development of a novel model mental disorders, called “Architectonic Psychopathology”. Recently he has founded the Volitronics-Institute for Basic Research, Psychopathology and Brain Philosophy. These research programs are currently published in international journals and presently in 14 book publications.


Dr. Mitterauer has patented the most important findings of his biocybernetic brain research. To date a total of 11 international patents have been granted to him. He has also developed a new brain theory, which not only considers the neuronal systems but also accounts for the glial systems of the brain. Based upon this theory, which was detailed in 1998 in Biosystems, Dr. Mitterauer has shown that enormous consequences arise from our understanding of consciousness, psychiatric disorders, and finally, even for the development of “brain-similar” computers or robots. In addition, concerning his research on consciousness, his study entitled Some Principles for Conscious Robots, published in the Journal of Intelligent Systems in 2000, deserves mention. Based upon his new brain theory, Dr. Mitterauer has also developed a new type of computer hardware called clocked perception mechanism.


Having realized that molecular Biology is making fascinating discoveries, Dr. Mitterauer, in also pursuing this avenue, has postulated molecular biologically-oriented hypotheses concerning the etiology of Sudden Infant Death Syndrome, and manic-depressive as well as schizophrenic disorders. He has also founded the Gotthard Günther Archives for the research and publication of the posthumous works of Günther at the University of Salzburg.



[ back to "Publications & Special Reports" ]
[ BWW Society Home Page ]