The Eternal Now:
By Professor Bernhard J. Mitterauer, Institute of Forensic Neuropsychiatry and Gotthard Günther Archives,
Abstract: This paper presents a new explanatory model for schizophrenia based upon molecular and neurobiological hypotheses, Barbour´s theory of the universe and years of experience in observing and treating these patients. I start out with the psychiatric hypothesis that in delusions and hallucinations the self-boundaries are lost. First, the concept of the Self is defined as a self-reflective system consisting of many subsystems in the brain striving for self-realization in the environment. Whenever a system treats non-realizable programs as if they were realizable its ability to "test the reality" is lost, and consequently a loss of self-boundaries may occur. On the molecular level I will try to show how "non-splicing" of introns during the mRNA splicing process is equivalent to a loss of the rejection of non-realizable programs. At the cellular level in the brain, I have in previous work attributed a spatio-temporal boundary setting function to the glial cells such that glial cells determine the grouping of neurons into functional units. Mutations in genes that result in non-splicing of introns can produce aberrant versions of neurotransmitter receptors that lack protein domains encoded by entire exons and can also have protein sequence encoded by introns that have not been properly spliced out. I propose that such "chimeric" receptors are generated in glial cells and that they cannot interact properly with their cognate neurotransmitters. The glia will then lose their inhibitory-rejecting function with respect to the information processing within neuronal networks. The loss of glial boundary-setting may result in a 'borderless' generalization of information processing such that the structuring of the brain in functional domains is almost completely lost. This loss of glial boundary setting could be an explanation of the loss of self-boundaries in schizophrenia. The loss of temporal boundaries may cause a sense of an “eternal Now” in the brain of schizophrenics, comparable to the theory of Barbour. Pertinent examples of case studies are given attempting to deduce the main symptoms of schizophrenia from the proposed hypotheses. Tying all arguments and hypotheses together, an interdisciplinary definition of the etiology of schizophrenia is attempted.
The primary symptoms of acute schizophrenia for which an explanation must still be sought include the occurrence of hallucinations, delusions and thought disorder (Frith, 1979;1987; Hemsley, 1982; 1987; Gray, 1991). There are numerous hypotheses concerning the etiology of schizophrenia, most of which focus on biological, psychological and sociological factors (Carpenter and Buchanan, 1995; Johnstone et al, 1999; Maynard et al, 2001; Shastry, 2002). However, the presumption, or even conviction, that schizophrenia has a multifactorial etiology arising from a combination of various factors seems to force itself upon most clinically versatile psychiatrists. Explanatory models of this psychobiological disorder should, therefore, be based upon an interdisciplinary approach. My explanatory approach to the schizophrenic disorder and symptomatology is based upon molecular and neurobiological hypotheses as well as on years of experience in observing and treating these patients. From a physic point of view I draw parallels between the schizophrenic brain and Barbour´s theory of the universe (Barbour, 1999).
Psychiatrists generally explain delusions and hallucinations in terms of a “loss of ego boundaries” or “inner/outer confusion” (Fisher and Cleveland, 1968; Sims, 1991)) Instead of the rather uninformative concept of ‘ego’, I introduce a neurophilosophical concept of the Self. According to the theory of subjectivity of Günther (1962), the boundary-setting between the Self and Non-Selves is essentially based on a rejection function or mechanism. Supposing that schizophrenic symptoms are due to serious brain dysfunction with a biological basis (Werner et al, 1982; Heyman and Murray, 1992), it should be possible to find out how this dysfunction on a molecular and cellular level may occur.
On the molecular level it will be shown in the context of mRNA splicing that a “non-splicing” of introns is equivalent to a loss of the rejection function (Mitterauer, 2001). This in turn leads to the production of an aberrant protein, which in some cases could result in a chimeric receptor being expressed on the surface of a neuron or glial cell (see section 3).
On the cellular level, I will focus on glial-neuronal interaction by attributing to glial cells a spatio-temporal boundary-setting function such that the glial cells determine the grouping of neurons into functional units (Mitterauer, 1998; 2000a; Mitterauer et al, 2000). If we suppose that “chimeric” receptors are generated and expressed on the surface of glial cells, these receptors cannot be occupied by their cognate ligands resulting in glia that lose their inhibitory-rejecting function with respect to the information processing within neuronal networks. This boundary loss, which may occur in localized regions in normal individuals, affects many brain areas simultaneously in schizophrenia (for review see Lewis, 2000), such that the brain structuring in functional domains is almost completely lost. This neurobiological explanation for a borderless generalization of neuronal information processing can be applied as an explanatory model for the “loss of self-boundaries” in schizophrenia. Since the loss of self-boundaries concerns both space and time, the schizophrenic brain embodies not only an infinite universe, but also a timeless universe. This state of existence is comparable to Barbour´s universe, in which time has no reality and everything is now.
After elaborating these hypotheses in detail, I will discuss the clinical correlations and finally attempt an interdisciplinary definition of the etiology of schizophrenia.
2. The concept of the Self
In discussing a “loss of self-boundaries” it is necessary to at least attempt to define the concept of the Self. Generally speaking, the prefix ‘Self’ points out that a system is capable of formal recursion or mechanic feedback. On higher levels, as in the human brain, terms like self-observation or self-consciousness are based on the ability of reflective thinking. In reflective thinking a thought becomes the object of the same computation-like process. A distinction from recursion lies in the fact that in the process of reflection additional new arguments may enter the process. Reflective thinking is the activity of a participant observer constituted as a Self acting as initiator, participant and observer of the process. Self-reflection is a generalization of this situation insofar as a Self, which is the subject of first-person thoughts and first-person reference, posits itself as a thought (object) for reflective thinking. The agent in self-reflection is not only subject and object (argument and outcome) of the reflective process, but – as part of reflective thinking – it is also able to say “I am thinking this and that; which is my Self”. Therefore, a theory of the Self implies the problem of consciousness.
2.2. Neurophilosophical approaches
I have postulated that self-reflection may be represented in a manifold manner in the brain (Mitterauer, 1998), similar to the self-systems of “Many Cartesian Theaters” (Damasio, 1992), which normally do not reach self-consciousness. Presumably, these are places in the brain where information is stored in relation to specific areas of reality (persons, experiences, etc.). Most of the spatio-temporally limited structures of the brain are probably used to process current information, but the allocation of neurobiological operational figures can steadily change. Although we know that certain areas of the brain have priority for special tasks, it has not been possible to find a topological allocation for the different and complex reflection processes or to localize self-systems.
We should, however, be able to find the part of the brain that integrates all of the different self-systems in the undisturbed self-consciousness. Several decades ago, the group working with McCulloch considered the formatio reticularis in the brain stem as an ‘integrative matrix’ (Scheibl and Scheibl, 1968) as well as a ‘central command system’ (Kilmer et al, 1969). Lately, Newman (1997) has suggested an ‘extended reticular-thalamic activating system’ as a neural correlate for a ‘central conscious system’ (see also Steriade, 1996). According to Churchland (2002), the most basic level of inner coordination and regulation occurs in the brain stem , anchoring what Damasio (1999) refers to as “the protoself”.
From an anatomic-functional point of view, Baars (1996) provides numerous examples (e.g. split-brain patients, sensorimotor homunculus) which show that different self-systems can be represented in the brain: “The nervous system abounds in such maps, some of which appear to serve as ‘self-systems’, organizing and integrating vast amounts of local bits of information”. Damasio (1994) refers to a ‘neuronal self’. In this view, a neuronal system capable of producing subjectivity must be equipped with sensory and motor cortical areas as well as subcortical nuclear areas (thalamus, basal ganglia) having convergence properties. Edelman (1992) is also of the opinion that there is a biological self which he confines to subcortical homeostatic systems. It is questionable whether such a local allocation is possible for ‘self-systems’. (Concerning the synchronization hypothesis of consciousness and the chaos-theoretical approach see Mitterauer, 2000a).
A Self is always the Self of a living system having biological “hungers” (Iberall and McCulloch, 1969) or intentions. Therefore, a living system permanently strives to realize its intentional programs in an appropriate environment. According to the logic of acceptance and rejection (Günther, 1962), appropriate objects may be accepted, but inappropriate objects must be rejected.
Table 1. Interpretation of Basic Schizophrenic Symptoms
Table 1 shows an example of an intentional program (1, 3, 2, 4), which either accepts or rejects objects (1, 2) in the environment. Let us suppose that a subject is trying to realize its intentional program by moving through an environment in four steps. The intentional values (iv) are 1, 3, 2, 4. Two objects, with their respective object values (ov) 1, 1, are found in the environment. In the first step, the detected object (ov) 1 can be accepted. In the second step, the intended value (iv) 3 rejects both objects (ov) 1, 2. In the third step, one of the two objects (2) corresponds to the subject´s intention, hence it accepts the object. In the fourth step, finally, the intended value (iv) 4 results in another rejection of both objects (ov) 2, 2.
Without doubt, to stay alive we must often change our intentional program adjusting it to the environment. However, if we would do so constantly, such a slavish behavior would occur at the cost of our individuality. The intentional programs of self-conscious systems such as the human one are highly specified by their genomes and experiences during life history. Therefore, to cope with individuality, a Self must be able to reject non-realizable programs at a point of time, in the sense of self-realization. One could also say that the rejection mechanism is essential for setting boundaries between the Self and the many Non-Selves.
Understood in this sense, the question arises as to what makes a Self or a brain incapable to reject the inappropriate and to set a boundary between itself and the environment.
3. The loss of self-boundaries
3.1. Molecular hypothesis
3.1.1. The splicing mechanism
For a better understanding of my interpretation of rejection, I would like to refer to the example of the structure and protein producing function of a gene. Most genes of higher living beings are constructed such that protein coding sequences (exons) alternate with non-protein coding sequences (introns). However, the chemical structure of nucleotides that make up exons and introns is the same, rendering them isomorphic even though with respect to the realizability of their genetic coding they are different. The genetic code of the exons is realizable, since it leads to a production of proteins. The genetic code within the intronic sequences is not realizable since it does not supply an instruction for the production of a protein. Introns are therefore spliced out of mRNA shortly after mRNA synthesis. Theoretically speaking, this means the rejection of non-realizable programs.
3.1.2. Non-splicing of introns, alternative and abnormal splicing
As already mentioned, virtually all genes of higher organisms have non-coding introns interspersed between the coding exons that must be spliced out in order to generate a mature messenger RNA molecule used to encode proteins. I have taken the novel approach of considering the process of splicing to be a rejection mechanism. Mutations in genes that control the splicing process of other genes can have serious consequences to the organism because the correct splicing patterns are not obtained. In some cases exons are spliced out when they should be retained, and in other cases introns are retained when they should be spliced out. Non-splicing is particularly serious and is essentially the loss of the elementary rejection mechanism in which introns that must be rejected, or spliced out, are not. The resulting messenger RNA thus contains introns and when this mRNA is used to encode protein, the inappropriate intronic sequence results in the production of a faulty protein product. The protein will have additional amino acid sequence that will usually disrupt its proper functioning. Furthermore, an unspliced intron will often have an inframe stop codon that will generate a premature truncation. The truncated proteins lack their carboxy-termini and are often unstable and shortlived, so these proteins are usually non-functional as well.
A variation of the splicing mechanism is alternative splicing. Alternative RNA splicing means that a cell can splice the primary transcript in different ways and thereby make different polypeptide chains from the same gene. Alternative splicing can produce different proteins with normal or abnormal functions (Clark et al, 2002). Abnormal splicing is based on a “splicing error”, which was already found in brain tissues of schizophrenic patients (Liu et al, 1994; Schmauss, 1996). This research group identified truncated dopamine receptors in the brains of chronic schizophrenic patients. Abnormal splicing could play a role in subgroups of schizophrenics, but the decisive argument of my hypothesis is that a non-splicing of introns is at least responsible for the positive or productive symptoms, such as delusions and hallucinations.
3.2. Neurobiological hypothesis
3.2.1. The boundary-setting function of the glial system in its interaction with the neuronal system
Glia have been shown to play an important role in the inactivation of neurotransmitters (Martin, 1995; Sykova et al, 1998). Glia divide the brain into compartments on the one hand, and create functional units in various time scales with the neurons, on the other hand (Mitterauer et al, 1996). I have hypothesized that the glial networks have a boundary-setting function in their interaction with the neuronal networks (Mitterauer, 1998). Various experimental indications support the hypothesis that the glial-neuronal networks are organized in the form of compartments in which the glial cells are responsible for the formation of self-organizing units (Mitterauer, 1998; 2000a). Glial cells (particularly astrocytes with their processes that contact or even enfold a synapse) modulate the “efficacy of synaptic transmission” (Teichberg, 1991; Mitterauer et al, 1996; Sykova et al, 1998; Mitterauer, 2000a; Oliet et al, 2001; Fields and Stevens-Graham, 2002). Signals between astrocytes and neurons can be mediated by glutamate (Gallo and Ghiani, 2001), acetylcholine (Smit et al, 2001) and other neurotransmitters (Kimelberg et al, 1998). GABA is released from glial cells upon glutamate receptor stimulation (Gallo et al, 1989) and inhibits neuronal signalling. Also involved are complex ionotrophic and metabotrophic interactions (Teichberg, 1991; Reichenbach et al, 1998). Intracellular calcium oscillations in astrocytes have been hypothesized to affect synaptic cleft calcium concentrations (Cooper, 1995; Newman and Zahs, 1997) and, subsequently, the amount of neurotransmitter released from presynaptic terminals. In addition to modulating synaptic transmission in neuronal cells, astrocytes may play a direct role in generating pacemaker rhythms (Mitterauer et al, 2000).
This originally speculative assumption was recently experimentally verified. Parri et al (2001) showed that astrocytes in situ can act as a primary source for generating neuronal activity in the mammalian central nervous system. Slow glial calcium oscillations (every 5-6 minutes) occur spontaneously and can cause excitations in nearby neurons. Although there is experimental evidence that neuronal-glial interactions also occur in the millisecond range (Murphy et al, 1993; Mennerick et al, 1996), until now rapid glial oscillations within a second have not been found. Following the rationale of my brain model, rapid glial oscillations might be observed in the near future. It is notable in this respect that short (about 1 min.) song rhythms of Drosophila are controlled by the clock gene per, whose expression is observed only in glia (Hall, 1995).
The neuronal principle of compartmentalization (Rall, 1995) may also be applied to glial-neuronal interaction if one assumes that glia divide or combine neurons in functional units (Varon and Somjen, 1979). Steindler (1993) describes transient glial boundaries that surround functional groups of neurons, their dendrites, and axons during neural development, referred to as “cordons”. Another convincing experimental result indicates that glia have a boundary-setting function and that this function divides the neuronal system into spatio-temporal compartments (Mitterauer, 1998). Recently, it has even been demonstrated that the number of synapses is controlled by glia (Ullian et al, 2001) and that glial protein S100B modulates long-term neuronal synaptic plasticity (Nishiyama et al, 2002). But also a glial cell itself may consist of hundreds of independent compartments (“micro-domains”) capable of autonomous interactions with the particular group of synapses that they ensheath (Grosche et al, 1999). According to Smolin (1997), the setting of boundaries is an absolute prerequisite for a description of the universe. The universe can only be described if we set boundaries around regions and describe what is inside in terms of information that is associated with each boundary.
Two astrocytes (Aci, Acj) which can activate or deactivate n-neurons (N1…N4) via their processes are displayed in Figure 1. Here the neurons are interconnected in the sense of a neuronal network. The interactional structure of an astrocyte with n-neurons can be defined as an elementary compartment of nerve cells (compartment x,y). By simultaneously regulating neurotransmission in all of the synapses (sy) enveloped by an astrocyte, the astrocyte calcium wave may coordinate synapses into synchronously firing groups (Antanitus, 1998). Depending upon the number of neurons connected with the processes of astrocytes, various combinations of neuronal activation or deactivation are possible generating a big potency of information structuring. I call this glial function ‘spatio-temporal boundary setting’ in neuronal networks. Figure 1 shows two simple examples. In compartment x the astrocyte is activating only two neurons (N2, N3, thick lines). In compartment y three neurons are activated (N1, N2, N4, thick lines). This implies that in the neuronal network only these activated neurons are ready for information processing. Compartments are linked via gap junctions (g.j.). Gap junctions are essential to astrocytic signalling function and it is estimated that more than 50,000 gap junction channels interconnect each astrocyte with its neighbours (Cotrina et al, 2001). In addition to neuronal networks these gap junctions form glial networks (syncytium). A glial syncytium can structure information provided by a local Ca 2+ wave into a distinct spatial and temporal pattern of Ca2+ oscillations (Strahonja-Packard and Sanderson, 1999).
Admittedly, the setting of boundaries between functional units by glial networks leaves open the question of what is controlling the glia. How do glia and neurons self-organize into functional units? At the present stage of research, one can only speculate. One explanation could be that molecular feedback mechanisms on the cellular level play a role (Mitterauer, 2001). Let us take circadian feedback loops as an example. A circadian system can be made up of one or more interconnected feedback loops. The constituents of a loop are heterodimeric proteins such as the BMAL1-CLOCK pair which has domains allowing dimer formation. These dimers act as positive elements to turn on a gene, such as the per gene in mice. The encoded PER protein acts as a negative element in the feedback loop to suppress the activation of the positive elements (Dunlap, 1998; Hardin, 2000; Lee et al, 2000; Mitterauer, 2000b; Grima et al, 2002). A comparable negative feedback mechanism could exist between glial cells and neurons (Haydon, 2000; Mitterauer, 2001). The firing of neurons might stimulate glial cells to release certain substances, such as neurotransmitters, ions, etc., which subsequently deactivate the neurons. In this case glia may not only be able to form functional units with neurons, but they could also set a time limit for the functional processes (Mitterauer, 2001). The turning off of neurotranmission can logically be interpreted as a rejection mechanism. Now, what happens when glial receptors are “chimeric” (intron-containing) due to mutations in splicing controlling genes?
3.2.2. Loss of the glial boundary-setting function
First let us suppose that mutations in genes which control the splicing mechanism will lead to non-splicing of introns. If non-splicing changes the structure of glial receptors (“chimeric” receptors), then these receptors cannot be occupied appropriately by their neurotransmitter ligands so that the inactivating function of synaptic transmission by glial cells is disturbed or lost. It makes no difference if an excitatory or an inhibitory transmitter system is affected. The point is that glial receptors cannot be occupied and that, at least locally, neuronal transmission cannot be interrupted. As a result, neither excitatory nor inhibitory transmitters are able to act in well defined spatio-temporal functional units in the brain. The type of imbalance of transmitter systems will depend on the brain area and the neuronal circuits affected. A variety of neurotransmitter systems are involved in regulating information flow via the corticostriatothalamocortical loops, any of which could be altered in schizophrenia (Wyatt et al, 1995).
Recently, immunohistochemical findings suggest that in the entorhinal and inferior temporal cortex of the schizophrenic brain the expression of the GABA (B) receptor is reduced, raising the possibility that GABA (B) receptor dysfunction is involved in the pathophysiology of schizophrenia (Mizokami et al, 2002). Huntsman and coworkers (1998) found that the levels of an alternatively spliced form of GABA receptor mRNA are reduced by 51% in the brains of schizophrenic patients, which should have severe consequences for cortical function. Extending these considerations further, we are not surprised by the fact that alterations in various transmitter systems have been found in brains of schizophrenic patients, for instance decreased excitatory synapses in the median temporal lobe (Harrison and Eastwood, 1998). Therefore, it has been hypothesized that the antipsychotic action of neuroleptic drugs is due to combined neurotransmitter effects and not to a primary abnormality of dopamine neurotransmission alone (Johnstone et al, 1999).
Such a loss of the glial boundary setting function is depicted in Figure 2. The astrocytes (Aci, Acj) have chimeric receptors (asterisks), so that their processes cannot influence or structure the neuronal information processing. This genetically determined disturbance results in a “compartment-less” neuronal network displayed as a graph of eight neurons with 28 connecting lines (according to the formula n/2(n+1)). Such a brain is “measure-less” informed, i.e. unable to structure the environmental information. One may argue that the neuronal system is also compartmentalized per se. As already mentioned, Rall (1995) has developed a compartment model based on the neuronal system which divides a neuron into a number of compartments (soma, dendrites, axons). He was able to show that the complete functions of the neurons could only be demonstrated if their different functional parts were separated (compartmentalization). According to my view, there is a qualitative difference between the purely neuronal compartments and the glia-determined compartments. Neuronal compartments are merely functional for information processing, whereas glial-neuronal compartments may, in addition, have an information structuring potency. Depending on the brain areas affected by mutations in the splicing controlling genes, a “boarder-less” generalization of functional units (neuronal groups; Edelman, 1981; Costa, 1992; Gupta et al, 2000) results in the inability to reject information on the behavioral level. Therefore, the boundary between the brain and its environment is also lost.
The inability to reject non-realizable or “intronic” ideas may result in delusions and hallucinations, and could explain why schizophrenic patients are unable to test the reality of their ideas and are at times absolutely convinced that all which occurs in their brains is real. In other words, the basic flaw that results in delusions and hallucinations is the loss of the capability to reject impossibilities concerning the realization of ideas in the environment. It can be argued that there are diseases caused by genetic changes in neurotransmitter receptors which still do not produce schizophrenic symptoms, as for instance in the congenital myasthenic syndromes, which are due to mutations in acetylcholine receptors (Engel et al, 1998). In the hypothesis now being presented, schizophrenia will only occur if the following conditions are met:
1) The functions of rejection and boundary setting with respect to the environment that glial cells perform in the brain must be severely disturbed or lost due to mutations in genes that control splicing. These genetic lesions affect not only molecular and cellular processes, but also the psychobiological behavior of the individual.
2) Stressors (life events, object loss, organic disorders, viral infections, etc.) must occur to trigger schizophrenic symptoms in the genetically vulnerable individual (vulnerability-stress model of schizophrenia; McGlashan and Hoffman, 1995).
4. The timeless brain
If one accepts my hypothesis that the schizophrenic brain has lost the compartmental boundaries within the brain, it follows that it is also incapable to set boundaries between the Self and the Non-Selves or the environment. It generalizes, so to speak, to an infinite universe. Psychiatrists would call this state an inner/outer confusion. Reality-testing is therefore impossible. But what are the implications of such a borderless brain for the experience of time?
In a schizophrenic brain time may not really matter. Everything is Now. This sounds like Barbour´s theory of existence, in which time has no reality. “Time and motion are nothing more than illusions” (Barbour, 1999). Because I draw possible parallels between my brain model and Barbour´s theory, a short pertinent outline of his ideas is necessary.
Barbour´s universe is a geometrically structured, static tableau composed of Platonic bodies (triangles). Therefore, he termed it “Platonia”. Specific configurations are covered by a mist, under which a time capsule is hidden. A time capsule in the sense of a configuration (composed of triangles) exactly respresents a Now. Every now is a complete, self-contained, timeless, unchanging universe. The intensity of mist does not vary in time, but it does vary from position to position. Its intensity at each given point is a measure of how many configurations corresponding to that point are present. Any continuous path in Platonia corresponds to a sequence of triangles: they are the points through which the path passes. At any one point in Platonia many of them pass through.
Supposing that the brain of a schizophrenic patient embodies a physical universe without the biological compartmentalization, perhaps he or she is capable to tap into the many Nows hidden in the structure of the neuronal network. This ability could also explain how delusions and hallucinations arise. These basic schizophrenic symptoms could be based on a read out of configurations or Nows from the physical structure of the “brain tableau”. In such a static brain structure everything is appropriate and nothing rejected. Nows do not have intentions. “We are all part of one another, and we are each just the totality of things from our own viewpoint”(Barbour, 1999). Most remarkably, this does not only express the view of a great scientist´s world, but it also describes how the schizophrenic patient experiences his world. Barbour confesses in his book that he tends to pantheism. The contents of delusions also support a pantheistic interpretation of the universe.
The revolutionary ideas of Barbour represent a big challenge for a comprehensive brain theory. If my hypothesis that the glia have a spatio-temporal boundary-setting function in so called normal brains is correct, then the loss of this function could open the realm of Platonic physics as Barbour claims. In Figure 2 a graph is depicted where each point (neuron) is interconnected , termed as a compartmentless neuronal network. From a geometrical point of view, this network is composed of many triangels like Barbour´s Platonia. Considering that the human brain consists of about 1011 neurons (points), the number of possible connecting paths is enormous. There is in fact a mist over our brains. But what are the clinical correlations of the spatio-temporal loss of self-boundaries?
5. Clinical correlations
5.1. Interpretation of the loss of spatial self-boundaries
The phenomenology of schizophrenia is multi-fold. My hypothesis attempts to explain the multiple symptoms of schizophrenia in terms of loss of self-boundaries. As already discussed, mutations in the genes that control splicing may result in a "borderless generalization of functional units" causing an incapacity to reject information on the behavioral level. Therefore the patient is unable to test the reality of his ideas.
We should first assume that the ability of the human brain to develop new ideas is nearly unlimited. For example, in the dream state our brains produce scenes which are not realizable during waking. Man is only able to fly in his dreams. If a schizophrenic patient states that he has just been flying, to him this scene produced by his brain has really taken place, because he cannot differentiate between his inner world and the outer world. Therefore, everything taking place in the brains of schizophrenic patients is reality as far as they are concerned. There is a loss of the capacity to accept information which contradicts the ability to fly and to reject the delusion as a consequence.
Hallucinations are caused by the same disorder. If a patient hears the voice of God giving him commands, then he must obey because he is convinced that the voice belongs to God. The patient is in no way accessible to the argument that God did not give the command, because he cannot distinguish between his inner and outer reality. The loss of self-boundaries is also evident in the content of delusions. For example, one of my patients is absolutely convinced that he is simultaneously Ceasar, Napoleon, Churchill and "Urbi". "Urbi" is a schizophrenic neologism, that is a novel verbal construction that has a mysterious meaning only to the patient.
If a patient believes he is God and the Devil in one person, to an observer this might appear as a split mind and thus schizophrenic. However, I interpret this delusion to a loss of self-boundaries, since the patient is unable to distinguish between God and the Devil.
Depending on the brain areas affected, the loss of the boundary setting function and the corresponding generalization of brain functions may show up in the motor, affective, or cognitive behavior of the patient. For instance, catatonic agitation in which a disinhibited discharge of nearly all motor systems occur, is an expression of motor generalization with raging and screaming as behavioral components. Here we are probably dealing with an excess in excitatory transmitter systems. If a catatonic stupor occurs, which implicates a state of complete motor inhibition, presumably the inhibitory transmitter systems predominate.
Affective flattening is regarded as a negative schizophrenic symptom (Dollfus and Petit, 1995). 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. This dysfunction specifically affects the limbic system. Dysfunction of thought in schizophrenic patients appears as an incoherence (loss of meaning) of thought processes. Since the contents cannot be distinguished with respect to their qualitative independence, the patient is unable to meaningfully sort his thoughts or to reject meaningless ideas. The loss of spatial boundary function can also appear as megalomania. For example, one patient said: "I am the universe".
5.2. Interpretation of the loss of temporal self-boundaries
During extensive explorations schizophrenic patients confess their convictions that “everything is as it is”. Typical statements are: “I am living in eternity” or even “I am eternity”. One of my patients, able to speak with the almighty God, aks him day by day: when does the world break down? The voice of God is always disappointing: “no change!” There is obviously a loss of the temporal boundary-setting function. One could call it a delusion of eternity.
With regard to a pertinent question about time, a patient answered: “There is nothing which I cannot perceive. Perhaps I am not aware of some things, but the things are here. Since everything is here and now, evolution is nonsense.” This schizophrenic sense of existence could be characterized as an “eternal Now”. In fact, this patient describes his existence similar to Barbour´s everlasting tableaux that includes everything in the universe at any given moment. Barbour calls each of these possible still-life configurations a “Now” as I already did. Again, schizophrenics have absolutely no problem with the real existence of a delusional idea or the content of a hallucination; they are “Nows”.
From the perspective of Barbour´s theory, one severe schizophrenic symptom seems to be especially impressive. It is the so-called catatonic stupor. Except for the basic cardiac and respiratory functions, the patient shows no movement or reaction in the sense of a complete psychomotor rigidity. No communication is possible. Such a patient embodies a “motionless Now”. In his book “The end of time”, Barbour quotes people with specific types of brain damage who are unable to see motion where normal people would. His conclusion is rather surprising: “If the mind can do these things, it may be creating the impression of motion in undamaged brains.” Similar considerations may also hold for schizophrenia.
6. Attempting an interdisciplinary definition of the etiology of schizophrenia
On the molecular level the non-rejection or non-splicing implies a severe disturbance of neurotransmission caused by the production of truncated or short-lived proteins and chimeric receptors such that the glial cells lose their spatio-temporal boundary-setting function. From a spatial point of view, the loss of glial barriers may lead to a generalization of neuronal information processing. With regard to the loss of temporal boundary-setting, the schizophrenic brain may be interpreted as a timeless universe in line with Barbour´s theory. This may explain the loss of self-boundaries and the typical symptoms of schizophrenia, especially delusions and hallucinations (Figure 3). Churchland (2002) also describes a schizophrenic patient suffering from deep confusion about Self-/Non-Self boundaries, e.g. responding to a tactile stimulus by claiming that the sensation belongs to someone else or that it exists somewhere outside himself. However, Churchland does not offer any explanatory model of the confusion of Self/Non-Self boundaries.
Now tying all arguments together, schizophrenia could be defined as follows:
Schizophrenia is a conscious state of a “timeless” misinterpretation of the Self and the environment due to the inability to set boundaries between the subsystems (compartments) of the Self within the brain as well as between the Self and the Non-Selves or the environment. This state is caused by a non-splicing (non-rejecting) of introns leading to a glia determined disturbance of neurotransmission and to the loss of the glial spatio-temporal boundary-setting function. The typical symptoms are delusions and hallucinations.
Up to now, the etiology of schizophrenia is unknown. The investigation of this psychobiological disorder is difficult, because of its multifold sympomatology and multifactorial genesis. Therefore, a theory of schizophrenia should be based on an interdisciplinary approach.
I started out with the psychiatric hypothesis that the main symptoms of schizophrenia (delusions and hallucinations) may be caused by a loss of self-boundaries. First, I defined the concept of the Self as a self-reflecting system consisting of many subsystems or Selves in the brain. A Self has intentional programs striving for self-realization in the environment. Basically, appropriate objects may be accepted, but inappropriate ones must be rejected. This rejection mecahnism has a boundary-setting function. Therefore, the loss of self-boundaries may be caused by an ability of the brain to reject non-realizable programs. This is my basic hypothesis.
At a molecular level, a non-splicing of introns may correspond to a non-rejection. This would lead to “chimeric” receptors and a significant disturbance of neurotransmission. Concerning normal brains, I proposed that glia have a spatio-temporal boundary-setting function grouping neurons into functional units or compartments. It is assumed that “chimeric” receptors in glial cells cannot interact properly with their cognate neurotransmitters. The glia will lose their inhibitory-rejecting function with respect to the information processing within neuronal networks. The loss of glial barriers may result in a “borderless” generalization of information processing such that the structuring of the brain in functional domains is almost completely lost. This loss of glial boundary-setting could offer an explanation of the loss of self-boundaries in schizophrenia.
Understood in this sense, the main schizophrenic symptoms can be deduced both from the loss of spatial self-boundaries and from the loss of temporal self-boundaries. Most interestingly, the temporal loss of self-boundaries corresponds to Barbour´s theory of the universe in the sense of a timeless, everlasting existence or a “Now”. Specifically, many delusions arise from the conviction that time does not really matter. The subjective universe of those patients represents an “eternal Now”.
Finally, I attempted to define schizophrenia by tying all my arguments together towards an interdisciplinary theory. Since my explanatory model of schizophrenia is testable at least on a molecular level, its further elaboration towards a comprehensive theory depends on pertinent experimental results.
This paper is dedicated to John Pellam, the great mediator between sciences. I am very indepted to Birgitta Kofler-Westergren for preparing the final version of the paper.
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Table 1. A subject tries to realize its intentional program, depicted as intentional values iv (1, 3, 2, 4), in four steps (step 1…4). Two objects, with their respective object values ov (1, 2), are found in the environment. In the first step, the detected object ov (1) can be accepted. In the second step, the intended value iv (3) rejects both objects ov (1, 2). In the third step, ov (2) is accepted. In the fourth step, finally, iv (4) rejects both object values ov (2, 2) (Mitterauer, 2000a).
Figure 1. Glial boundary-setting function in its interaction with the neuronal system:
An astrocyte (Aci) is connected with four neurons (N1…N4) via processes building a glial-neuronal compartment (x). Only two processes are activated influencing the neurotransmission in the synapses (sy) of N2 and N3 (thick lines). In the second compartment (y), the astrocyte (Acj) activates three neurons (N1, N2, N4). These two compartments are connected via a gap junction (g.j.). Dashed lines outline the neuronal network determined by the activated neurons in both compartments.
Figure 2. Loss of glial boundary-setting function and generalization of neuronal information processing:
In the glial-neuronal compartments (x, y) the astrocytes (Aci, j) are unable to activate any of the neurons (N1…N4). They cannot influence the neurotransmission in the synapses (asterisks). This loss of glial boundary-setting (as depicted in Fig. 1) results in a ‘compartmentless’ neuronal network where all neurons are interconnected.
Figure 3. Outline of an interdisciplinary theory of schizophrenia.
On the molecular level, a non-splicing of introns results in truncated proteins or “chimeric” receptors. On the cellular level, a loss of the glial spatio-temporal boundary-setting function may cause a disturbance of neurotransmission. In generalizing the neuronal information processing the brain functions as a compartmentless neuronal network (see Figure 2). From a physical point of view, such a brain can also be interpreted as a timeless brain. Therefore, schizophrenia may be caused by the loss of spatio-temporal self-boundaries within the brain and between the Self and the environment (Non-Selves). This disorder leads to a delusional misinterpretation of reality. Typical symptoms are delusions and hallucinations.
Dr. Bernhard Mitterauer is Professor of Neuropsychiatry at the University of Salzburg's Institute of Forensic Neuropsychiatry. He recived his M.D. from the University of Graz and eight years later received his academic degree in Neuropsychiatry and Psychoanalysis. Dr. Mitterauer studied Philosophy with Gotthard Gunther, the famous Philosopher of Cybernetics, in Hamburg. He developed a close friendship and intensive scientific collaboration with Gunther, whose philosophy has influenced Dr. Mitterauer's work up to this day. In 1984 Dr. Mitterauer was appointed Professor of Neuropsychiatry at the University of Graz and he has been serving as a Professor and Head of Forensic Neuropsychiatry at the University of Salzburg since 1989. 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. Dr. Mitterauer decisively advanced the methodology of the assessment of criminal offenders and has published numerous pertinent basic research studies. He is the founder of the Gotthard Gunther Archives for the research and publication of the posthumous works of Gunther at the University of Salzburg.
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