Confidence analyses of self-interpretation and self-description in depressive behaviour.

The present paper represents an investigation in the procedure to validate a new questionnaire (Salzburg Subjective Behavioural Analysis, SSBA). This questionnaire is based on a new approach to the diagnosis of depressive behaviour. It is hypothesized that a patient suffering from a depressive disorder loses the ability to produce one or more modes of behaviour at a given time and simultaneously has the urge to produce one or more modes of behaviour constantly. Although the patient is capable of describing this behavioural disorder, he/she is unable to interpret it confidently. This inability of interpretation of depressive behaviour assessed with the SSBA may represent a special kind of cognitive impairment in depression that is tested in conducting an analysis of confidence. The analysis of confidence shows that the capability of interpretation in the patient group is significantly impaired. Finally, a discriminant analysis allows to differentiate between depressive behaviour and normal behaviour based on the questionnaire.

Comprehensive behavioral analysis of patients with a major depressive episode.

BACKGROUND: A major depressive episode diagnosed according to DSM-IV criteria can be accompanied by symptoms that DSM-IV does not include. These symptoms are sometimes classified as comorbidities. Our study assessed altered behavioral modes during a major depressive episode; ie, if 1 or more modes of behavior operated less or even not at all ("never"), or if the operation of others was more frequent or even constant ("always"). We hypothesize that these altered behavioral modes, especially the extreme positions "never" (hypomodes) and "always" (hypermodes) might correlate with depression scores and thus represent a typical symptom of depression. MATERIAL/METHODS: We used the 35-item Salzburg Subjective Behavioral Analysis (SSBA) questionnaire to measure altered behavioral modes in 63 depressed patients and 87 non-depressed controls. Depression was assessed using the Hamilton Depression Scale. RESULTS: In our test group (n=63) we found a total of 888 extreme positions. The mean number of extreme positions per patient was 11.15±5.173 (SD). Extreme positions were found in all 35 behavioral modes. The mean Hamilton score was 22.08±7.35 (SD). The association of the incidence of extreme positions and the Hamilton score in our test group was highly significant (Spearman's Rho=0.41; p=.001). In the control group (n=87), only 11 persons were found to display extreme positions, with a total of only 25. CONCLUSIONS: Although this study has several limitations, such as the small sample or the use of a questionnaire in the validation procedure, the significant correlation of extreme positions and the Hamilton score indicate that altered modes of behavior as detected with the SSBA might be typical symptoms in a major depressive episode.

[Dissociation (conversion) - malingering - antisocial personality disorder: differential diagnostic reflection on the basis of a case study]. / Dissoziation (Konversion) - Simulation - Dissozialität: Differentialdiagnostische Überlegungen anhand eines Fallbeispiels.

In this case report we refer to the big challenge of making a diagnosis in a deliberate malingering in the field of mental disorders. We specifically describe the difficulty regarding the differentiation between a conversion disorder and malingering of a serial delinquent. For such a person avoiding criminal persecution is one of the most frequent reason to deceitfully simulate a mental illness. In this field, symptoms of conversion disorders exceed the average; furthermore, a great number of organic-neurological illnesses may appear to be very similar to a conversion disorder or in many cases a neurological disorder can actually be detected in the course of a somatic examination. A further obstacle for the differential diagnosis can be seen in the difficulty to discern it from factitious disorders. However, it is quite possible to discern the deliberate malingering of a mental disorder from a conversion disorder by means of the diligent diagnosis of a competent and experienced doctor/assessor who specialises.

[Method and empirical results from expert opinions on 90 offenders concerning the question of complete intoxication]. / Methodik und Empirie der Begutachtung von 90 Straftätern zur Frage der vollen Berauschung.

Based on a 3-year sample of expert opinions concerning the question of complete intoxication (n = 90), methodology and results are presented. Since more than half of the offenders (n = 53) claim amnesia regarding the circumstances of the offence, this subjective amnesia is considered methodologically. If the file contains observations on the offender's behaviour, it is generally possible to assess if the offender was still able to self-reflect and act in a purposeful way. If so, complete intoxication must be negated independent of the objective degree of alcohol or drug intoxication, and the subjective amnesia claimed by the offender is implausible. In the assessment procedure of complete intoxication a decision tree is used. 37/90 offenders showed no significant memory impairment as well as no psychiatric diagnosis, thus excluding both criminal irresponsibility and complete intoxication. The assessment of subjective amnesia and total intoxication was based on the following information from the decision tree: in 51 (47 males, 4 females) of the 53 offenders claiming subjective amnesia the file contained behavioural observations at the time of the offence. Only in two cases, a considerable lack of information prevented a clear decision regarding the question of complete intoxication. Despite the fact that only in about 50% of the offenders claiming subjective amnesia evidence of alcohol or drug influence was demonstrated according to the files, the question of complete intoxication could be successfully evaluated in all but two cases according to the decision tree.

The incoherence hypothesis of schizophrenia: based on decomposed oligodendrocyte-axonic relations.

Based on the findings of white matter abnormalities in brains with schizophrenia, it is hypothesized that this disorder may be responsible for symptoms of incoherence of schizophrenia. It is supposed that the processes of oligodendrocytes tie the various properties of axonic information conductance together into categories. For this oligodendrocytic computation capacity a formalism is proposed. In the case of a decrease or loss of oligodendroglia, a brain with schizophrenia is unable to categorize information processing, so that on a behavioral level symptoms of incoherence (thought disorder, etc.) occur. Similarities and differences in the pathophysiology of multiple sclerosis and schizophrenia are also shortly discussed. Together, a decomposition of the oligodendrocyte-axonic system may be responsible for symptoms of incoherence in schizophrenia.

Nonfunctional glial proteins in tripartite synapses: a pathophysiological model of schizophrenia.

A model for the pathophysiology of schizophrenia is proposed that focuses on an unbalance of transmission in tripartite synapses. Synaptically associated astrocytes should be viewed as integral modulatory elements of tripartite synapses consisting of the presynapse, the postsynapse, and the glial element. Astrocytes may secrete glial binding protein into the synaptic cleft, thus binding free neurotransmitters and thereby reducing the levels of neurotransmitters available for stimulating the postsynapse. Astrocytes also have membrane-bound receptors for neurotransmitters, and when these bind neurotransmitters, the astrocytes upregulate the amount of binding protein secreted into the synapse, resulting in a negative feedback to the presynaptic terminal. The hypothesis presented here is that glia lose their negative feedback function due to loss of function mutations in the genes encoding the binding proteins and glial receptors. The mutations generate proteins that cannot be occupied by their cognate substances of the neuronal system, primarily neurotransmitters. Therefore, the glial-neuronal interaction in tripartite synapses affected becomes totally unbalanced, and the glia lose their inhibitory or boundary-setting function. As a result, neural flux is unconstrained by normal glial boundaries, also the flux of thought on the phenomenological level. Schizophrenia may be caused by the inability to delimit conceptual boundaries.

Model of the Reticular Formation of the Brainstem Based on Glial-Neuronal Interactions.

A new model of the reticular formation of the brainstem is proposed. It refers to the neuronal and glial cell systems. Thus, it is biomimetically founded. The reticular formation generates modes of behavior (sleeping, eating, etc.) and commands all behavior according to the most appropriate environmental information. The reticular formation works on an abductive logic and is dominated by a redundancy of potential command. Formally, a special mode of behavior is represented by a comprehensive cycle (Hamilton loop) located in the glial network (syncytium) and embodied in gap junctional plaques. Whereas for the neuronal network of the reticular formation, a computer simulation has already been presented; here, the necessary devices for computation in the whole network are outlined.

Balancing and imbalancing effects of astrocytic receptors in tripartite synapses. Common pathophysiological model of mental disorders and epilepsy.

Based on a logic of balance mechanisms influencing information processing in tripartite synapses are proposed. It is hypothesized that the number of expressed astrocytic receptors determines balanced and imbalanced synaptic states. Synaptic information processing in mental disorders is underbalanced in depression, overbalanced in mania, and completely unbalanced in schizophrenia. The synaptic pathophysiology of the epileptic syndrome may also be based on comparable imbalances. In addition, this model of synaptic balancing enables a deduction in explaining the therapeutic effect of ECT in therapy resistant depression. Together, the model proposed may represent a contribution to the search for common synaptic mechanisms in normal brains and its various disorders.

Imbalance of glial-neuronal interaction in synapses: a possible mechanism of the pathophysiology of bipolar disorder.

There is a wave of new information suggesting that glia, especially astrocytes, are intimately involved in the active control of neuronal activity and synaptic transmission. Synaptically associated astrocytes should be viewed as integral modulatory elements of tripartite synapses consisting of the presynapse, the postsynapse, and the glial element (astrocytes). Smit and coworkers proposed a model of a cholinergic tripartite synapse based on the identification of a glial-derived binding protein (BP) that is secreted into the synapse and binds free acetylcholine (ACh), thus reducing the levels of ACh available for stimulating the postsynapse. Here the author proposes an explanatory model of the pathophysiology of bipolar disorder focusing on the possible dynamics in cholinergic tripartite synapses. The hypothesis is that an imbalance between neurotransmitters and glial BPs in the synaptic cleft is determined by glia. If glial BPs are overexpressed, synaptic transmission is suppressed because of reduced levels of bioavailable neurotransmitters. This state could cause a depression on the behavioral level. In contrast, if glial BPs are underexpressed, the excess of neurotransmitters in the cleft leads to an overbalanced state of synaptic information transmission. This state could cause manic behavior. Under certain conditions, underbalanced and overbalanced synapses at different locations in the same brain could disturb brain function in parallel causing a mixed episode of bipolar disorder. If glial BPs and mutations in genes expressing glial BPs in the various synapses of the brain are identified, this hypothesis can be experimentally tested.

Astrocyte mega-domain hypothesis of the autistic savantism.

Individuals with autism who show high abilities are called savants. Whereas in their brains a disconnection in and between neural networks has been identified, savantism is yet poorly understood. Focusing on astrocyte domain organization, it is hypothesized that local astrocyte mega-organizations may be responsible for exerting high capabilities in brains of autistic savants. Astrocytes, the dominant glial cell type, modulate synaptic information transmission. Each astrocyte is organized in non-overlapping domains. Formally, each astrocyte contacting n-neurons with m-synapses via its processes generates dynamic domains of synaptic interactions based on qualitative computation criteria, and hereby it structures neuronal information processing. If the number of processes is genetically significantly increased, these astrocytes operate in a mega-domain with a higher complexitiy of computation. From this model savant abilities are deduced.

Intuition in autistic savantism: a hypothetical model based on glial-neuronal interactions.

The previously proposed hypothesis on the astrocyte mega-domains of autistic savantism is here further elaborated with regard to the faculty of intuition. Two mechanisms may essentially be responsible for the intuition of autistic savantism. First, the increased number of contacted synapses via the astrocyte processes enables the brain to generate a comprehensive perception of a scene in the environment. Second, to inhibit a further reflection process neuronal synapses responsible for pertinent information must be rejected by retraction of the same astrocyte processes. This second mechanism may exert the disconnections of neuronal systems and is experimentally verified. Therefore, the break-off of further social contacts may also be necessary. The testing of the hypothesis in living brains is difficult but at least partly possible in post-mortem brains.

Neuromodulatory systems.

We examine the interactions and interdependencies between Neuroglia, the Brain-Cell Microenvironment, and the processes commonly subsumed under Neuromodulation. The interactions of the component processes covering a wide spectrum of frequencies are designated as Neuromodulatory Systems (NMS). This implies NMS's scale-invariance as the capacity of linking actions across many time scales, and self-similarity at any scale. These features endow NMS with the ability to respond adaptively to neural impulse traffic of an unpredictably wide frequency spectrum. In this preliminary perspective, the components of NMS are only outlined based on concepts of Complex Systems Dynamics. However, their interactions must be formally elaborated in further investigations.

Downregulation and upregulation of glial connexins may cause synaptic imbalances responsible for the pathophysiology of bipolar disorder.

The model of the pathophysiology of bipolar disorder proposed is based on imbalances in tripartite synapses caused by dysregulations of connexin expression in the astrocytic syncytium. If the expression of connexins is downregulated, a compensatory upregulation of astrocytic receptors may occur and be responsible for the pathophysiology of depression. Conversely, if the expression of connexins is upregulated, the expression of the astrocytic receptors may be downregulated and be responsible for the pathophysiology of mania. In depression, a relative lack of neurotransmitters exerts a protracted synaptic information processing, whereas in mania a relative increase of neurotransmitters may accelerate synaptic information processing. In addition, the modulatory role of gliotransmitters may be affected in bipolar disorder. Since the dysregulations of connexins impair the astrocytic syncytium, these disorders could be explanatory for cognitive impairment both in depression and in mania. Finally, the testability of this model is discussed.

The gliocentric hypothesis of the pathophysiology of the sudden infant death syndrome (SIDS).

The hypothesis is based on glial-neuronal interactions in the cardio-respiratory centre of the brainstem. Recently, it has been experimentally verified that glial cells, especially astrocytes, exert a modulatory function in the maintenance of homeostasis in this brain region. In addition, astrocytes may also control the rhythms of heartbeat and breathing in a pulsatile manner. Based on a model of the glial-neuronal-vascular interactions in the networks of the cardio-respiratory centre in the brainstem, possible impairments of glial function that may be responsible for the sudden infant death syndrome (SIDS) are proposed. Finally, general approaches for testing the hypothesis are outlined.

Possible role of glia in cognitive impairment in schizophrenia.

Cognitive impairment is a core disorder of the schizophrenia syndrome. Based on glial-neuronal interactions, a pathophysiological model is proposed that could be explanatory for cognitive impairment in schizophrenia. The model consists of three main hypotheses concerning the pathophysiology in tripartite synapses, oligodendrocyte-axonic interactions, and in the glial networks (astrocytic syncytium). In tripartite synapses nonfunctional astrocytic receptors may cause an unconstrained synaptic information flux, since they cannot be occupied by neurotransmitters (NTs). Therefore, a generalization of information processing may occur in the brain causing hallucinations, delusions, and thought disorder. If the oligodendrocyte-axonic system decomposes, the brain is unable to process information in qualitative domains or categories. This may lead to severe incoherence phenomena such as thought disorder. Supposing that in the astrocytic syncytium gap junctions (g.js) normally form plaques functioning as memory devices, loss of function of g.j. may also cause cognitive impairment, since the syncytium decomposes and g.j. plaques cannot be generated. These hypotheses are experimentally testable. Finally, the problem of treatment of patients with schizophrenia is discussed, in case the presented model of schizophrenia might be verified.

Possible effects of synaptic imbalances on oligodendrocyte-axonic interactions in schizophrenia: a hypothetical model.

A model of glial-neuronal interactions is proposed that could be explanatory for the demyelination identified in brains with schizophrenia. It is based on two hypotheses: (1) that glia-neuron systems are functionally viable and important for normal brain function, and (2) that disruption of this postulated function disturbs the glial categorization function, as shown by formal analysis. According to this model, in schizophrenia receptors on astrocytes in glial-neuronal synaptic units are not functional, loosing their modulatory influence on synaptic neurotransmission. Hence, an unconstrained neurotransmission flux occurs that hyperactivates the axon and floods the cognate receptors of neurotransmitters on oligodendrocytes. The excess of neurotransmitters may have a toxic effect on oligodendrocytes and myelin, causing demyelination. In parallel, an increasing impairment of axons may disconnect neuronal networks. It is formally shown how oligodendrocytes normally categorize axonic information processing via their processes. Demyelination decomposes the oligodendrocyte-axonic system making it incapable to generate categories of information. This incoherence may be responsible for symptoms of disorganization in schizophrenia, such as thought disorder, inappropriate affect and incommunicable motor behavior. In parallel, the loss of oligodendrocytes affects gap junctions in the panglial syncytium, presumably responsible for memory impairment in schizophrenia.

The syncytiopathy hypothesis of depression: downregulation of glial connexins may protract synaptic information processing and cause memory impairment.

Astrocytes interconnected via gap junctions build an astrocytic syncytium. Gap junctions are composed of connexin proteins that are activated by substances of the neuronal system. It is hypothesized that disorders in the astrocytic syncytium may represent a main component of the pathophysiology of depression, called syncytiopathy. If the expression of connexin proteins is downregulated, a compensatory upregulation of astrocytic receptors may occur leading to an overproduction of these. Such an excess of astrocytic receptors exerts an imbalance of synaptic neurotransmission, because of a relative lack of neurotransmitters for the occupancy of astrocytic receptors so that neurotransmission is protracted. This delay of information processing may be responsible for the main symptoms of depression. In addition, the downregulation of connexin expression may also lead to an incomplete syncytium formation, responsible for memory impairment in severe depression. Finally, general approaches for testing the hypothesis are outlined.

Synaptic imbalances in endogenous psychoses.

Based on the formalism of logical balance, imbalances of information processing in tripartite synapses are described as a possible explanation for the pathophysiology of endogenous psychoses like depression, mania and schizophrenia. A tripartite synapse consists of the presynapse, the synaptic cleft, the postsynapse (neuronal components) and the glia (glial components). According to the logic of balance in a living system, the number of values and the number of variables must be equal. In a tripartite synapse the neuronal components are interpreted as values, the glial components as variables. In line with this novel synaptic model, three elementary synaptic imbalances can be deduced. First, tripartite synapses are underbalanced if the variables outnumber the values. Such a system state may cause depression. Second, if the values outnumber the variables, the tripartite synapses are overbalanced which may be responsible for mania. Third, if no functional variables are available at all, tripartite synapses process information unbalanced which may cause schizophrenia. The basic symptoms of these psychobiological disorders can be deduced from this novel synaptic model.

Loss of function of glial gap junctions may cause severe cognitive impairments in schizophrenia.

A generalized cognitive deficit is at the core of schizophrenia. It is hypothesized that a loss of function of glial gap junctions may cause severe cognitive impairment in schizophrenia. Glial gap junctions are electrical channels that may register the neuronal activation frequencies of glial-neuronal compartments by generating gap junction plaques. The various proteins (connexins) of gap junctions may be capable to differentiate between the operation qualities of the cognate synapses defined by the neurotransmitter types. Thus, the brain is capable of distinguishing between different cognitive qualities (domains or categories). If the function of glial gap junction proteins is lost, the brain is incapable to distinguish between same and different qualities of information processing. Dependent on the brain regions affected, this disorder may be responsible for severe cognitive impairment in schizophrenia. Finally, general approaches for testing the hypothesis are outlined.