My Original Theory-2: Pathological Hypothesis of Schizophrenia: First/Second World Model, Time-delay Hypothesis, Temporal profiles of Neurons

Tadashi Kon(Shinagawa Psychosomatic medicine Clinic)

〒108-0075　2-14-10-10F　Kounan,Minato-Ku,Tokyo,Japan

In this section, the pathological hypotheses studied by Dr. Kon are introduced in order to explain (1)the process from ARMS to onset of schizophrenia, (2)disturbances of ego characteristic of schizophrenia, (3)depressive moods seen with schizophrenia.

First, a pathological model of the process from ARMS to onset of schizophrenia will be explained. What a person considers to be proper interpersonal-distance is thought to be relative to the sensitivity of his dopamine receptors. If a person is sensitive to dopamine, he may tend to take larger interpersonal-distances. Some people are sensitive to dopamine from birth (for example, those who possess excessive dopamine receptors), and they have sensitive traits when coping with the world and others. Even if they have the same experiences as others, they tend to release excessive dopamine which makes them suffer. As a result, they tend to select a lifestyle that involves fewer interpersonal relationships.

In a life in which they tend to be solitary, they may become familiar with the arts, nature, and animals. In this way, they grow up with sensitiveness to dopamine and they acquire a lifestyle that helps them avoid the onset of schizophrenia. However, in adolescence, living conditions change greatly. “They are given roles and assignments that require interpersonal relationships,” “they become sexually mature,” and “they are placed in situations that require more assertiveness and responsibility” etc.. Life and interpersonal relationships become increasingly complicated, and they come to the point where their withdrawal strategy is no longer sufficient.

In the midst of this, strongly stressful situations related to “sexual affairs, money, honor, and health” cause excessive dopamine to be emitted, and combined with high sensitivity to dopamine, they face the crisis of the onset of schizophrenia. In addition, it is easy to predict these kinds of crises exist prior to the obvious onset. Psychotic-like experiences (PLEs, later ARMS : at risk mental state), which are attracting attention recently, possibly correspond to these situations.

Next is the pathological hypothesis of disturbances of the ego, which is specific to schizophrenia. The animal’s nervous system, in general, forms the loop of (1)reception of stimulation at the sensory organ→(2)conditional reaction in the brain→(3)reaction through motor system, autonomic nervous system, etc. →(4)real outcomes→(5)reception of stimulation at the sensory organ. Since there is no part to confirm the generation of self-consciousness in this loop, the sense of active control of the ego , an obvious experience in humans, cannot be explained.

“The first world model” and “the second world model” hypothesis is introduced here, for further discussion. For humans, “the first world model” is the same process of “(1)reception of stimulation through the sensory organ→(2)conditional reaction in the brain→(3)reaction through motor system, autonomic nervous system, etc.,” as for other animals. In addition, humans have “the second world model” in the brain concurrently, and two kinds of signals from “the first world model” and “the second world model” are compared. When there are differences, “the second world model” will be modified to coincide with “the first world model”. The function of “the second world model” to compare and transcribe the “the first world model” resembles that of cerebellum transcribing kinetic signals of cerebrum during exercise.

Further hypothesis is that a time lag exists between the two outputs from “the first world model” and “the second world model,” and output from “the second world model” is always begin adjusted so that it reaches the place where comparison is made slightly earlier (than the first world model). Sense of active control and sense of self in behavior, that is to say, formation of ego-consciousness can be explained by this time-delay hypothesis. For example, although the two compulsive computers give almost the same conclusions, the second evolutionary newer computer gives the answer slightly earlier and the older one reaches the same conclusion afterwards. This time-delay generates the sense of active control and the sense of self that humans experience.

Basically, “the first world model” is good enough for humans to live (as other animals), but the appearance of “the second world model” generated self-consciousness, which is the fundamental feature of humans. Because self-consciousness has been generated at the latest stage of the evolution, it can be easily destroyed. When self-consciousness breaks down, the following are seen according to the Jacksonism principle; “negative symptoms of schizophrenia triggered by the break down,” and “positive symptoms caused by the loss of inhibition”.

Humans can confirm the existence of ego-consciousness because they express their inner world through words, and other animals (to varying degrees by species) are assumed to have gained some similar mechanisms through the evolutionary process as well. Although animals cannot express themselves clearly, it is possible for them to have a sense of active control and a sense of self. People also behave unconsciously, when they are out of mind (for example, people pass through the train station ticket gate without being conscious of it). This is a situation in which signals from “the second world model” are weak and, so to say, the brain is nearly in the “automatic-drive” state. In addition, when people are concentrating intensely and showing their highly proficient skills, signals of “the second world model” perfectly coincide with those of “the first world model,” and by contrast, signals from “the second world model” sometimes feel as if they are being blocked out. People describe this situation using words such as “I did it without thinking about it,” “as if in a dream,” ”my body reacted automatically,” etc. Based on the “time-delay hypothesis,” free will is an illusion, and disturbance of ego is an experience (filled with pain) that is generated when illusion is lost. There are many theses on “rivet experiment,” a passive-consciousness hypothesis, which　is related to this discussion.

Come to think of it, signals transmitted from each sensory organ do not reach the brain’s processing site simultaneously. But the arrival time is supposed to be adjusted to be simultaneous, and thus a subjective real world is composed. In that case, processing sites that adjust the time-lag of signals arriving from each sensory organ are considered to exist in the brain. Similarly, it should be possible to assume there are sites in the brain, where the signals from “the first world model” and “the second world model” are compared, and the time adjusted. Also, it is assumed that trouble at these sites will cause a disturbance of ego.

When the output from “the second world model” arrive after those of “the first world model,” the disturbance of ego occurs. According to the amount and sort of delay, they can be “passivity experiences (experiences controlled by others), part of obsessive-compulsive experiences, auditory hallucinations, autochthonous ideas,” and so on.

As for autochthonous ideas, arrival of both output are assumed to be almost simultaneous. These situations are the first stages of schizophrenia. For example, auditory hallucinations are explained as follows; when the contents of what the person wants to say, which are output of “the second world model,” arrive after those of “the first world model,” they are perceived as “others are talking” or “made to listen to.”

Next hypothesis is that “the dopamine antagonist delays the output of ‘the first world model’ and ‘the second world model’ each to a different extent because of its pharmacological traits”. Antipsychotic drugs delay the output of “the first world model”, but it is assumed to delay those of “the second world model” only slightly or not at all. This hypothesis would be able to explain the mechanism of how medicines cure the disturbance of ego.

As facts concerning time-delay hypothesis and medicines’ effects, it is possible to state the different effects of medicine on the mesolimbic system and the mesolimbic-cortical system, or to give examples of different effects to the prefrontal area. For example, aripiprazole is said to inhibit dopamine at the mesolimbic system and increase it at the mesolimbic-cortical system; it is possible to explain the medicinal effect using time-delay hypothesis. As seen in the above discussion, if we suppose the dopamine system has some role at the site in the brain where two signals from the first and second world model are compared, time-delay hypothesis combines with dopamine hypothesis.

As to the last theme, that is, a hypothesis on symptom of depression, localization of the pathology is not adopted, and a patient’s condition is considered in terms of neurons’ temporal profile. There might be a localized symptom of depression caused by a certain site in the brain, but true mechanism is not clear. The symptoms of depression in the course of schizophrenia can be seen through all the stages from ARMS to far advanced stage to residual phase. Usually, depression of ARMS and residual phase is related to the negative symptoms of schizophrenia, and depression of far advanced stage is related to the positive symptoms. Examined more precisely, it is possible to understand as follows; at ARMS, people recognize their sensitiveness and understand the differences between the world and themselves at least to some extent, so they think it is dangerous to express their inner selves without defense; they become passive in relationships with others in order to avoid being hurt. This extends to the symptoms of depression at ARMS. You may say, excessive caution resembles depression. The symptom of depression, at the latter stage of residual phase, also assumes the same mechanism.

On the other hand, at the far advanced stage of schizophrenia, the patients are forced to face completely uncommon experiences, and they experience serious damage and loss of ego. Neurological mechanism of the symptoms of depression that occurs at this stage isn’t clear yet. When the acute phase of schizophrenia is calmed down by an antipsychotic drug, symptoms of depression also improve. Therefore, the dopamine system tends to be considered as a contributing factor to depression. However, it is better understood as a result of sharply blocking increased dopamine at the receptors’ level. So, the sharply increased dopamine is assumed to trigger symptoms of depression. At the same time, symptoms of apathy, which occurs along with Parkinson’s disease, are well known as resembling the symptoms of depression. This is one example of symptoms of depression accompanied by a decrease in dopamine. Once the localization of pathology is clarified, it might be possible to propose a hypothesis that explains these contradicting movements of the dopamine system.

This hypothesis best explains depressive symptoms in the early residual phase. There, the mechanism that is common to the depressive symptoms of bipolar disorders is assumed. “A group that responds to repeated stimulation with increasing reactions” is assumed as a trait of brain neuron cells. Because in the case of acute phase of schizophrenia and bipolar disorders maximum stimulation is given to neurons, the function of “a group which responds to repeated stimulation with increasing reactions” is possible to break down. The depressive symptom is supposed to start from here.

From this point of view, the depressive symptoms of schizophrenia and bipolar disorders are classified into two categories; that is (1)results of functional breakdown of “a group which responds to repeated stimulation with increasing reactions,” and the breakdown is triggered by excessive stimulation; (2)pathology of endogenous origin and positive onset of depression. Dr. Kon’s hypothesis supposes the former symptoms． In the case of medical treatment, medicine relevant to the dopamine system are good for symptoms relating to time-delay, and medicine relevant to the serotonin system are effective in aiding recovery of exhaustion depression. When cognitive-behavioral therapy mainly works on behavioral aspects, the target of therapy is “the first world model” in the above hypothesis. Whereas, interventions that emphasize cognitive modification mostly target “the second world model,” and through them attempts are made to alter “the first world model.”

If therapists become very aware of whether to approach “the first world model” through behavior or to get closer to “the second world model” through cognition, there may be clinical merits. If patients understand the above hypothesis through psychoeducation, the therapeutical effect of cognitive-behavioral therapy for their schizophrenia may increase. On the other hand, SST tries to change “the first world model” through behavior, of which the effect modifies “the second world model,” resulting in desirable change in cognition.