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

see also http://shinbashi-ssn.blog.so-net.ne.jp/2008-05-04

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,

障害のヨーロッパを食べる上で統計

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

にきび治療における昇華硫黄の成功率

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

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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.