1

CHAPTER I
INTRODUCTION

Background
Schizophrenia is a severe chronic mental illness which occurs mostly during adolescence and late adulthood. It affects 0.7
percent of adulthood population in United States with an average mean around 15 to 35 years old. The median lifetime
prevalence estimates for persons were 4.0 per 1000 and for lifetime morbid risk were 7.2 per 1000. It means that the
likelihood of developing schizophrenia during lifetime in population is 7 per 1000 people.

Although it is a rare disease, the prevalence is high due to its chronicity. The worldwide prevalence shows that 1 percent
world population may diagnosed with schizophrenia. On 2009 it was predicted that 1.2 percent Americans (4.2 million)
and 1.5 million of world population already diagnosed with schizophrenia.

WHO data shows that 24 million world
populations already suffering from schizophrenia.

Individual with schizophrenia being burdened from the lifelong duration of the illness and a high rate of relapse.
1,2
Patient
with schizophrenia may have a two- to threefold increased risk of dying compared to general population.
2
This
phenomenon associated with the increasing rate of suicide and a wide range of comorbid somatic conditions in individual
with schizophrenia.
1,3

Schizophrenia may involve several clinical pictures, which may vary among individual.
4
The consistent signs and
symptoms mainly involve hallucinations, delusions, disorganized speech and catatonic or bizarre behavior. These clinical
picture make patient with schizophrenia being isolated from normal function role in their life. This decline in function
particularly observed with Global Assessment Function (GAF) scale.
3
Individual diagnosed with schizophrenia did more
poorly in multiple domains (e.g. symptomatology, social diability and work functioning).
3
The diagnosis of schizophrenia is based on the criteria of diagnosis of Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition, Text Revision (DSM-IV-TR) or International Classification of Disease (ICD-10). The DSM-
IV-TR particularly often used as diagnosis tool in United State of America regions. Meanwhile, the ICD-10 is used in
European countries region. The countries in Asian regions, including Indonesia, use the DSM-IV-TR which is already
translated into each national language of each country.

Although the exact pathophysiology of schizophrenia is still need further researches to established, the treatment for
schizophrenia is already developed. The increasing studies in efficacy of medication and treatment approach may
significantly increase the rate of remission in schizophrenia.
1
This allow individual with schizophrenia to achieve normal
functions in daily activities, occupation, marriage and having family, migration, and even travelling.

There is no specific regulation regarding individual with schizophrenia to take a travelling, whether in same country or
crossing another country. But some researches may suggest that travelling was associated with the risk of relapse in
schizophrenia.
5,6,7


There are some factors contribute to relapse rate of schizophrenia during travelling.
6
This phenomenon might be
associated with psychosocial stress during travelling, nature of destination, culture shock, substance misuse, and drug
tolerability during travelling, particularly in individual with established schizophrenia.
6


The diagnosis assessment of schizophrenia related to travelling may become a challenge to physicians to provide health
care service in travel medicine setting. This is particularly true regarding the chronicity of schizophrenia, the relapse risk
in already stable-schizophrenia, the increasing probability of individual with schizophrenia to take travelling, and several
factors associated to relapse or acute psychotic symptoms during travelling.
Problem Identification
There are some questions related to diagnosis and assessment of schizophrenia in travel medicine, such as
1. How to diagnose schizophrenia in travel medicine setting?
2. How does travelling correlates with schizophrenia?

Aims
General aims
Be familiar with diagnosis assessment of schizophrenia in travel medicine setting.

Specific aims
Be specifically aware of the correlation between travelling and schizophrenia.

2

Benefits
1. Having an appropriate approach in diagnosis assessment of schizophrenia in travel medicine setting.
2. Having knowledge about the correlation between travelling and schizophrenia.
CHAPTER II
LITERATURE REVIEW

Schizophrenia
Schizophrenia is a chronic mental disease characterized by disorders of cognition, affect and behavior which all involve
bizarre aspects.
4,9-11
The onset has its peak in adolescence and adult period, although a rare but severe form may occur
during childhood.
2,4,11-14
The incidence peak is between 10 to 35 years old for men, and between 25 to35 years old for
women. Women may have another peak of incidence during their midlife after the age 40. Small group of population
experience the first onset after age 60, known as very-late-onset schizophrenia-like psychosis.
10


The onset of first symptoms might be acute or insidious.
4
The acute onset tends to occurs in weeks or months involving
confusion or depressive symptoms.
4
Patient might realize some problems occur and tried to reorganize their life
experience. Meanwhile, the insidious onset might take months or years to develop.
4
This onset involving evanescent
changes occur when patient may not any have problems at all.

The prodromal symptoms may or may not occur before the actual onset of psychosis symptoms.
4,12,16
prodomal symptoms
of schizophrenia characterized by early specific and non-specific symptoms preceding the first psychotic episode.
12
If the
prodromal symptoms occur during childhood, it will involve introversion and peculiar interests. When prodromal
symptoms occur later in life, patient family may describe a transition time of the changing of behavior of patient.
4


There are some perspective models to explain the pathophysiology of schizophrenia.
4,
It is believed that several
multifactorial etiologies might interact in genetic and environmental aspect in order to develop schizophrenia.
4,13,14
It
could be said that schizophrenia might occur in susceptible person that has increased risk due to environmental exposures.

Some studies suggest that neurodevelopmental impairment may cause schizophrenia earlier or later in life.
4,11,13,14
The
neurodevelopmental disorders may involve defect in neuronal migration resulting in thalamic and cortical atrophy. These
neurodevelopmental abnormalities present at the onset of disease and might be worsen over time.
14


There are some researches show the association between the degree of ventricular dilation and cortical atrophy with the
severity of schizophrenia symptoms.
4
Thalamic atrophy may become prominent in schizophrenia with cannabis-use.
15
Other studies shows neurodevelopmental disorders may occur from normal single nucleotide polymorphisms (SNPs) and
copy number variants (CNVs) within population, or mutation lead to manifestation of schizophrenia.
13


Inheritance also plays a big role in the development of schizophrenia.
4,13,14
It is showed by the increase of lifetime
prevalence of schizophrenia in first-relative degree into 5 percent compare to general population which is about 1
percent.
4
Although further studies are needed to establish the specific gene linkage to schizophrenia, but some researches
suggest the linkage to loci on chromosome 6,8 and 22.
4

Other biological factors proposed to contribute on development of schizophrenia are reduction in neuropeptide Y,
alterations in neurotransmission, involvement of phosphatidylinositol signaling and decomposition of oligodendrocytic-
axonic systems.
14
Cognitive impairment also proposed as one of the factor contributes to development of schizophrenia
and also is part of the core feature of this illness.
9,14
The imbalance of neurotransmitter concept helped researchers in
developing drug modalities to treat schizophrenia.
14

Regardless the improvement of treatment modalities to achieve remission, some studies show that individual with
schizophrenia still has a risk for being relapse. Compete recovery only occur in 23 percent of patient with schizophrenia.
18
schizophrenia in children and adolescent is a chronic or relapsing disorder followed by disability and deterioration in
adaptive function from already impaired premorbid levels. Adult schizophrenia may have 50 percent of partial remission.
Meanwhile, adolescent may have 25 percent improved but suffering from continuing symptoms or occasional relapse.
18


Diagnosis Assessment of Schizophrenia
The clinical manifestation of schizophrenia is varied widely among individuals.
4
There are some signs and symptoms
which persistently occur such as hallucinations, delusion, disorganized speech and catatonic or bizarre behavior.
4
The
negative symptoms (e.g. flattening of affect, mutism, autism) often occur but in some patient might be in milder degree.

Hallucination
3

Hallucinations which occur in schizophrenia might involve auditory, visual, smell and taste, and tactile hallucination.
4
Auditory hallucination is the most common hallucinations experienced by patient with schizophrenia. The voices may
come from any sources; God, angels, towels, television or radio, wall, family member, and the most common source is the
stranger voices. The content of voices is also varied such as comments on patients act, two voices argue about patient,
the echoing patients thought, commanding or suggesting voices.
4


A visual hallucination is common but less prominent experienced compare to auditory hallucination.
4
Frequently the
visual hallucination is not so obvious seen by patient, but in other case it might be so obvious and so realistic to patient.
This may varied from alien in front of patient, devil crossing the street, insects or just something may walk through the
door.
4

Olfactory and gustatory hallucination is not so common, but these hallucinations might contribute to paranoid symptoms
related to suspicious thought of being poisoned. Patient may smell poisonous gas, putrefied flesh from corpses buried, or
even perfumes form others hand.
4
They may also taste a foul and bitter without any substances entering their mouth.
Sometimes following their food and drink they may taste poison and/or medicine. These tastes make them to refuse to
take the food and drink because of their increase suspicion for being poisoned.
4


Delusion
Delusion is common in almost all patients with schizophrenia. The content may vary in which this belief develops slowly.
At the beginning there may be only inkling, a suspicion, but as the time goes a conviction occur. Some patients may
consider the reality and all things become clear immediately. Other may persistently develop into false belief about the
reality. They may against other who are not in the same belief with them or only isolate them self from nonbelievers.
4


Almost delusion types are poorly coordinated each other, contradictory and poorly elaborated. But there is a systematized
one in paranoid subtype. It is possible that one patient might develop more than one delusion type.
4


Delusion of persecution involving a belief there is a conspiracy against patient. This may be described as a spy agent
following them anywhere with a high-tech trap or their family member intends to poison their food at home. This could
lead patient to build a defense against people or avoid that situation by moving to other place.
4


Grandiose delusion occurs frequently adding to persecution delusion. This make patient think that they are attacked by
jealous enemies. They belief they were a very important people in their country or even in the world regardless the real
fact about themselves. This delusion may not make them act in grandiose belief, but some patient may act according to
their delusion.
4

Delusion of reference involving a belief that all things happen refer to patient interest. There is no random or by chance
occurrence, everything happening has a special meaning to them. Some patients develop a peculiar bizarre belief about
thinking such as thought broadcasting, thought withdrawal and/or thought insertion. Thought broadcasting may described
as the television or radio echoing their thoughts. Thought withdrawal may make patient difficult on conversation. Patient
think they are loss their thoughts, so that they cannot thinking anything anymore. Thought insertion involves belief about
some forces entering their mind and control their thoughts.
4


Disorganized speech
The form of speech of the patient is disorganized compare to normal speech structure. This may reflect the disruption of
formal thought characterized as loosening of association. Patients are hardly understood by other people during
conversation. In severe form, it leads to word salad in which patient put all incoherent words in one sentence, or all
incoherent sentences in one conversation.
4


Catatonic symptoms
This involves negativism, catalepsy posturing, stereotypes and echolalia or echopraxia. Negativism showed by instinctual
opposition to any course of action suggested or commanded. It has two forms, active negativism and passive negativism.
The active negativism is the severe one may showed when patient asked to enter a certain room, they run to enter the
wrong room. The passive patient may choose not to enter any room, they do not moving, they just staying in the previous
room.
4


Catalepsy or waxy flexibility involves a state of continual and most abnormal muscle tension. In this stage they may
maintain uncomfortable, grotesque and and strenuous positions for hours.
4


Bizarre behavior
4

The odd behaviors are mannerism, bizarre affect or overall disorganization and deterioration of behavior. Mannerism is
an odd gestures, speech, or behavior. This makes patient obviously abnormal compare to surrounding people. Bizarre
affect characterized as distortion of normal association between felt emotion and affective expression. Patient may
express unprovoked and mirthless laughter. Patient with overall disorganization symptom characterized by untidy and
neglect to bathe or wash their clothes and their grooming become bizarre.
4


Negative symptoms
The negative symptoms are including flattening of affect, alogia or poverty of speech and thought and avolition. The
flattening of affect may characterized by lifeless and wooden facial expression with an absence of all feelings. Alogia
occur in normal amount of talking but it seems patient say very little. The content of talking may be only repetition or
stock phrases. Avolition occur when patient has no capacity to any goal-directed activity.
4

The features of schizophrenia are ambivalence and double bookkeeping. The ambivalence state between patients desire
and patient act shows incoherency of inner self. Double bookkeeping reflect the acceptance state of patient regarding
their real world and their psychotic world. It means that patient with schizophrenia may live in the two worlds, they may
accept the real world is exist as well as their psychotic world.
4


DSM-IV-TR Diagnosis Criteria for Schizophrenia
Diagnosis criteria for schizophrenia are based entirely on clinical signs and symptoms and duration and course of illness.
9

The diagnostic tool for schizophrenia in Indonesia is based on DSM-IV-TR diagnosis criteria. Schizophrenia is diagnosed
when the following criteria are fulfilled.
A. Characteristic Symptoms:
Two (or more) of the following, each present for a significant portion of time during a 1-month period:
1. Delusions
2. Hallucinations
3. Disorganized speech
4. Grossly disorganized or catatonic behavior.
5. Negative symptoms, i.e., affective flattening, alogia, or avolition.
B. Social / Occupational Dysfunction:
For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning
such as work, interpersonal relations, or self-care are markedly below the level achieved prior to the onset.
C. Duration:
Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1
month of symptoms that meet Criterion A and may include periods of prodromal or residual symptoms.
D. Schizoaffective and Mood Disorder Exclusion:
Schizoaffective Disorder and Mood Disorder with Psychotic Features have been ruled out because either
1. No Major Depressive, Manic, or Mixed Episodes have occurred concurrently with the active-phase
symptoms; or
2. If mood episodes have occurred during active-phase symptoms, their total duration has been brief
relative to the duration of the active and residual periods.
E. Substance / General Medical Condition Exclusion:
The disturbance is not due to the direct physiological effects of a substance or a general medical condition.
F. Relationship to a Pervasive Developmental Disorder:
If there is a history of Autistic Disorder or another Pervasive Developmental Disorder, the additional diagnosis
of Schizophrenia is made only if prominent delusions or hallucinations are also present for at least a month.

Schizophrenia Sub-Types
Based on the range of symptoms that present in individual, schizophrenia may classified into several subtypes; paranoid,
catatonic, disorganized or hebephrenic, residual and undifferentiated type. The diagnosis criteria for each schizophrenia
subtype based on DSM-IV-TR is as following:
1. Diagnostic Criteria for Paranoid Type: A type of Schizophrenia in which the following criteria are met:
A. Preoccupation with one or more delusions or frequent auditory hallucinations.
B. None of the following are prominent: disorganized speech, disorganized or catatonic behavior, or flat or
inappropriate affect.

2. Diagnostic criteria for Catatonic Type: A type of schizophrenia in which the clinical picture is dominated by at
least two of the following:
A. Motoric immobility as evidenced by catalepsy (including waxy flexibility).
B. Stupor excessive motor activity (that is apparently purposeless and not influenced by external stimuli).
5

C. Extreme negativism (an apparently motiveless resistance to all instructions or maintenance of a rigid posture
against attempts to be moved) or mutism.
D. Peculiarities of voluntary movement as evidenced by posturing (voluntary assumption of inappropriate or
bizarre posture), stereotyped movements, prominent mannerisms, or prominent grimacing.
E. Echolalia or echopraxia.

3. Diagnostic Criteria for Disorganized Type: A type of Schizophrenia in which the following criteria are met:
A. All of the following are prominent:
1. Disorganized speech.
2. Disorganized behavior.
4. Flat or inappropriate affect.
B. The criteria are not met for Catatonic Type.

4. Diagnostic Criteria for Undifferentiated Type: A type of Schizophrenia in which symptoms that meet Criterion A
are present, but the criteria are not met for the Paranoid, Disorganized, or Catatonic Type.

5. Diagnostic Criteria for Residual Type: A type of schizophrenia in which the following criteria are met:
A. Absence of prominent delusions, hallucinations, disorganized speech, and grossly disorganized or catatonic
behavior.
B. There is continuing evidence of the disturbance, as indicated by the presence of negative symptoms or two or
more symptoms listed in Criterion A for schizophrenia, present in an attenuated form (e.g., odd beliefs,
unusual perceptual experiences.

It is already established individual with schizophrenia have on average a lower IQ compare to healthy mentally individual
or individual with other kind of mental illness.
9
IQ was measured as part of routine clinical assessment in schizophrenia.
This IQ test not used as diagnosis criteria, but only to help physicians to predict the negative impact of schizophrenia on
patients future behavior and social functioning.
9


IQ test may have positive value when used in patients who might not able or willing to disclose ad give details of
psychotic symptoms needed to meet diagnosis criteria for schizophrenia.
9
When there is a decline in result of IQ test or
average a lower result of IQ test, they could be referred to further evaluation to establish the diagnosis. IQ test in already
confirmed diagnosis of schizophrenia may help physicians to predict the functional outcome of patient.
9


Travelling related to schizophrenia
Schizophrenia is a chronic mental disorder which is believed occurs due to interaction between various biological factors
with environmental exposure.
1,13,14
One of the environmental exposures may contribute as triggering factor, particularly in
relapse state of schizophrenia is psychosocial stress. Psychosocial stress involves stressful life events such as
bereavement, losing home or job, divorce, and physical, sexual, emotional or racial abuse.
6,7


There is an association between stress inducing effects and stress sensitivity in individual with schizophrenia.
11
Social
factors also contribute to effect upon risk for schizophrenia.
11
Some studies show the role of hypothalamic-pituitary-
adrenal (HPA) axis is involved in high-risk population for schizophrenia.
11
This axis is activated by stress exposure and
individual with schizophrenia has dysregulation of HPA axis. The increase of cortisol level during acute stress response is
associated with increasing of activity of dopamine pathways.
11


For patient with schizophrenia or at high-risk for developing schizophrenia, less stressful event such as meeting new
friend or travelling may trigger psychotic symptoms or induce the relapse in stable schizophrenia.
5,6,7,11
As the increasing
efficacy of antipsychotics drugs, individual with schizophrenia may attain normal life function in remission state and also
achieve the possibility to travelling cross their country and another country.

There are some factors contribute to the probability of schizophrenia relapse or psychotic symptoms during travelling.
7

This may include stressful events, substance misuse or even reduction in drug compliance during travelling.

Stressful event during travelling may involve jet lag, nature of destination, unfulfilled expectations and/or needs and
culture shock.
5,6
Jet lag reflects de-synchronization between body and environmental rhythms.
5
This condition may induce
physical and psychological stress associated with insomnia confusion when arrive at destination.
5


6

The nature of destination which particularly has a strong emotional or psychological effect to traveler may induce
psychotic symptoms in certain cases.
5,6
Jerusalem syndrome is one of example of acute onset of schizophrenia occurs
during travelling of some religious pilgrim in Isreael.
5


Travelers during religious travelling have a risk for psychosis.
5
They become intoxicated and overwhelmed with their
surroundings, disassociating from reality, they end up dressing like historical or religious figures, conducting purification
ceremonies, chanting loudly or causing a public disturbance.
5


Psychotic symptoms occur during travelling is the risk factor to develop schizophrenia, particularly in highly susceptible
person. The disturbance that occur prior to the onset of psychosis are perception, cognition, motoric function, willing,
energy level and stress tolerance.
12


Unfulfilled expectations and/or need at destination place may induce psychological stress, including anxiety, depression,
and/or frustration.
7
Unfamiliar environments without supportive networks, a disrupted daily routine, language barriers,
difficulty understanding social mores may contribute to threat mental and physical well-being of travelers with
schizophrenia.
7

Sociocultural factors such as close family support and interaction may be disrupted during travelling. Family support as
caregiver is needed to monitor the therapy of individual with schizophrenia to improve the outcome.
17
Family is also a
part of therapy given to ensure the stability of mental state of individual with schizophrenia.
17


Adventure traveler is at greater risk of developing acute situational psychosis. Exposure to a physically and mentally
demanding environment without adequate sleep, appropriate food and fluid intake and substance misuse could cause the
stress reaction mentally and physically.
7


Culture chock defined as a temporary psychological stress occurs when overwhelmed by a new culture, and not know
how to adapt or fit into new environment.
6
There are some factors contributing to culture shock such as not speaking the
language, not understanding the local customs, not knowing the appropriate behavior, disliking the food,
accommodations, or lifestyle, being visible minority and witnessing or experiencing situations so different and
unimaginable to own life (e.g. poverty, starvation, homeless, discrimination, racial and war).
6


Substance misuse during travelling is common in destination country that legally or illegally supplies substance to
travelers. The possibility of cannabis use as one of the factor that contribute increasing the likelihood and risk of
transition to schizophrenia is suggested in one study.
15
Cannabis use in individual with high-risk of schizophrenia
associated with bilateral thalamic volume loss.
15


Canabbis use may increase the risk for schizophrenia which is also has a dose-dependent effect.
11
Cannabis use also
associated with grey matter loss in people who already established schizophrenia. The volume reduction of thalamus has
been observed to occur between the vulnerability state and frank psychosis.
15


Discontinuation of drug treatment may induce the relapse episode in already stable-schizophrenia.
19
Drug adherence is
affected by the side effect and tolerability of the drug for patient with schizophrenia. The major side effect of older
generation of antipsychotic drugs is extrapyramidal systems manifestations, such as tardive dyskinesia.
1,16,19,
This side-
effect may make patient feel uncomfortable during the travelling, so that they decide to discontinued the treatment.

Family support may not occur effectively during travelling and affect the increasing of relapse state of patient with
schizophrenia. Drug adherence is improved when the family members are involving as supervisor to monitor drug
schedule.
16
Psychoeducational therapy to improve skill in problem solving, communication and interpersonal relationship
also involve family members actively.

All of those factors above might associated with the increase of the risk of relapse in patient with schizophrenia. Those
factors also associated with the increasing of the risk of psychotic symptoms during travelling.
CHAPTER III
CONCLUSION

Schizophrenia is a chronic mental disease characterized by disorders of cognition, affect and behavior which all involve
bizarre aspects. The clinical manifestation of schizophrenia is varied widely among individuals.

There are some signs and
symptoms which persistently occur such as hallucinations, delusion, disorganized speech and catatonic or bizarre
behavior.

7


Schizophrenia in Indonesia is diagnosed based on the criteria on DSM-IV-TR. There are some criteria of diagnosis need
to be fulfilled to establish the diagnosis of schizophrenia. The characteristic symptoms must fulfill at least two of the
following including; delusion, hallucinations, disorganized speech, grossly disorganized or catatonic behavior and
negative symptoms during one month. The symptoms lead to significant social or occupational dysfunction which is
persisting for at least 6 months. This mental disorder is not caused substance use and/or drug use related to psychotic
symptoms.

Schizophrenia is believed occurs due to interaction between various biological factors with environmental exposure.

One
of the environmental exposures that contribute as triggering factor is psychosocial stress. For patient with schizophrenia
or at high-risk for developing schizophrenia, less stressful event such as travelling may induce psychotic symptoms or
induce the relapse in stable schizophrenia.



As the increasing efficacy of antipsychotics drugs, individual with schizophrenia may attain normal life function and also
achieve the possibility to travelling cross their country and another country. But due to its chronicity, individual with
schizophrenia is still having a risk for relapse.

Travelling is associated with the relapse state or acute onset of schizophrenia or psychotic symptoms. There are some
factors contribute to the probability of schizophrenia relapse or psychotic symptoms during travelling. This may include
stressful events during travelling, substance misuse during travelling or even reduction in drug compliance during
travelling.

Regarding the association between travelling and schizophrenia on its natural history, diagnosis assessment of travelers
with relapse state of schizophrenia or acute onset of psychotic symptoms is an important aspect in travel medicine.