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Psychopathology And Treatment Approaches Of Schizophrenia

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DOI: 10.37896/jxu16.12/053

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Journal of Xidian University https://doi.org/10.37896/jxu16.12/053 ISSN No:1001-2400

Psychopathology And Treatment Approaches Of

Schizophrenia
A.Fhamitha Saara *1, S.Jayakumari #2,
Department of Pharmacy Practice, School of Pharmaceutical Sciences, Vels Institute of Sciences, Technology and Advanced
Studies, Pallavaram, Chennai-600117, Tamil Nadu, India*1.
Department of Pharmacognosy, School of Pharmaceutical Sciences, Vels Institute of Sciences, Technology and Advanced
Studies, Pallavaram, Chennai-600117, Tamil Nadu, India#2.

Abstract :
Around 21 million people around the world suffer from schizophrenia. Schizophrenia is a mental disorder that influences how an
individual believes, senses and functions. It is one of the most complicated, persistent and difficult psychotic illnesses. It is a
heterogeneous condition defined by jumbled ideas, misconception, daydreams and low mental health outcomes. Schizophrenia is
typically expressed by three categories of symptoms such as positive symptoms, negative symptoms and cognitive symptoms.
Schizophrenia is a polygenic disorder. The diverse manifestation of schizophrenia is the result from a combination of variables,
including genetic predisposition, environmental impacts, the use of cannabis and childhood adversity. The pathophysiology of
schizophrenia is based on the aberrations within the neurotransmission. The majority of the concepts revolve around either surplus or
lack of neurotransmitters such as glutamate, dopamine and 5-hydroxytryptamine(serotonin). Generally, there are no specific tests or
indicators to diagnose patients with schizophrenia. It was usually diagnosed by observing the patient’s medical records and evaluation
of their state of mind as per the diagnostic and statistical manual of the American psychiatric association (DSM5) and the ICD-10
Classification of Mental and behavioral disorder. Atypical antipsychotics are the most often used medications for the treatment of
schizophrenia nowadays owing to its minimal adverse reactions and higher effectiveness. An oral antipsychotic, which includes
olanzapine or risperidone, is the very first therapy for a patient experiencing their initial symptoms of schizophrenia. Cognitive behavior
therapy is given to adjust patterns of thoughts and behavior in terms of bringing about a favorable improvement in the patient’s
emotions and style of life. Cognitive behavior therapy with medicine and continuous psychoeducation among patients is necessary to
control the disease.

Key-words: Schizophrenia, positive symptoms, negative symptoms, atypical antipsychotics and Cognitive behavior therapy

INTRODUCTION :
Schizophrenia is a mental condition that influences how an individual believes, senses and functions. It is one of the most
complicated, persistent and difficult psychotic illnesses. It is a heterogeneous condition defined by jumbled ideas, misconception,
daydreams and low mental health outcomes. Positive signs like hallucinations, delusions and formal questioning abnormalities
have historically been related to schizophrenia and negative signs like paucity of speech, anhedonia and absence of drive 1.

Schizophrenia has a worldwide prevalence of about 1 percent. It is the effect of a mix of hereditary and environmental factors.
Schizophrenia is commonly associated with significant discomfort and dysfunction in important aspects of life, such as emotional,
economic, academic, career, and others2. The aetiology and pathologic mechanism of schizophrenia are not completely understood
due to the disorder's considerable difficulty and diversity. This article's primary objective is to summarise and provide information
about the epidemiology, clinical presentation, aetiology, types, pathophysiology, and treatment of schizophrenia for better
understanding.

EPIDEMIOLOGY:
According to a survey, there are around 21 million people around the world who suffers from schizophrenia 3. Men have higher
prevalence about 76% to be affected by schizophrenia spectrum disorder than women 4. It was found that black Americans were
affected by schizophrenia at a greater rate than white Americans5.

Schizophrenia is also associated with increased rate of comorbidities and the majority of extra facilities are caused by pre- existing
medical illness, particularly chronic disease such as ischemic heart disease, cerebrovascular accident, diabetes mellitus,
respiratory ailments and certain malignancies. Suicide and other natural causes account for fewer than 15 percent of excess
fatalities3.

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CLINICAL PRESENTATIONS (SIGNS AND SYMPTOMS):

There are three kinds of symptoms, such as positive symptoms, negative symptoms, and cognitive symptoms, are frequently used
to describe schizophrenia6.

SCHIZOPHRENIA

Positive Negative Cognitive

symptoms symptoms symptoms

Poor Poor
Disorganized
Delusion Hallucination Flat affect Alogia Avolition Anhedonia executive working
speech
functioning memory

Figure 1 – Symptoms of schizophrenia

Positive symptoms comprise of delusion, hallucination and disorganized speech & thinking. Delusion is a person’s faith which
was openly spurious by that specifies impairment in the content of thought 7. Hallucination is the act of insensible matter into
perception due to the progress of mental condition8. Disorganized speech and thinking are the impairment of communication with
the society9.

Negative symptoms comprise of flat affect, avolition and anhedonia. Flat affect is an undemonstrative facial expression. Alogia
was giving concise replies during interrogations. Avolition was an inability to start and be determined of venture due to reduced
motive. Anhedonia is a diminished experience of happiness10.

Cognitive symptoms comprise of poor executive functioning and poor working memory. Poor executive functioning is an
impairment in reply investiture, keen attention, resolving of query and information creation 11. Poor working memory is
represented by longer replying time and decreased exactness12.

ETIOLOGY:
In spite of a greater extent of research done over a decade, the exact origin of schizophrenia was obscure. However, it is broadly
recognized that the diverse manifestations are the result of a combination of variables, including hereditary predisposition and
ecological impacts13.

Schizophrenia is a polygenic disorder. Positive family record is the significant risk factor for developing schizophrenia. The
society has a lifespan probability of about 1%, for first degree blood relation of sufferers was 6.5% and it was increased about
40% in identical twins of affected victims14. Neuregulin gene 1 possibly takes part in an important participation in the cognitive
development and chemical messenger province. Researchers observed an ostensible connection with schizophrenia was spotted
with three neuregulin gene 1 polymorphisms15.

On chromosome 6p22.1, a meta-analysis study had discovered a range of interrelation of typical single nucleotide polymorphisms
in the company of schizophrenia. The range covers various sorts of genes of possible intrigue. The absolute indication for
interrelation was detected in and close by a bunch of histone protein genes, which may be important to schizophrenia due to their
functions in DNA transcript and restore or through their participation in antimicrobic shielding16.

The environmental features have to be recognized as the origin of neuropsychiatric conditions because it has been well known to
affect a greater rate of medical illness including schizophrenia. Environmental vulnerability such as malnourishment, neurolysin
and contagious disease are the reason for neuropsychiatric conditions and it is the powerful disturbance of cognitive development,
it was put forward to take part as an important function in the cause of schizophrenia 17.

Substance usage is more predominant in mental illness patients18. A meta-analysis study noted a compelling link between use of
cannabis can lead to psychosis at a higher rate 19. Moreover, these connections are the impact of tobacco usage 20. A study has
discovered that constantly the prevalence of schizophrenia rises straightaway with a rise in urbanicity 21. Childhood adversity like
losing father and mother or molestation are correlated with high chances of developing schizophrenia 22.

PATHOPHYSIOLOGY:
The pathophysiology of schizophrenia is based on the aberrations within the neurotransmission. The majority of the concepts
revolve around either surplus or lack of neurotransmitters such as glutamate, dopamine and 5-hydroxytryptamine(serotonin)13.

Dopaminergic is generated in the brain’s substantia nigra and ventral tegmental areas, and the modifications of dopaminergic are
linked towards schizophrenia23. Ever since, subsequent antipsychotics have largely followed the dopamine theory, which states
that people with schizophrenia possess elevated dopaminergic activities that might be regulated with anti-dopaminergic, notably
the Dopamine receptor D2 blocker.

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The dopaminergic receptor D2 is a seven-transmembrane receptor that is a common target for neuroleptic drugs. The major route
of action of neuroleptic medicine in managing psychopathic manifestations is assumed to be the dopaminergic receptor D2
antagonist in the mesolimbic route. An anti-dopaminergic, on the other hand, was not therapeutically beneficial in managing
cortical related manifestations of schizophrenia such as cognitive impairments 24.

According to the revised dopamine theories, schizophrenia is a condition marked by unusually decreased prefrontal dopaminergic
function (producing negative manifestations), which results in increased dopaminergic functions in the mesolimbic dopamine
nerve cells (producing positive manifestations). Therefore, these theories assume that the coexistence of increased and decreased
dopaminergic functions in separate neural pathways, which might describe the occurrence of both positive and negative
manifestations25.

Medicines that stimulate dopamine discharge or accelerate dopamine transference, including amphetamine and levodopa, that
will aggravate mentally ill-like conditions in people with schizophrenia and it can also generate schizophrenia manifestations in
healthy people if used frequently or in large dosage 26. It was found that amphetamine – induced dopamine discharge is elevated
in the striatum, based on the brain imaging studies in persons with schizophrenia27.

Glutamate is the brain’s commonest ample of stimulative amino acid neurotransmitter 28. Glutamatergic concepts of schizophrenia
are founded about the effectiveness of N-methyl-D-aspartate receptor blockers to generate schizophrenia manifestations29. In
addition to mediating glutamate, the N-methyl-D-aspartate receptor also connects to the thalamus, limbic system, and cortex, all
of which have been associated to schizophrenia. The relationship between glutamate impairment and schizophrenia may have
resulted from the fact that those with schizophrenia had decreased quantities of glutamate in their cerebrospinal fluid. 24.

It was believed that in schizophrenia, N-methyl-D-aspartate receptor (NMDAR) impairment results in elevated glutamate
discharge, which often has excitotoxic consequences. Frontal area glutamate levels were found to be lower in persons with
schizophrenia and greater in fit subjects. Curiously, the levels of glutamine and glutamate in the anterior areas of individuals with
schizophrenia drop significantly by age, suggesting significant decline of synaptic function 30.

The concept that glutamate imbalance in the prefrontal brain leads to dopaminergic hyperactivity as a consequence is an
interesting and relatively new discovery in psychotic studies. The N-methyl-D-aspartate hypoactivity concept of psychosis in
particular, proposes that dysfunctional N-methyl-D-aspartate receptor at Gamma-aminobutyric acid (GABA) associative neurons
in the frontal lobe, possibly as a result of aberrant neurodevelopment, contribute to excessive downstream glutamate signaling. It
is possible that the increased stimulation of the mesolimbic dopamine route in the ventral tegmental region is the source for
auditory hallucination (hearing of voices) and paranoid delusion (delusion of persecution) 31.

Serotonin or 5-hydroxytryptamine (5-HT) functions as a chemical messenger in the brain and spinal cord which regulates the
activities of various peripheral organs32. The overactivation of 5-HT2A receptors on glutamate nerve cells might cause psychosis.
This overactivation might be caused by an overabundance of serotonin, increased 5-HT2A receptor, or a consequence of 5-HT2A
agonist, many of which can result in glutamate discharge. The discharge of glutamate in the ventral tegmental region may
stimulate the mesolimbic route, leading to an overload of dopamine in the ventral striatum 31.

DIAGNOSIS:
Generally, there are no specific tests or indicators to diagnose patients with schizophrenia. It was usually diagnosed by observing
the patient’s medical records and evaluation of their state of mind 33.

The diagnosis of schizophrenia is based on a criteria which includes conditions such as the patient will experience two or numerous
of the following symptoms as a substantial part for a period of about one month. Symptoms such as

• Hallucination
• Disorganized speech
• Negative symptoms
• Delusion
• Extremely disordered or catatonic behavior

But those symptoms must include delusion, hallucination or disorganized speech34.

For diagnosing persons with schizophrenia, they must experience a minimum of one extremely obvious symptom pertaining to
any of the below mentioned set of symptoms visible for the majority of time throughout a month or over.

• Idea inclusion or removal and idea streaming

• Delusion of power, dominance or inactivity
• Voices in the patient’s head produce a continual commentary on his or her behavior.
• Pertinacious illusions of various types that are traditionally incorrect and absolutely impracticable35.

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TREATMENT:
For understandable reasons, management of schizophrenia now has entirely concentrated on the moment where individuals appear
with distinct clinical manifestations, i.e., schizophrenia. In spite of the fact that there are a growing number of research, namely
the at-risk mental state (ARMS) is currently creating therapy at initial phase of the illness or concentrate on the relief of cognitive
impairments in patients with chronic conditions, the majority of research closely monitors on the treatment of schizophrenia 36.

The most often prescribed drugs for the treatment of schizophrenia are atypical antipsychotics, due to their minimal adverse
reactions and higher effectiveness37. An oral antipsychotic, which includes olanzapine or risperidone, is the very first therapy for
a patient experiencing their initial symptoms of schizophrenia 14.

Olanzapine primarily affects 5-HT and dopaminergic receptors. It works by obstructing the mesolimbic route's dopamine D2
receptors, which stops dopamine from functioning at the post-synaptic receptor. The action of olanzapine on serotonin results in
a reduction of negative manifestations. Olanzapine’s adverse effects are weight gain and decreased insulin resistance38. Research
had discovered higher food consumption in the olanzapine used patients indicating hyperphagia which is the contributing factor
for weight gain39.

Risperidone exerts its pharmacological activity by inhibiting certain D2 receptors, but mostly via inhibiting serotonin receptors
such as 5HT2A. Second generation antipsychotics attach to D2 receptors lightly and detach fast, which may account for their
decreased risk of eliciting extrapyramidal manifestations. Risperidone’s adverse effects are sedation, weight loss and metabolic
alterations40.

Clozapine is the best antipsychotic medicine for 20-30% of people who are treatment resistant, according to a meta- analysis.
Treatment resistant is described as the lack of response to two or more antipsychotics (as a minimum one of it must be an atypical
antipsychotic) while taken at a sufficient dose for a minimum of 2 months and after confounding variables like concordance
breakdown or substance dependence have been eliminated. A complete blood count should be performed on a frequent basis to
prevent granulopenia, which affects below 1% of clozapine users. Clozapine is the only antipsychotic that really can help people
with treatment resistance lessen both positive and negative manifestations, and it must be provided as early as treatment resistance
is identified14.

Clozapine, an atypical antipsychotic, is commonly regarded as the “gold standard” for the management of schizophrenia since
being one of the very effective antipsychotics41. Clozapine inhibits dopaminergic and 5-Hydroxytryptamine receptors. It attaches
towards dopaminergic D1-5 receptors, by tenfold preference for D4 receptors over D2 receptors. Both of the D4 and 5-HT2A
antagonist characteristics help to reduce negative manifestations and onset of extrapyramidal adverse reactions. Clozapine’s
action on 5-HT2A receptor pointing varies from that of traditional G-protein coupled receptor antagonists in that it also causes 5-
HT2A receptor incorporation and stimulates Akt pointing through a 5-HT2A receptor facilitated function42. Clozapine’s benefit
is its established greater effectiveness among first generation antipsychotics, which includes improvement in areas apart from
positive manifestations such as suicide ideation, aggression and standard of living. Clozapine’s negative consequences are very
extensively observed, particularly the uncommon but potentially fatal agranulocytosis possibility 43.

Cognitive behavior therapy is a type of treatment that is organized, instructive and targeted. The method is interactive and
practical, with the therapist and client working collaboratively to adjust patterns of thoughts and behavior in terms of bringing
about a favorable improvement in the patient’s emotions and style of life. It is utilized to aid with a variety of issues and therapy
procedures are adjusted to the patient’s condition and concerns44. A meta-analysis has discovered that cognitive behavior therapy
was proven to reduce distress in a minor but substantial way 45.

Family psychoeducation’s primary goal is to incorporate the patient’s families, careers or interested friends in the management
and rehabilitation process throughout the phases. Cognitive, behavior and helpful ideas are mixed with family education elements
throughout the session. Such therapies comprise education for families to assist them in assisting their patients in developing
stress management, gaining techniques to relieve their excessive reactive feelings and improving their issue- resolving and
communication abilities. Family education has been shown to strengthen patient-family interactions, lower patient’s perception
of tension and increased patient therapeutic efficacy. As a result, relapses and hospital stays are reduced and the rate of recovery
improves46.

CONCLUSION:
Although the provenance of schizophrenia is undetermined, it might arise due to ecological and hereditary aspects. Therefore,
this condition can be managed by cognitive behavior therapy along with medication and continuous psycho education among
patients is necessary to control the disease. There are a limited number of studies that have been focused on cognitive behavioral
therapies. Further studies in the advancements in the treatment of schizophrenia are ideal to manage and treat the patients
according to their needs.

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CONFLICT OF INTEREST:
The authors have declared no conflict of interest in the creation of this manuscript.

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