Volume 4, Issue 12, December – 2019 International Journal of Innovative Science and Research Technology

ISSN No:-2456-2165

Schizophrenia: Its Complications and Treatments

Sonali B. Kotwal, Sonali Y.Shitole
Ajinkya Charitable Foundation’s
Mahadev Kanchan College of Pharmaceutical Education and Research
Uruli kanchan. Pune, INDIA

Abstract:- Schizophrenia affects a person ability to Cognitive symptoms are difficult to analyze in few
think, feel and behave clearly. Schizophrenia patient but in other severe symptoms are notice associated
characterized by disorganize speech or behavior, with schizophrenia, symptoms include time inability,
decrease participation in daily activities, difficulties in inability to make decisions, problem in concentration, poor
concentration and memory. Causes of schizophrenia are working of memory function.
still unknown so treatment focuses on eliminating the
symptoms of the disease. This article summarizes the Most people who have schizophrenia do not
mechanisms of action of antipsychotics with respect to experience a total disappearance of symptoms. However,
the treatment of schizophrenia. There are many this disorder can be managed by a combination of different
different medications and types of therapy and support psychosocial therapies and medications.
that can be used to eliminate different symptoms of
schizophrenia. The most effective treatment for II. ETIOLOGY OF SEIZOPHRENIA
schizophrenia is a combination of using antipsychotic
medications and therapeutic and social support. There The exact causes schizophrenia of still unknown,
is no one best treatment for this mental illness that etiology of schizophrenia include combination of different
causes hallucinations, delusions, disorganized thoughts, physical factor, genetic factor, drug abuse,
and other symptoms that make life challenging, but neurotransmitter, pregnancy and birth complications.
most patients respond well to this combination.
 Genetic factor: If both parents affect with, risk of
Keywords:- Schizophrenia, Antipsychotics, Cognitive schizophrenia is greater in offspring. Monozygotic
Deficit & Treatment, Dopamine. twins are more susceptible than dizygotic tweens.
 Physical factor: physiological conditions not cause
I. INTRODUCTION TO SEIZOPHRENIA schizophrenia, they only trigger in its development. The
main psychological trigger of schizophrenia are
Schizophrenia is a serious mental disorder which stressful life event such as divorce, physical, emotional
affect a person’s ability to perceive the world around them, & sexual abuse, loosing home and loosing family .
Most people with untreated schizophrenia hear voices or  Drug Abuse: Misuse of drugs increases the risk of
see things that aren’t there. They may also have false developing schizophrenia or similar illness.
beliefs about the world that vary in content, but share the  Neurotransmitter: Dopamine and Serotonin are two
common characteristic of being untrue. Language, neurotransmitter present in brain, change in level of this
Perception, Thinking, Volition, Social activity are affected neurotransmitter causes schizophrenia.
in schizophrenia. The etiology of schizophrenia is complex  Pregnancy and birth complications: Low birth
and it involves neurodevlopemental, environmental and weights of child, premature labor, lack of oxygen during
psychological functions. birth are also the causes of Schizophrenia. [1]

The symptoms of schizophrenia fall into three III. CLASSIFICATION OF SCHIZOPHRENIA

categories positive symptoms, negative symptoms and
cognitive symptoms.  Paratinoid schizophrenia: patient act on things may be
extreme and behave oddly, have inappropriate
“Positive” symptoms of schizophrenia include emotional responses and show little pleasure in life
psychotic behaviors which are not generally seen in healthy  Cationic schizophrenia: The person shuts down
teenagers. Hallucinations (distortion of reality), Delusions emotionally, mentally and physically. “People appear to
(false beliefs, they are not based on reality), Thought be
disorders (unusual or dysfunctional ways of  Undiffentiated schizophrenia: The patient shows
thinking),movement disorders (agitated body movements) various vague symptoms. “They might be talk or
express themselves much. They can be confused and
“Negative” symptoms are associated with disruptions paranoid
to normal emotions and behaviors. This include reduce  Schizoaffective disorders: The person suffering from
facial expression & voice tone, reduction of excitement in mood disorders ,mania,depression.[ 2]
everyday life, difficulty in beginning and strengthen
activities& reduce speaking are also the symptoms seen in
schizophrenia.

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Volume 4, Issue 12, December – 2019 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
IV. PATHOPHYSIOLOGY OF SEIZOPHRENIA which is discovered by dr. kraepelin. [3]. Various
neuropathologists are fail to find causes of schizophrenia,
The individual having symptoms associated with so some famous neurologist’s said that “Schizophrenia is
schizophrenia are similar to “Dementia Praecox” disease the graveyard of neuropathologists” [4].

Fig 1:- Area of Brain Associated with Pathophysiology of Schizophrenia.[5]

There are several parts of brain that are affected in This disorder is more complex than originally
patients with schizophrenia such as prefrontal cortex, visual suppose, it involves combination of genetic and
and auditory cortices. Basal ganglia, hippocampus, other abnormalities related to neurotransmitter such as
medial Temporal and limbic regions [6] Dopamine, Glutamate, and Serotonine. Most of theories of
pathophysiology of schizophrenia based on excess or a
 Prefrontal cortex: it involves in memory encoding deficiency of neurotransmitters, including dopamine,
 Hippocampus: It is located in temporal region and serotonin, and glutamate. Other theories based on aspartate,
responsible for memory functions. glycine, and gamma-amino butyric acid (GABA) as part of
 Visual& Auditory Cortices: responsible for facilitate the neurochemical imbalance of schizophrenia.[7]
language, also associated with memory & emotions.
 Basal Ganglia: Balance of muscle activation, voluntary
motor functioning and rapid actions are associated with
basal ganglia.

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 Volume 4, Issue 12, December – 2019 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165

Fig 2:- Pathophysiology of schizophrenia [8]

There are 4 major dopamine pathways.  Increased activation of temporal regions during
hallucinations –auditory hallucinations associated with
 Mesocortical pathway is dopaminergic pathway middle and superior cortex. [13]
connects ventral tegmentum to prefrontal areas.  Electrophysiological abnormalities-abnormalities in
 Nigrostriatal pathway that connects substancia nigra electrophysiological activities were seen in
with dorsal striatum. Schizophrenia.
 Mesolimbic pathway connects ventral areas of  Diminished prepulse inhibition of startle response –
midbrain to ventral areas of forebrain. Prepulse inhibition of startle reflex response state the
 Teberoin fundibular pathway connects infundibular ability of weak Prestimulus to transiently inhibit the
nucleus to hypothalamus. response to strong sensory stimulus. [14]
 Abnormalities in gamma oscillations-Brain Areas
V. KEY FACTS IN THE PATHOPHYSIOLOGY OF related to visual, motor and cognitive information
SCHIZOPHRENIA processing are accompanied by gamma oscillations.
[15]
A. Abnormalities in Brain Structure:
 Ventricular enlargement – excess fluid in the brain C. Oxidative, Immunological Neuroendocrine
gradually enlarges the ventricle. [ 9] Dysfunctions
 Subtle reductions in total gray matter volume-lack of  Clinical status of markers of oxidative stress is elevated
grey matter, psychotics have lower grey matter than [16]
healthy people [10 ]  Abnormal dexamethasone suppression takes place and it
 Reductions in gray matter volume of the hippocampus is responsible for dysfunction of the hypothalamic–
and other medial pituitary–adrenal axis [17, 18]
 Inflammatory response of cytokines increases
Temporal and limbic regions- hippocampus is a part abnormally [19]
of limbic system & plays an important role in consolidation
from short term memory to long term memory. Grey mater D. Neuropathology
reduction also takes place in hippocampus, medial temporal  Size of pyramidal neurons and dendritic spines
and limbic regions.[ 11] Reduces. [20]
 Relative preservation of total number of neurons [21]
B. Abnormalities in Brain Functions:  The absence of gliosis and other neurodegenerative
 Hypofrontality- It is a state of decrease cerebral blood features [ 22 , 21 ]
flow in the prefrontal cortex it leads into decreased  Reduced expression of GAD-67 in the dorsolateral
activation of prefrontal cortex- auditory with middle prefrontal cortex [23]
and superior temporal cortex. [12]

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Volume 4, Issue 12, December – 2019 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
E. Neurochemical  PME (marker of membrane phospholipid synthesis)
 N –acetyl aspartate reduces in frontal and temporal reduces in prefrontal Regions [25]
regions of brain [24]  Presynaptic dopamine function elevated [24]

VI. CLASSIFICATION OF ANTIPSYCHOTICS

Generation First generation Second Third generation

(Typical Antipsychotics) generation (atypical
(Atypical Antipsychotics)
Antipsychotic)
Drug Butyrophenones Phenothiazines Thioxanthenes Clozapine
Haloperidol Chlorpromazine Chlorprothixene Olanzapine Aripiprazole
Droperidol Fluphenazine Clopenthixol Risperidone
Perphenazine Flupenthixol Quetiapin
Prochlorperazine Thiothixene Ziprasidone
Thioridazine Zuclopenthixol Amisulpride
Trifluoperazine Asenapine
Mesoridazine Paliperidone
Periciazine Iloperidone
Promazine Zotepine
Triflupromazine Sertindole
Levomepromazine Lurasidone
Promethazine
Cyamemazine
Pimozide
Table 1:- Classification of Antipsychotic Drugs with Reference to Schizophrenia [26]

VII. TREATMENT OF SCHIZOPHRENIA team can be made up of community mental health nurses,
pharmacists, ounselors and psychotherapists ,psychologists
Schizophrenia is usually treated with combination of and psychiatrists.
therapy and medicine. Most people with schizophrenia are
treated by community mental health teams .The goal of this Current Forms of Treatment: First-Generation
team to provide day-to-day support and treatment while Antipsychotics and Second-Generation Antipsychotics
ensuring you have as much independence as possible. This [27]

Fig 3

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Volume 4, Issue 12, December – 2019 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
VIII. CLINICAL PHARMACOLOGICAL PROFILES OF ANTIPSYCHOTIC DRUG

Antipsychotic Drug Classes: Potencies and Toxicities

Table 2:- Antipsychotic Drugs with their Extra Pyramidal Effect, Potency, Sedation [28]

1-low, 5-very high

IX. FUTURE STRATEGIES FOR DRUG Hypothesis of impairment of an individual’s mental

DEVELOPMENT IN SCHIZOPHRENIA processes in schizophrenia separately implicate
dopaminergic, cholinergic, noradrenergic, serotonergic,
Dopamine plays a important role in psychiatric and glutamatergic deficits. This neurotransmitter actually
movement disorder. In schizophrenia tied to hallucinations involves in dysfunctoning. To overcome this dysfunctoning
and delusions, that’s why brain area become overactive. creative approaches are necessary. [32]
Antipsychotic drugs stop this over activity .Development of
new generation antipsychotics start from clozapin. The D2 One more approach to the future strategy of treatment
receptor [Dopamine receptor] very important in of schizophrenia is development of those drugs which are
development of antipsychotics drug and act as Holy Grail specifically target the prefrontal cortex, medial temporal
for the development of antipsychotics. therapeutic region and limbic association area. Preclinical and clinical
mechanism of psychosis is represent by D2 receptor by studies of drug action on specific brain regions is very
reducing neurotransmission.[ 29,30,31,32,33,34] . By important in developing such a drug.[36]. Some
studding the complexity of schizophrenia and diversities in neuropathologist done important progress in identifying
the symptoms, it seems logical to develop compound with various susceptibility genes associated with schizophrenia.
at least a small moiety with affinity to D2 receptor. Another Susceptibility genes includes neureglin1 (NRG1),
strategy is to developed single-target-agent. This single- dysbindin (DTNBP1), regulator of g protein signaling
target-agent increases the activity of multitarget agent. 4(RGS4), catechol–o –methyl transferase (COMT).[37]
Until the pathophysiology of schizophrenia fully explained
the mystery of single-target-agent versus multitarget agent Identification of individual treatment plan is necessary
will remain in most important position in development of to optimize development of novel method. Cytochrome
antipsychotics drug. P450 (CYP) is the enzymes which affect the metabolism of
antipsychotics, due to this efficacy and tolerability of
According to all above studies current and future drug antipsychotics is directly affected, to improve this
development strategies described below: development of genetic test for prediction of drug response
and side effect is more important in treatment of
 Remove unwanted moiety of previously develop schizophrenia.[38]
antipsychotics to modify mechanisms of action to
provide drugs with high efficacy. Proper treatment of schizophrenia require focus on
 Development of antipsychotics drug with novel early detection and early intervention.[39]
mechanism. pathophysiological changes occur in cortical and
 Development of drug particularly associated with those subcortical brain regions in patients with schizophrenia
symptoms of schizophrenia which are not eliminated by associated with disease progression, clinical deterioration
traditional antipsychotic drugs. antipsychotics drug and functional decline.[40] In early intervention aimed at
 There is need to focus on cognitive enhancing lack of confidence or reversing progressive
drugs.[35] pathophysiological processes in schizophrenia could yield

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[17]. Yeragani VK. The incidence of abnormal
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