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Pathophysiology of Schizophrenia

Pathophysiology of Schizophrenia 

Pathophysiology of Schizophrenia:

Pathophysiology of Schizophrenia – Schizopherenia is a most complex psychotic disorder marked by severly impaired thinking, emotions and behaviour. Schzophgernic patient are unable to filter sensory response and may have enhanced perceptions of sounds, colour and other features of their environment.

Most of the patients left untreated may gradually withdraw from social interactions with other peoples and lose the ability to take care of personal needs. Literally, it means fragmented mind and represent a heterogeneous syndrome of disorganised thoughts, delusions, hallucinations and impaired psychological functions.


While many factors have been associated with developing of disease. They include genetic, environmental, psychological and social processes, that exact cause of the disease is unknown.

  1. Schizophrenia may be triggered by many environmental event such as viral infection and immune disorders.
  2. Scientist recognised that disorder tend to run in the families and that a person inherits a tendency to develop the disease. Similar to other genetically related illness, schizophernia may be appear when the body undergoes abnormal changes related to hormonal and physical changes.


Schizophrenia is most commonly has it onset in late adolescence or early adulthood and really occur before adolescence are after the age of 40 years. The peak age of onset are 20 – 38 years for males and 26 – 32 years for females, slightly more mens are diagnosed with this diseasescompared to females.


Type of Schizophrenia:

There are five subtypes of Schizophrenia: Paranoid, Disorganised, Catatonic, Undiffrenciated and Residual.

Paranoid Schizophrenia:

The key feature is the combination of false beliefs (delusions) and hearing voices (auditory hallucinations) with more normal emotions. The delusion of paranoid Schizophrenia usually involve thoughts being persecuted or harmed by others are exaggerated opinion of their own importance. This type is more when compared with other subtypes. The risk for suicide or violent behaviour under the influence of their delusions are more.

Disorganised Schizophrenia:

It is marked by disorganised speech, thinking and behaviour on the patient’s part, coupled with flat or inappropriate emotions response to a situation.  The patient may be act silly or withdrawal socially to an extreme extent. Most patient in this category have weak personality structures prior to their initial acute psychotic episode.

Catatonic Schizophrenia:

Catatonic Schizophrenia is characterized by disturbance of movements that may include rigidity, stupor, agitation, bizarre posturing, and repetitive imitations of movemnts or speech of other people. The patient are at risk for malnutrition, exhaustion or self-injury.

Undifferentiated Schizophrenia

This category has the characteristic positive and negative symptoms of schizophrenia but does not meet any specific criteria for paranoid, disorganised or catatonic subtype.

Residual Schizophrenia:

This category has a least one acute schizophrenia episode but do not presently have strong positive psychotic symptoms such as delusions and hallucinations they may have negative symptoms such as withdrawal from others, or mild form of positive symptoms which indicate that the disorder has not completely resolved.

Signs and Symptoms of Schizophrenia:

Positive symptoms:

  1. Hallucination – Involving seeing are hearing the things that does not exist.
  2. Delusions –  False beliefs that are not based in reality.
  3. Disorganised speech and thinking –  Effective communication can be impaired and answer to the question may be partially are completely unrelated.
  4. Catatonia – Purposeless abnormal motor activity or aggressive behaviour.

Cognitive Symptoms:

  1. Poor executive functionalities –  Unable to understand information to make decision.
  2. Poor working memory – Unable to use information immediately after learning.

Negative Symptoms:

  1. Flat affect – Reducing expression of emotions via facial expressions and voice tone.
  2. Asociality – Withdrawal from social contact
  3. Alogia – Reduced speech.
  4. Avolition – Inability to begin our sustain activity.
  5. Anhedonia – Inability to experience pleasure.


Pathophysiology of Schizophrenia: (Pathogenesis)

As the exact pathophysiology of Schizophrenia is not known. The scientist has proposed 3 Hypothesis which are as follows.

Dopamine Hypothesis (Pathophysiology of Schizophrenia)

  • Numerous Positron Emission Tomography (PET) studies have shown dopaminergic hyperactivity in the nucleus accumbens and dopaminergic hypofunction in the fronto temporal
  • PET studies using D2-specific ligands provide data suggesting increased densities of D2 receptors in the nucleus accumbens.
  • PET studies assessing D1 function suggest that subpopulations of schizophrenics may have decreased densities of D1 receptors in the prefrontal

Thus positive symptoms are thought to result from overactivity in the mesolimbic dopaminergic pathway activating D2 receptors whereas negative symptoms may result from a decreased activity in the mesocortical dopaminergic pathway where D1 receptors predominate.

Glutamate Hypothesis (Pathophysiology of Schizophrenia)

  • NMDA receptor hypofunction is thought to reduce the level of activity in mesocortical dopaminergic neurons. This would result in a decrease in dopamine release in the prefrontal cortex and thus give rise to negative symptoms of Schizophrenia.
  • On the other hand, NMDA receptor hypofunction is thought to enhance activity in the mesolimbic dopaminergic pathway, perhaps because in this pathway the important NMDA receptors are those located on GABAergic interneurons.
  • Thus NMDA receptor hypofunction would result in reduced GABAergic inhibition (disinhibition) of mesolimbic dopaminergic neurons and thus give rise to enhanced dopamine release in limbic areas such as the nucleus accumbens.

5-HT Hypothesis (Pathophysiology of Schizophrenia)

  • 5-HT receptors are present on dopaminergic axons and it is known that stimulation of these receptors will decrease DA release in pre-frontal cortex.
  • Patients with schizophrenia with abnormal brain scans have higher whole blood 5-HT concentrations and these concentrations are correlated with increased ventricular size.
  • Atypical antipsychotics with potent 5-HT2 receptor antagonist effects reverse worsening of symptomatology induced by 5-HT agonists in patients with this disease.

Diagnosis in Pathophysiology of Schizophrenia:

Diagnostic Criteria for Schizophrenia – It include the criteria in the Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) published by American Psychiatric Association.

Medical History – A thorough medical history is the first step in the diagnosis of Schizophrenia. This may be done to find other problems could be the causing symptoms and to be check for it.

Blood tests and Imaging –  A complete blood count test is helpful to monitor the General Health and rule out the conditions that may be responsible for the symptoms. A blood test can be provided accurate information about involvement of recreational drugs. In some cases certain imaging techniques such as Magnetic resonance imaging and computed tomography scan may aid in the diagnosis.

Psychiatric Evaluation – A doctor or mental health professional check mental status by observing appearance,demeanor and asking about the thoughts, mood and awakeness. A person may be diagnosed if they have at least two of the following symptoms usually over a month –  delusions, hallucinations, disorganised thoughts, disorganised speech and Catatonic behavior.

Management of Schizophrenia:

Hospitalization – During crisis period or timing of severe symptoms, hospitalization may be necessary to ensure safety, proper nutrition, and adequate sleep and basic hygiene.

Psychological Interventions

Individual therapy  – Psychotherapy may help to normalise thought patterns. Also learning to cope with stress and identity  early warning signals of relapse can help the people to manage the illness.

Social Skill training – This focus on improvement of Communication, Social interaction and improving the abilities to participate in daily activities.

Family therapy  – This provides support and education to the patient family.

Vocational Rehabilitation and supported employment – This focus on helping the people with Schizophrenia for find and keep jobs.

Electroconvulsive therapy – for adult with Shizophrenia who do not response to the drug therapy, the electroconvulsive therapy may be considered electric conversion therapy may be helpful for someone who also have a depression, cognitive behavior.

Treatment of Schizophrenia:

The treatment of Schizophrenia depends on stage or phases. In Acute phase patient hospitalized in order to prevent harm to himself are other will be treated with antipsychotic medication.

Antipsychotic drugs control all positive symptoms of the disorder they have minimal effect on diagnosed behaviour and negative symptoms between 60 to 70% of Schizophrenic patient will response to anti psychotic during this acute phase the medications given by mouth are by intramuscular injection.

The antipsychotics fall into two categories:

  1. Dopamine receptor antagonist – The dopamine antagonist are also called as “neuroleptic drugs” such as haloperidol, chlorpromazine and fluphenazine.
  2. Serotonin dopamine antagonist –  It is also called as atypical antipsychotics, which include clozapine, risperidone and Olanzapine.

For more information on intresting topics of Pathophysiology go through our  Pharmacy Blog.

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1 Comment

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