Last updated on: December 13th, 2021

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Clinicals - History


Schizophrenia is a disorder characterized by a diverse range of disturbances of perception, thought, emotion, motivation, cognition, and motor activity.


Schizophrenia has a lifetime prevalence of ~7 per 1000, a lifetime risk of 7.2-10 per 1000 and an incidence of 0.16-1 per 1000. It is slightly more prevalent in men, with a male to female ratio of 1.4:1. The age of onset in men is generally earlier than in women. Schizophrenia appears to be heritable. If a single parent is affected, the risk of inheritance is ~8%; and if both parents are affected, the risk is ~40%.


Symptoms of schizophrenia include positive symptoms (i.e., delusions, hallucinations, and behavioral disorganization), negative symptoms (i.e., alogia, affective blunting, avolition, anhedonia, and asociality), and cognitive symptoms. Kurt Schneider’s “first rank” symptoms which were initially thought to be diagnostic of schizophrenia are no longer considered diagnostic.

It is widely believed that the positive symptoms of schizophrenia are due to hyperactivity of the mesolimbic dopaminergic pathways; and that the negative symptoms are due to hypoactivity of the mesocortical dopaminergic pathways and dysfunction of the prefrontal cortex and nucleus accumbens. There is also evidence that dysfunctional glutamate pathways and NMDA receptors are a root cause for the symptoms seen in schizophrenia.

Delusions and overvalued ideas

A delusion is a belief that is strongly held on inadequate grounds, despite evidence to the contrary, and not a conventional belief given the person's educational, cultural and religious background (i.e., a fixed false belief). Strongly held, non-delusional beliefs are called overvalued ideas. The most frequently encountered delusions and overvalued ideas in schizophrenia include: delusions of persecution, delusions of bodily control, and delusions of reference.

Hyperactivity of the mesolimbic dopaminergic pathways and dysfunction of the glutamate pathways (which regulate the previously mentioned dopaminergic pathways) are postulated to be the underlying cause.


A hallucination is a percept that occurs in absence of an external sensory stimulus to the corresponding sensory organ. Auditory hallucinations of a third-person nature are the most specific. Second-person auditory hallucinations are also common. Visual hallucinations are less common. Somatic hallucinations are common as well and may be associated with delusional misinterpretation.

Similar to delusions, hallucinations are also believed to be due to hyperactivity of the mesolimbic dopaminergic pathways and dysfunction of the glutamate pathways.

Affective blunting

Affective blunting, a key feature of chronic schizophrenia, can also occur in the acute phase. This manifests as diminished facial expressions, lack of emotional response and lack of intonation.

The pathophysiological hypotheses behind affective blunting include the hypoactive mesocortical dopaminergic pathways and dysfunction of the glutamate pathways.


“Weakened or disjointed will and motivation” is a characteristic negative symptom. Similar to other negative symptoms, this is also thought to be due to the hypoactive mesocortical dopaminergic pathways and dysfunctional glutamate pathways.

Behavioral disorganization

This is characterized by bizarre behavior, formal thought disorder and incongruent affect. The evidence pertaining to the pathophysiology of these symptoms is inconclusive; however, it is suggested that the aberrant neuronal pathways could be a cause.

Formal thought disorder

Thought disorder is arbitrarily divided into positive thought disorder and negative thought disorder. Positive thought disorder encompasses various aspects of the term “loosening of associations” coined by Bleuler. This describes the weakening of connections between ideas and words seen in schizophrenia. Tangentiality, derailment, incoherence, loss of goal, metronyms and neologisms are considered different aspects of positive thought disorder while poverty of speech and poverty of content are considered aspects of negative thought disorder.

Cognitive symptoms

A wide range of cognitive deficits occur in schizophrenia that may be discernible even prior to the onset of illness. During the acute phase of schizophrenia, attentional impairment is commonly seen. In chronic phase, impairments are seen in executive functions, working memory, long term memory, processing speed, social cognitions and verbal fluency.

Structural and functional anomalies in the relevant brain areas are thought to be the cause of these symptoms.

Motor symptoms

Catatonia, a disorder of initiation and organization of voluntary movements and posture, is a well-known motor phenomenon seen in schizophrenia. Catatonia can present as a “retarded” form with diminished motor activity; or an “exited” form in which there is excessive motor activity. In some patients, motor symptoms may manifest before the onset of schizophrenia.

The pathophysiology behind these symptoms includes aberrant neuronal pathways and structural anomalies in the motor regulatory areas of the brain.

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