Schizophrenia

Schizophrenia is a severe, chronic psychiatric disorder characterized by

a fundamental disturbance in thinking, perception, emotions, and behavior, leading
to impaired reality testing, social and occupational dysfunction, and a loss of contact
with reality.

Eugen Bleuler’s Fundamental Symptoms of Schizophrenia (Also called as 4 A’s of Bleuler)

1. Ambivalence: Marked inability to decide for or against

2. Autism: Withdrawal into self

3. Affect disturbances: Disturbances of affect such as inappropriate affect
4. Association disturbances: Loosening of associations; thought disorder

First Rank Symptoms (SFRS) of Schizophrenia

1. Audible thoughts: Voices speaking out thoughts aloud or ‘thought echo’.

2. Voices heard arguing: Two or more hallucinatory voices discussing the subject in third person.
3. Voices commenting on one’s action.
4. Thought withdrawal: Thoughts cease and subject experiences them as removed by an external
force.
5. Thought insertion: Experience of thoughts imposed by some external force on person’s passive
mind.
6. Thought diffusion or broadcasting: Experience of thoughts escaping the confines of self and as
being experienced by others around.
7. ‘Made’ feelings or affect.
8. ‘Made’ impulses.
9. ‘Made’ volition or acts: In ‘made’ affect, impulses and volitions, the person experiences feelings,
impulses or acts which are imposed by some external force. In ‘made’ volition, for example, one’s
own acts are experienced as being under the control of some external force.
10. Somatic passivity: Bodily sensations, especially sensory symptoms, are experienced as imposed
on body by some external force.
11. Delusional perception: Normal perception has a private and illogical meaning.

CLINICAL FEATURES

Schizophrenia is characterised by disturbances in thought and verbal behaviour, perception,

affect, motor behaviour and relationship to the external world. The diagnosis is entirely clinical
and is based on the following clinical features, none of which are pathognomonic if present
alone.

• Thought and Speech Disorders

Autistic thinking is one of the most classical features of schizophrenia. Here thinking is
governed by private and illogical rules. The patient may consider two things identical because
they have identical predicates or properties (von Domarus Law); for example, Lord Hanuman
was celibate, I am celibate too; So, I am Lord Hanuman.

Loosening of associations is a pattern of spontaneous speech in which things said in

juxtaposition lack a meaningful relationship or there is idiosyncratic shifting from one frame
of reference to another. The speech is often described as being ‘disjointed’.
Thought blocking is a characteristic feature of schizophrenia, although it can also be seen in
com- plex partial seizures (temporal lobe epilepsy). There is a sudden interruption of stream of
speech before the thought is completed. After a pause, the subject cannot recall what he had
meant to say. This may at times be associated with thought withdrawal.

Neologisms are newly formed words or phrases whose derivation cannot be understood. These
are created to express a concept for which the subject has no dictionary word. Sometimes,
normal words are used in an unconventional or distorted way but the derivation can be
understood, even if bizarre. These are called word approximations or paraphasias; for
example, describing stomach as a ‘food vessel’.

Delusions are false unshakable beliefs which are not in keeping with patient’s socio-cultural
and edu- cational background. These are of two types: primary and secondary.

The commonly seen delusions in schizophrenia include:

1. Delusions of persecution (being persecuted against, e.g. ‘people are against me’).

2. Delusions of reference (being referred to by others; e.g. ‘people are talking about me’).

3. Delusions of grandeur (exaggerated self-importance; e.g. ‘I am God almighty’).

4. Delusions of control (being controlled by an external force, known or unknown; e.g. ‘My
neighbour is controlling me”).

5. Somatic (or hypochondriacal) delusions (e.g. ‘there are insects crawling in my scalp’).

Disorders of Perception

Hallucinations (perceptions without stimuli) are common in schizophrenia. Auditory

hallucinations are by far the most frequent. These can be:
i. Elementary auditory hallucinations (i.e. hearing simple sounds rather than voices)
ii. ‘Thought echo’ (‘audible thoughts’)
iii. ‘Third person hallucinations’ (‘voices heard arguing’, discussing the patient in third person)
iv. ‘Voices commenting on one’s action’.

Only the ‘third person hallucinations’ are believed to be characteristic of schizophrenia. Visual
hallucinations can also occur, usually along with auditory hallucinations. The tactile, gustatory
and olfactory types are less common.

Disorders of Affect

The disorders of affect include apathy, emotional blunting, emotional shallowness, anhedonia
(inability to experience pleasure) and inappropriate emotional response (emotional response
inappropriate to thought).

Disorders of Motor Behaviour

There can be either a decrease (decreased spontaneity, inertia, stupor) or an increase in

psychomotor activity (excitement, aggressiveness, restlessness, agitation).
Mannerisms, grimacing, stereotypies (repetitive strange behaviour), decreased self-care, and
poor grooming are common features. Catatonic features are commonly seen in the catatonic
subtype of schizophrenia (and are discussed in detail under that heading).

Negative Symptoms

The prominent negative symptoms of schizophrenia include

• affective flattening or blunting,

• attentional impairment,
• avolition-apathy (lack of initiative associated with psychomotor slowing),
• anhedonia,
• asociality (social withdrawal), and
• alogia (lack of speech output).
• There is poor verbal as well as non- verbal communication with poor facial expression,
decreased eye contact, with usually poor self-care and social interaction.

Positive Symptoms

(Excess or distortion of normal mental functions)

• Delusions – false, fixed beliefs not in keeping with cultural norms (e.g., delusions of
persecution, reference, grandeur)
• Hallucinations – perception without external stimulus, most commonly auditory
hallucinations (voices commenting or discussing)
• Disorganized speech – incoherent speech, loosening of associations, tangentiality
• Disorganized or bizarre behavior – inappropriate, unpredictable, or purposeless
actions
• Catatonic symptoms – stupor, rigidity, posturing, echolalia, echopraxia

Negative Symptoms

(Reduction or loss of normal mental functions)

• Affective flattening – reduced emotional expression

• Alogia – poverty of speech
• Avolition – lack of motivation and initiative
• Anhedonia – inability to experience pleasure
• Asociality – social withdrawal and reduced interest in relationships
• Poor self-care – neglect of hygiene and daily activities

CLINICAL TYPES

Paranoid Schizophrenia

1. Delusions of persecution, reference, grandeur (or ‘grandiosity’), control, or infidelity

(or ‘jealousy’). The delusions are usually well-systematised (i.e. thematically well
connected with each other).
2. The hallucinations usually have a persecutory or grandiose content.
 3. No prominent disturbances of affect, volition, speech, and/or motor behaviour.

Personality deterioration in the paranoid subtype is much less than that seen in other types of
schizophrenias. The patient may be quite apprehensive (due to delusions and hallucinations)
and anxious, and appear evasive and guarded on mental status examination. The onset of
paranoid schizophrenia is usually insidious, occurs later in life

Disorganised (or Hebephrenic) Schizophrenia

1. Marked thought disorder, incoherence and severe loosening of associations. Delusions and
hallucinations are fragmentary and changeable.
2. Emotional disturbances (inappropriate affect, blunted affect, or senseless giggling),
mannerisms, ‘mirror-gazing’ (for long periods of time), disinhibited behaviour, poor self-care
and hygiene, markedly impaired social and occupational functioning, extreme social
withdrawal and other oddities of behaviour.

The onset is insidious, usually in the early 2nd decade. The course is progressive and downhill.

Catatonic Schizophrenia

The classic feature of the catatonic type is a marked disturbance in motor function; this
disturbance may involve stupor, negativism, rigidity, excitement, or posturing. Sometimes the
patient shows a rapid alteration between extremes of excitement and stupor. Associated
features include stereotypies, mannerisms, and waxy flexibility. Mutism is particularly
common. During catatonic excitement, patients need careful supervision to prevent them from
hurting themselves or others. Medical care may be needed because of malnutrition, exhaustion,
hyperpyrexia, or self-inflicted injury.

Residual Schizophrenia

The residual type of schizophrenia is characterized by continuing evidence of the schizophrenic

disturbance in the absence of a complete set of active symptoms or of sufficient symptoms to
meet the diagnosis of another type of schizophrenia. Emotional blunting, social withdrawal,
eccentric behavior, illogical thinking, and mild loosening of associations commonly appear in
the residual type. When delusions or hallucinations occur, they are neither prominent nor
accompanied by strong affect.

Undifferentiated Schizophrenia

This is a very common type of schizophrenia and is diagnosed either:

1. When features of no subtype are fully present, or

2. When features of more than one subtype are exhibited, and the general criteria for
diagnosis of schizophrenia are met.

Simple Schizophrenia
Simple schizophrenia is characterized by an insidious and progressive development of
negative symptoms without prominent delusions, hallucinations, or marked thought
disorder. The onset is usually early, and the course is chronic.

Key Clinical Features

• Gradual social withdrawal and isolation

• Loss of interest and motivation (avolition)
• Emotional blunting or flattening
• Poor self-care and neglect of personal hygiene
• Reduced speech and communication (alogia)
• Decline in academic or occupational performance
• Apathy and lack of initiative
• Anhedonia (reduced ability to experience pleasure)
• Odd or eccentric behavior without clear psychotic features
• Poor social functioning and interpersonal difficulties

Important Points

• No clear delusions or hallucinations

• No acute psychotic episodes
• Dominance of negative symptoms
• Often mistaken for depression or personality disorder
• Prognosis is generally poor due to late recognition

AETIOLOGY

Genetic Hypothesis - First-degree relatives have a higher risk than second- or third-degree
relatives. Monozygotic twins show about 50% concordance, which is much higher than that
seen in dizygotic twins or other first-degree relatives, indicating a major genetic contribution.

Biochemical Factors- The dopamine hypothesis of schizophrenia proposes that the

symptoms of schizophrenia are primarily due to abnormal dopamine activity in the brain.
According to this hypothesis, there is excess dopamine transmission, especially in certain
neural pathways, which leads to psychotic symptoms.

The hypothesis explains that hyperactivity of dopamine in the mesolimbic pathway is

responsible for positive symptoms such as hallucinations, delusions, and disorganized
behavior. This is supported by the fact that drugs like amphetamine, which increase dopamine
levels, can produce schizophrenia-like symptoms in healthy individuals.

At the same time, reduced dopamine activity in the mesocortical pathway (particularly the
prefrontal cortex) is believed to contribute to negative symptoms such as apathy, social
withdrawal, and impaired cognition.

Further support for the dopamine hypothesis comes from pharmacological

evidence: antipsychotic medications(especially typical antipsychotics) are effective in
reducing psychotic symptoms by blocking D₂ dopamine receptors. The greater the D₂
receptor blockade, the stronger the antipsychotic effect.
Serotonin. Current hypotheses posit serotonin excess as a cause of both positive and negative
symptoms in schizophrenia. The robust serotonin antagonist activity of clozapine and other
second-generation antipsychotics coupled with the effectiveness of clozapine to decrease
positive symptoms in chronic patients has contributed to the validity of this proposition.

Norepinephrine. Anhedonia—the impaired capacity for emotional gratification and the

decreased ability to experience pleasure—has long been noted to be a prominent feature of
schizophrenia. A selective neuronal degeneration within the norepinephrine reward neural
system could account for this aspect of schizophrenic symptomatology. However, biochemical
and pharmacological data bearing on this proposal are inconclusive.

GABA. The inhibitory amino acid neurotransmitter γ-aminobutyric acid (GABA) has been
implicated in the pathophysiology of schizophrenia based on the finding that some patients
with schizophrenia have a loss of GABAergic neurons in the hippocampus. GABA has a
regulatory effect on dopamine activity, and the loss of inhibitory GABAergic neurons could
lead to the hyperactivity of dopaminergic neurons.

Cerebral Ventricles. Computed tomography (CT) scans of patients with schizophrenia have
consistently shown lateral and third ventricular enlargement and some reduction in cortical
volume. Reduced volumes of cortical gray matter have been demonstrated during the earliest
stages of the disease.

Psychoanalytic Theories. Sigmund Freud postulated that schizophrenia resulted from

developmental fixations early in life. These fixations produce defects in ego development, and
he postulated that such defects contributed to the symptoms of schizophrenia. Ego
disintegration in schizophrenia represents a return to the time when the ego was not yet
developed or had just begun to be established.

MANAGEMENT

The treatment of schizophrenia can be discussed under the following major headings:
1. Somatic treatment

• Pharmacological treatment
• Electro-convulsive therapy (ECT)
• Miscellaneous treatments.

2. Psychosocial treatment and rehabilitation.

Pharmacological treatment- Antipsychotic medications are used to control psychotic

symptoms. Typical antipsychotics (e.g., haloperidol) are effective in reducing positive
symptoms, while atypical antipsychotics (e.g., risperidone, olanzapine) are preferred due to
better control of negative symptoms and fewer extrapyramidal side effects.

Electro-convulsive therapy (ECT) is indicated in cases of catatonia, severe psychosis,

treatment-resistant schizophrenia, or high suicidal risk, often as an adjunct to medication.

Miscellaneous treatments include adjunctive use of antidepressants, mood stabilizers,

benzodiazepines, and management of side effects to enhance compliance.
Psychosocial treatment and rehabilitation are essential for long-term recovery. These
include psychoeducation for patients and families to improve insight and medication
adherence, individual and group psychotherapy (especially supportive and cognitive-
behavioral therapy) to reduce distress and improve coping, and family therapy to lower
expressed emotion and prevent relapse. Rehabilitation programs, such as social skills
training, vocational rehabilitation, and community-based care, help patients achieve better
social, occupational, and independent functioning.

Other Psychotic Disorders

PERSISTENT DELUSIONAL DISORDERS

Delusional Disorder

Persistent delusions must be present for at least 3 months and these can include delusions of
persecution (being persecuted against), delusions of grandeur (inflated self-esteem and self
image), delusions of jealousy (infidelity), somatic (hypochondriacal) delusions, erotomanic
delusions (delusions of love), and/or other non-bizarre delusions. It is important to note absence
of prominent hallucinations, organic mental disorders, schizophrenia and mood disorders.

It is a disorder with usually a relatively stable and chronic course. It is characterised by presence
of well- systematised delusions of nonbizarre type (cf. bizarre delusions can occur in
schizophrenia). The emotional response and behaviour is often understandable in the light of
their delusional beliefs, with behaviour outside the ‘limits’ of delusions usually almost normal.
Very often, these individuals are able to carry on a near normal social and occupational life
without arousing suspicion regarding their delusional disorder. It is only when the area of
delusions is probed or confronted that the dysfunction becomes evident.

Delusion of Persecution- This is the most common type. The individual believes that they
are being harassed, harmed, cheated, poisoned, spied upon, or conspired against.
Clinically, patients are often suspicious, argumentative, hypervigilant, and may repeatedly
seek legal help or make complaints to authorities.

Delusion of Jealousy (Othello Syndrome)- The person firmly believes that their spouse or
partner is unfaithful, despite lack of evidence. Clinically, patients may check phones, follow
the partner, interrogate them repeatedly, and may show anger, irritability, or violent
behavior, posing a risk to the partner.

Delusion of Grandeur- The individual believes they possess exceptional abilities, wealth,
identity, or special relationship with powerful people or divine figures. Clinically, they
may appear overconfident, boastful, and engage in unrealistic plans but otherwise function
normally.

Delusion of Reference- The person believes that ordinary events, remarks, gestures, or
media content refer specifically to them. Clinically, they may misinterpret conversations,
television programs, or social media posts as having special personal meaning, leading to
social withdrawal or confrontation.

Somatic Delusions- These involve false beliefs related to the body, such as being infested with
parasites, emitting foul odors, or having a serious undetected illness. Clinically, patients often
make repeated medical consultations, insist on investigations, and remain dissatisfied with
reassurance.

Erotomanic Delusion (De Clérambault Syndrome)- The person believes that another
individual (often of higher status) is secretly in love with them. Clinically, they may attempt
to contact, follow, or write letters to the imagined lover, sometimes leading to legal or social
problems.

Other Persistent Delusional Disorders

This is a residual category in ICD-10 for other persistent delusional disorders, which do not
fulfil the criteria for delusional disorders. The examples of disorders included here are:

1. Delusions associated with persistent hallucinatory voices (but a diagnosis of schizophrenia

cannot be made).

2. Delusional disorders with duration of less than 3 months.

INDUCED DELUSIONAL DISORDER

This is an uncommon delusional disorder characterised by a sharing of delusions between

usually two (folie å deux) or occasionally more persons (folie å trios, folie å quatre, folie å
famille), who usually have a closely knit emotional bond. Only one person usually has
authentic delusions due to an underlying psychiatric disorder, most often schizophrenia or
delusional disorder.

On separation of the two, the dependent individual may give up his/her delusions and the
patient with the primary delusions should then be treated appropriately.

ACUTE AND TRANSIENT PSYCHOTIC DISORDERS

According to ICD-10, these disorders have an abrupt (less than 48 hours) or acute (less than 2
weeks) onset. The onset is often associated with an easily identifiable acute stress (though not
necessarily always so) that would be regarded as stressful to most people in similar
circumstances, within the culture of the person concerned. The typical events would include
bereavement, unexpected loss of partner or job, marriage, or the psychological trauma of
combat, terrorism, and torture. Longstanding difficulties or problems are not included here as
stressful.

Acute onset is probably associated with a good outcome, and it seems that more abrupt the
onset, the better is the outcome. A complete recovery usually occurs within 2-3 months, often
even much earlier.

These disorders should not satisfy the criteria for organic mental disorders, psychoactive
substance use disorders, schizophrenia, or mood disorders.
SCHIZOAFFECTIVE DISORDER

This is a disorder which lies on the borderland between schizophrenia and mood disorders. In
this disorder, the symptoms of schizophrenia and mood disorders are prominently present
within the same episode. The symptoms of both disorders may be present simultaneously or
may follow within few days of each other.

There are three types described:

1. Schizoaffective disorder, manic (or bipolar) type. 2. Schizoaffective disorder, depressed
type.
3. Schizoaffective disorder, mixed type.

The course is usually episodic (particularly in manic subtype), although a chronic course in
some patients has been described (particularly in the depressed subtype). The prognosis is
better than that in schizophrenia but is worse than that in mood disorders. The treatment is
with mood stabilisers (such as lithium or valproate), antipsychotics, antidepressants and/or
ECT, depending on the predominant symptomatology.

Treatment

Hospitalization. A patient who is acutely psychotic may need brief hospitalization for both
evaluation and protection. Evaluation requires close monitoring of symptoms and assessment
of the patient’s level of danger to self and others. In addition, the quiet, structured setting of a
hospital may help patients regain their sense of reality. While clinicians wait for the setting or
the drugs to have their effects, seclusion, physical restraints, or one-to-one monitoring of the
patient may be necessary.

Pharmacotherapy. The two major classes of drugs to be considered in the treatment of brief
psychotic disorder are the antipsychotic drugs and the benzodiazepines. When an antipsychotic
drug is chosen, a high-potency antipsychotic drug, such as haloperidol, or a serotonin dopamine
agonist such as ziprasidone may be used.

Psychotherapy. Although hospitalization and pharmacotherapy are likely to control short-term

situations, the difficult part of treatment is the psychological integration of the experience (and
possibly the precipitating trauma, if one was present) into the lives of the patients and their
families.

Biological Theories of Schizophrenia

The biological theories of schizophrenia propose that the disorder results from genetic
vulnerability, neurochemical imbalance, brain structural abnormalities, and
neurodevelopmental disturbances. These theories emphasize schizophrenia as a brain-
based disorder with strong biological underpinnings.

Genetic theory suggests that schizophrenia has a significant hereditary component. Family,
twin, and adoption studies show a higher risk among first-degree relatives of affected
individuals. Concordance rates are highest in monozygotic twins compared to dizygotic twins,
indicating a strong genetic influence, though no single gene is responsible. Instead,
schizophrenia is considered a polygenic disorder, with multiple susceptibility genes
interacting with environmental stressors.
Neurochemical theories focus mainly on neurotransmitter dysregulation. The dopamine
hypothesis proposes that hyperactivity of dopamine in the mesolimbic pathway leads to
positive symptoms, while hypoactivity in the mesocortical pathway contributes to negative and
cognitive symptoms. In addition, the glutamate hypothesis suggests hypofunction of NMDA
receptors, leading to impaired cortical regulation of dopamine. The serotonin hypothesis is
supported by the effectiveness of atypical antipsychotics that block both dopamine and
serotonin receptors.

Neuroanatomical and neuroimaging theories describe structural brain abnormalities in

schizophrenia. Common findings include ventricular enlargement, reduced cortical
volume, decreased gray matter in the prefrontal cortex, hippocampus, and temporal
lobes, and altered connectivity between brain regions. These changes are associated with
deficits in cognition, emotion regulation, and executive functioning.

Neurodevelopmental theory proposes that schizophrenia arises from early brain

insults such as prenatal infections, obstetric complications, malnutrition, or hypoxia, which
disrupt normal brain maturation. These abnormalities remain latent until adolescence or early
adulthood, when stress and neurobiological changes trigger the onset of psychotic symptoms.