Diagnosis Classification and Differential Diagnosis of Schizophrenia

The diagnosis, classification, and differential diagnosis of schizophrenia

Topics covered

  • The diagnosis of schizophrenia
  • Diagnostic criteria
    • ICD10
    • DSM IV
    • DSM 5
  • Basis of classification
    • Atheoretical: Schneider's first-rank symptoms
    • Theoretical
  • Early diagnosis? 
  • Differential diagnosis
    • Other psychiatric disorders
      • Other psychoses
      • Affective disorders
      • The presence of mood-incongruent delusions (or hallucinations)
      • The duration and acuteness of onset criteria
      • Social and occupational disturbance
    • Organic conditions
      • Symptoms
    • Drug-induced psychoses
      • Prescribed medication 
  • The diagnostic process  
  • References

The diagnosis of schizophrenia

Until the early 1970s, the diagnosis of schizophrenia was one of the most contentious and fraught issues in the whole of psychiatry. Since then a massive international effort has been put in motion out of which explicit diagnostic criteria emerged. Some achieved widespread and even multinational agreement, allowing the painstaking process of calculating diagnostic specificity, sensitivity, reliability, and (perhaps) validity to begin. Although criticism of the diagnosis of schizophrenia continues, mostly from outside psychiatry, the vast majority of psychiatrists look upon the major sets of diagnostic criteria with weary acceptance, seeing them as flawed but useful and possibly ‘as good as it gets' given our current state of knowledge/ignorance.

Throughout the 1970s and early 1980s there was an overabundance of criteria including the St Louis criteria (1) and the Research Diagnostic Criteria, (2) followed by the Present State Examination (PSE-CATEGO), the ICD-9, and finally the DSM-III. Perhaps because of the ‘cookbook' explicitness of the DSM-III or the pervasive influence of American psychiatric practice, dubbed by some ‘neo-colonial', the DSM, now in its fourth revision, is perhaps the mostly widely used, or at least quoted. The ICD-10 is also used throughout the world, but seldom in North America.

Diagnostic criteria

The signs and symptoms of schizophrenia and related disorders are discussed in detail here: Descriptive clinical features of schizophrenia. As noted, the signs and symptoms, weighted in terms of their typicality or specificity, combined with additional clinical factors such as onset, duration, social consequences, etc., are used to make a diagnosis of schizophrenia and subsequently to classify the disorder into subtypes. The DSM and ICD criteria are described below (Table 1, Table 2 and Table 3).

Table 1  ICD-10 Diagnostic Criteria for Schizophrenia
General criteria for Paranoid, Hebephrenic, Catatonic and Undifferentiated type of Schizophrenia:
G1. Either at least one of the syndromes, symptoms and signs listed below under (1), or at least two of the symptoms and signs listed under (2), should be present for most of the time during an episode of psychotic illness lasting for at least one month (or at some time during most of the days).
  1. At least one of the following:
    1. Thought echo, thought insertion or withdrawal, or thought broadcasting.
    2. Delusions of control, influence or passivity, clearly referred to body or limb movements or specific thoughts, actions, or sensations; delusional perception.
    3. Hallucinatory voices giving a running commentary on the patient's behavior, or discussing him between themselves, or other types of hallucinatory voices coming from some part of the body.
    4. Persistent delusions of other kinds that are culturally inappropriate and completely impossible (e.g., being able to control the weather, or being in communication with aliens from another world).
  2. or at least two of the following:
    1. Persistent hallucinations in any modality, when occurring every day for at least one month, when accompanied by delusions (which may be fleeting or half-formed) without clear affective content, or when accompanied by persistent over-valued ideas.
    2. Neologisms, breaks or interpolations in the train of thought, resulting in incoherence or irrelevant speech.
    3. Catatonic behavior, such as excitement, posturing or waxy flexibility, negativism, mutism and stupor.
    4. “Negative” symptoms such as marked apathy, paucity of speech, and blunting or incongruity of emotional responses (it must be clear that these are not due to depression or to neuroleptic medication).
G2. Most commonly used exclusion criteria: If the patient also meets criteria for manic episode or depressive episode, the criteria listed under G1.1 and G1.2 above must have been met before the disturbance of mood developed.
G3. The disorder is not attributable to organic brain disease, or to alcohol- or drug-related intoxication, dependence or withdrawal.
Comments: In evaluating the presence of these abnormal subjective experiences and behavior, special care should be taken to avoid false-positive assessments, especially where culturally or sub-culturally influenced modes of expression and behavior, or a subnormal level of intelligence, are involved.
From World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders. Geneva: World Health Organization; 1992. 

In ICD-10, the symptom criterion is defined in more detail than in DSM-IV-TR and has greater emphasis on Schneiderian first-rank symptoms. ICD-10 also makes a clear distinction between primary and secondary negative symptoms. Another important difference from DSM-IV-TR is the strict requirement of 1-month duration of symptoms regardless of successful treatment.Table 1 Tasks more or less likely to be affected in schizophrenia

DSM IV Diagnostic Criteria for Schizophrenia

A.  Characteristic symptoms: Two (or more) for the following, each present for a significant portion of time during a 1-month period (or less if successfully treated):
  1. delusions
  2. hallucinations
  3. disorganised speech (for example frequent derailment or incoherence)
  4. grossly disorganised or catatonic behaviour
  5. negative symptoms, that is,, affective flattening, alogia, or avolition
Note: Only one Criterion A symptom is required if delusions are bizarre or hallucinations consist of a voice keeping up a running commentary on the person’s behaviour or thoughts, or two or more voices conversing with each other. 
B.  Social/occupational dysfunction: For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning such as work, interpersonal relations, or self-care are markedly below the level achieved prior to the onset (or when the onset is in childhood or adolescence, failure to achieve expected level of interpersonal, academic, or occupational achievement).
C. Duration: Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1 month of symptoms (or less if successfully treated) that meet Criterion A (that is, active-phase symptoms) and may include prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or two or more symptoms listed in Criterion A present in an attenuated form (for example, odd beliefs, unusual perceptual experiences).
D. Schizoaffective and Mood Disorder exclusion: Schizoaffective Disorder and Mood Disorder With Psychotic Features have been ruled out because either (1) no Major Depressive, Manic, or Mixed Episodes have occurred concurrently with the active-phase symptoms; or (2) if mood episodes have occurred during active-phase symptoms, their total duration has been brief relative to the duration of the active and residual periods.
E. Substance/general medical condition exclusion: The disturbance is not due to the direct physiological effects of a substance (for example, a drug of abuse, a medication) or a general medical condition.
F. Relationship to a Pervasive Developmental Disorder: If there is a history of Autistic Disorder or another Pervasive Developmental Disorder, the additional diagnosis of Schizophrenia is made only if prominent delusions or hallucinations are present for at least a month (or less if successfully treated).
DSM 5 and schizophrenia
On 18th May 2013 the DSM 5 (formerly known as DSM-V) was published, superseding the DSM-IV-TR, which was published in 2000.
The new Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) has a number of changes to schizophrenia and other psychotic disorders. Some of the major changes to schizophrenia diagnosis are covered here.
According to the American Psychiatric Association (APA), the publisher of the DSM-5, some of the biggest changes in this chapter were made to better refine the diagnostic criteria based upon the past decade and a half of schizophrenia research.
Two changes were made to the primary symptom criteria for schizophrenia.
According to the APA, “the first change is the elimination of the special attribution of bizarre delusions and Schneiderian first-rank auditory hallucinations (e.g., two or more voices conversing). In DSM-IV, only one such symptom was needed to meet the diagnostic requirement for Criterion A, instead of two of the other listed symptoms. This special attribution was removed due to the nonspecificity of Schneiderian symptoms and the poor reliability in distinguishing bizarre from nonbizarre delusions.
“Therefore, in DSM-5, two Criterion A symptoms are required for any diagnosis of schizophrenia.”
The second change was the requirement for a person to now have at least one of three “positive” symptoms of schizophrenia:
  • Hallucinations
  • Delusions
  • Disorganized speech
The APA believes this helps increase the reliability of a schizophrenia diagnosis.

What the DSM 5 actually says:


Schizophrenia is the commonest and most important disorder of this group. Schizotypal disorder possesses many of the characteristic features of schizophrenic disorders and is probably genetically related to them; however, the hallucinations, delusions, and gross behavioural disturbances of schizophrenia itself are absent and so this disorder does not always come to medical attention. Most of the delusional disorders are probably unrelated to schizophrenia, although they may be difficult to distinguish clinically, particularly in their early stages. They form a heterogeneous and poorly understood collection of disorders, which can conveniently be divided according to their typical duration into a group of persistent delusional disorders and a larger group of acute and transient psychotic disorders. The latter appear to be particularly common in developing countries. The subdivisions listed here should be regarded as provisional. Schizoaffective disorders have been retained in this section in spite of their controversial nature.

F20 Schizophrenia

The schizophrenic disorders are characterized in general by fundamental and characteristic distortions of thinking and perception, and by inappropriate or blunted affect. Clear consciousness and intellectual capacity are usually maintained, although certain cognitive deficits may evolve in the course of time. The disturbance involves the most basic functions that give the normal person a feeling of individuality, uniqueness, and self-direction. The most intimate thoughts, feelings, and acts are often felt to be known to or shared by others, and explanatory delusions may develop, to the effect that natural or supernatural forces are at work to influence the afflicted individual's thoughts and actions in ways that are often bizarre. The individual may see himself or herself as the pivot of all that happens. Hallucinations, especially auditory, are common and may comment on the individual's behaviour or thoughts. Perception is frequently disturbed in other ways: colours or sounds may seem unduly vivid or altered in quality, and irrelevant features of ordinary things may appear more important than the whole object or situation. Perplexity is also common early on and frequently leads to a belief that everyday situations possess a special, usually sinister, meaning intended uniquely for the individual. In the characteristic schizo-phrenic disturbance of thinking, peripheral and irrelevant features of a total concept, which are inhibited in normal directed mental activity, are brought to the fore and utilized in place of those that are relevant and appropriate to the situation. Thus thinking becomes vague, elliptical, and obscure, and its expression in speech sometimes incomprehensible. Breaks and interpolations in the train of thought are frequent, and thoughts may seem to be withdrawn by some outside agency. Mood is characteristically shallow, capricious, or incongruous. Ambivalence and disturbance of volition may appear as inertia, negativism, or stupor. Catatonia may be present. The onset may be acute, with seriously disturbed behaviour, or insidious, with a gradual development of odd ideas and conduct. The course of the disorder shows equally great variation and is by no means inevitably chronic or deteriorating (the course is specified by five-character categories). In a proportion of cases, which may vary in different cultures and populations, the outcome is complete, or nearly complete, recovery. The sexes are approximately equally affected but the onset tends to be later in women.

Although no strictly pathognomonic symptoms can be identified, for practical purposes it is useful to divide the above symptoms into groups that have special importance for the diagnosis and often occur together, such as:

  • (a) thought echo, thought insertion or withdrawal, and thought broadcasting;
  • (b)delusions of control, influence, or passivity, clearly referred to body or limb movements or specific thoughts, actions, or sensations; delusional perception;
  • (c)hallucinatory voices giving a running commentary on the patient's behaviour, or discussing the patient among themselves, or other types of hallucinatory voices coming from some part of the body;
  • (d)persistent delusions of other kinds that are culturally inappropriate and completely impossible, such as religious or political identity, or superhuman powers and -79 - abilities (e.g. being able to control the weather, or being in communication with aliens from another world);
  • (e)persistent hallucinations in any modality, when accompanied either by fleeting or half-formed delusions without clear affective content, or by persistent over-valued ideas, or when occurring every day for weeks or months on end;
  • (f)breaks or interpolations in the train of thought, resulting in incoherence or irrelevant speech, or neologisms;
  • (g)catatonic behaviour, such as excitement, posturing, or waxy flexibility, negativism, mutism, and stupor;
  • (h)"negative" symptoms such as marked apathy, paucity of speech, and blunting or incongruity of emotional responses, usually resulting in social withdrawal and lowering of social performance; it must be clear that these are not due to depression or to neuroleptic medication;
  • (i)a significant and consistent change in the overall quality of some aspects of personal behaviour, manifest as loss of interest, aimlessness, idleness, a self-absorbed attitude, and social withdrawal.
Diagnostic guidelines

The normal requirement for a diagnosis of schizophrenia is that a minimum of one very clear symptom (and usually two or more if less clear-cut) belonging to any one of the groups listed as (a) to (d) above, or symptoms from at least two of the groups referred to as (e) to (h), should have been clearly present for most of the time during a period of 1 month or more. Conditions meeting such symptomatic requirements but of duration less than 1 month (whether treated or not) should be diagnosed in the first instance as acute schizophrenia-like psychotic disorder (F23.2) and reclassified as schizophrenia if the symptoms persist for longer periods. Symptom (i) in the above list applies only to the diagnosis of Simple Schizophrenia (F20.6), and a duration of at least one year is required.

Viewed retrospectively, it may be clear that a prodromal phase in which symptoms and behaviour, such as loss of interest in work, social activities, and personal appearance and hygiene, together with generalized anxiety and mild degrees of depression and preoccupation, preceded the onset of psychotic symptoms by weeks or even months. Because of the difficulty in timing onset, the 1-month duration criterion applies only to the specific symptoms listed above and not to any prodromal nonpsychotic phase.

The diagnosis of schizophrenia should not be made in the presence of extensive depressive or manic symptoms unless it is clear that schizophrenic symptoms antedated the affective disturbance. If both schizophrenic and affective symptoms develop together and are evenly balanced, the diagnosis of schizoaffective disorder (F25.-) should be made, even if the schizophrenic symptoms by themselves would have justified the diagnosis of schizophrenia. Schizophrenia should not be diagnosed in the presence of overt brain disease or during states of drug intoxication or withdrawal. Similar disorders developing in the presence of epilepsy or other brain disease should be coded under F06.2 and those induced by drugs under F1x.5."

Schizophrenia subtypes
Schizophrenia subtypes have been dumped in the DSM-5 because of their “limited diagnostic stability, low reliability, and poor validity,” according to the APA. (The old DSM-IV had specified the following schizophrenia subtypes: paranoid, disorganized, catatonic, undifferentiated, and residual type.)
The APA also justified the removal of schizophrenia subtypes from the DSM-5 because they didn’t appear to help with providing better targeted treatment, or predicting treatment response.
The APA proposes that clinicians instead use a “dimensional approach to rating severity for the core symptoms of schizophrenia is included in Section III to capture the important heterogeneity in symptom type and severity expressed across individuals with psychotic disorders.” Section III is the new section in the DSM-5 that includes assessments, as well as diagnoses needing further research.

Another group of psychotic disorders which may be distinguished on the basis of formal phenomenological properties are the delusional disorders (3,4) formally known as paranoia.

Basis of classification

Atheoretical:Schneider's first-rank symptoms 

These are still important for the diagnosis using the ICD-10 frame of reference. They are too rare to achieve high levels of sensitivity and their specificity has been challenged. Nevertheless, first-rank symptoms perform creditably on these parameters when compared to negative symptoms. (5,6) On the other hand, the lack of aetiological and prognostic significance of first-rank symptoms has undermined the prominence claimed for them. (7,8 and 9) Negative symptoms relate more consistently to outcome/prognosis and show more stability over time. (10) They have poor diagnostic specificity and must be distinguished from depression and parkinsonism, chronic drug dependence, and organic brain damage.


Attempts at a theoretical classification have been made. The first in the modern era was Crow's Type I and Type II distinction, (11) although it echoes older notions of ‘process'—chronic and deteriorating versus ‘reactive' (relapsing and remitting) typologies. The innovation was to link the distinction with proposed differences in dopamine receptor hyperactivity (Type I), associated with positive symptoms and good response to dopamine antagonist drugs, and on the other hand, to neurological damage (Type II) as evidenced by ventricular enlargement on CT brain scans, associated with chronicity, poor premorbid functioning and poor response to treatment.

Building on this was the ‘aetiological classification' proposed by Murray et al. (12) which contrasted cases with a presumed genetic aetiology and those who had other putative risk factors such as early brain damage. Although these attempts have served as useful stimuli for research, they have not been found to aid clinical decision-making. In fact the search for ‘biological markers' which might validate diagnostic distinctions has yet to yield conclusive positive results. For example, the presence of ventricular enlargement or cortical thinning, as detected using CT and now magnetic resonance imaging ( MRI), is a case in point. Meta-analyses have confirmed that indices of ‘cerebral atrophy' are strongly associated with schizophrenia but the effect sizes are small (approximately 10 per cent). (13) Hence, there is substantial overlap between normal controls and schizophrenia cases.

Positive family history remains an important finding in the psychiatric history of an individual patient. Although none of the diagnostic criteria permits the influence of family history, in clinical settings, ‘odd' or withdrawn behaviour takes on a very different meaning if seen in the first-degree relative of someone with a firm schizophrenia diagnosis.

Early diagnosis?

The premorbid personality in schizophrenia is typically described as emotionally and socially detached. Such people have few friends, are often cold and aloof, and engage in solitary occupations. Their behaviour may be eccentric and they are indifferent to praise or criticism. Recent studies, including United Kingdom national cohort studies (14) and a Swedish conscript cohort study (15) indicate that children who later develop schizophrenia are more likely to have lower IQs and educational achievements than other children. They are also more likely to have interpersonal and behavioural difficulties. Parents recognize ‘preschizophrenic' children as being different from their other siblings. However, such characteristics are very common in the general population so have virtually no positive predictive value.

Early diagnosis is only successful when based on psychotic symptoms. Here the diagnosis of schizophreniform psychosis (DSM-IV) and the acute schizophrenia-like psychotic disorder of the ICD-10 are relevant. The former must last for more than 1 but less than 6 months (otherwise the diagnosis is brief reactive psychosis). Hence the disorder is substantial by any common-sense definition, and unsurprisingly many cases (70 per cent) go on to develop full-blown schizophrenia, affective disorder, or schizoaffective disorder. (16) The temporal stability of the diagnosis is poor, with around 30 per cent recovering over follow-up periods averaging 16 months in one study.

Differential diagnosis

Other psychiatric disorders

Other psychoses

It could be argued that distinguishing schizophrenia from schizoaffective disorder, schizophreniform disorder, delusional disorder, etc. is a largely academic exercise. Until recently, treatment in psychiatry was entirely symptom or syndrome based. Thus manic symptoms respond to antimanic agents including lithium, psychotic symptoms respond to neuroleptics, and depressive symptoms respond to antidepressants. (17,18) Other ‘mood-stabilizing' agents are also of value especially when combined with neuroleptics. However, it is possible that with increasing clinical experience and research using the new generation of ‘atypical' antipsychotic agents such as clozapine, risperidone, and olanzapine, more specific indications will emerge. A recent report of efficacy of olanzapine in schizoaffective disorder in comparison to haloperidol is a case in point. (19) However, a tendency to reduce all psychotic disorders to ‘serious mental illness' is unfortunate. It encourages a sloppy approach to history taking and the mental state examination, and a loose attitude to making a diagnosis and, if pursued, would prevent the discovery of specific treatments.

Although predicting outcome in individual patients is notoriously difficult (20) because of the influence of idiosyncratic factors such as services, relationships within the family, compliance, intelligence, personality, demographics, etc., the more a disorder approaches ‘typical' schizophrenia, the poorer the prognosis tends to be. (21) 

That said, schizoaffective disorder is the closest disorder, phenomenologically, to schizophrenia but combines schizophrenic symptoms with affective symptoms. 

Schizophreniform (DSM-IV) or acute schizophrenia-like disorders (ICD-10) differ only in terms of duration, as operationally defined. Delusional disorders differ from schizophrenia in being based around ‘non-bizarre' delusions and few or no hallucinations. The onset and course are characteristically later and more benign respectively.

Affective disorders

Typical presentations of either mania or depression usually cause few diagnostic difficulties. Overdiagnosis of schizoaffective disorder is to be resisted although the distinction from schizophrenia proper remains controversial and debatable. The guidelines given in DSM-IV attempt to exclude transient mood disturbances (< 2 weeks) in people with psychosis as a basis for a schizoaffective diagnosis.

In practice reaching a diagnosis of schizophrenia in a person with evidence of one or more core symptoms of psychosis (listed under the DSM-IV and ICD-10) may be complicated for the following reasons.

The presence of mood-incongruent delusions (or hallucinations)

‘Congruence' is somewhat in the eye of the beholder, especially where mood may be labile or where disturbed mood is suspected but fails to follow clinical stereotypes. The clinician should try to determine if a ‘grandiose' delusion is being enjoyed by the patient, and whether the content (e.g. elevated status, magical powers, material riches) is seen as justified by the patient. Similarly a delusion of depressive content (e.g. physical illness, imminent death) must be seen as undeserved or inexplicable to be deemed ‘incongruent'. Auditory hallucinations may be comforting, complimentary, or, more commonly, hostile and critical. It is probably their complexity and personification which makes them ‘schizophrenic' rather than their mood-incongruent content. (22)

The duration and acuteness of onset criteria

A good history may simply not be available. Symptoms may wax and wane. Partial or successful treatment may modify or curtail a potentially long episode, and onset may be complicated by the use of psychoactive drugs.

Social and occupational disturbance

This is critical to the diagnosis of schizophrenia, especially the DSM-IV criteria. Here the difficulty is in distinguishing ‘premorbid deficits', an illness prodrome and the illness itself. Premorbid personality factors will obscure or set in relief discontinuities in an individual's social trajectory. Objective information and informant testimony is crucial as in most of the diagnostic process. Other individual differences such as intelligence will also shape the presentation of schizophrenia. At the extreme, people with mental retardation (learning disability) may manifest psychosis in less obvious ways. The old diagnosis of ‘simple schizophrenia', retained in the ICD-10 describes ‘insidious and progressive development of oddities of conduct' and the ‘inability to meet the demands of society' that is, social disturbance of long duration. The progressive element distinguishes it from personality disorder although problems adjusting to changing social demands through the lifecycle may give the appearance of progression in a fixed personality disorder.

Organic conditions

Differentiation of a ‘primary' psychotic illness from one secondary to an organic condition may arise in essentially two situations:

  • a person with a clear-cut diagnosis of a medical or neurological syndrome in which psychosis is a recognized complication (e.g. epilepsy)
  • a person with a presumptive diagnosis of schizophrenia in whom significant abnormalities are detected usually following special investigation (e.g. CT brain scanning).

The list of medical conditions that could potentially give rise to psychosis is enormous. These have been the subject of extensive reviews. (23,24) While it appears that almost any disease that causes a cerebral perturbation can give rise to psychosis, abnormalities affecting the temporal lobes and diencephalon are somewhat more likely to do this.

The time course is obviously important in this context. Chronic inflammatory lesions (e.g. sarcoidosis), degenerative disorders (e.g. presenile dementias), chronic infections (e.g. neurosyphilis, AIDS), space-occupying lesions (e.g. tumour or abscesses), metabolic disorders (e.g. hyper- or hypothyroidism and vitamin deficiencies) may mimic schizophrenia by virtue of a gradual deterioration in social functioning and self-care punctuated perhaps by odd or inexplicable behaviour and rarely hallucinations and delusions. The features of the primary disease are usually evident. Rarer conditions may be misdiagnosed, for example, Wilson's disease (hepatolenticular degeneration). This usually presents with a motor disorder with bulbar features and abnormal liver function, but personality changes and psychotic symptoms are also associated. Diagnosis is made on other associated clinical features (e.g. Kayser–Fleischer rings), copper studies, and liver biopsy. Huntington's disease is characterized by chorea and cognitive decline. Affective disorder and occasionally psychotic symptoms may occur. The main differential diagnosis is with patients with chronic psychosis and tardive dyskinesia and is usually clarified by the family history, inexorable progression, and caudate atrophy on CT or MRI. Neurosyphilis is still encountered from time to time and in the ‘general paralysis of the insane' form, may present with chronic delusions (often grandiose) plus dementia. Diagnosis is by appropriate serological testing of blood and cerebrospinal fluid. Finally, metachromatic leukodystrophy, a rare inherited progressive demyelinating condition, has recently been identified as a cause of a schizophrenia-like psychosis, when onset is in childhood or early adult life. (25) Arylsulphatase-A is a diagnostic marker detectable in peripheral white blood cells.

Acute disturbances following head trauma, acute infections (viral encephalitis), cerebrovascular accidents, metabolic abnormalities (e.g. electrolyte disturbances, porphyria), or drug intoxication or withdrawal (including prescribed medication) (see below) may present with a florid psychotic picture, classically dominated by visual distortions or hallucinations and fluctuating levels of alertness, rather than the stereotyped auditory hallucinations in clear consciousness which are characteristic of schizophrenia.(26)

In practice there are few common conditions that ever give rise to real diagnostic uncertainty. The most important is epilepsy. It is well established that epilepsy, particularly focal (complex partial or ‘temporal lobe epilepsy') can give rise to psychosis and there are inter-ictal and post-ictal patterns. A survey from a large neurology clinic showed that the incidence of schizophrenia is about nine times that of the rest of the population. (27)

Inter-ictal psychoses include the chronic schizophrenia-like psychoses described by Slater et al.,(28) and Trimble.(29) These almost always arise in people with many years of well-established temporal lobe seizures, while the post-ictal variety occurs earlier in the lifecycle but again in a person with previously diagnosed epilepsy. In post-ictal psychosis the temporal relationship to seizures, sometimes occurring in a cluster, is diagnostic, although a lucid interval is often observed. A clear history and independent description of seizures is the foundation of a diagnosis of epilepsy, with EEG confirmation. Resting EEGs show slight and subtle abnormalities in a substantial minority of patients with schizophrenia which may be accentuated by neuroleptic medication. As such, the EEG may be of limited value in differential diagnosis unless pronounced slowing or frank seizure activity is picked up.


Symptoms of schizophrenic psychosis in relative isolation may give rise to diagnostic difficulties.

Auditory hallucinations may occur in alcoholic hallucinosis (see below). Hallucinations in the context of dissociation (voices representing figures from the patients past or embodiments of aspects of their personality) must also be distinguished from typical schizophrenic hallucinations. These are often multimodal. Pure auditory hallucinations in organic conditions including epilepsy in the absence of other psychotic features are surprisingly rare.

Certain forms of delusion suggest alternative diagnoses. Transient ill-formed but usually paranoid delusions occur in the context of confusion, memory impairment, or dementia (i.e. things going missing, strange people loitering). Delusions of misidentification are particularly associated with organic illness such as dementia or stroke.

Thought disorder may be confused with a fluent aphasia following stroke or cerebral tumours.

Personality deterioration and inappropriate or disinhibited behaviour can occur in many organic conditions in the absence of overt psychotic features. Isolated frontal lesions may cause diagnostic problems since general cognitive impairments may be absent. The widespread availability of CT and MRI in the more developed world has reduced the likelihood of such patients being misdiagnosed.

A small proportion (approximately 5 per cent) of prevalent and incident cases of schizophrenia, if investigated thoroughly, are found to have a variety of ‘organic' conditions which may contribute to the illness. (30) These include metabolic abnormalities, cerebral tumours, multisystem autoimmune disease, cerebrovascular disease, etc. Some of these may be incidental; others may have precipitated the psychosis. The range of diseases counts against any specific aetiological mechanism. Similarly, the phenomenology found in such ‘organic' patients is usually indistinguishable from their ‘functional' counterparts. (31)

Thanks to increased application of non-invasive neuroimaging techniques to psychiatric patients, particularly those with schizophrenia, another class of organic abnormalities have been noted, namely cerebral anomalies which are often congenital. These include agenesis of the corpus callosum, cavum septum pellucidum, aqueduct stenosis, etc. Again, it is difficult to know how often such findings occur in the normal population and are asymptomatic, although the widespread use of MRI for ‘minor' complaints such as mild head injury and headache is uncovering such anomalies. The examples above certainly appear to be associated with psychiatric disorders in general more than would be expected by chance. They tend to be associated with below-average IQ and other neurological problems (epilepsy in the cases of callosal agenesis). (32)

Other factors to be taken into account in the differential diagnosis from organic conditions include the presence of a family history of schizophrenia, and abnormal premorbid personality, both of which weight aetiological judgement in favour of the functional diagnosis. This applies to the psychoses of epilepsy and those related to drug abuse especially. ‘Secondary' schizophrenias also tend to have less pervasive effects on the person's personality. Treatment is again based on symptoms with the added complication that neuroleptic drugs lower the epileptic seizure threshold, and will tend to worsen extrapyramidal symptoms in patients with primary movement disorders. Treatment of the primary condition (if this has remained undiagnosed for some time) may be disappointing but should always be attempted especially in the case of chronic infections. Reversal of metabolic abnormalities, even long-standing, can lead to dramatic improvements in the mental state.

Drug-induced psychoses

Many drugs of abuse and prescribed drugs can cause psychotic symptoms. In the context of a differential diagnosis, drugs of abuse—in adolescents and young adults—must be considered. Chronic amphetamine psychosis may be indistinguishable from schizophrenia. The psychosis is florid and may include visual and auditory hallucinations. Phencyclidine (PCP or angel dust) is a drug of abuse in the United States and causes an acute psychosis with prominent affective symptoms as well as perceptual distortions and depersonalization. Other psychotogenic drugs include cocaine, ecstasy, and LSD.

Cannabis is widely used, especially in large metropolitan areas and by certain ethnic groups (e.g. African-Caribbeans); hence an apparent association with schizophrenia may be a chance finding. Cannabis intoxication is more characterized by perceptual distortions and depersonalization than frank psychosis. Clinical experience suggests that cannabis has a propensity to precipitate psychotic relapse in patients with established schizophrenia, although hard data on this issue are lacking.

Delusions and hallucinations may occur rarely during states of alcohol intoxication but are more commonly associated with withdrawal syndromes. Alcoholic hallucinosis is a chronic hallucinatory state of uncertain nosological status in which the patient with long-standing alcohol dependence often hears ‘voices' which may be derogatory and commenting, in clear consciousness, after a lengthy withdrawal period.

Prescribed medication

Again the list of agents that can cause psychotic reactions to be distinguished from schizophrenia is very long, and psychotropic drugs are particularly liable to cause psychotic reactions. Two classes of drug deserve mention because of their widespread use and relatively high incidence of major psychiatric adverse effects:

  • steroids can cause a wide range of psychiatric disturbances including psychosis
  • dopamine agonists used in the treatment of Parkinson's disease and some pituitary adenomas.

Frank psychosis and affective disorders may be seen. In the treatment of neurological diseases, such as Parkinson's disease, and the use of steroids for diseases of the central nervous system, there is often an interaction between the agent and the underlying condition which increases the likelihood of a drug-induced psychosis.

The diagnostic process

It used to be argued that a diagnosis of schizophrenia in itself caused disability and morbidity due to social ‘labelling' and stigmatization. Evidence that this accounts for schizophrenic disability is lacking but the reality of the stigma of mental illness and negative attitudes towards ‘schizophrenics' cannot be denied. Hence, making a diagnosis of schizophrenia should not be taken lightly. In the author's experience, very few psychiatrists spontaneously convey the diagnosis to the patient. If a patient asks whether he or she has schizophrenia, the clinician should first try to understand the motivation behind the question and the patient's knowledge and understanding of the term. Ultimately there is seldom justification in withholding the diagnosis if it is established. A schizophrenic diagnosis can be framed in a relatively positive light—this is a condition which we are now beginning to understand and for which there are effective treatments—and may lessen the burden of responsibility and blame that the patient and his or her family may carry for the disorder. 


1. Feighner, J.P., Robins, E., Guze, S., Woodruff, R.A., Winokur, G., and Munoz, R. (1972). Diagnostic criteria for use in psychiatric research. Archives of General Psychiatry, 26, 57–62.

2. Spitzer, R.L., Endicott, J., and Robins, E. (1977). Research diagnostic criteria for a selected group of functional disorders (3rd edn). Biometrics Research Division, New York State Psychiatric Institution, New York.

3. World Health Organization (1992). F20-F29 Schizophrenia, schizotypal and delusional disorders. The ICD-10 classification of mental and behavioural disorders. Clinical descriptions and diagnostic guidelines, pp. 97–109. WHO, Geneva.

4. American Psychiatric Association (1994). Schizophrenia and other psychotic disorders. Diagnostic and statistical manual of mental disorders, DSM-IV (2nd edn), pp. 284–306. American Psychiatric Association, Washington, DC.

5. David, A.S. and Appleby, L. (1992). Diagnostic criteria in schizophrenia: accentuate the positive. Schizophrenia Bulletin, 18, 551–7.

6. Andreasen, N.C. and Flaum, M. (1991). Schizophrenia: the characteristic symptoms. Schizophrenia Bulletin, 17, 27–39.

7. Wing, J.K., Cooper, J.E., and Sartorius, N. (1974). Measurement and classification of psychiatric symptoms. Cambridge University Press.

8. McGuffin, P., Farmer, A., Gottesman, I.I., et al. (1984). Twin concordance of operationally defined schizophrenia: confirmation of familiality and heritability. Archives of General Psychiatry, 41, 541–5.

9. Kendell, R.E., Brockington, I.F., and Leff, J.P. (1979). Prognostic implications of six alternative definitions of schizophrenia. Archives of General Psychiatry, 30, 25–34.

10. Andreasen, N.C. and Olsen, S. (1982). Negative v. positive schizophrenia: definition and validation. Archives of General Psychiatry, 39, 789–94.

11. Crow, T.J. (1980). Molecular pathology of schizophrenia: more than one disease process? British Medical Journal, 280, 1–9.

12. Murray, R.M., Lewis, S.W., and Reveley, A.M. (1985). Towards an aetiological classification of schizophrenia. Lancet, i, 1023–6.

13. Van Horn, J.D. and McManus, I.C. (1992). Ventricular enlargement in schizophrenia. A meta-analysis of studies of the ventricle/brain ratio (VBR). British Journal of Psychiatry, 160, 687–97.

14. Jones, P. (1997). The early origins of schizophrenia. British Medical Bulletin, 53, 135–55.

15. Malmberg, A., Lewis, G., David, A., and Allebeck, P. (1998). Premorbid adjustment and personality in schizophrenia. British Journal of Psychiatry, 172, 308–13.

16. Strakowski, S.M. (1994). Diagnostic validity of schizophreniform disorder. American Journal of Psychiatry, 151, 815–24

17. Johnstone, E.C., Crow, T.J., Frith, C.D., and Owens, D.G.C. (1988). The Northwick Park ‘functional' psychoses study: diagnosis and treatment response. Lancet, ii, 119–26.

18. Siris, S.G., Bermanzohn, M.D., Gonzalez, A., Mason, S.E., White, C.V., and Shuwall, M.A. (1991). The use of antidepressants for negative symptoms in a subset of schizophrenic patients. Psychopharmacology Bulletin, 27, 331–5.

19. Tran, P.V., Tollefson, G.D., Sanger, T.M., Lu, Y., Berg, P.H., and Beasley, C.M. (1999). Olanzapine versus haloperidol in the treatment of schizoaffective disorder. Acute and long-term therapy. British Journal of Psychiatry, 174, 15–22.

20. Cloninger, C.R., Martin, R.L., Guze, S.B., and Clayton, P.J. (1985). Diagnosis and prognosis in schizophrenia. Archives of General Psychiatry, 42, 15–25.

21. David, A.S. (1997). Atypical psychosis. In Essentials of postgraduate psychiatry (3rd edn) (ed. R. Murray, P. Hill, and P. McGuffin), pp. 352–61. Cambridge University Press.

22. Nayani, T.H. and David, A.S. (1996). The auditory hallucination: a phenomenological survey. Psychological Medicine, 26, 177–89.

23. Davison, K. and Bagley, C.R. (1969). Schizophrenia-like psychoses associated with organic disorders of the central nervous system. In Current problems in neuropsychiatry (ed. R.N. Herrington). British Journal of Psychiatry Special Publication No 4. Headley Brothers, Ashford, Kent.

24. Lishman, W.A. (1997). Organic psychiatry: the psychological consequences of cerebral disorder (3rd edn). Blackwell Science, Oxford.

25. Hyde, T.M., Ziegler, J.C., and Weinberger, D.R. (1993). Psychiatric disturbances in metachromatic leukodystrophy. Insights into the neurobiology of psychosis. Archives of Neurology, 50, 131.

26. Cutting, J. (1987). The phenomenology of acute organic psychosis: comparison with acute schizophrenia. British Journal of Psychiatry, 151, 324–32

27. Mendez, M.F., Grau, R., Doss, R.C., et al. (1993). Schizophrenia in epilepsy: seizure and psychosis variables. Neurology, 43, 1073–7.

28. Slater, E., Beard, A.W., and Glithero, E. (1963). The schizophrenia-like psychoses of epilepsy. British Journal of Psychiatry, 109, 95–150.

29. Trimble, M.R. (1990). First-rank symptoms of Schneider. A new perspective? British Journal of Psychiatry, 156, 195–200.

30. Johnstone, E.C., Cooling, N., Frith, C.D., Crow, T.J. and Owens, D.G.C. (1988). Phenomenology of organic and functional psychoses and the overlap between them. British Journal of Psychiatry, 153, 770–6.

31. Johnstone, E.C., Macmillan, J.F., and Crow, T.J. (1987). The occurrence of organic disease of possible or probably aetiological significance in a population of 268 cases of first episode schizophrenia. Psychological Medicine, 17, 371–9.

32. David, A.S., Wacharasindhu, A., and Lishman, W.A. (1993). Severe psychiatric disturbance and abnormalities of the corpus callosum: review and case series. Journal of Neurology, Neurosurgery and Psychiatry, 56, 85–93.