Descriptive Clinical Features of Schizophrenia

Descriptive clinical features of schizophrenia

Topics covered:

  • Disorders of thought and perception
    • Delusions
    • Hallucinations
    • Schneiderian first-rank symptoms
    • Disorders of the form and flow of thought
    • Insight Impaired cognition
  • Disorders of emotion
    • Blunted affect
    • Inappropriate affect
    • Excitation and depression
  • Motor disorders
  • Disorders of volition
  • Anxiety and somatoform disorders
  • Dimensions of psychopathology in schizophrenia
    • Positive and negative symptom dimensions
    • Three dimensions of characteristic symptoms 
  • References

Introduction

The clinical features of schizophrenia embrace a diverse range of disturbances of perception, thought, emotion, motivation, and motor activity. It is an illness in which episodes of florid disturbance are usually set against a background of sustained disability. The level of chronic disability ranges from a mild decrease in the ability to cope with stress, to a profound difficulty in initiating and organizing activity that can render patients unable to care for themselves.

Disorders of thought and perception

Delusions

Delusions have traditionally been regarded as the hallmark of insanity. Although there are no features that provide an unambiguous distinction between the delusions of schizophrenia and those of other psychotic illnesses, the delusions that are most typical of schizophrenia have an enigmatic character rarely seen in other disorders. In contrast to the delusions of affective psychosis, which have a content consistent with the prevailing emotional state, in schizophrenia delusions often appear to reflect a fragmentation in the experience of reality. This fragmentation is manifest in several ways.

  • The content of the delusional belief often contains contradictions. There is a lack of logical consistency between the components of the belief, or between the belief and common understanding of what is possible. For example, a patient was very distressed by the belief that he had no head and also that there was blood all over his face. Another patient believed that his head was split in two by an axe.
  • The relationship between the delusional belief and any action that might flow from it is unpredictable. In some instances, the patient believes he has a special role or identity, yet for the most part, lives a life that is scarcely influenced by the belief. In the words of Bleuler: (1) ‘Kings, Emperors, Popes, and Redeemers engage for the most part, in quite banal work, provided they still have any energy at all for activity'. In other instances, patients might act in unexpected ways.
  • At least in the chronic phase of the illness, patients often acknowledge that a former delusion was not justified, yet in the same interview they reiterate the delusional belief. Bleuler (1) reported: ‘sometimes the patients even produce thoughts which are only understandable if it is assumed that the delusions still retain some reality for these patients even though consciously they may reject them. Sometimes the manner in which the delusion is declared to be senseless shows that in a way it is still alive.'

The mental mechanism of schizophrenic delusions remains to be ascertained. It is not a lack of capacity for logical thought; rather it appears that certain ideas acquire an attribute that exempts them from the normal processes of validation. This phenomenon is illustrated by the historic case of Daniel Schreber, (2) a high-ranking judge from Leipzig, who suffered a late-onset schizophrenic illness. His first episode of illness occurred when he was standing for election to the Reichstag at the age of 42. A second, more protracted, episode occurred when he was facing a heavy burden of work after appointment as Presiding Judge of the Appeal Court in Dresden at the age of 51. After obtaining a court order for his discharge from hospital 9 years later, in 1902, he published his memoirs (3) in a volume that includes his own account of his beliefs, and also the report prepared by the asylum director, Dr Weber, opposing his discharge. Schreber eventually suffered a third episode of illness at the age of 55, after his wife suffered a stroke, and he remained in an uncommunicative disorganized state until his death. 

Schreber believed that he had a mission to redeem the world and restore humankind to its lost state of bliss. His system of delusions included the belief that he was being transformed into a voluptuous female partner of God. Dr Weber reported that at the onset of his second episode of illness, Schreber's mental life was dominated by delusions and hallucinations. However, prior to discharge from hospital in 1902, he exhibited lively interest in his social environment, a well-informed mind, and sound judgement, while nonetheless maintaining his delusional beliefs in a manner that would accept no contrary argument. Schreber himself agreed that his beliefs were unchangeable. He considered that they belonged to a domain that was exempt from normal logic: ‘I could even say with Jesus Christ: My kingdom is not of this world; my so-called delusions are concerned solely with God and the beyond'. Furthermore, he maintained total conviction in his core beliefs despite recognizing that he had previously suffered distorted perceptions of reality. He had believed that his surroundings had been ‘miracled up' by rays. He stated:

Having lived for months among miracles, I was inclined to take more or less everything I saw for a miracle. Accordingly, I did not know whether to take the streets of Leipzig through which I traveled as only theatre props, perhaps in the fashion in which Prince Potemkin is said to have put them up for Empress Catherine II of Russia during her travels through the desolate country, so as to give the impression of a flourishing countryside.

For the purpose of understanding the nature of delusions in schizophrenia, Schreber's account is of special value because, by virtue of his keen intellect, we have access to his own perceptions of his condition in addition to detailed accounts by his physicians. In particular, his case illustrates the frequently observed phenomenon of a delusion engrossing the patient fully during the acute phase, while in the chronic phase it is still held, but coexists with an acknowledgement that it defies normal logic.

The late onset of Schreber's illness and his high level of professional achievement are unusual for an individual with schizophrenia, and raise questions about the diagnosis. However, the fact that he had delusions that were sustained independently of affective disorder, together with persisting difficulty in coping with stress, and eventually suffered a marked deterioration during his third episode of illness strongly supports the diagnosis of schizophrenia. His keen intellect illustrates a paradoxical feature of schizophrenia that can be discerned across the full spectrum of disability—the coexistence of markedly abnormal mental activity with well-integrated mental function. Even patients with symptoms affecting many domains of mental function exhibit this incongruity. Bleuler (1) noted: ‘Even the most demented schizophrenic can under proper conditions exhibit productions of a highly integrated type'.

Adherence to delusional beliefs despite the ability to understand the logic of a counter-argument sometimes creates what appears to be playfulness with logic. Bleuler(1) reports the case of a well-educated socially competent patient who complained that he had made her pregnant while she was asleep, and that he had cut the infant out of her arm. When Bleuler attempted to convince her that in reality he could not have been with her in the night, she asked: ‘Then why do you come in the dream?'

In many instances, the delusions of schizophrenia appear to arise from an altered experience of self or of external reality. The phenomena identified by the German psychiatrist, Kurt Schneider (4) as first-rank symptoms of schizophrenia (discussed in greater detail below) include several symptoms that entail an aberrant experience of ownership of one's own thought, will, action, emotion, or bodily function, which the patient attributes to alien influence. In some cases, delusions might arise from a delusional mood, i.e. an altered sense of reality in which the current circumstances acquire an indefinable transcendental quality.

Although the delusions most characteristic of schizophrenia have an incongruous quality, it is not uncommon for schizophrenic patients to have coherent delusions that are internally consistent and produce predictable behavioural responses. In particular, coherent persecutory delusions are common, and can lead to defensive actions such barracading oneself in one's room with blinds drawn. Ideas of reference and delusions of reference are also prevalent. For example, a patient might report that television programmes refer specifically to him or her. In the International Pilot Study of Schizophrenia (5) conducted by the World Health Organization, ideas of reference were reported in 70 per cent of cases, suspiciousness in 66 per cent, and delusions of persecution in 64 per cent.

Hallucinations

Hallucinations in any modality can occur, but auditory hallucinations are the most prevalent in schizophrenia. Hearing voices speaking in the third person is the most specific. This experience is listed among the Schneiderian first-rank symptoms. Sometimes the content is mundane, as in the instance when a patient of Bleuler (1) heard a voice saying ‘Now she is combing her hair' while she was grooming in the morning. In other instances there is an implied criticism, as in the case reported by Schneider (4) of a woman who heard a voice saying ‘Now she is eating; here she is munching again', whenever she wanted to eat.

Second-person auditory hallucinations are also common. In the International Pilot Study of Schizophrenia, (5) voices speaking to the patient were reported in 65 per cent of cases. Such voices are often derogatory, although it is not uncommon for a patient to hear both derogatory and comforting voices. Voices might issue commands that the patient obeys. In some instances, the patient engages in a dialogue with the voices.

During the acute phase of illness, auditory hallucinations usually have the same sensory quality as voices arising from sources in the external world. The patient might change accommodation in a fruitless attempt to escape from them. In some instances the voice is attributed to a radio-transmitter implanted in the body, especially in the teeth. In the chronic phase, the voices are often recognized as coming from within the person's own mind. Kraepelin (6) reports: ‘at other times they do not appear to the patient as sense perceptions at all; they are “voices of conscience”; “voices which do not speak with words”'. These experiences are pseudohallucinations, but nonetheless they are a significant feature in many cases.

In schizophrenia, visual hallucinations are less common than auditory hallucinations, but do occur. Somatic hallucinations are also relatively common, and often are associated with a delusional misinterpretation. For example, a young man reported sensations in his belly that he attributed to a snake, which he believed had crawled up his anus.

Schneiderian first-rank symptoms

Kurt Schneider (4) identified a set of phenomena that he considered were strongly indicative of schizophrenia in the absence of overt brain disease. These symptoms, listed in Table 1, have become known as first-rank symptoms. Schneider did not consider that the diagnosis could be made simply on the presence of one such symptom; on the contrary, he warned (4), ‘a psychotic phenomenon is not like a defective stone in an otherwise perfect mosaic'. Schneider did not define the phenomena precisely, and clinicians have interpreted his writings differently. Mellor (7) formulated a precise set of definitions and found that, according to these strict criteria, 72 per cent of patients with schizophrenia exhibited at least one first-rank symptom. Applying the same criteria, O'Grady (8) found that in a series of cases assessed at admission to hospital, 73 per cent of schizophrenic patients exhibited at least one first-rank symptom, while no cases of affective psychosis did. However, applying less strict criteria, O'Grady found more broadly defined first-rank symptoms in 14 per cent of patients with affective psychosis.

Table 1  First-Rank Symptoms of Kurt Schneider
Audible thoughts Auditory hallucinations of a person's voice being spoken aloud
Voices arguing or discussing Auditory hallucinations of two or more voices arguing or discussing, usually about the person experiencing the hallucination
Voices commenting on patient's actions Auditory hallucinations commenting on a person's behaviors
Somatic passivity Tactile or visceral hallucinations that are imposed by some external agent; can be combinations of different somatic hallucinations
Thought withdrawal Sensation of thoughts being actively removed from a person's mind
Thought insertion Thoughts inserted into a person's mind by some external agent
Thought broadcasting The sense that a person's thoughts are experienced as real phenomena by others— the thoughts are made audible, or may be experienced by others through telepathy
Made feelings Feelings that are not a person's own are imposed on that person by an external agent
Made impulses or drives An impulse for action is imposed on a person by some external agent
Made volitional acts A person's actions are from and are controlled by an external agent; the person is a passive participant in the action
Delusional perception A perception that has a unique and idiosyncratic meaning for a person, which leads to an immediate delusional interpretation

Three of the first-rank symptoms (voices commenting, voices discussing, and audible thoughts) involve auditory hallucinations, while the remainder entail delusional attributions to experiences or perceptions. Although Schneider himself avoided speculating on the theoretical implications of these phenomena, it is notable that most of them involve a disorder of the sense of ownership of one's own mental or physical activity. Thought broadcast, thought withdrawal, and thought insertion reflect the experience of loss of autonomy over thought, while made will, made acts, made affect, and somatic passivity reflect loss of autonomy over action, will, affect, and bodily function.

Mellor (7) emphasizes that there are two aspects to these phenomena: the experience of loss of autonomy and the delusional attribution to alien influence. As an illustration of made acts, Mellor reports a patient who reported that his fingers moved to pick up objects ‘but I don't control them ... I sit there watching them move, and they are quite independent, what they do is nothing to do with me. I am just a puppet ... I am just a puppet who is manipulated by cosmic strings'. To illustrate made affect, Mellor quotes a young woman: ‘I cry, tears roll down my cheeks and I look unhappy, but inside I have a cold anger because they are using me in this way, and it is not me who is unhappy, but they are projecting unhappiness into my brain.'

Delusional perception, in which an entirely unwarranted conclusion is drawn from a normal perception, illustrates the incongruity between a delusional idea and concurrent mental activity, which is characteristic of schizophrenia. However, the way in which delusional perceptions often crystallize from a delusional mood indicates that it is not merely a matter of illogical inference; the delusional idea is more like a divine revelation. Mellor (7) gives the example of an Irishman who experienced a sense of foreboding while seated at the breakfast table in a lodging house. When another lodger innocently pushed the salt cellar towards him, he suddenly knew this meant that he must return home to greet the Pope who was visiting his family to thank them because Our Lord was to be born again to one of the women.

Disorders of the form and flow of thought

The speech of schizophrenic patients is often difficult to understand because of abnormalities of form of the underlying thought. However, the clinical assessment of thought form disorder remains a major challenge. This is due in part to the fact the essential features of the impediments to verbal communication in schizophrenia have yet to be defined in a fully satisfactory manner. Furthermore, thought disorder is usually manifest during spontaneous speech, making it difficult to create circumstances in which the phenomena can be elicited reliably.

Bleuler (1) coined the term loosening of associations to describe the weakening of the connections between words and ideas that bind thoughts into a coherent whole. While this term is a useful label for one of the major types of disorder of the form of speech and thought, it does not encompass the entire range of such disorders. In addition to disordered connections between words and ideas, there are oddities in the use of language. One of the most comprehensive catalogues is the Thought, Language, and Communication Scale compiled by Andreasen. (9) This scale includes several items that involve different aspects of the loosening of associations:

  • derailment—wandering off the point during the free flow of conversation
  • tangentiality—answers to questions that are off the point
  • incoherence—a breakdown of the relationships between words within a sentence so that the sentence no longer makes sense
  • loss of goal—failure to reach a conclusion or achieve a point.

The Thought, Language, and Communication Scale also includes several items that refer to unusual use of language:

  • metonyms—unusual uses of words (e.g. hand-shoe instead of glove)
  • neologisms—new words invented by the patient.

The various aspects of loosening of associations and peculiarities of language use are commonly regarded as positive thought disorder. The Thought, Language, and Communication Scale also includes negative thought disorders that entail impoverishment of thinking:

  • poverty of speech is a disorder of the flow of speech in which the rate of speech production is reduced
  • poverty of content is a disorder in which the amount of information conveyed is relatively little in proportion to the number of words uttered.

The Thought, Language, and Communication Scale has proved to be one of the most successful of recent attempts to define and quantify formal thought disorder, but it has several limitations. Most important of these is that the positive thought disorder items defined in the scale do not discriminate well between manic thought disorder and florid schizophrenic thought disorder. (10) Secondly, the scale is not sensitive to the subtle thought form disorders that occur in first-degree relatives of schizophrenic patients.

These limitations are dealt with, at least partially, in the Thought Disorder Index devised by Holzman. (11) This scale employs ratings based on thought and speech elicited by the Rorschach inkblot figures and during an assessment of IQ. Two categories of disorder, disorganization (comprising vagueness, confusion, and incoherence) and idiosyncratic verbalizations, appear to discriminate fairly well between schizophrenic and manic thought. (11) Furthermore, the Thought Disorder Index is sensitive to subtle thought disorder present in first-degree relatives of schizophrenic patients. Unfortunately, this scale is too cumbersome for routine clinical use.

Positive formal thought disorder is usually a transient feature of acute episodes of illness. Nonetheless, after resolution of the acute episode there is often a subtle residual thought disorder that is manifest as vague, wandering speech or minor idiosyncrasies of word usage or ideas.

Negative formal thought disorder has a greater tendency to be persistent. Chronic poverty of speech is associated with impairment in several domains of cognition (12) including abstract reasoning. It leads to impaired social relationships, (13) although it is also influenced by the social milieu. Transient poverty of speech can occur during acute episodes of illness. It is less strongly associated with cognitive impairment and, at least in some cases, appears to reflect an obstruction of the articulation of speech that is catatonic in character. At its most severe, the patient is mute.

Insight

Lack of insight is one of the defining characteristics of psychotic illness. Lack of insight entails a failure to accept that one is ill and to appreciate that symptoms are due to illness. In the International Pilot Study of Schizophrenia (5) lack of insight was the most prevalent symptom reported in schizophrenic patients. It occurred in approximately 90 per cent of cases. Insight is often partial. In particular, even in instances in which a patient acknowledges suffering from an illness, he or she might fail to accept that psychotic symptoms such as delusions or hallucinations are a manifestation of that illness. Lack of insight is one factor that contributes to unwillingness to accept treatment. However, the clinician should be aware that other factors, including lack of appropriate education about the illness and justified fear of side-effects of treatment, can also impede the development of a therapeutic collaboration between physician and patient.

Impaired cognition

In addition to delusions and disorders of thought form, a wide range of cognitive deficits occur in schizophrenia. These are discussed in here: The neuropsychological features of schizophrenia. This article focuses on the relationship between cognitive impairment and other features of the illness.

In the acute phase of the illness, attentional impairment is common and is often associated with psychomotor excitation and/or formal thought disorder. It might also reflect preoccupation with delusions and hallucinations.

During the chronic phase of illness, many schizophrenic patients exhibit persistent cognitive impairments. Longitudinal studies of individuals who subsequently develop schizophrenia reveal that the deficits are discernible during childhood, suggesting that these deficits are an aspect of the redisposition to schizophrenia. The major cognitive impairments are in the realm of executive function, working memory, and long-term memory. Executive dysfunction includes impaired ability to initiate and select self-generated mental activity. Impaired ability to form and initiate plans is associated with chronic poverty of speech, blunted affect, and lack of spontaneous activity, while impaired ability to inhibit inappropriate responses is associated with chronic formal thought disorder. (12)

Disorders of emotion

An extensive range of disorders of emotion occur in schizophrenia. Blunted affect and inappropriate affect are the most characteristic, and also tend to be the most persistent, but transient excitation, irritability, lability, and depression are also common.

Blunted affect

Blunting of affect is manifest as decreased responsiveness to emotional issues, loss of vocal inflection, and diminished facial expression. These objective signs of affective blunting are sometimes accompanied by awareness of loss of emotional tone that, paradoxically, patients find to be distressing. More commonly, there is a lack of concern and even a lack of awareness of the problem. Affective blunting is one of the hallmarks of chronic schizophrenia. Bleuler (1) remarked that when the affects disappear, the illness becomes chronic. While blunted affect is usually chronic, it can also be a feature of acute episodes of the illness that resolves as the acute episode resolves.

Inappropriate affect

Inappropriate or incongruous affect is the expression of affect that is inappropriate in the circumstances. At its most severe it takes the form of hollow laughter that is unrelated to any apparent stimulus. More common is inappropriate giggling that differs from normal nervous giggling in having a more fatuous character.

Excitation and depression

During acute exacerbations of schizophrenia, excitation, manifest as irritability, sleeplessness, agitation, and motor overactivity, is common. Depression is also common around the time of an acute episode of schizophrenia, (14) and is often a feature of the prodromal phase of the illness. It is not uncommon for patients presenting in the first episode of schizophrenia to report having suffered bouts of minor depressive symptoms over a period of several years.

Depression also occurs during the chronic phase of the illness. Although the cross-sectional rate is approximately 10 per cent in the chronic phase, (15) schizophrenic patients have a high probability of suffering depression at some time during their illness. In a longitudinal study, Johnson (16) found that 65 per cent of schizophrenic patients exhibited an episode of depression in a period of 36 months after a florid psychotic episode.

Motor disorders

Subtle disturbance of motor co-ordination is common in schizophrenia. Home videos of children who subsequently develop schizophrenia demonstrate that even in infancy they are noticeably more clumsy than their siblings, suggesting that disturbed motor co-ordination is an aspect of the predisposition to schizophrenia. (17)

More dramatic than subtle motor incoordination are the rare catatonic motor disorders. Catatonia entails disturbance of voluntary motor activity and posture. The level of activity can be either decreased or increased. In extreme cases of hypoactivity the patient is in a stupor, and is unresponsive to stimuli, but usually retains conscious awareness. In hyperactive states the patient often maintains a stereotypic activity for prolonged periods. Even less common are conditions such as waxy flexibility, in which a patient's body can be moulded into an unusual posture, which is then sustained for lengthy periods, and echopraxia, in which the patient mimics the voluntary motor actions of the examiner.

Disorders of volition

Among the most disabling of the clinical phenomena of schizophrenia are disruptions of motivation and will. Voluntary activity can be disjointed or weakened. Disjointed volition is manifest in poorly organized ill-judged activities which appear to be prompted by impulse. For example, an artistic, intelligent young woman felt cold so she lit a fire on the carpet in her bedroom, even though she was able to appreciate that this was a dangerous thing to do. Weakened volition results in prolonged periods of underactivity. The patient might lie in bed or sit in an armchair for hours.

Anxiety and somatoform disorders

Various forms of anxiety and somatic symptoms are common in schizophrenia. Huber(18) described a non-characteristic defect state which is dominated by anxiety and asthenia. Coenesthesia, in which the patient suffers unusual or debilitating bodily experiences that do not have an apparent somatic cause, occurs frequently.

Dimensions of psychopathology in schizophrenia 

Schizophrenia is heterogeneous in its clinical presentation, suggesting that several different pathophysiological processes might contribute to the illness.

Positive and negative symptom dimensions

Positive symptoms are those that reflect the presence of an abnormal mental process, and include delusions, hallucinations, and formal thought disorder. Negative symptoms reflect the diminution or absence of a mental function that is normally present. They include poverty of speech and blunted affect. In schizophrenia, positive symptoms tend to be transient, while negative symptoms tend to be chronic. In an influential hypothesis, Crow (19) proposed that positive symptoms arise from dopaminergic overactivity, while negative symptoms reflect structural brain abnormality. While a substantial body of evidence supports this hypothesis, it does not account adequately for the complexity of the heterogeneity of the clinical features in schizophrenia.

Three dimensions of characteristic symptoms The preponderance of evidence (12,13,20) from factor analysis of schizophrenic symptoms indicates that the characteristic symptoms of schizophrenia segregate into three syndromes, as shown in Bullet list . These syndromes do not reflect separate illnesses, but different dimensions of illness, in the sense that a patient might exhibit more than one of the syndromes. In an individual case, the three syndromes vary independently in severity over time, while the symptoms from within each syndrome tend to vary in parallel. (20)

Bullet list 1 Three syndromes of symptoms characteristic of schizophrenia

  • Reality distortion
    • Delusions
    • Hallucinations
  • Disorganization
    • Thought form disorder
    • Inappropriate affect
    • Bizarre behaviour
  • Psychomotor poverty (core negative symptoms)
    • Poverty of speech
    • Blunted affect
    • Decreased spontaneous movement

The three syndromes embrace only the characteristic symptoms that are given weight in making a diagnosis of schizophrenia. In addition, there are two affective syndromes, depression and psychomotor excitation, that are prevalent in schizophrenia, (12) despite being more characteristic of mood disorders. These affective syndromes are usually transient.

An accumulating body of evidence (12) from brain imaging studies indicates that the three characteristic syndromes are associated with three distinguishable patterns of cerebral malfunction involving the areas of association cortex and related subcortical nuclei, which serve higher mental functions. Overall, the evidence indicates that the heterogeneity of symptom profiles in schizophrenia does not reflect the existence of several discrete illnesses, but rather, the existence of several dimensions of psychopathology, each arising from disorder of a specific neuronal system that serves an aspect of higher mental function. In an individual case, several of these neural systems might be involved.

Although many details of the relationships between the diverse clinical features of schizophrenia remain uncertain, a growing understanding of the neural pathways involved is beginning to provide the foundation for understanding the protean manifestations of this disorder.

References 

1. Bleuler, E. (1950). Dementia praecox or the group of schizophrenias (trans. J. Zinkin). International Universities Press, New York.

2. Spitzer, R.L., Gibbon, M., Skodol, A.E., Williams, J.B.W., and First, M.B. (ed.) (1989). DSM-IIIR casebook. American Psychiatric Press, Washington, DC.

3. Schreber, D.P. (1955). Denkwurdigkeiten eines Nervenkranken (Memoirs of my nervous illness) (trans. I. Macalpine and R. Hunter). Dawson, London.

4. Schneider, K. (1959). Clinical psychopathology (trans. M.W. Hamilton). Grune & Stratton, New York.

5. World Health Organization (1973). The international pilot study of schizophrenia. World Health Organization, Geneva.

6. Kraepelin, E. (1919). Dementia praecox and paraphrenia (trans. R.M. Barclay). Facsimile edition, 1971. Kreiger, New York.

7. Mellor, C.S. (1970). First rank symptoms of schizophrenia. British Journal of Psychiatry, 117, 15–23.

8. O'Grady, J.C. (1990). The prevalence and diagnostic significance of first-rank symptoms in a random sample of acute schizophrenia in-patients. British Journal of Psychiatry, 156, 496–500.

9. Andreasen, N.C. (1979). Thought language and communication disorders. I Clinical assessment, definition of terms and evaluation of their reliability. Archives of General Psychiatry, 36, 1315–21.

10. Andreasen, N.C. (1979). Thought, language and communication disorders. II Diagnostic significance. Archives of General Psychiatry, 36, 1325–30.

11. Holzman, P.S., Shenton, M.E. and Solovay, M.R. (1986). Quality of thought disorder in differential diagnosis. Schizophrenia Bulletin,

12, 360–71. 12. Liddle, P.F. (1999). The multi-dimensional phenotype of schizophrenia. In Schizophrenia in a molecular age (ed. C.A. Taminga), pp. 1–28. American Psychiatric Press, Washington, DC.

13. Liddle, P.F. (1987). The symptoms of chronic schizophrenia: a re-examination of the positive-negative dichotomy. British Journal of Psychiatry, 151, 145–51.

14. Siris, S.G. (1991). Diagnosis of secondary depression in schizophrenia: implications for DSMIV. Schizophrenia Bulletin, 17, 75–98.

15. Barnes, T.R.E., Curson, D.A., Liddle, P.F., and Patel, M. (1989). The nature and prevalence of depression in chronic schizophrenic inpatients. British Journal of Psychiatry, 154, 486–91.

16. Johnson, D.A.W. (1988). The significance of depression in the prediction of relapse in chronic schizophrenia. British Journal of Psychiatry, 152, 320–3.

17. Walker, E. and Lewine, R.J. (1990). Prediction of adult-onset schizophrenia from childhood home videos of the patients. American Journal of Psychiatry, 89, 704–16.

18. Huber, G., Gross, G., and Schuttler, E. (1975). A long term follow-up study of schizophrenia: psychiatric course of illness and prognosis. Acta Psychiatrica Scandinavica, 52, 49–57.

19. Crow, T.J. (1980). The molecular pathology of schizophrenia: more than one disease process. British Medical Journal, 280, 66–8.

20. Arndt, S., Andreasen, N.C., Flaum, M., Miller, D., and Nopoulos, P. (1995). A longitudinal study of symptom dimensions in schizophrenia. Archives of General Psychiatry, 52, 352–60.