Gerald Hurowitz, M.D.·Published 7 May 2009·9 min read
Key points
Interest in negative symptoms re-emerged in the 1970s, as exemplified by Strauss and Carpenter (1974) and Andreasen (1979a,b,c).
A more recent strategy for addressing the heterogeneity of the phenotype in schizophrenia is the dimensional approach.
A newer alternative, the unitary model, draws from the tradition of Bleuler (1911/1950), who attempted to identify what he considered to be the single fundamental abnormality in schizophrenia.
Patients with type I schizophrenia presented clinically with positive symptoms such as delusions and hallucinations; Crow posited that the underlying pathophysiological mechanism for this subtype was a biochemical imbalance, such as an excess of dopamine D2receptors.
Categorical models
Interest in negative symptoms re-emerged in the 1970s, as exemplified by Strauss and Carpenter (1974) and Andreasen (1979a,b,c). The turning point came perhaps from the works of Crow who, in 1980, proposed a new typology for schizophrenia, which integrated clinical presentation, pathophysiology and treatment response in a single model (Crow 1980; Crow et al. 1981). Patients with type I schizophrenia presented clinically with positive symptoms such as delusions and hallucinations; Crow posited that the underlying pathophysiological mechanism for this subtype was a biochemical imbalance, such as an excess of dopamine D2receptors. Therefore, he hypothesized that the resulting clinical manifestations would be more likely to respond favourably to antipsychotic medication, to be characterized by exacerbations and remissions, and to have a more favourable outcome. Conversely, patients with type II schizophrenia, presenting with symptoms such as affective flattening and poverty of speech, were said to be manifestating an underlying structural/anatomical abnormality reflected by ventricular enlargement and cortical atrophy in neuroimaging studies. These symptoms therefore would tend to be poorly responsive to somatic treatment, follow a chronic course, and predict poor outcome.
Crow's original model did not specify which of the various descriptors of type I vs. type II should be used in studies designed to disconfirm or verify the hypothesized dichotomy; that is, clinical presentation, pathophysiology or treatment response. Therefore the model was difficult to test. Andreasen developed two detailed standardized rating scales, the Scale for the Assessment of Negative Symptoms (SANS) (Andreasen 1983) and the Scale for the Assessment of Positive Symptoms (SAPS) (Andreasen 1984), for reliably assessing symptoms and exploring other aspects of the relationships between positive symptoms, negative symptoms and cognitive, psychosocial and neurobiological correlates of schizophrenia. One result from validation studies of these scales was Andreasen's proposal of three subtypes of patients with schizophrenia: negative, positive and mixed (Andreasen & Olsen 1982). Both Crow (1980) and Andreasen et al. (1982) proposed that the negative symptoms of schizophrenia were indicators of a single 'subtype'.
Dividing patients into mutually exclusive subgroups is firmly rooted in the 'disease model' in medicine. Symptomatology is the measure used to identify a category, and at this point the categories are referred to as 'syndromes' (literally, a running together), because they constitute an identifiable clinical pattern that makes sense in the context of observed relationships of the symptoms.
Once a specific pathophysiology or aetiology is identified, syndromes are elevated to the status of recognized diseases. In the 'categorical approach' it is assumed that the subtypes identified will differ from one another (and that this will eventually be discovered and documented) in terms of their pathophysiological mechanisms or aetiology, which may be reflected in differing responses to treatment, course of morbidity and underlying neurobiology.
Written and revised by
Gerald Hurowitz, M.D.
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The typology of schizophrenia proposed by Crow was inherently categorical, with subjects classified as either type I or II.
The expansion of this conceptualization by Andreasen to include a mixed type was also categorical. The research produced from the categorical approach was prolific throughout the 1980s, but eventually the need for a new type of explanatory model arose. Dividing patients into mutually exclusive groups based on positive and negative symptoms was eventually abandoned, for several reasons. First, most patients were of a 'mixed' subtype, and many fewer were purely 'positive' or 'negative' (Andreasen 1985). Secondly, longitudinal studies revealed that the symptoms of patients varied over time (Breier et al. 1987; Marneros et al. 1991).
One of the most difficult problems in the investigation and assessment of negative symptoms in schizophrenia involves the recognition that their measurement may be confounded by a variety of other factors. The four most commonly implicated factors are:
1neuroleptic side-effects, such as akinesia;
2depression, which has been reported to be present in schizophrenia in the early course of the illness (Knights & Hirsch 1981; Wassink et al. 1999), not to decrease in severity as the psychotic symptoms abate with medication (Knights & Hirsch 1981) and to be frequent during the residual phase (Siris 1991);
3a response to positive symptoms, for example avoiding social interactions because of paranoia; and
4environmental understimulation resulting from chronic institutionalization (Carpenter et al. 1985).
Carpenter and his group have been most active in their attempts to disentangle 'primary' and 'secondary' negative symptoms (Carpenter & Kirkpatrick 1988). Carpenter defines primary, or 'deficit', symptoms as enduring core-negative symptoms of schizophrenia such as anhedonia and blunted affect.
The secondary symptoms, however, are those negative symptoms that may be considered consequential to other symptoms or treatment of schizophrenia. Carpenter's deficit symptoms include flattened affect, anhedonia, poverty of speech, curbing of interest and decrease in curiosity, lack of sense of purpose and diminished social drive. By definition, these symptoms must not be fully accounted for by depression, anxiety, medication effects or environmental deprivation. The non-deficit syndrome is defined by an absence of these deficit symptoms with the presence of any other schizophrenia symptoms, such as disorganized thought or hallucinations.
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Dimensional models
A more recent strategy for addressing the heterogeneity of the phenotype in schizophrenia is the dimensional approach. While 'categories' traditionally arise from disease models, 'dimensions' are often derived from the study of normal psychology; therefore, students of dimensional approaches have shown less concern about identifying brain - behaviour relationships. Dimensions define groups of symptoms that co-occur, but the cooccurrence is noted through statistical techniques such as factor analysis. While categories classify individuals, dimensions classify symptoms. Therefore, dimensions can overlap within a given individual and be additive.
Bilder et al. (1985) identified three distinct clusters of symptoms using correlative analysis of symptom ratings and neuropsychological data, providing the first validating evidence for the distinction between symptom dimensions.
1The disorganization cluster included alogia, attentional impairment, positive formal thought disorder and bizarre behaviour.
2The blunted affect and volition cluster included affective flattening, avolition/apathy and anhedonia.
3The florid psychotic cluster included delusions, hallucinations and 'breadth of psychosis'.
Impaired neuropsychological performance was strongly association with the disorganized symptoms and, to a lesser extent, was associated with the blunted affect symptoms but was not associated with the psychotic symptoms. Andreasen and Grove (1986) replicated this finding in the second study, validating this distinction of three symptom dimensions, and subsequently many others have had similar findings (Kulhara et al. 1986; Liddle 1987a,b; Arndt et al. 1991; Gur et al. 1991; Brown & White 1992; Minas et al. 1992; Miller et al. 1993). Arndt et al. (1995) found that the negative symptoms, unlike the psychotic or disorganized symptoms, are stable over time. Liddle (1987b) used factor analysis to examine the relationship between symptoms in a group of patients with schizophrenia and began using the often cited dimension names of 'disorganization', 'psychomotor poverty' and 'reality distortion'. He also provided further validating evidence for these dimensions with imaging data (Liddle et al. 1992;).
Later studies have further validated the finding that the negative and disorganized dimensions are associated with impairments in cognitive functioning (Liddle 1987a,b; Liddle & Morris 1991). O'Leary et al. (2000) further specified the nature of the impairment by investigating a large sample (134) of patients with schizophrenia. Negative symptoms were related to generalized brain dysfunction, the disorganized symptoms were related to verbal processing abnormalities and the psychotic symptoms showed no relationship to cognitive impairment.
One potential drawback of the dimensional approach is its disregard for the boundaries of the classical disease model which searches for the underlying construct of an illness. A comparable approach would be to search for the principal basis of a feature existing both in schizophrenia and other diseases, e.g. hallucinations, as they are found in schizophrenia, mania and epilepsy.
The consequence of many investigations has been to treat dimensions as categories, resulting in attempts to localize specific symptoms.
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Unitary models
A newer alternative, the unitary model, draws from the tradition of Bleuler (1911/1950), who attempted to identify what he considered to be the single fundamental abnormality in schizophrenia. Bleuler defined the fundamental symptoms of schizophrenia as those caused by a 'loosening of associations', which were present in all patients, tended to occur only in schizophrenia and therefore were pathognomonic of the illness.
Thus, the unitary model stresses that there is a single unifying construct which explains the heterogeneity of the phenotype of schizophrenia. This model proposes that schizophrenia has one fundamental problem in a basic cognitive process.
One recent unitary model suggests that the fundamental deficit is a disruption of the fluid co-ordination of mental activity, called 'cognitive dysmetria' (Andreasen et al. 1996, 1998, 1999; Andreasen 1997, 1999). Synchrony refers to the normal fluid processing of information required during thought and speech, and 'dysmetria of thought' (Schmahmann 1991) or 'cognitive dysmetria' conveys its disturbance. This disruption would manifest itself in cognition, emotion and behaviour. Thus, the phenotype is defined by a unitary cognitive abnormality (cognitive dysmetria), which leads to the varied symptoms experienced by patients. This abnormality, not the symptoms, should be used to define the phenotype of the illness.
According to this unitary model, schizophrenia is a neurodevelopmental and cognitive disorder with an aetiology reflecting the interaction of genetics and environment and a pathophysiology consisting of the resultant abnormalities of brain development (which continues into early adulthood). Similar to the 'multiple hit' model of cancer, the unitary model suggests that the development of schizophrenia results from multiple aetiological factors leading to a shared pathophysiology and neurobiology in all people with schizophrenia. These complications in brain development from conception to early adulthood lead to disruptions in anatomic and functional connectivity, resulting in neural 'misconnections' expressed as 'cognitive dysmetria' and ultimately manifested as symptoms such as flattened affect, avolition, disorganized thought, hallucinations or delusions.
Several other theories have also attempted to explain the symptoms of schizophrenia via impairment in a single underlying cognitive process. These are the theories of willed action (Frith 1992), working memory (Goldman-Rakic 1994) and information processing and attention (Braff 1993).
Frith proposed that the general mechanism underlying the symptoms in schizophrenia is a disorder of consciousness or self-awareness, impairing one's ability to think with 'metarepresentations' (higher order abstract concepts which are representations of mental states) (Frith 1992). The impairment in self-awareness is the basis for three features of schizophrenia.
1A disorder of willed action which leads to an inability to generate spontaneous or willed acts, resulting in poverty of action, perseveration or inappropriate action.
2A disorder in self-monitoring. An inability to monitor willed intentions may lead to delusions of control, auditory hallucinations or thought insertion.
3A disorder in monitoring the intentions of others, which leads to delusions of reference or paranoid delusions.
Goldman-Rakic (1994) suggested that another cognitive operation, working memory, may be disrupted in schizophrenia, leading to behavioural disorganization and certain positive and negative symptoms. Working memory is defined as a memory system in which items are held 'on-line' while needed and then discarded after use. There is evidence that the prefrontal cortex is involved in the organization and processing of this transitory memory system. Dysfunction in one or more components of working memory could result in the diverse symptoms of schizophrenia. Alogia would result from impaired information retrieval. The inability to hold a concept in mind may lead to thought disorder. A failure to reference internal or external stimuli against established memories may lead to misrepresentations of causality, resulting in delusions and hallucinations.
Thus, the prefrontal cortex and its circuitry may be disrupted in schizophrenia, leading to impairments in working memory which surface as some of the positive symptoms and negative symptoms.
Braff (1993) hypothesized that patients with schizophrenia may have a fundamental deficit in information processing and attention. Patients are unsuccessful in allocating attentional resources to relevant tasks while inhibiting attention towards irrelevant stimuli. Subjectively, they may report trouble 'focusing' and feeling overwhelmed by external stimuli. On a wide variety of experimental paradigms to assess information processing and attention (such as prepulse inhibition, P50 gating, ocular motor function, continuous performance task and event-related potentials), patients with schizophrenia are less able to process information rapidly and efficiently, particularly in the context of distractions, high processing loads and multiple tasks.
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