A number of authors have shown that unawareness is not related to general cognitive16,17 or frontal lobe18–21 impairments. Cuesta and colleagues, for instance,19 administered to 35 schizophrenics the Wisconsin Card Sorting Test (WCST), a classic measure of abstract conceptual skills and cognitive flexibility which is very sensitive to the acute effects of frontal lobe injury. No correlation was found between poor performance on WCST and unawareness. These results lead to consider unawareness still a primary symptom of schizophrenia or a consequence of clinical/individual variables.16,19 However, several other papers suggested that unawareness might be linked to a poor performance in tests assessing the frontal lobe functions. For instance, Young and colleagues22 conducted three separate studies testing 108 patients with chronic schizophrenia diagnosed via the revised 3rd edition of the Diagnostic and Statistical Manual (DSM-III-R) criteria. Subjects were administered the standard WCST, measuring the level of awareness with two instruments of demonstrated validity and reliability: the Scale for the Assessment of Unawareness of Mental Disorder (SUMD) and the basic activities of daily living (ADL). The authors showed a clear and consistent association between poor WCST performance and unawareness. In another study, it was proved that such a kind of correlation can be highly specific.23 In detail, the authors recruited 21 subjects with a diagnosis of schizophrenia based on the Structured Clinical Interview (SCID) for the 4th edition of the DSM (DSM-IV). Unawareness was evaluated with the SUMD. The subjects also underwent an extensive neuropsychological examination and it was found that SUMD correlated significantly only with WCST but not with the other neuropsychological test. The relationship between tests assessing frontal lobe functions and unawareness has been confirmed also in several other papers.24–32
These results about the associations between unawareness and frontal functions tests are somewhat conflicting. However, the authors must emphasize that many of the above-mentioned studies cannot be easily compared because of several methodological differences such as a-priori hypotheses, sample recruitment, chronicity, unawareness measures and symptomatology. Additionally, unawareness was measured as a unitary variable without considering possible dissociations within the symptomatology (e.g. positive vs negative symptoms or subcomponents of executive functions). Indeed, they often limited the analysis to WCST, which is a non-specific insight measure. As pointed out by Donohoe et al.,33 it is essential to prone patients to cognitive tests which can subdivide executive functions into their different components: inhibition, planning, working memory, regulation of emotion, motivation and so on.
Accordingly, other authors explored whether the association between unawareness and frontal lobe functions could be a domain-specific phenomenon, measuring it separately for positive and negative symptoms. Mohamed and colleagues34 tested 25 patients with schizophrenia according to DSM-III-R diagnostic criteria. They assessed unawareness of the illness with the SUMD adding four additional subscales based on the breakdown of items from the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS). The scores were unawareness of negative symptoms (UNS), attribution of negative symptoms (ANS), unawareness of positive symptoms (UPS), and attribution of positive symptoms (APS). Patients also had to perform four tests to evaluate executive functions: Verbal Fluency Test, the Design Fluency Test, the Trail-Making Test and a modified version of the WCST. The authors proved that only unawareness for negative symptoms was significantly correlated to a deficit of the executive functions. This link has been described in other papers.15,35–38 On this basis, Mohamed and colleagues proposed that negative symptoms could be a consequence of damage to the executive functions while the positive symptoms follow damage to other cognitive functions, a general cognitive deterioration or an attempt to protect one’s own psychological wellbeing. However, some of these authors and others described a link between positive symptoms and unawareness.35,37,39,40 Both Amador et al.7 and Kemp and Lambert37 noted that increased psychosis and grandiosity (both positive symptoms) were associated with increased misattribution of psychiatric symptoms. This might be a specific aspect of insight that may have a different etiology than unawareness. As has been demonstrated, schizophrenia patients may have selective unawareness of some attributes of their illness, but not of others.7,10,33,41
Recently, Brebion and colleagues42 examined 40 in-patients meeting DSM-IV criteria for schizophrenia. Positive and negative symptoms were assessed by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). The authors confirmed the correlation between positive symptoms and unawareness but, in addition, found that unawareness was inversely correlated with unawareness of emotions or social interactions that are considered typical negative symptoms. The authors claimed that positive and negative symptomatology appears to have opposite links to awareness. The variable correlations between different symptom clusters (positive vs negative) may suggest that different elements of awareness may be differentially associated to distinct aspects of schizophrenia.
In summary, neuropsychological findings regarding the association between positive/negative symptoms and executive functions is still a matter of debate. Even when unawareness is analyzed deeply in its subcomponents, the relationships are still unclear. Donohoe et al.,33 for instance, found that unawareness was correlated to working memory deficits but also to general cognitive functions impairments rather than to frontal lobe impairments. These considerations imply that further experiments and theoretical reflections are necessary to shed light on this puzzling topic. Nonetheless, it is fundamental to take into account also the most recent neuroanatomical studies, which have tried to examine directly the association between brain regions and unawareness with structural and functional imaging.
The first attempts examined the correlation between awareness and the brain whole volume without taking into account different brain areas. In one of the previously mentioned studies,38 for example, the authors assessed the relationship between unawareness and the whole brain volumes in a sample of 78 patients with DSM-IV schizophrenia. Unawareness was related to poor WCST performance but not to any global brain measures. The same lack of correlation has been found when considering only the cerebral ventricular enlargement.43 Nonetheless, other authors looked at the possible association with specific brain regions and subregions. David,44 for instance, demonstrated that unawareness was specifically associated to dysfunction of prefrontal or parietal lobes. In one of the most ‘in-depth’ anatomical studies,45 the relationship between unawareness and eight different frontal lobe subregions was analyzed in 15 patients with chronic schizophrenia. The authors found that unawareness was associated with a bilateral volume reduction in the middle frontal gyrus, gyrus rectus, and left anterior cingulate gyrus. More interestingly, they tried to correlate specific aspects of unawareness with each anatomic subregion. Overall, unawareness of psychiatric illness was associated with smaller mid-frontal gyrus, right gyrus rectus, and left anterior cingulated gyrus, while the misattribution of specific symptoms was associated with reduced superior frontal gyrus volume. The involvement of these frontal lobe areas in unawareness onset has been confirmed in another study.36 One problem is that these studies were performed on patients with chronic schizophrenia, thereby making it difficult to identify the effects of illness chronicity and exposure to antipsychotic medications. Shad and colleagues46 investigated a sample of 35 patients without effects of long-term use of antipsychotic medications and illness chronicity. The authors assessed the unawareness through single questions derived from the items of the Hamilton Depression Rating Scale (HDRS). They analyzed the relationship between dorsolateral prefrontal cortex (DLPFC) volume and unawareness. Unawareness was significantly correlated with a smaller right DLPFC volume as compared to those with preserved insight, independently of global cognitive functioning and illness severity. In a recent paper,47 the possible dissociation between specific aspects of unawareness and brain subregions45 was confirmed. The authors demonstrated that the DLPFC was linked to unawareness per se, while Orbito Frontal Cortex (OFC) was linked to symptoms misattribution.
Interestingly, in a different research field, some authors gained important results in order to understand the neuroanatomical basis of unawareness in schizophrenia. Certain data show common cerebral dysfunctions between schizophrenia and dementia with frontal lobes atrophy48 on the one hand, and common deficits between schizophrenia and dementia in tests for frontal or executive functions on the other.49 These data reinforce the idea of a close relationship between unawareness in schizophrenia and frontal lobes.