Disorders of Awareness in Neuropsychiatric Syndromes: An Update

Laura A. Flashman, PhD

Address Neuropsychology Program, Department of Psychiatry, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA. E-mail: Laura.A.Flashman@dartmouth.edu Current Psychiatry Reports 2002, 4:346353 Current Science Inc. ISSN 1523-3812 Copyright 2002 by Current Science Inc.

Impaired awareness has been reported in a number of neuropsychiatric disorders. The purpose of this review is to provide an update on the current understanding of impaired awareness in neuropsychiatric syndromes, including Alzheimers disease (AD), Parkinsons disease (PD), Huntingtons disease (HD), traumatic brain injury (TBI), schizophrenia, mood disorders, and obsessive-compulsive disorder (OCD). Unawareness of illness or deficits can have important diagnostic, treatment, and functional implications, and further understanding of its clinical and neural correlates will be extremely helpful in mediating its impact. Nevertheless, the area of unawareness has received relatively little attention as compared with other manifestations of neuropsychiatric illness. Evidence supporting a role for the involvement of frontal and parietal lobes across disorders is presented. Although most research has used neuropsychologic measures to assess brain functioning, more recent, limited literature in AD and schizophrenia has begun to examine neural correlates of unawareness using structural and functional imaging.

and has a significant impact on an individuals willingness to participate in treatment or rehabilitation. Although awareness deficits have frequently been attributed to psychologic mechanisms in these populations, poor insight in neuropsychiatric disorders shares a number of common features with anosognosia in neurologic disorders. It has been suggested that unawareness of illness in neurologic disorders might serve as a model for understanding unawareness of illness in these populations. There have been several hypotheses about the brain mechanisms that may be involved in neurologic anosognosia. For example, one theory attributes neurologic anosognosia to right hemisphere areas of the parietal lobes and its connections [1]. It has been hypothesized that neurologic unawareness may result from an interaction between frontal system impairment, which compromises the ability to self-monitor, self-correct, and draw proper inferences, and parietal lobe dysfunction, which affects the complex integration of various sensory input [2]. The appropriateness of this neurologic model for explaining the awareness deficits seen in other disorders has been controversial. Further, it has become clear that unawareness of illness is not a unitary concept, but rather can be conceptualized as composed of distinct dimensions and components. Unawareness of illness or deficits can have important diagnostic, treatment, and functional implications, and further understanding of its clinical and neural correlates may be extremely helpful in mediating its impact. The purpose of this review is to provide an update on the current understanding of impaired awareness in neuropsychiatric syndromes.

Introduction
Impaired awareness has been reported in a number of neuropsychiatric disorders. In addition to the frank unawareness of symptoms or deficits ( ie, neurologic anosognosia) reported following cerebrovascular accidents, a recent literature review identified articles related to this topic in patients with Alzheimers disease (AD), Parkinsons disease (PD), Huntingtons disease (HD), traumatic brain injury (TBI), chronic alcoholism, schizophrenia, affective disorders, and stress. In addition, incidents of denial or unawareness were reported in other medical disorders such as breast cancer, heart disease, and HIV or AIDS. It can be seen that impaired awareness is very common across disorders. Unawareness of illness or deficits contributes to excessive disability in these patients,

Impaired Awareness in Healthy Individuals

It is important to note that even healthy individuals engage in inaccurate self-representation at times, which is not always deliberate or conscious. The cognitive distortions displayed by healthy individuals are believed to represent a normal pattern of functioning, and have been positively linked to well being and positive self-esteem [3]. Research has suggested that such self-deception is most likely to occur when 1) there is a lack of concrete information (ie, one is making predictions about the future or recalling certain information from the past), and 2) the motivation to self-deceive is high (ie, one wants to make a good impression on someone, or believes strongly in his or her

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abilities and capabilities). Sackeim and Wegner [4] found that normal control individuals use self-serving biases in their appraisals of their behaviors and outcomes, as follows: If an outcome is positive, I controlled it, I should be praised, and the outcome was very good. If an outcome is negative, I did not control it (as much), I should not be blamed, and it was not so bad anyway. Individuals with neurologic or psychiatric impairments may also use this defense mechanism in every day life; however, the unawareness of symptoms discussed in this review is significantly different in both its magnitude and pervasiveness, and is likely a distinct, neurologically driven phenomenon.

depressed mood when evaluating the relationship between dementia severity and unawareness. Relationship of awareness deficits to neural correlates of Alzheimers disease Unawareness of deficits found in AD has been hypothesized to be associated with the disruption of frontalsubcortical system circuitry. Imaging studies have suggested that unawareness in AD is associated with right frontal hypoperfusion. For example, Reed et al. [12] found rightsided dorsolateral frontal regional cerebral blood flow (rCBF) hypometabolism in patients with AD who manifested unawareness. Single photon emission computed tomography (SPECT) studies [8,21] have also indicated abnormalities. Starkstein et al. [21] reported a decrease in the rCBF to the frontal inferior and superior (dorsal) areas of the right hemisphere. Derouesne et al. [8] found that perfusion deficits in AD patients with unawareness were most frequently seen in parietotemporal regions, and with predominate right hemisphere involvement. The relationship between impaired insight and neurocognitive deficits has been less consistent. Several studies have reported a relationship between unawareness of deficits and cognitive decline [11,22,23]. Decreased performance on frontal or executive measures has been reported in patients with AD who are unaware of their deficits [16,17,19,22,24]; however, other studies have failed to find a significant relationship between unawareness and frontal lobe dysfunction [15,18,25]. Parkinsons disease Parkinsons disease has a different anatomic-pathologic substrate than AD, and a comparison of awareness deficits in these two groups might help elucidate the neural basis of unawareness. In one such study [25], patients with AD were noted to show more severe anosognosia and disinhibition than patients with PD, which further suggests that these deficits may be related to more severe frontotemporal cortical dysfunction. A recent study [26] compared patients with AD and PD in terms of their awareness of cognitive, emotional, and motor-related neurologic deficits, by comparing patient self-reports and caregiver ratings. Although both groups of patients rated themselves as less impaired than their caregivers did, there were differences in terms of the ratings between the two groups. For example, patients with AD were more likely to be unaware of their cognitive skills; patients with PD and their caregivers did not differ significantly on their ratings of cognitive impairment. Both groups displayed impaired awareness of motor-related neurologic functioning. Of note, impaired awareness in PD (but not AD) was associated with poorer overall cognitive functioning, and performance on tests measuring memory, attention, and constructional ability. In another study, Vitale et al. [27] evaluated unawareness of levodopa-induced dyskinesia, and found a significant relationship between unawareness

Unawareness in Dementia
Alzheimers disease Unawareness of deficits is commonly reported in individuals with AD. When present, lack of insight can range from very mild (eg, acknowledgment of memory impairment but minimization of its severity) to very severe (eg, claims of good or very good memory skills). Further, there is some evidence to suggest that in the AD population, awareness of psychiatric and behavioral problems may be more preserved relative to awareness of cognitive impairment [5]. As has been noted previously, unawareness is a complex phenomenon that cannot be easily characterized as present or absent, because of its multiple dimensions [6]. Relationship of awareness deficits to disease severity and other clinical correlates Little evidence has been found for a relationship between unawareness and a number of demographic variables, such as education, age at onset, or duration of illness [7]. Evidence for a relationship between unawareness and age has been inconsistent, with both a positive relationship ( see [8]) and no relationship between decreased awareness and age [7,9] being reported. A recent study by Harwood et al. [9] examined the relationship of unawareness to psychiatric and behavioral disturbances, and found that insight was positively associated (ie, greater insight, more symptomatology) with symptoms of affective distress, and negatively associated (ie, less insight, greater symptomatology) with symptoms of hostility, agitation, inattention, and tension. Anxiety and apathy have also been reported to be associated with unawareness [8]. Depression has been examined in several studies, with mixed findings [1013]. Evidence of a link between severity of dementia and unawareness has been equivocal [7,14]; some studies suggest that impaired insight increases with dementia severity (see [1517]), and others fail to support this finding [10,12,18,19]. A more recent study by Smith et al. [20] suggested that depressive symptomatology may confound the relationship between unawareness and symptom severity, and argued for the importance of considering

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of standing and hand pronation-supination difficulties (measured by the Unified Parkinsons Disease Rating Scale) and scores on the Abnormal Involuntary Movement Scale (the greater the impairment, the more unawareness). Huntingtons disease Patients with HD frequently demonstrate denial of symptoms and an unawareness of the motor, cognitive, and emotional changes that accompany the disease. Although earlier work focused on the psychologic underpinnings of this denial [28], more recent studies have identified neurologic correlates of this unawareness [29]. For example, Deckel and Morrison [29] used a self-report measure in patients with HD, and asked them to rate their cognitive and motoric abilities. Two staff members provided independent ratings of the patients abilities. Based on the difference between self- and staff-ratings, patients were divided into those with high and low awareness. Patients with poorer awareness of their symptoms were found to perform more poorly on a number of neuropsychologic measures, including the Wisconsin Card Sorting Test (WCST) and picture completion from the Wechsler Adult Intelligence Scale, Revised, and also demonstrated larger verbal intelligence quotient (IQ) or performance IQ splits. This study provided evidence of impaired prefrontal functioning, and possible right hemisphere dysfunctioning in patients with greater unawareness of their symptoms. Vitale et al. [27] also examined unawareness of involuntary movements in patients with HD, and found significant correlations between unawareness, disease duration, and severity.

or behavior such as irritability, impulsivity, and affective instability that are reported by relatives [31,32]. Relationship of awareness deficits to injury severity Although the initial severity of TBI, as measured by Glasgow Coma Scale (GCS) score on admission, has been related to patients psychosocial outcomes [33,34] and long-term performance on neuropsychologic tests [35,36], the relationship between initial GCS scores and awareness deficits is less clear. Prigatano and Altman [37] found no relationship between admission GCS scores and later lack of awareness in TBI, although others have found a significant inverse correlation between admission GCS score and later impaired awareness (ie, the more severe the injury, the greater the unawareness) [38,39]. Clinicians working to rehabilitate individuals with TBI report that unawareness is a major factor in determining longterm functional recovery, including eventual return to work [4043]. These data provide strong, though not unqualified, evidence of a positive association between deficits in awareness and poor employment outcome following TBI. Relationship between awareness deficits and injury profile in traumatic brain injury It is not surprising that awareness deficits of various types are a common and challenging problem in individuals with TBI. The typical profile of brain injury in accelerationdeceleration injuries includes contusions in the both the dorsolateral and orbitofrontal regions of the frontal lobe, and related circuitry (subcortical white matter, basal ganglia, and thalamus), as well as in the anterior and inferior temporal regions. In moderate and severe TBI, diffuse axonal injury, particularly evident in the corpus callosum, the superior cerebellar peduncle, the basal ganglia, and the periventricular white matter, occurs. Stuss [1,44] has suggested that the frontal lobes, or, perhaps, frontal systems, play a critical role in the maintenance of full awareness (including self-awareness, self-reflectiveness, and self-monitoring), although the knowledge of specific deficits is associated with posterior brain functions. An important component of the indifference often manifested by patients with unawareness may relate to selective inattention or neglect. Watson et al. [45] suggested that lesions in several interconnected regionsincluding the midbrain reticular formation, selected thalamic nuclei, and frontal cortex may result in problems with neglect, or the motor intention system, and could result in an individual appearing somewhat unconcerned by obvious deficits. The frontal lobes also may be important, as they play a role in the affective response to a given stimulus. For example, individuals with dorsolateral frontal injury often display muted, bland, apathetic responses to significant stimuli. Thus, there is significant overlap between the brain regions that play a role in awareness, and those regions most commonly involved in TBI. The known role these

Unawareness of Deficits in Traumatic Brain Injury

Individuals who have sustained a TBI are not always aware that significant changes that have occurred in functioning are consequences of the TBI, or even that there have been significant behavioral or cognitive changes. Up to 45% of individuals with moderate to severe TBI demonstrate awareness deficits [30]. Failure to recognize cognitive, emotional, and behavioral limitations or impairments may be one of the most disabling effects of TBI. Such unawareness is often permanent and can be an enormous impediment to successful rehabilitation. Furthermore, as noted in patients with AD, deficits in awareness can be function specific. Many can accurately assess their physical status, but are less reliable in their assessment of their capacity for sound judgment, cognitive skills, interpersonal skills, and other aspects of social behavior. Unfortunately, lack of awareness of cognitive deficits, personality changes, and abnormal behavior are commonly observed sequelae, particularly of moderate to severe TBI. In general, although patients exhibit some awareness of their intellectual, memory, and speech deficits, they rarely acknowledge the changes in personality

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regions play in cognition and behavior, self-monitoring, self-awareness, and other meta-cognitive processes, make it readily apparent why challenging behaviors, coupled with failure to acknowledge the significance of those behaviors, inappropriate response to the behaviors, and difficulty comprehending the implications of these behaviors and other deficits, are such a common and vexing problem in individuals with TBI.

Unawareness of Illness in Schizophrenia

It has been suggested that the majority of patients with schizophrenia demonstrate unawareness of their illness, including difficulty identifying their symptoms and recognizing that they have a mental disorder. This unawareness can impact significantly on treatment compliance. Several explanations of unawareness of illness in schizophrenia have been proposed, including psychologic defense mechanisms, cultural differences, and neuropsychologic impairment [46]. It has been noted that neurologic unawareness (ie, anosognosia) may be comparable with unawareness in schizophrenia [47]. Poor insight in schizophrenia shares a number of common features with anosognosia; for example, both are largely resistant to direct confrontation, and delusional explanations are often provided to explain circumstances such as hospitalization [48]. Relationship of awareness deficits to disease severity and other clinical correlates The relationship between symptoms of schizophrenia and unawareness of illness remains unclear, although it has been reported in 67% to 89% of patients with schizophrenia. Unawareness in schizophrenia does not appear to be associated with gender, ethnicity, or age at onset of illness. It does not appear to be consistently associated with epidemiologic variables, neurologic signs, or positive and negative symptoms [46,48,49]. Lower levels of depression have been reported to be associated with greater unawareness of illness [50,51]. There is some literature to suggest that unawareness of illness may correlate with the severity of psychosis [52], although the relationship is rather weak. Others have not found any relationship between unawareness of illness and global severity of psychopathology [49,53,54]. Of note, deficits of awareness are associated with poorer medication compliance, poorer prognosis, and response to treatment, and poorer social and vocational functioning. Relationship of awareness deficits to neural correlates Several studies have found a modest inverse correlation between unawareness of illness and overall IQ [49,55,56], although the literature does not support the notion that unawareness of illness is simply a function of global cognitive impairment [48,57]. Studies specifically examining the hypothesis of frontal lobe involvement in unaware-

ness of illness have yielded inconsistent findings, with reports both supporting [5861] and failing to support [57,62,63,64] this hypothesis. Finally, McEvoy [65] and Flashman (unpublished data) reported significant correlations between unawareness of illness and performance on parietal lobe tests. There is very little work to date examining the relationship between brain anatomy and unawareness of illness ( see Table 1 for a review). The author examined the relationship between lobar volumes and unawareness of illness in schizophrenia, using several measures of awareness from the Scale to Assess Unawareness of Mental Disorders (SUMD) [66], and hypothesized frontal and parietal lobe involvement. No relationship between awareness and lobar volumes was found, although a significant correlation between awareness and whole brain volume was found. That is, patients with unawareness of illness were found to have smaller brain size and intracranial volume (ICV) than patients with schizophrenia who were aware of their symptoms. However, lobar volumes may not be sensitive to subtle frontal and parietal lobe subregion differences, and there are now more refined methods to explore the structural correlates of unawareness. Examination of frontal lobe subdivisions [67] indicated large significant inverse correlations (P0.01) between level of awareness and bilateral middle frontal gyrus volume when intracranial volume was used as a covariate, indicating that greater levels of unawareness were associated with smaller middle frontal gyri. This implicates the dorsolateral prefrontal cortex, known to be involved with deficits in working memory (WM) [68]; patients with schizophrenia have been shown to demonstrate impairment on WM tasks (eg, WCST, N-back) both during cognitive assessment [69,70] and during functional imaging [7173]. In contrast, misattribution of symptoms was significantly negatively correlated with bilateral superior frontal gyrus, indicating that patients with smaller superior frontal gyri were more likely to attribute their symptoms to reasons other than mental illness (Table 1).

Unawareness of Illness in Mood Disorders

There has been some question as to whether awareness deficits are more common or severe in patients with schizophrenia than in patients with mood disorders. At least two studies have reported no difference between patients with schizophrenia and patients with bipolar disorder [74,75], although both of these groups were found to have poorer insight compared with patients with schizoaffective disorder and major depression. Peralta and Cuesta [76] found that patients with mania (with and without psychosis) had more severe awareness deficits compared with patients with depression, and patients with psychotic depression had poorer insight compared with depressed patients without psychosis. Ghaemi et al. [77] found that insight was similarly impaired, to a degree

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Table 1. Studies examining the relationship between unawareness of illness in schizophrenia and structural findings Authors Takai et al. [89] David et al. [49] Morgan et al. [90] Flashman et al. [66] Flashman et al. [67] Sample size, n 22 128 82 30 16 Patient sample Chronic schizophrenic inpatients Mixed, acute psychotic patients First-episode psychotic patients Acute schizophrenia and schizoaffective disorder Acute schizophrenia and schizoaffective disorder Significant correlations Increased VBR (MRI) None (CT) Volume differences in cingulate gyrus and left insula grey matter (MRI) Smaller whole brain volumes (MRI) Smaller bilateral middle frontal gyrus, right gyrus rectus, left cingulate (MRI)

CTcomputed tomography; MRImagnetic resonance imaging; VBRventrical to brain ratio.

greater than in anxiety disorders, in bipolar and unipolar major depressive disorders. Relationship of awareness deficits to disease severity and other clinical correlates Weiler et al. [75] reported that many patients show improved insight as their acute symptoms improve. Studies that have examined different subtypes of bipolar disorder [78] indicate that there are differences in awareness profiles. For example, DellOsso et al. [78] reported that among bipolar patients with psychotic features, the mania group had poorer insight into the social consequences of their illness compared with the mixed mania and depressed groups, and less insight regarding their impaired attention and judgment than did the depressed group. Overall level of insight into illness significantly discriminated the mixed mania from the mania group, but not from the depressed group. Pallanti et al. [79] examined awareness of illness in patients with bipolar type I and bipolar type II disorder, and found that patients with bipolar II disorder had significantly more awareness deficits than patients with bipolar I disorder. Ghaemi et al. [80] reported little change in awareness scores in acutely manic patients from admission to discharge, despite marked improvement in other psychiatric symptoms. In another study, they found that initial awareness deficits did not correlate with poor outcome in patients with affective and anxiety disorders, although improvement in awareness correlated with better outcome, particularly in patients with bipolar I disorder [77]. In summary, these studies suggest that the literature on unawareness in patients with bipolar disorder is unclear, although mania appears to be associated with greater awareness deficits, and bipolar II patients may be more impaired than patients with bipolar I. Relationship of awareness deficits to neural correlates Little work has been done examining the neural correlates of awareness in mood disorders. In a preliminary study of bipolar patients with acute mania who received neuropsychologic evaluation, no correlations were found between awareness and cognitive performance [81].

Unawareness of Illness in ObsessiveCompulsive Disorder

Several studies have addressed the issue of unawareness in patients with obsessive-compulsive disorder (OCD) [8286]. Again, several types of awareness deficits have been identified. By definition, individuals with OCD have recurrent, unwanted obsessions or compulsions that are experienced, at some point during the disturbance, as intrusive and inappropriate [87]. During the diagnosis, there is an opportunity to specify the degree of this insight; the descriptor with poor insight is used if, for most of the time during the current episode, the person does not recognize that obsessions and compulsions are excessive or unreasonable. In addition, individuals with OCD can be assessed in terms of their awareness of how others view their concerns, beliefs, and obsessions. Relationship of awareness deficits to disease severity and other clinical correlates Insel and Akiskal [85] proposed a model suggesting that OCD represents a psychopathologic spectrum varying along a continuum of insight. At the severe end of this spectrum are patients with delusions, certainty that their beliefs are realistic, and poor or no insight. Research suggests that there is a range of insight and awareness in OCD, and that deficits in awareness are significantly less prevalent in this population than in individuals with schizophrenia. For example, when individuals with OCD were compared with patients with schizophrenia on the Brown Assessment of Beliefs Scale [88], patients with schizophrenia were significantly more likely to rate themselves higher in terms of conviction (how certain someone is about their beliefs), explanation of differing views (how one accounts for the discrepancy between ones explanation for a symptom or belief and those of other people), fixity of ideas (how easily can one be convinced that ones beliefs are not accurate), attempts to disprove ideas (how much effort is spent trying to convince ones self that ones beliefs are not accurate), and insight attribution (what has caused you to have these beliefs; are they due to a mental illness?) (Eisen, personal communication).

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Research suggests that 20% to 30% of individuals with OCD report reasonable certainty (ie, poor insight) that their obsessions are realistic or that significant consequences (other than anxiety) will occur if they do not perform their rituals or compulsions [84,85]. Similarly, approximately 25% to 30% report impaired awareness regarding whether other people think their concerns are excessive [84,85]. In an attempt to characterize the demographic and clinical features of patients with OCD and psychotic symptoms, Eisen and Rasmussen [82] identified 67 of 475 (14%) patients with OCD who also had psychotic symptoms. Of those, 27 (40%) were labeled OCD without insight; that is, their only psychotic symptom was lack of insight and high conviction about the reasonableness of their obsessions. At least two studies suggest that insight improves with decreasing OCD symptom severity [83,86]. Eisen et al. [83] further reported that degree of insight at baseline did not predict response to treatment (16 weeks of open-label sertraline).

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: Of importance Of major importance
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Conclusions
Deficits in awareness are very prevalent, and demonstrated across a number of neuropsychiatric disorders. It is one of the most dramatic symptoms manifested by patients, contributes to the disability seen by these patients, and has a significant impact on treatment and rehabilitation. Nevertheless, it is a relatively understudied area relative to other manifestations of neuropsychiatric illness. Evidence from the literature continues to support the notion that awareness is not a unitary concept, and that patients with these disorders can have knowledge of some deficits, and absence of knowledge of other deficits. These features argue against unawareness representing simply a psychologic construct, and suggest a role for brain involvement. Although there is little evidence to support the notion of a central awareness mechanism, there is a body of work that provides evidence of a role for the frontal and parietal lobes across disorders. The majority of this research has used neuropsychologic measures to assess brain functioning. More recently, a small body of literature in AD and schizophrenia has begun to examine neural correlates of unawareness using structural and functional imaging. This work is very exciting and will likely lead to significant advances in the understanding of deficits of awareness in neuropsychiatric disorders.

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