LA JOLLA, CALIF—Plentiful research in patients with chronic schizophrenia has regularly reported unawareness of at least some part of their disorder in a range of 67% to 89%. Two large studies with cohorts of more than 800 subjects have shown that unawareness of illness was the most prevalent symptom in schizophrenic patients, stated Laura A. Flashman, PhD, at the American Neuropsychiatric Association’s 13th Annual Meeting. “The very significant correlations between unawareness of illness and medical compliance and poor outcome are troubling, as patients who are unaware of illness are less likely to cooperate with treatment plans or accept help from their families, doctors, or treatment team,” she acknowledged. Patients who are unaware of their illness may also attempt to perform activities that are unrealistic given their impairment deficits.

Other work has found significant relationships between awareness and severity of psychopathology scores, duration of illness, and frequency and length of hospitalization, Dr. Flashman reported. “And you may ask why this is important—because it helps us understand the concept of unawareness. If it’s just a reflection of symptom severity, or delusions, or something else that can’t be distinguished, it’s probably not worth all the time and effort I’ve been putting into it. I would prefer to think that unawareness is an independent, phenomenological feature, and that understanding more about it would help us in terms of possible treatment,” she said. Dr. Flashman is an Assistant Professor of Psychiatry at Dartmouth Medical School, Hanover, New Hampshire.

“Obviously, if people don’t think they have a mental illness, they are very unwilling to take medication.” Dr. Flashman went on to explain that the largest single correlation that has been found between schizophrenia and awareness is the relationship with poorer medication compliance. This patient non-compliance has also been associated with poorer prognosis and response to treatment, “whether measured by chronicity, or number of hospitalizations, poorer work or social functioning, and poorer performance on neuropsychological tests.”

AWARENESS AND ATTRIBUTION DEFICITS

In the cohort Dr. Flashman studied, the only significant difference noted between subjects was a slightly higher IQ in the aware group of patients with schizophrenia. Study participants underwent clinical assessment including Structured Clinical Interview for DSM-IV (SCID) for confirmation of diagnosis, the Schedule for Assessment of Positive Symptoms, the Schedule for Assessment of Negative Symptoms, the Brief Psychiatric Rating Scale (BPRS), and the Schedule to Assess Unawareness of Mental Disorders (SUMD). Dr. Flashman noted that for her two studies, patients were divided into aware and unaware groups based on their SUMD scores; a score of 1, 2, or 3 classified the aware group, and a score of 4 or 5 denoted unawareness.

No significant correlation between positive and negative symptoms of schizophrenia and lack of awareness of symptoms was found in this cohort, but the researchers did find a significant correlation between the total BPRS score, a measure of severity of psychopathology, and awareness of symptoms. “So that the more unaware you were, the worse the symptom severity,” she summated.

When asked directly, 43% of the patients demonstrated a lack of awareness of their mental illness. But when the aware group was asked more specifically about their mental illness, Dr. Flashman found that patients would instead describe their schizophrenic spectrum disorder as a less severe illness, such as a bad case of nerves or depression.

She related a case that demonstrated the awareness and attribution deficits often seen in schizophrenia. One patient (male, age 27, 12 years of education) had a low average IQ, a score of 51 on the BPRS (moderate severity), and hallucinations, delusions, bizarre behaviors, and anhedonia. “He was very unaware of the symptoms he had, and thought everything was due to the fact that one day he got pulled over for speeding, and that ‘they’ had targeted him, and he was put under state and federal investigation, and ‘they’ implanted a device in his ear to record and control his movements. They had ruined his life. I was very concerned when he went in for his MRI, as he was dying to see the implanted device. When it didn’t show up, without blinking an eye, he said, ‘Oh well, then it must not be metal.’ Didn’t slow him down a bit.”

A lack of awareness regarding the social consequences of their illness, being hospitalized, having difficulty maintaining employment, or experiencing impairment in their relationships was recognized by only 43% of the patients in the sample. In contrast, 70% of the patients felt that their medication was helping them. But as Dr. Flashman elaborated, “When you asked them how they felt the medications were helping, they described non-specific improvements, such as it helped them calm down or sleep better. Very few people said they liked it because it made their delusions go away.”

Citing a number of studies, Dr. Flashman stated that while 41% of reports show no correlation between neuropsychological performances and any of the awareness measures, 23% of studies showed a correlation between IQ and awareness measures. These results upheld a common hypothesis, that “if you were not bright, it would be easier for you to be unaware of your illness,” she said. A correlation between frontal lobe measures and awareness was found in 41% of studies and “this has really been where the neuropsychiatric money has been—using the Wisconsin Card Sort, the Trail Making, and verbal fluency tests.”

BRAIN MATTERS

Subjects in Dr. Flashman’s study were also given a full, comprehensive neuropsychological battery of tests to measure attention and concentration, memory and visual-spatial abilities, language abilities, motor and sensory functioning, and executive ability. The tests were divided into those thought to be measures of frontal lobe functioning and those thought to measure parietal lobe functioning. It was found that aware patients performed somewhat better on the parietal lobe index than the unaware group. “There is also some evidence to suggest frontal lobe and parietal lobe involvement both with neuropsychiatric measures and with some anatomical tracings,” she allowed.

In addition, although there was no correlation demonstrated between the frontal parietal lobe index and lack of awareness, there was a correlation between a number of the tasks that assessed frontal lobe functioning, such as Trail Making B (which has been reported); a correlation between unawareness of the social consequences of illness and left-handed finger tapping was also seen.

Data from the same 30 patients were also examined by Dr. Flashman to explore a possible relationship between unawareness and brain volume. Consistent with other literature, no group differences in terms of severity of illness or intellectual ability were found in the high- versus low-awareness group. But, she continued, patients with lack of awareness of illness demonstrated smaller overall brain size and less intracranial content than either subjects with awareness of their mental illness or the healthy controls. “This was evidence that suggested to us that perhaps something different was going on in the brains of these patients. We also found that bilateral frontal volumes correlated with level of awareness of current symptoms, and there was a modest correlation between right parietal lobe volume and level of awareness of illness.”

Concerned that examining the whole lobe volumes was too gross and not specific, Dr. Flashman also assessed subregions of the frontal lobe and possible correlations with unawareness of illness. She divided 16 subjects into two groups and found a significant inverse correlation between the middle central gyrus and awareness of symptoms; for example, the correlation between unawareness and the volume of the right frontal middle gyrus was .92. “Although there was a small number of subjects, even when we used a more conservative alpha value the correlates remained significant. There were strong correlations between the superior frontal gyrus and attribution of symptoms. So, awareness of symptoms correlated with middle frontal gyrus, and attribution correlated with superior frontal gyrus; in both cases, unawareness and misattribution were associated with smaller volume estimates, that is, the more unaware, the smaller the brain region,” she reported.

THE GOOD, THE BAD, THE UNAWARE …

“The good news is that we’re starting to understand some of the correlates associated with unawareness of illness in patients with schizophrenia. The bad news is we’re not done yet, and the hardest part is going to be to figure out how to deal with unawareness and its relationship to treatment,” Dr. Flashman concluded. “It’s pretty clear that insight or awareness is a multidimensional construct, and what part you’re looking at may influence the results that you find,” she cautioned. There is some evidence that unawareness is an autonomous entity, independent of symptom severity, Dr. Flashman revealed, and that poor insight will often persist even if other clinical features improve.

Lack of awareness of negative symptoms was most significant in terms of impact on outcomes, according to the researchers. That is, while the presence of insight does not predict good outcomes, unawareness has been shown to predict poor outcomes. How can clinicians use awareness deficit in treatment planning? “It might give you an idea who is going to be cooperative and compliant and for whom you’ll have to spend a little more time coming up with clever ways to treat. It gives you an indication of how reliable a patient is going to be as an informant because you have some idea of how accurately they’re able to assess their own performance.” Dr. Flashman advised that “therapies that are aimed at increasing insight should probably target specific aspects of awareness. The focus might be on engaging patients with psychoeducation as further research bears out that it’s a helpful way to work. You might need different strategies for different symptoms. You might use a goal that is important to them, such as remaining out of the hospital, as a hook, without forcing them to recognize or directly acknowledge their unawareness.”

—Heidi W. Moore

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