Scientists Search for Roots Of Apathy in Schizophrenia

Some people seem to be so alive, so alert, whereas others appear to be so inert, so indifferent. And all too often, persons with schizophrenia fall into the latter category. Apathy, in fact, is a common negative symptom of schizophrenia, one that is tough to alter medically.

Yet what is the origin of schizophrenia apathy? Robert Roth, Ph.D., a clinical associate and instructor in psychiatry at Dartmouth Medical School’s Neuropsychology and Neuroimaging Program, and colleagues conducted a preliminary study to find out. Apathy appears to be related to abnormally small frontal lobes, they reported in the January American Journal of Psychiatry.

“Our findings thus suggest that apathy in schizophrenia is due to a brain abnormality,” Roth told Psychiatric News “and is not simply the product of, as society so often unfortunately assumes, laziness, lack of motivation, or being oppositional.”

The study Roth and his coworkers conducted included 18 subjects with schizophrenia or schizoaffective disorder who exhibited little or no apathy; 20 subjects with schizophrenia or schizoaffective disorder who exhibited severe apathy; and 12 healthy comparison subjects. Apathy grouping was based on scores achieved on the Scale for the Assessment of Negative Symptoms.

The low-apathy and high-apathy groups were similar as far as age, handedness, gender, and depression scores were concerned, although the high-apathy group did score higher on positive symptoms than did the low-apathy group. Healthy comparison subjects were comparable to the low-apathy and high-apathy subjects as far as age, handedness, and gender were concerned.

Probing Biology of Apathy

Roth and his colleagues used structural magnetic resonance imaging to measure the sizes of the frontal, temporal, and parietal lobes in both the left and right hemispheres of all 50 subjects. They then compared the sizes of the lobes.

Both low-apathy and high-apathy subjects had somewhat smaller left and right parietal lobes than did the healthy control group, but the difference was not statistically significant. Both the low-apathy and high-apathy subjects had smaller left temporal lobes and right temporal lobes than did the healthy control group, and this difference was statistically significant.

But what was especially noteworthy is that the high-apathy subjects—but not the low-apathy subjects—had significantly smaller left and right frontal lobes than did the healthy control subjects. Thus, it looks as if having smaller left and right frontal lobes is linked to the apathy exhibited by many people with schizophrenia.

But what regions in the frontal lobes might actually give rise to this apathy? “We are continuing to enlarge our sample of persons with schizophrenia and healthy controls in order to permit a more detailed look at structural MRI and functional MRI brain changes that may underlie apathy in schizophrenia,” Roth told Psychiatric News. “In particular, we are interested in determining whether specific regions within frontal-striatal circuitry may be involved, as well as testing the hypothesis. . .that apathy may be related to abnormal processing of novel stimulation.”

Apathy and Psychological Functioning

In addition to exploring the biological origins of schizophrenia apathy, the researchers also probed the effects of apathy on psychological functioning. Roth and his team gave all 50 of their subjects neuropsychological tests to see how the three groups compared. Both the high-apathy group and low-apathy group, they found, performed worse than did healthy controls on I.Q., visuomotor speed, verbal learning, and verbal recall. However, the high-apathy group scored even worse in these areas than the low-apathy group did. These findings held when depression or severity of psychopathology in schizophrenia subjects were taken into consideration.

Thus, when schizophrenia patients have apathy as a prominent symptom, it looks as if the inertia they experience intensifies problems they may have already had with I.Q., visuomotor speed, verbal learning, or verbal recall.

The study was financed by the National Alliance for Research on Schizophrenia and Depression (NARSAD), the Ira DeCamp Foundation, and the New Hampshire Hospital.

The study, “Apathy in Schizophrenia: Reduced Frontal Lobe Volume and Neuropsychological Deficits,” is posted online at http://ajp.psychiatryonline.org/cgi/content/full/161/1/157?. ▪

Am J Psychiatry 2004 161 157