Hypofrontality in Neuroleptic-Naive Patients and in Patients With Chronic Schizophrenia

TLDR

The hypofrontality hypothesis has mixed support in neuroimaging studies, possibly due to sample heterogeneity. The study measured regional cerebral blood flow with xenon‑133 SPECT during a Tower of London task versus a passive viewing control in 13 neuroleptic‑naive, 23 non‑naive, and 15 healthy participants. Patients with schizophrenia, regardless of medication status, showed absent left mesial frontal and right parietal activation during the Tower of London, with deficits linked to negative symptoms, indicating hypofrontality is associated with negative symptoms rather than treatment or chronicity.

Abstract

• The "hypofrontality hypothesis" has been supported by many neuroimaging studies, but not all, perhaps because of heterogeneity of samples. The present study examined three different samples that permitted assessment of a variety of confounders, such as effects of long-term treatment, chronicity of illness, and presenting phenomenology: (1) 13 neuroleptic-naive schizophrenic patients, (2) 23 nonnaive schizophrenic patients who had been relatively chronically ill but were medication free for at least 3 weeks, and (3) 15 healthy normal volunteers. Regional cerebral blood flow was measured using single-photon emission computed tomography with xenon 133 as the tracer. The control condition consisted of looking at undulating colored shapes on a video monitor, while the experimental task was the Tower of London. We observed the Tower of London to be a relatively specific stimulant of the left mesial frontal cortex (probably including parts of the cingulate gyrus) in healthy normal volunteers. Both the neuroleptic-naive and the nonnaive patients lacked this area of activation, as well as a related one in the right parietal cortex (representing the circuitry specifically activated by the Tower of London). Decreased activation occurred only in the patients with high scores for negative symptoms. These results suggest that hypofrontality is related to negative symptoms and is not a long-term effect of neuroleptic treatment or of chronicity of illness.