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59

Section 2

The neurology of schizophrenia

Serge A. Mitelman, Jane Zhang, and Monte S. Buchsbaum
Acknowledgments
: This work was supported by
circulation-borne products of the liver and pancreas
NIMH grants P50 MH 66392–01, MH 60023, and

have made blood chemistry sampling and postmortem
MH 56489 to Dr. Buchsbaum and by NARSAD

assessment fruitful approaches, the regional com-Young Investigator and NIMH MH 077146 awards to
plexity and behavioral productions of the brain have
Dr. Mitelman.

made these methods less informative for the brain,
the target organ of schizophrenia. In this review, we
Facts box

describe brain–function research in psychiatry from
its inception with the electroencephalogram (EEG)
1. Functional imaging has shown decreases in

to the current advances in regional metabolism,

resting activity and the amount of activation

blood flow, receptor chemistry, and most recently,
by cognitive tasks in the frontal lobe,

the deficiencies in the dynamic connectivity of

temporal lobe, cingulate gyrus, and thalamus

circuits.

in schizophrenia.

2. Decreases in activity appear in regions that

Electroencephalography, cerebral

also show decreases in volume when

anatomical imaging techniques are used.

blood flow, and the earliest functional

3. The underlying etiology and pathogenesis of

imaging of schizophrenia

these activities and volume changes remain

Among the earliest observations in Jena, Germany, of
unclear.

Hans Berger, the developer of the electroencephalo-4. Psychotic symptoms include auditory and
gram, was the observation of diminished occipital
visual hallucinations, paranoid delusions or

alpha activity in patients with schizophrenia
[1].
This
paranoid trends, ideas of reference, ideas of

reduction in smooth rhythmic resting activity over
influence, catatonia, and atypical features

the visual cortex, which is observed in normal indi-such as complex perceptual distortions.

viduals when they open their eyes, is consistent with
Although a link between psychotic

modern computer analysis of the electrical signals
symptoms and basal ganglia, temporal lobe,

and with concepts of heightened sensory responsive-and frontal lobe pathology is supported,
ness, the symptoms of hallucinations, and complex
symptoms appear to be variable after the

regional changes in brain function seen in schizophre-onset of neuronal damage, and remission has
nia. The earliest cerebral blood oxygen and glucose
also been reported.

studies by Joseph Wortis and colleagues
[2]
at Belle-5. Treatment is largely symptomatic but links
vue Hospital in New York assessed arteriovenous dif-between brain region change and symptom
ference and did not find patients with schizophre-change are being established.

nia to be different from controls. Seymour Kety and
colleagues, in 1948 at the University of Pennsylva-nia, studied cerebral blood flow (CBF) and simi-

Brain function and schizophrenia

larly did not find differences in total CBF, but sug-Instruments for observing and assessing organ
gested that regional blood flow abnormalities might
function have been technical eye-opening scientific
exist
[3].The
current regional approach to brain imag-advances in understanding of disease in the last 100

ing in schizophrenia began with the work of David
60

years. Although the uniform tissue composition and
Ingvar and coworkers in Lund, Sweden
[4]
who

Chapter 5 – Functional neuroimaging in schizophrenia

Figure 5.1
Hypofrontality: individual
unmedicated patient with schizophrenia

showing areas in prefrontal cortex (including

Brodmann areas 10, 47, 9, 46) with relative

metabolic rate two standard deviations below

the normal control comparison group.

introduced regional functional imaging and staged
remains to be elucidated, for although hypofrontality
cognitive tasks to identify specific brain regions acti-has been demonstrated in neuroleptic-na¨ıve patients
vated by different mental activities and initiated the
[25],
treatment with antipsychotic agents may con-current direction of research in functional brain imag-tribute to its severity
[26].

ing in schizophrenia.

The newly emergent imaging technologies have