958

Am J Psychiatry 158:6, June 2001

BRIEF REPORTS

4. Manoach DS, Gollub RL, Benson ES, Searl MM, Goff DC, Halpern

E, Saper CB, Rauch SL: Schizophrenic subjects show aberrant
fMRI activation of dorsolateral prefrontal cortex and basal gan-
glia during working memory performance. Biol Psychiatry
2000; 48:99–109

5. Cohen JD, Perlstein WM, Braver TS, Nystrom LE, Noll DC,

Jonides J, Smith EE: Temporal dynamics of brain activation dur-
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man Brain. New York, Thieme Medical, 1988

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ness in schizophrenia: now you see it—now you don’t! J Clin
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Brief Report

Cerebral Phosphate Metabolism in First-Degree Relatives

of Patients With Schizophrenia

Silke Klemm, Ph.D.
Reinhard Rzanny, Ph.D.
Stephan Riehemann, Ph.D.
Hans-Peter Volz, M.D.
Beate Schmidt, M.D.
Uwe-Jens Gerhard, M.D.
Christina Filz, M.A.
Anke Schönberg
Hans-Joachim Mentzel, M.D.
Werner A. Kaiser, M.D.
Bernhard Blanz, M.D.

Objective: Most phosphorus-31 magnetic resonance spectros-
copy (

31

P-MRS) studies have described measures of lower mem-

brane anabolism or greater catabolism in the frontal lobes of

patients with schizophrenia. The purpose of the present study

was to evaluate whether these findings can also be detected in

young subjects at genetic risk for schizophrenia.

Method: Fourteen children and siblings of patients with

schizophrenia (mean age=16.7 years) and 14 comparison sub-

jects (mean age=16.9 years) were included in a

31

P-MRS study of

the frontal lobe.

Results: The high-risk subjects had significantly lower mean ra-

tios of phosphomonoesters to phosphodiesters (0.25 versus

0.31) and higher mean phosphodiester values (37.59% versus

34.87%) than comparison subjects.

Conclusions: These findings suggest greater phospholipid

breakdown even in young first-degree relatives of patients with

schizophrenia. This suggestion is discussed with respect to the

membrane phospholipid hypothesis of schizophrenia.

(Am J Psychiatry 2001; 158:958–960)

S

chizophrenia is considered a neurobiological disor-

der. The examination of relatives of subjects with schizo-
phrenia is one approach in the effort to find the fundamen-
tal neurobiological characteristics more directly linked to
gene expression. In recent years, a neurobiochemical para-
digm of disturbed membrane phospholipid metabolism
has been established for schizophrenia (1). Corresponding
to this hypothesis, most phosphorus-31 magnetic reso-
nance spectroscopy (

31

P-MRS) studies have found lower

levels of phosphomonoesters (suggesting reduced phos-
pholipid building processes) and higher levels of phos-
phodiesters (indicating greater phospholipid breakdown)
in the frontal lobes of adult patients experiencing their first
episode of schizophrenia and neuroleptic-naive adult pa-
tients with schizophrenia (2, 3). In contrast, lower phos-
phodiester levels were observed in chronically ill but neu-
roleptic-naive patients with schizophrenia (4).

Early-onset schizophrenia has a dismal prognosis (5).

Therefore, it is important to detect subjects at risk as early
as possible. So far, only a few proton magnetic resonance
spectroscopy (

1

H-MRS) studies in first-degree relatives of

patients with schizophrenia (6, 7) and in young subjects
with symptoms of schizophrenia spectrum disorders (8, 9)
have shown results that can be interpreted as suggesting
higher membrane catabolism in several brain regions.
This possible vulnerability is a phenomenon of distinct di-
mensions and triggered by genetic conditions as well as
environmental influences. Therefore, we hypothesize that
young subjects at genetic risk for schizophrenia have a
membrane phospholipid imbalance with higher phos-
phodiester levels and/or lower phosphomonoester levels.

Method

Fourteen children or siblings of patients hospitalized for a

schizophrenic disorder diagnosed according to DSM-III-R crite-

Am J Psychiatry 158:6, June 2001

959

BRIEF REPORTS

ria and 14 comparison subjects who were matched for age, sex,
and diagnosis were examined. The mean age of the first-degree
relatives of patients with schizophrenia was 16.7 years (SD=1.9);
four were male and 10 were female. The mean age of the compar-
ison subjects was 16.9 years (SD=2.6); four were male and 10 were
female.

The psychiatric status of subjects in both groups was deter-

mined by using the Schedule for Affective Disorders and Schizo-
phrenia (10) or the Schedule for Affective Disorders and Schizo-
phrenia for School-Age Children (11). Potential comparison
subjects with a first- or second-degree relative showing any
schizophrenic symptoms were excluded, as were those suffering
from an internal or neurological disorder, schizophrenic or affec-
tive symptoms, or substance abuse and subjects under dietary re-
strictions. Two subjects in each group had an adjustment disorder.

The study was approved by the ethical commission of the Uni-

versity of Jena. After a full explanation of the procedure, written in-
formed consent was obtained from the children and their parents.

The

31

P-MRS procedure was performed with a 1.5-T magnetic

resonance tomograph (Philips Gyroscan ACS II); we used a

31

P-

quadrature head coil. An image-selected in vivo spectroscopy se-
quence (12) with double volume-selective adiabatic high-fre-
quency pulses was performed. The standard sequence (repetition
time=3000 msec, sampling rate=2 kHz, sampling time=0.5 seconds,
number of sampled points=1,024) was used. The regions of interest
were placed bilaterally in the frontal region with a mean size of 28

×

28

×

50 mm

3

each. Magnetic field homogeneity was shimmed be-

fore the measurement over an area containing both acquired re-
gions of interest with respect to the

1

H line (full width at half maxi-

mum

<

15 Hz). The examination happened simultaneously in both

volumes and was averaged over 768 measurements.

An iterative nonlinear least-square fit in the frequency domain

(total line-shape analysis, implemented in Peak Research
[PERCH] software [13]) was used to analyze all spectra. The spec-
tra were evaluated independently by two investigators without
any knowledge of the proband status (S.R. and S.K.). Interrater re-
liability for phosphodiester and phosphomonoester values was
between 0.86 and 0.90. We used the nonparametric Mann-Whit-
ney U test to determine statistical differences between the
groups, focusing our special attention on phosphodiester and
phosphomonoester measures.

Results

Table 1 presents the

31

P-MRS measures for the two

regions of interest combined. The total percent of phos-
phodiesters was significantly higher and the total phos-
phomonoesters-phosphodiesters ratio was significantly
lower in the high-risk group than in the comparison
group. The median values were not influenced by outliers,

but the spread of phosphodiester values was greater in the
high-risk group. The high-energy phosphate phosphocre-
atine level, ratio of phosphate phosphocreatine to adeno-
sinetriphosphate, inorganic phosphate, and pH values
were similar in both groups.

Discussion

The higher phosphodiester levels and lower phospho-

monoesters/phosphodiesters ratios could correspond to a
greater phospholipid breakdown in the subjects at genetic
risk for schizophrenia. This main result is in accordance
with the findings in unmedicated, first-episode patients
with schizophrenia and in subjects genetically at risk for
schizophrenia assessed by

1

H-MRS (6, 7). To our knowl-

edge, this is the first study to detect an altered phospho-
lipid membrane metabolism in a young genetic high-risk
group. Under the assumption that the higher phosphodi-
ester levels are caused by phospholipid breakdown prod-
ucts (contradictory results were presented in references 14
and 15), the higher phospholipid catabolism may be an in-
termediate phenotype of schizophrenia. However, this ev-
idence is limited because of the small number of subjects
investigated. Obviously, only longitudinal studies would
be able to show whether these alterations are subclinical
phenomena of the schizophrenic prodromal phase or vul-
nerability indicators. It is also necessary to determine the
specific and the potential relative contribution of these al-
terations to the schizophrenic disorder.

Received June 8, 2000; revision received Jan. 4, 2001; accepted Jan.

11, 2001. From the Department of Child and Adolescent Psychiatry,
Department of Psychiatry, Institute of Diagnostic and Interventional
Radiology, University of Jena. Address reprint requests to Dr. Klemm,
Department of Child and Adolescent Psychiatry, University of Jena,
Philosophenweg 3-5, D-07740 Jena, Germany; silke.klemm@
med.uni-jena.de (e-mail).

Supported by Deutsche Forschungsgemeinschaft (DFG) grant BL

435/4-1.

References

1. Horrobin DF: The membrane phospholipid hypothesis as a

biochemical basis for the neurodevelopmental concept of
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TABLE 1. Measures of Cerebral Phosphate Metabolism in 14 Children or Siblings of Patients With Schizophrenia (High-Risk
Subjects) and 14 Comparison Subjects With No First-Degree Relative With Schizophrenia Spectrum Disorder

Measure

a

High-Risk Subjects

Comparison Subjects

Result of Mann-

Whitney U Test

Mean

SD

Mean

SD

U

p

Phosphodiesters (%)

37.59

4.35

34.87

2.36

51.0

0.03*

Phosphomonoesters (%)

9.18

2.75

10.72

2.11

70.0

0.21

Ratio of phosphomonoesters to phosphodiesters

0.25

0.08

0.31

0.06

51.5

0.03*

Total adenosinetriphosphate (%)

34.57

3.22

34.65

3.58

93.0

0.84

Phosphate phosphocreatine (%)

9.93

1.77

10.97

1.16

55.0

0.05

Ratio of phosphate phosphocreatine to total adenosinetriphosphate

0.29

0.05

0.32

0.05

65.0

0.14

Inorganic phosphate (%)

8.43

2.62

8.72

2.09

86.0

0.60

pH

6.99

0.06

7.01

0.04

70.0

0.21

a

Determined with phosphorus-31 magnetic resonance spectroscopy. Values are relative peak areas.

*p

<

0.05.

960

Am J Psychiatry 158:6, June 2001

BRIEF REPORTS

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Brief Report

The One-Child Family and Violent Criminality: A 31-Year

Follow-Up Study of the Northern Finland 1966 Birth Cohort

Liisa Kemppainen, M.D.

Jari Jokelainen, M.Sc.

Marjo-Riitta Järvelin, M.D., Ph.D.

Matti Isohanni, M.D., Ph.D.

Pirkko Räsänen, M.D., Ph.D.

Objective: Serious defects in social skills acquired during child-

hood may be associated with aggressive behavior in later life.

The authors studied whether being an only child was associated

with criminality in adulthood and, secondly, if parental factors

increased the putative risk.

Method: The authors used an unselected, prospectively col-
lected large birth cohort. Data on crimes were linked with being
an only child as well as with perinatal risk and maternal and pa-
ternal psychological risk factors among male subjects.

Results: The risk for violent crimes later in life was elevated
among the only children. If perinatal or parental risks were
combined with being an only child, the odds ratios for violent
offending increased four-fold to eight-fold. A corresponding risk
increase between being an only child and nonviolent offending
was not detected.

Conclusions: These results support the hypothesis that grow-
ing up as an only child is associated with violent criminality
among male subjects.

(Am J Psychiatry 2001; 158:960–962)

I

t has been suggested that, because they do not have

older siblings, only children in the family acquire more au-
tocratic, less interactive interpersonal styles and that this

has negative consequences for peer popularity (1). How-
ever, previous studies of these psychosocial developmen-
tal risks among only children are incompatible. Many in-