27
Evoked Potentials, Serotonin, and Suicidality
G. Jucke!. U Heger!
Laboratory of Clinical Psychophysiology, Department of Psychiatry, Free University of Berlin, Berlin, Germany
Introduction
One of the most robust findings in biological
psychiatry is the association between diminished central sero-
tonergic neurotransmission as reflected by lowered CSF 5-
HIAA and suicide attempts in various groups of psychiatric
patients (Asberg et al., 1987; Roy and Linnoila, 1990). The same
relationship was demonstrated for completed suicides (Mann et
al. , 1989; Stan!ey and Stan!ey, 1990). 1t was additionally shown
that low 5-HIAA levels predict suicide attempts (Träskman et
al., 1981; Roy et al., 1989). In order to prevent suicide attempts,
monitoring of serotonergic activity seems to be useful for iden-
tifying high-risk patients. As a noninvasive indicator of low
central serotonergic function, a strong intensity dependence of
evoked potentials has been discussed (Heger! and Jucke!, 1993;
Jucke! et al., 1993). This intensity dependence is a measure of
evoked activity changes to sensory stimuli of different inten-
sities. We investigated the relationship between the intensity
dependence ofauditory evoked potentials (AEP) and suicidality
in three independent sampIes of psychiatric patients.
Suicidality in patients with
alcohol addiction
The intensity dependence of AEP was investi-
gated in 25 unmedicated hospitalized alcoholics (3 females;
IDC 10 criteria) one week after withdrawal. Using dipole source
analysis, the intensity dependence of the primary auditory cor-
tex (tangential dipole) and that of secondary auditory areas
(radial dipole) were analyzed separately (for method details see
Heger! and Jucke!, 1993). Since the primary auditory cortex is
much more densely innervated by serotonergic fibers than sec-
ondary areas (Lewis et al., 1986), interindividual differences in
serotonergic activity should be reflected mainly by the intensity
dependence of the tangential dipole. Ten of the alcoholic pa-
tients reported at least one suicide attempt in the past. Table 1
shows the comparison of these 10 patients with the 15 patients
without a history of suicide attempts. The two groups did not
differ in regard to age, depressed mood, or anxiety. Patients with
a history of suicide attempts exhibited a significantly weaker
intensity dependence ofthe tangential dipole than patients with-
out such a history. The intensity dependence of the radial di-
pole, which is not supposed to reflect modulating serotonergic
effects on cortical auditory processing, was not found to be
related to suicidality.
Pharmacopsychiat. 27 (1994) (Supplement) 27-29
© Georg Thieme Verlag Stuttgart . New York
Suicidality in patients
with major depression
The intensity dependence of AEP was recorded
from central electrodes referenced to linked mastoids in 22
unmedicated patients with major depression after three days of
drug wash-out (RDC criteria; for method details see Heger! et
al. , 1991). The seven patients with a history of suicide attempts
did not differ from those without such a history in regard to age,
gender, and depressed mood (Table 2). Patients with a history
of suicide attempts tended to have a weaker intensity depen-
dence than patients without a suicidal history. Subc1assification
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of the 22 depressed patients into two groups according to the
median of the intensity dependence showed that more patients
with a history of suicide attempts or with relatives who had
attempted or completed suicide were found in the group with
the weak intensity dependence (Table 3). Surprisingly, patients
who had acute suicidal ideas (Hamilton item 3) at the time of
the recording were found mainly in the group with the strong
intensity dependence.
Suicidality in patients with
affective disorders
Patients with recurrent affective disorders (IDC
9 criteria) under long-term prophylactic lithium treatment were
investigated. They were outpatients from the Berlin Lithium
Clinic and did not show any affective symptoms. Seven patients
reported past suicide attempts, six patients did not. There was
no difference between the two groups in regard to age, gender,
diagnosis, lithium plasma level at time of recording, and dura-
tion of lithium therapy (Table 4). The intensity dependence
recorded from central electrodes (for method details see also
Heger! et al., 1991) was significantly weaker for patients with
a history of suicide attempts than for those without such a
history.
Discussion
The results of the three studies presented above
revealed that patients with a history of suicide attempts are
characterized by a weak intensity dependence of AEP. This is in
line with a study using somatosensory evoked potentials that
reported weak intensity dependence to be related to suicidal
acts in depressed patients (Agren et al., 1983). In contrast, a
strong intensity dependence of visual evoked potentials was
found in psychiatric patients with a history of suicide attempts
and in healthy subjects with a family history of suicides or
suicide attempts (Buchsbaum et al., 1977; Coursey et al., 1979).
The latter findings were however only significant in males.
28 Pharmacopsychiat. 27 (1994) (Supplement) G. Juckei. U Hegerl

Tab. 1 History of suicide attempts and intensity dependence Tab.3 Suicidality in depressed patients with weak (n = 11) and
of auditory evoked dipole activity in alcoholics. strong intensity dependence (n = 11).

History of No history of t-test Patients with Weak Strong intensity

suicide attempts suicide attempts dependence
(n = 10) (n = 15)
History of suicide attempts 5 2
Age (years) 48.0 ± 10.3 44.1 ±8.6 n.s. Relatives with
Depressed mood 31.1 ± 7.1 28.6 ± 7.5 n.s. - history of suicide attempts 4 o
(Zungs' SDS) - completed suicides 2 1
Anxiety 30.9 ± 5.9 30.9 ±4.5 n.s. Acute suicidal ideas 3 6
(Zungs' SAS) (Hamilton item 3)
Intensity dependence
(l!V /10 dB)
- tangential dipole 0.13± 0.05 0.19±0.07 0.02 Tab. 4 History of suicide atempts and intensity dependence of
- radial dipole 0.06± 0.08 0.05±0.05 n.s. AEP in patients with affective disorders.

History of No history of t-test

suicide attempts suicide attempts
Tab. 2 History of suicide attempts and intensity dependence
(n= 7) (n =6)
of AEP in depressed patients.
Age (years) 46.4 ± 15.4 38.8±9.7 n.s.
History of No history of t-test Gender 3 females 4 females
suicide attempts suicide attempts 4 males 2 males

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(n= 7) (n = 15) Diagnosis 4 bipolar 4 bipolar
1 unipolar 2 unipolar
Age (years) 58.7±8.3 62.1 ± 10.9 n.s. 2 schizoaffective
Gender 5 females 11 females Lithium
2 males 4 males - plasma level 0.57± 0.19 0.59±0.32 n.s.
Depresssed mood 22.3±2.6 21.1 ± 4.5 n.s. (mmol/Il
(Hamilton) - duration (months) 10.1 ± 12.7 11.2 ±8.1 n.s.
Intensity dependence Intensity dependence
(l!V/10dB) (l!V/lO dB)
- Cz 1.0±0.8 1.9 ± 1.7 n.s. - Cz 0.7 ± 1.0 2.1 ± 1.6 0.03
-C3 0.9±0.5 1.2± 1.0 n.s. - C3 0.5 ± 0.7 1.4±0.9 0.05
-C4 0.6±0.4 1.2± 1.0 0.05 - C4 0.7 ± 0.4 1.8±0.9 0.01

Since the intensity dependence of AEP is sup- of suicide attempts (Ninan et al., 1984; Roy et al., 1985). It can
posed to be an indicator of central serotonergic function, our therefore be assumed that serotonergic dysregulation in suici-
findings support the concept that suicidality is related to sero- dality is a dynamic process in which acute suicidality is related
tonergic dysfunction. Serotonergic dysregulation in suicidality to a transient decrease of serotonergic activity in subjects with
seems however to be more complicated than was originally an unstable serotonin system (see Asberg et al., 1986). In this
thought (see Arato et al., 1991; van Praag et al., 1986). Most regard, a weak. intensity dependence of AEP indicating high
studies reported 10w serotonergic activity to be associated with serotonergic activity may characterize subjects with an en-
suicide attempts. However, the weak. intensity dependence hanced risk for developing suicidal states, and a strong intensity
found in our patients with a history of suicide attempts indicates dependence indicating low serotonergic activity may charac-
high serotonergjc activity in these patients. This discrepancy terize subjects with acute suicidality. If this speculative model
could be explained by the fact that the suicide attempts of our is correct, monitoring of the intensity dependence could
patients had occurred in the past and were unrelated to the become of c1inical value for the assessment of suicidality and
current medical contact, and that the relationship between low its therapeutic prevention.
serotonergic activity and suicide attempts was mainly found
during the acute suicidal state. Lowered CSF 5-HIAA levels
were found in patients immediately after a suicide attempt (van
Praag, 1986) and in patients with recent suicide attempts (As-
berg et al., 1976; see also Asberg et al., 1987). Acute suicide
ideas as measured by the Hamilton item 3 were related to low
5-HIAA (Lopez-Ibor et al., 1985; Peabodyet al., 1987; Meltzer,
1989). This is supported by the relationship between acute
suicidality assessed with Hamilton item 3 and a strong intensity
dependence that was observed in one of our studies. In this
context it is of interest that one research group found low 5-
HIAA to be related to suicidal ideation, but not to the history
 Evoked Potentials, Serotonin, and Suicidality Pharmacopsychiat. 27 (1994) (Supplement) 29

Summary spinal flui<!, dexamethasone suppression test and therapeutic re-

The link between suicidality and serotonergic
dysfunction is a consistent finding in biological psychiatry. In
three independent studies we found weak intensity dependence
of auditory evoked potentials, which may be related to high
serotonergic activity, in psychiatrie patients with a history of
suicide attempts. This result seems to contradict studies report-
ing low serotonergic activity in acute suicidal patients. As an
explanation for this discrepancy we propose that serotonergic
activity may be low only in acute suicidal states, and that high
serotonergic activity, as reflected by a weak intensity depend-
ence, may characterize high-risk patients, in whom a transient
decrease of serotonergic activity is accompanied by acute sui-
cidality.
Acknowledgments
Supported in part by Deutsche Forschungsgernein-
schaft (He 91617). We gratefully acknowledge the help ofProf. Dr. H.
Rommelspacher. Priv.-Doz. Dr. L. G. Schmidt, Dr. Mackert, and Prof.
Dr. B. Mü//er-Oer/inghausen.
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