P.
1 Affective disorders and antidepressants
• Adenosine A1 and A2A receptors in serotonin
transporter deficient mice
R. M6ssner, D. Albert, A.M. Persico, B. Holtmann, D.L. Murphy, R.
Simantov, J. Deckert, K.P. Lesch. Department of Psychiatry, University
of Wiirzburg, Wiirzburg, Germany
Background: We have generated mice deficient for the serotonin trans-
porter (5-HTT), which exhibit elevated concentrations of extracellular
serotonin (5-HT). These mice display neurochemical changes suggestive
of lipid peroxidation (Persico et al., 1998). We therefore investigated
whether adenosine receptors, which are known to be involved in neuro-
protection, are modulated in these mice.
Methods: Autoradiography for adenosine AI and A2A receptors was
performed in wildtype and 5-HTT knockout mice, and number of binding
sites (fmol/mg tissue) were determined.
Results: Adenosine A1 receptor was upregulated by 21% in the dorsal
raphe nucleus of 5-HTT knockout mice (103 versus 85 fmol/mg; p <
0.05). No changes in A1 receptors were found in any of the serotonergic
projection areas. Adenosine A2A receptor showed a trend towards down-
regulation in all areas analyzed (caudate putamen, accumbens nucleus,
olfactory tubercle), with a down-regulation by 28% in the core of the
accumbens nucleus (221 versus 308 fmol/mg; p = 0.06).
Conclusions: Upregulation of adenosine A1 receptors has been re-
ported to be associated with neuronal survival in ischemia (Jacobson et
al., 1996). The observed adenosine receptor alterations may therefore
have neuroprotective effects in 5-HTT deficient mice.
References
[1] Jacobson KA et al., Trends Pharmacol. Sci. 17:108 (1996)
[2] Persico AM et al., Soc. Neurosci. Abstr. 24:1111 (1998)
• Quality of life for patients with body dysmorphic
disorder
K.A. Philipps. Butler Hospital Department of Psychiatry and Human
Behavior, Brown University School of Medicine, Providence, US
Background: Body dysmorphic disorder (BDD) is associated with high
levels of distress and impaired functioning. However, the quality of life
for patients with BDD has never been assessed. In this study, the health-
related quality of life of patients with BDD was compared to published
norms for the general U.S. population and for patients with depression,
diabetes, or a recent myocardial infarction.
Method: Sixty-two consecutive outpatients with DSM-IV BDD were
evaluated with the Medical Outcomes Study 36-Item Short-Form Health
Survey (SF-36), a widely used, reliable, and valid self-report measure
of health status and health-related quality of life. SF-36 scores were
compared to scales, including the Yale-Brown Obsessive Compulsive
Scale Modified for BDD (to assess BDD severity) and the Hamilton
Depression Rating Scale.
Results: Physical health status and physical health-related quality of
life scores for patients with BDD were worse than norms of the general
population and better than scores of outpatients with a medical illness
or depression (major depression and/or dysthymia). However, on all four
scales assessing mental health status and mental health-related quality of
life (mental health, social functioning, role limitations due to emotional
problems, and vitality), scores of BDD patients were markedly lower
than norms for the general U.S. population. They were also notably lower
than norms for patients with depression, diabetes, or a recent myocardial
infarction. The more severe the BDD symptoms, the lower were patients'
quality of life scores on the SF-36 mental health (r = -.63, p = .000)
and social functioning (r = -.55, p = .000) scales, even after controlling
for severity of depression.
Conclusions: These findings suggest the BDD is associated with
notably poor mental health status and mental health-related quality of
life.
$219
Patient categorisation of the severity of major
depression agrees with clinician judgement
C.J. Hawley, T.M. Gale, T. Sivakumaran, J. Hayes, E Hassan, A. Munns.
Hertfordshire Neuroscience Research Group. Mental Health Unit, QEII
Hospital, WelwynGarden City, Hertfordshire;Department of Psychology,
University of Hertfordshire, HaO'ield, Hertfordshire, UK
Much research, and clinical practice, assumes the reliability and validity
of observer rated depression scales be they ordinal (e.g. Global Impres-
sion Scales) or interval (e.g. Montgomery /~sberg Depression Rating
Scale, and Hamilton Rating Scale for Depression). However, an unchal-
lenged axiom is that patients would agree with the judgements made
about them by clinicians. We obtained 200 patient ratings on the 7 point
Clinical Global Impression Scale for Severity (CGIs) and also on a self-
rated modification of the CGIs which we called the 'Patient Assessment
of Severity Scale' (PASS). The state labels were almost identical between
the PASS and CGIs except that 'borderline ill' and 'markedly ill' were
modified to render these concepts more understandable to all patients.
We examined the correlation and categorical agreement between patient
scores on the two scales.
Agreement between patients and clinicians was high (Kendall's Tau-b
= 0.74). In 49% of cases the score on the CGIs and PASS were identical
and in 40% of instances the scores on the PASS and CGIs differed by
only one point. Overall, 39% of patients assigned themselves to a higher
score on the PASS than the clinician had indicated on the CGIs. The
converse applied in 12% of cases. It appears that both Major Depressed
patients and their clinicians apply broadly similar semantic labels to
grades of depression severity. The data provides some reassurance that
there is no large discrepancy between clinicians and patients about the
labels applied to the severity of illness. We would also posit that a
simple patient global severity rating may be able to capture much useful
information on patient status in situations where it is not possible to use
observer rated, or structured self rated, scales.
• Oestrus cycle and the regional brain NPY
concentrations in Fllnders sensitive rats, an animal
model of deprassion
P.A. Jim6nez 1, E Ghorbaninasab I *, D.H. Overstreet2, A.A. Math61 .
1Dept. of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
2Dept. of Psychiatry, Univ. of North Carolina, Chapel Hill NC, USA
Background: Accumulated data indicate that neuropeptides, in particu-
lar neuropeptide-Y (NPY), may be involved in depression and anxiety.
Although it has been known for many years that there is a gender differ-
ence in the incidence of depressive disorders, with females outnumbering
males 2 to 1, there is no clear understanding of the biological basis of this
difference. The present study examined the concentrations of NPY-like
immunoreactivity (LD in several brain regions in three strains of female
rats: Flinders Sensitive Line (FSL) "depressed", Flinders Resistant Line
(FRL) and Sprague-Dawley (SD) "healthy" animals. The FSL meets
most of the characteristics of a valid animal model of depression;
e.g. it resembles depressed humans in several ways: reduced activity
and appetite, increased REM sleep and a therapeutic (anti-immobility)
response to antidepressants (Overstreet, 1993; Overstreet et al., 1995).
As control, the FRL and outbred SD rats were examined. Our previous
experiments indicated that regional brain NPY-LI concentrations are
different between male and female animals and, within the same sex,
between different strains ("depressed" vs. controls). Moreover, pilot data
showed that the response to electroconvulsive stimuli (ECS) is sex
dependent. Consequently, the aim of this study was to explore whether
the day of the oestrus cycle has an effect on brain NPY.
Methods: The phase of the cycle was established by daily microscopic
examination of vaginal smears. Six to seven animals in each of the
four phases: diestrus, proestrus, oestrus or metoestrus were used. The
rats were sacrificed with focused high energy microwave irradiation, the