Ultrastructural immunocytochemical localization of noradrenaline in locus coeruleus neurons of control and suicide brains

Ultrastructural immunocytochemical localization of noradrenaline in locus coeruleus neurons of control and suicide brains

Poster A. Clinical (blood donors) as controls. All patients and controls were Greeks, unrelated among them and were personally examined by the use of...

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Poster A. Clinical

(blood donors) as controls. All patients and controls were Greeks, unrelated among them and were personally examined by the use of a structured psychiatric questionnaire (Schedules for Clinical Assessment in Nemopsychiatry-SCAN). For the genotyping of the DRD2 gene a dinuclentide repeat marker was analysed by polymerase chain reaction (PCR) and electrophoresis after end-labeling with Y-~*P. For the genotyping of the DRD3 gene, a restrictive enzyme digestion was used for the Bali polymorphism. The results of genotyping were read by investigators blind to clinical diagnosis. Regarding the DRD2 gene, no differences were observed in allelic frequencies between the groups of patients and controls (p=O.223). For the DRD3 gene, however, a statistically significant association was found with the patients allelic and genotypic frequencies differing from those of controls (p=O.O14 and p=O.O19 respectively). This association was more prominent among female subjects. The results of the present study suggest that polymorphisms of the DA receptor D3, but not D2, may be implicated in the pathogenesis of affective disorder.

Manki H, Kanba S, Muramatsu T et al, 1996. Dopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood disorders. J Affect Disord 40:7-13. Souery D, Lipp 0, Mahieu et al, 1996. Association study of bipolar disorder with candidate genes involved in catecholamine neurotransmission: DRD2, DRD3, DATl, and TH genes. Am J Med Genet (Neuropsychiat Genet) 67:55!-555.

Treatment of panic disorder betes mellitus

DrDragih

in insulin dependent

Persky, H. (1974). Reproductive hormones, moods. and the menstrual cycle. In R.G. Friedman, R.M. Richard and R.L.. Vande Wiele (Eds.), Sex Differences in Behaviour. New York: Wiley. Parke, R.D. and Slaby, R.G. (1983). The development of aggression. In E.M. Hetherington (Ed.), Carmicael’s Manual of Child Psychology, Vol. IV, New York: Wiley, p. 561. Scamarella, T.C., and Brown, W.A. (1978). Serum testosterone and aggressiveness in hockey players, Psychosomatic Medicine, 40, pp. 262-265.

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D. KostiC. Department of Psychiatry, KBC” MiSoviC, 11000 Beograd, N.H. Milana TepiCa 1, Yugoslavia

V Diligenski,

Humans who have the rates of these neurochemical substances in low levels present overexcitation because suspension of the action of the monoaminoxidase (MAO) has as result the increase of the activation of neurotransmitters substances i.e. dopamine (DA). Dogmatyl neutralizes dopamine restraining hormone of pro&tin (PRL). This entails increase of the paragon for the release of prolactin (PRF) because prolactin is excreted as connection with paragon of the release of the prolactin from hypothalamus. Prolactin acts on the breast glands putting the production of the milk. Prolactin (it does not clear scientifically) causes rousing of the globus pallidus and excretion of progesterone, sometimes in notable quantities (gonadotrope action). But, by our intervention (dogmatyl), this does not happen, as it turns out of the release of the caused menstruation. This entails (indirect evidence) decrease of the aggressiveness against others. But subjects do not avoid the aggressiveness against theirself because the aggressiveness does not vanish but this is oppressed producing undesirable effects (side effects) which evidently are due to the uncontrolled action of the ascending testosterone. References

References

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V Adamovic,

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AZ. In the group of patients of insulin dependent diabetes (58 patients) we found that 28% meet criteria of DSM IV classification for partial or complete panic disorder. From 13 classified possible symptoms for panic disorder, this group had at least 4 symptoms, or one or more symptoms with anticipatory anxiety in the last one month. So high percentage of panic disorder is surprising because in general population it is up to 3%. It is result of the bad regulated diabetes, hereditary hypersensibility disposition, often hypoglycaemic crisis, which all contribute to the high neurotic degrees of these patients, particularly high anxiety. We used to regulate panic attacks Clonazepam in dosage of 0,5 up to 4 mg per day, for at least 6 months, in the combination with cognitive-behaviour therapy. The results were very quick, and with the glycaemia regulation, the treatment was effective. Diabetic hypoglycaemia highly overlapped panic attacks in their symptoms. Sometimes it was necessary to add TCA or SSRI antidepressants in small dosage.

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Neuropsychopharmaceutical control of the correlation between testosterone and aggressiveness

C.V. Dimoulas. Health Services

Sll

Department of Medical Laboratory Technology, and Welfare, T.E.I. of Larissa, Greece.

School of

Purpose of this study is to prove neuropsychopharmaceutically the correlation among aggressiveness and level of testosterone in the blood. Against contradictory picture whom data of researches with human subjects offer in this matter, in some forms of aggressive behaviour the influence of androgenes hormones has more general empirical support. But data of researches with human as subjects report lower - comparatively to their sample - correlations between level of testosterone and aggressiveness. Such higher correlations are remarked during some phases of the periodical circle, especially at the phase of excretion of the progesterone. Notable is ascertainment that while the level of the testosterone presented fluctuations during the several phases of the periodical circle, the measurements of the aggressive behaviour remained firm. Parallelly, there are indications of increased aggressive behaviour at the phase that precedes the menstruation. Periodical circle before women present notable emotional instability (others of them subside into depressiveness and others present overexcitation). This behaviour, depends on the rate of the harmonic substances which affect the hypothalamus and limbic system (tonsil and diaphragm). These feminine hormones (progesterone and oestrogones) wane the rates of stoppers of monoaminoxidase.

Peculiarities of blood serotonin system in psychogenic depressive disorders

Drozdov,

B.M.

National Research Russ&

Kogan,

T.S. Filatova,

IV. Mankovsky.

Centre for Social and Forensic

Psychiatry,

Serbsky Moscow,

Despite of large number of studies there are some contradictory opinions about the state of platelet indoleamine uptake system in affective disorders up to now. 66 males in the age of 18-51 years with psychogenic depressive disorders correspondingly subdivided into three groups with hysterical, anxiety and asthenic syndromes were examined. There were two comparative groups composed of (1) 20 psychopathic persons without depression and (2) 15 healthy subjects. A serotonin content in the blood plasma and platelets by means of HPLC-EC methods were determined. Parameters of the ‘H-serotonin platelet uptake (V,,, and K,) were also measured. V“lax of the serotonin uptake by platelets in patients with depressive disorder exceeds control figures only in persons with anxious-depressive manifestations (606252 pmol/ lO”/min, p
Ultrastructural immunocytochemical localization of noradrenaline in locus coeruleus neurons of control and suicide brains M.R. Issidorides”.“, M. Chrysanthou-Piterou”, S. Havaki”,V. Krihoh, G.D. Pappass. aDepartment of Psychiatry, University of Athens, Eginition Hospital, Greece, bDepartment of Anatomy and Cell Biology, Medicine, University of Illinois at Chicago, (ISA

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Extensive studies have shown that a large fall in noradrenaline (NA) concentration in the locus coeruleus (LC) is critically involved in

Poster A. Clinical

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mediating behavioral depression (Weiss and Simson, 1985). With the potassium permanganate (KMnO,) method for electron microscopy (EM), designed to demonstrate catecholamines as dense cores inside vesicles (Hokfelt and Jonsson, 1968), we have shown that in the normal human LC perikarya numerous large globules contain dense cores, presumably indicating the presence of NA (Issidorides et al., 1996). This is a new phenotype, compared to animals, where few and small dense core vesicles are usually present in these neurons. This accumulation of large dense core globules in man could represent a back-up storage compartment of neurotransmitter necessary for meeting the increased demands to cope with unpredictable stresses, inherent in man’s ecological (social) environment. Our objective was to confirm the involvement of the globules in the fall of NA in depression by studying ten suicides with a diagnosis of major depression. We applied the KMnO,/EM method, as well as a rabbit monoclonal anti-serum to NA, visualized by colloidal gold EM immunostaining. We found that the globules in the LC neurons of the suicide cases were as numerous as those in normal controls, but their electron density was greatly reduced, indicating depletion of NA. This was confirmed by the decreased immunoreactivity of NA. Abnormalities in the ultrastructure of the double membranes surrounding the dense bodies, such as dissociations, splits and blebs, indicating increased membrane fluidity, support the hypothesis that defective membrane chemistry and structure may be the cause of this neurotransmitter leakage. Membrane fluidization, a result of low cholesterol, could be an important biological substratum in major depression for the wide spectrum of dysfunctions which are expressed in many body systems aside from the brain.

References I. Weiss, J.M., Simson, P.G., (1985) Neurochemical basis of stressinduced depression. Psychopharmacol. Bull. 21, 447-457. 2. Hokfelt, T., Jonsson, G., (1968) Studies on reaction and binding of monoamines after fixation and processing for electron microscopy with special reference to fixation with potassium permanganate. Histochemie 16, 45-67. 3. Issidorides, M.R., Kriho,V., Pappas, G.D., (1996) The fine structure of large dense-core organelles in human locus coeruleus neurons. Neurol. Res. 18, 57-63.

References Smale, G., Nichols, N.R., Brady, D.R., Finch, C.E., Horton, W.E., Jr (1995) Evidence for apoptotic cell death in Alzheimer’s disease. Exp. Neurol. 133, 225-230. Su, J.H., Anderson, A.J., Cummings, B.J., Cotman, C.W., (1994) hnmunohistochemical evidence for apoptosis in Alzheimer’s disease. Neuroreport 5, 2529-2533. Issidorides, M.R., Katsorchis, T., (1981) Dispersed and compact chromatin demonstrated with a new EM method: Phosphotungstic acid hematoxylin block-staining. Histochemistry 73, 21-31.

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Brain perfusion spet in unipolar major depression before and after treatment

Margareta Kocmur”, Metka Mil&nskih, Natasa V Budihna’. “Psychiatry, ‘Nuclear Medicine, University Medical Centre, ‘Nuclear Medicine, Oncology, 1525 .Ljubljana, Slovenin Aim of our study was to evaluate regional cerebral blood flow (r-CBF) in unipolar depression before therapy and the effect of antidepressant drugs on r-CBF. Methods: Clinical criteria for depression without psychosis were met according to psychiatric evaluation. Severity of depression was assessed with Hamilton Depression Rating Scale (HAMD) just before every scintigraphic study. r-CBF was measured using 99m-Tc-HMPAO-SPET or 99m-Tc-ECD in 10 patients with severe unipolar depression before beginning of the antidepressant drug therapy, three weeks and 6 months after. Only pts with no change in antidepressant medication during the study were included. No antipsychotic drug was used. In each patient r-CBF was compared to cerebellar blood flow in all studies and separate regions were evaluated on repeated studies. r-CBF was evaluated semiquantitatively as equal to cerebellum, decreased, and severely decreased. CBF in basal ganglia vs. cortex was scored as equal, diminished or increased. Results: all pts were clinically depressed.

This work was supported by the Theodor Theohari Cozzika Foundation and the Ministry of Development, General Secretariat of Research and Technology (Grant No 90Hz124). Greece b&xc

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Ultrastructural evidence for apoptotic neuronal changes in frontal cortex of alzheimer’s disease

M.R. lssidorides”.b M. Chrysanthou-Piterou”, S. Havaki’, V. Krihob and G.D. Pappasb. “Department of Psychiatry, University of Athens and ‘Department of Anatomy & Cell Biology, University of Illinois at Chicago, USA Neuronal death is a prominent feature of Alzheimer’s disease (AD). Evidence has been provided, using the in situ labeling technique TUNEL, for apoptosis occurring in a high incidence in the hippocampus of AD patients compared to controls (Smale et al., 1995). The main morphological characteristics of apoptosis are changes in the nucleus involving chromatin condensation and aggregation into dense, often crescent-shaped masses under the nuclear membrane and around the nucleolus (Su et al., 1994). We designed to study apoptosis in the frontal cortex of 3 AD patients and 3 controls, using the phosphotungstic acid hematoxylin (PTAH) in to the staining method for electron microscopy (EM) after glutaraldehyde fixation. PTAH differentiates loose from condensed chromatin in a “black and white” contrast (Issidorides and Katsorchis, 198 I), so that results are evaluated by reliable ultrastructural morphological criteria. In the patients’ samples, we found several neurons in various stages of chromatin condensation and nuclear fragmentation, which are similar to the stages occurring in apoptotic human epidermal keratinocytes that usually precede the cleavage of DNA. These EM data offer the possibility to pin-point the initial site of chromatin condensation, i.e. the site of origin of the apoptotic process, and probe us to search for inhibitory factors and processes targeted to the prevention of its evolution. (Supported by NATO Collaborative Research Grant No 910753 and by Grant No 90HZl24 of the General Secretariat of Research and Technology, Greece)

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Serotonin content in blood plasma and in platelets of patlents with panic disorder

B.M. Kogan, AZ. Drozdov, E.V. Koroleva, E.D. Jukovsky. Serbsky National Research Centre for Social and Forensic Psychiatv, Moscow, Russia A lot of evidence suggests that serotonin system plays a significant role in the pathogenesis of affective disorders. For example, the effectiveness of serotoliin reuptake inhibitors in treating depressive, obsessive-compulsive, anxiety, and panic disorder has been demonstrated. However, the precise role of serotonergic system in the pathogenesis of panic attacks is still unclear. Particularly, there are some contradictory results in regard to level of sexotonin uptake in human platelets in panic disorder.