Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims.

BACKGROUND: There is evidence indicating that serotonin uptake and density of 5-HT2A receptors are altered in brain regions of depressed suicide victims and in platelets of depressed suicidal subjects. The present investigation tested the hypothesis that these changes in the serotonergic system in depressed suicide victims are trait rather than state markers and associated with a polymorphism in respective candidate genes. METHODS: Two polymorphic variants (102T/C polymorphism and His452Tyr functional polymorphism) of the 5-HT2A receptor gene and a functional polymorphism in the 5' regulatory region of the 5-HT transporter gene, have been determined in genomic DNA obtained from postmortem brain samples of 24 depressed suicide victims and 31 control subjects of the same ethnic background. In a subset of subjects, density (Bmax) of 5-HT uptake sites (labeled with 3H-paroxetine) and of 5-HT2A receptors (labeled with 3H-ketanserin) was also determined in prefrontal cortex samples. RESULTS: The major finding of this study was a significantly higher frequency of the 5-HT transporter gene long (L) allele (chi 2 = 3.9, df = 1; p = .048) in depressed suicides. No significant differences between suicides and controls were observed for the 102T/C polymorphism and His452Tyr polymorphism of 5-HT2A receptor gene. The density of 3H-paroxetine binding sites tended to be higher in subjects expressing the short (S) allele of 5-HT transporter gene. Furthermore, there was a significant difference in serotonin transporter binding sites between the genotype S/S and combined genotypes S/L and L/L. CONCLUSIONS: Our finding provides the first evidence suggesting that a functional polymorphism in the regulatory region of serotonin transporter gene may be associated with suicide in depressed subjects.

5-HT uptake sites and 5-HT2 receptors in brain of antidepressant-free suicide victims/depressives: increase in 5-HT2 sites in cortex and amygdala.

The density (Bmax) of 5-HT2 receptors labelled with [3H]ketanserin was significantly increased in prefrontal cortex (by 67%) and amygdala (by 97%) from suicide/depressives in comparison with controls. There were no differences in Kd of [3H]ketanserin binding between the two groups. The density (Bmax) and affinity (Kd) of [3H]paroxetine sites were not significantly different in the suicide/depressives and controls. The ratio between the density of presynaptic 5-HT uptake sites and postsynaptic 5-HT2 receptors in amygdala was significantly lower in suicide/depressives than in controls. The data confirm and extend some of the previous findings of increases in 5-HT2 receptors in post-mortem brains of suicide victims and depressives who died of natural causes and lend support to the view that an abnormality in brain serotonergic system is associated with depression and suicidal behaviour.

Suicide in subtypes of primary major depression.

Among 100 consecutive suicide victims with primary major depression at the time of their suicide, 46% were found to have had bipolar II depression, 1% bipolar I disorder and 53% non-bipolar major depression. Since the lifetime prevalence rates of bipolar II and bipolar I depressions are relatively low compared to primary major non-bipolar depression, the present findings suggest that bipolar II disorder gives a particularly high risk of suicide among the different subtypes of primary major affective illness. Fifty-nine percent of the patients had medical contact during the depressive episode, but the depression was frequently undiagnosed, untreated or undertreated. The implications of these findings for suicide prevention are discussed briefly.

The asymmetry of 3H-imipramine binding may predict psychiatric illness.

The Bmax and Kd values for 3H-imipramine binding were measured in post-mortem human brains from drug-free selected psychiatric subject homicide victims (n = 15) and normal controls (n = 15). The two groups were comparable in age and gender. The number of imipramine binding sites (Bmax) in the frontal cortices of psychiatric subjects had significantly higher Bmax values in the left hemisphere than in the right hemisphere. Inversely, the number of imipramine binding sites (Bmax) in the frontal cortices of normal controls were significantly higher in the right brain than in the left brain. It was postulated that the inhibiting effect of central serotonin (5-HT) has weakened in psychiatric cases, therefore the change of presynaptic serotonergic activity might be associated with psychiatric illness in the left hemisphere of human brain.

Does 3H-imipramine binding asymmetry indicate psychiatric illness?

We have accepted that serotonin is essentially an inhibitory neurotransmitter in the human brain, so we propose that it is precisely this inhibiting effect that has weakened in psychiatric cases. We have investigated the asymmetry of tritiated imipramine binding sites (Bmax) in the frontal cortices of homicide victims (n = 6) and controls (n = 6) who died of natural causes. Of these homicide victims examined in our experiment, five proved to have been psychiatric cases and one case had no psychiatric record. The two groups were comparable in age, gender and postmortem delay. The number of imipramine binding sites (Bmax) in the frontal cortices of controls was significantly higher in the right hemisphere than in the left hemisphere. But the homicide victims who were psychiatric cases had significantly higher (Bmax) values in the left hemisphere. While we only found higher Bmax values in the left hemisphere of homicide victims with mental diseases, our data may serve to prove the direct role of the serotonergic mechanism in the development of psychiatric cases.

Retrospective psychiatric assessment of 200 suicides in Budapest.

Based on an interview with the closest family member, using the Schedule of Affective Disorders and Schizophrenia--SADS, a retrospective psychiatric assessment and diagnostic classification was carried out on 200 completed suicides. Eighty-one per cent of the victims had a recent psychiatric disorder, in 63% depression. The prevalence of psychiatric illnesses was similar to that of other studies from countries with lower suicide rates.

The forgotten surgical foreign body.

Instruments and drains left in the abdomen following surgery may be responsible for bizarre and varied complications. The patient may remain asymptomatic for months or even years. Complications include adhesion formation, intestinal obstruction, abscesses, and erosion into the gastrointestinal tract. We report 3 patients in whom retained surgical material eroded into the duodenum and colon, respectively, and produced unusual radiologic findings and complications.

Umbilical flow in the normal and pre-eclamptic placenta. A study in vitro.

In order to develop a simple in vitro method for assessing adequacy of placental perfusion, umbilical flow was measured in placentae from 10 normal control women and from 10 women with pre-eclampsia, by infusing through the umbilical arteries a heparinized 0.9% saline solution. The average induced umbilical flow in placentae from uneventful pregnancies was 276 +/- 16 SE ml/min compared with 163 +/- 12 ml/min (p less than 0.001) in the pre-eclamptic group. In angiographic studies, 79 +/- 2 SE% of the cotyledons from the normal series, and only 56 +/- 3% (p less than 0.001) from the pre-eclamptic series were functional. Additionally, gross and histological examination revealed three distinct types of cotyledon. Placental areas that blanched following saline infusion showed no blood in the collapsed villi or in the intervillous space; areas distinguished by a ruddy appearance following perfusion showed blood trapped in the villi and in the intervillous space; in a third area, the findings were mixed. When compared with placental zones identified by perfusion with 5% Hypaque solution, these three anatomical regions corresponded to normal, reduced, or absent flow (blanched, intermediate, or ruddy regions, respectively). We conclude that under the conditions of this in vitro study, pre-eclamptic placentae had a greater proportion of umbilical perfusion deficits than had normal placentae.

Dexamethasone suppression test as an aid for selection of specific antidepressant drugs in patients with endogenous depression.

The dexamethasone suppression test (DST) and response to two different antidepressant drugs (maprotiline as a specific noradrenergic, and amitriptyline as a predominantly serotoninergic drug) were investigated in 44 endogenously depressed female inpatients. The more anxious and/or agitated patients were mostly treated with amtiriptyline, the non-anxious and retarded patients with maprotiline. It was found that among maprotiline responders (N = 15) there were significantly more abnormal DSTs and postdexamethasone serum cortisol levels were significantly higher than among amitriptyline responders (N = 16). On the other hand, DST abnormalities among amitriptyline non-responders (N = 10) were similar to those among maprotiline responders. The results confirm earlier reports by Brown et al. (1980), Ettigi et al. (1983) and Fraser (1983) and indicate that abnormal DST may identify the "noradrenergic" subtype of endogenous depression and that the DST represents a good way of selecting a specific antidepressant drug for the treatment of endogenously depressed patients.

Colour associations as predictors of the effectiveness of anti-depressant pharmacotherapy in endogenous depressive patients.

The authors examined the number of associations given for the 8 Lüscher colours by 20 endogenous depressive patients (11 unipolar and 9 bipolar II) before anti-depressant pharmacotherapy and on the 7th, 14th and 21st day of treatment. The depressive patients gave significantly fewer total responses before treatment than the 15 healthy control persons. While the number of associations obtained from the control persons was unchanged at the end of the 1st week, the depressive patients responding to the treatment (responders, n = 15) furnished significantly more responses on the 7th day than before treatment, although there had been no change in the intervening period in the severity of their depression measured by Hamilton depression scale; their clinical state showed a gradual improvement only from the end of the 2nd week. The number of associations obtained from non-responder depressive patients (n = 5) increased only slightly (not significantly). Our preliminary findings suggest that this method could be used to follow changes in the state of depressive patients and to predict their response to anti-depressant pharmacotherapy.

The dexamethasone suppression test in psychotic versus non-psychotic endogenous depression.

The authors investigated the dexamethasone suppression test (DST) in 93 female patients with primary (endogenous) major depression; in 20 female paranoid schizophrenics, and in 17 healthy females. Depressed patients had a significantly higher rate of abnormal DST response and significantly higher post-dexamethasone serum cortisol levels than schizophrenics and normal controls. The unipolar and bipolar depressives showed a similar profile of DST abnormalities. Depressed patients with psychotic features had a significantly higher rate of positive DST results than non-psychotic patients.

Uterine and ovarian artery blood flow in the rhesus monkey near term.

Uterine and ovarian artery blood flow (UABF and OABF) were measured in six pregnant monkeys near term by means of the electromagnetic flowmeter. The average UABF was 21.4 ml/min and OABF was 1.9 ml/min. Complete aortic occlusion reduced UABF from 21.4 to 2.4 ml/min, while OABF increased from 1.9 to only 2.1 ml/min. In six pregnant monkeys near term, chronic partial constriction of the abdominal aorta for an average of 10 days produced a parallel reduction in UABF but no increased circulation through the ovarian or round ligament arteries. The ovarian arteries were not visualized on angiography in these pregnant monkeys even when the abdominal aorta was acutely or chronically constricted; the uterine arteries were readily seen. The authors concluded that acute or chronic aortic constriction in the pregnant monkey at term results in a noncompensated uterine blood flow (UBF) reduction. The possible implications in pregnant women are discussed.

Uterine and ovarian artery blood flow in the pregnant dog. Attempt at comparative study in pregnant women.

UABF and OABF were measured in dogs with the electromagnetic flowmeter. In eight nonpregnant animals, UABF was on the average 3.2 ml/min and OABF 0.4 ml/min. In 10 pregnant bitches near term UABF was 27.3 ml/min and OABF 1.3 ml/min. Complete aortic occlusion in the pregnant bitch at term reduces UABF to 2.4 ml/min (loss of 24.9 ml/min) and increases OABF to only 1.6 ml/min (gain of 0.3 ml/min). The conclusion is that most of the blood flow to the uteroplacental unit in the pregnant bitch is channelled through the uterine artery and the marked drop in UABF produced by acute aortic occlusion is not compensated by an increase in OABF. The conditions are different in human pregnancy where the progressive nature of the aortic compression by the pregnant uterus allows, under the most favorable circumstances, the gradual development of a collateral circulation mostly through the ovarian arteries. However, this does not occur all the time as demonstrated by angiographic studies in a series of 12 patients and in similar studies reported in the literature. This could result in a placental insufficiency.