Polyglutamine tracts: no evidence of a major role in bipolar disorder.
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Base Sequence↗
Biomedical subjects
A Berghöfer
Publications and source records attributed to A Berghöfer.
Antidepressants and suicidal risk.
Only 5% of suicidal patients on the average use their prescribed antidepressant to commit suicide. Underprescription of antidepressants and failure of antidepressant therapy appear to be of greater practical importance than the toxicity of individual compounds. Prescribing less toxic agents, therefore, will not be of great advantage, especially if they are less efficacious. Several antidepressants including the selective serotonin reuptake inhibitors (SSRIs) may increase suicidal behavior by energizing depressed patients to act along preexisting suicidal thoughts or by inducing akathisia with associated self-destructive impulses. For acutely suicidal patients, the use of more sedating antidepressants is recommended. Clinical trials could not confirm a superiority of SSRIs over tricyclics in reducing the number of suicide attempts. There is evidence from large international data sources and a large multicenter controlled trial that lithium prophylaxis decreases the suicide risk and overall mortality in affective disorders. A suicide-preventing effect has not been demonstrated conclusively for antidepressants or non-lithium mood stabilizers.
Antidepressive Agents↗
MAOA: association and linkage studies with lithium responsive bipolar disorder.
A number of association studies have investigated the role of the monoamine oxidase A (MAOA) gene in the susceptibility to bipolar disorder. Although some studies have reported positive findings, there remains some controversy, because results from different studies have not been consistent. A common explanation for inconsistencies between studies is genetic heterogeneity. We have focused on lithium responsive bipolar disorder as a way to reduce heterogeneity. In this study, we investigated the role of MAOA in lithium responsive bipolar patients using association and linkage study designs. The investigation used 138 patients and 108 normal controls. In addition, 25 families were also studied. Our results were not supportive of a major role of MAOA in the predisposition to bipolar disorder.
Alleles↗
Evidence for a role of phospholipase C-gamma1 in the pathogenesis of bipolar disorder.
Several studies have indicated that patients with bipolar disorder (BD) who respond well to lithium prophylaxis constitute a biologically distinct subgroup. Lithium is thought to stabilize mood by acting at the phosphoinositide cycle. We have investigated a polymorphism located in the gene (PLCG1) that codes for a gamma-1 isozyme of phospholipase (PLC), an enzyme that plays an important role in the phosphoinositide second messenger system. A population-based association study and a family-based linkage study were carried out on patients who were considered excellent responders to lithium prophylaxis. Response to lithium was evaluated prospectively with an average follow-up of 14.4 +/- 6.8 years. The PLCG1 polymorphism was investigated in 136 excellent lithium responders and 163 controls. In addition, the segregation of this marker was studied in 32 families ascertained through lithium-responsive bipolar probands. The allele distributions between lithium-responsive bipolar patients and controls were different, with a higher frequency of one of the PLCG1 polymorphisms in patients (chi2 = 8.09; empirical P = 0.033). This polymorphism, however, confers only a small risk (OR = 1.88, CI 1.19-3.00). Linkage studies with the same marker yielded modest support for the involvement of this gene in the pathogenesis of BD when unilineal families were considered (Max LOD = 1.45; empirical P = 0.004), but not in the whole sample. Our results provide preliminary evidence that a PLC isozyme may confer susceptibility to bipolar disorder, probably accounting for a fraction of the total genetic variance. Whether this polymorphism is implicated in the pathogenesis of BD or in the mechanism of lithium response remains to be determined.
Adult↗
Course of illness and pattern of recurrences in patients with affective disorders during long-term lithium prophylaxis: a retrospective analysis over 15 years.
We analysed the recurrences of 86 patients with monopolar and bipolar mood and schizoaffective disorders treated with lithium over a period of 8.2 years on average in a specialized out-patient clinic. Lithium medication was discontinued by 24% of patients. Diagnosis, age and gender had no influence on the mean morbidity index. Bipolar and schizoaffective patients suffered from more severe recurrences, resulting in hospital admissions, than monopolar patients. A significant decrease in intensity of manic episodes and a significant shortening of depressive episodes was observed over a 10-year treatment period. However, the percentage of manic episodes among all episodes remained constant. There was no indication of a loss of the prophylactic effect in a subgroup of 30 patients who had been treated for a minimum of 10 years. The morbidity index also remained constant over 10 years in the whole sample. Furthermore, the mean lithium blood levels as well as the additional medication in this subgroup could be lowered in the second half of the treatment decade as compared to the initial 5 years.
Adolescent↗
Suicide attempts, age and duration of illness in recurrent affective disorders.
One of the strongest predictors of suicide is a suicide attempt in the history of the patient. The question, however, is to what extent age and duration of the illness affects the risk of a suicide attempt. In this study, we examined the course of 310 patients with primary affective disorders before lithium prophylaxis and compared the clinical data of those with and without suicide attempts in their history. In a subgroup of 98 patients with suicide attempts, measures for both suicide attempts and inpatient episodes were investigated. Comparing patients with suicide attempts and those without, we found no difference between duration of illness and number of previous episodes between the two groups. However, those with a suicide attempt in their history had an earlier onset of the illness. In the group of 98 suicide attempters, we found no significant correlation between age and rates for both episodes and suicide attempts, which indicates that these rates were not declining as the illness progressed and the patient aged. Dividing the sample into three different age groups, episode rates and rates of attempted suicide were found to be positively correlated in all age groups, again indicating that as long as episodes occur, the suicide risk does not decline. The results are not in favor of findings which suggest that the risk of attempting suicide might manifest itself primarily in the early course of the illness or that suicide attempts in the early course of illness provide a 'cathartic effect' which leads to a lower risk in the later course of the illness. Rather, the findings support the view that the risk of suicide attempts in recurrent affective disorders is unchanged in all age groups and throughout all stages of untreated illness.
Adult↗
Saccadic tracking test--normal data and reliability.
A saccadic tracking test, which involves the scanning of a path guided by the direction of a sequence of arrows, was administered to 102 healthy control subjects. The data show a gender effect and a slight age and education effect. The internal consistency--estimated by Cronbach's alpha--was high, .94. The test promises to be a sensitive estimator of the capacity of a subject to explore a visual display, a skill necessary for a wide range of other test performances.
Adolescent↗
Bradykinin-induced oedema formation proceeds from B2 receptor stimulation and is potentiated by concomitantly released prostaglandins.
Bradykinin, a stimulator of B1 and B2 receptors, significantly increased PGI2 synthesis and fluid extravasation, as assessed by the increase of organ weight when injected intraarterially into the artificially perfused rabbit hindquarters preparation. Diclofenac pretreatment prevented PGI2 synthesis and significantly reduced fluid extravasation. Oedema formation and PGI2 synthesis were also significantly reduced by a simultaneous infusion of papaverine. Selective stimulation of B1-type receptors with des-Arg9-bradykinin was not accompanied by edema formation nor PGI2 synthesis but by a significant rise in vascular resistance. The combined application of bradykinin and the selective B1 receptor antagonist des-Arg9-[Leu8]-bradykinin also resulted in oedema formation and PGI2 synthesis, the extent, however, being significantly reduced in comparison to the application of bradykinin only. The data suggest that bradykinin-induced oedema proceeds from B2 receptor stimulation and is potentiated by simultaneous stimulation of B1 receptors. The kinin-induced fluid extravasation seems to be augmented by concomitantly generated prostaglandins.
Animals↗
[Passive immunotherapy with polyvalent immunoglobulins in women with habitual abortions].
Intravenous immunoglobulins (IVIG) were used in an alternative approach to immunotherapy with allogeneic leukocytes to prevent recurrent spontaneous abortions (RSA). Twenty five women with a history of greater than or equal to 3 unexplained RSA were treated with IVIG during their next pregnancy. An initial dose of 30 g (0.5-0.6 g/kg body weight) was administered at gestational week 5-6. Treatment was continued every 3 weeks with 20 g (0.3-0.4 g/kg) and terminated by week 25. In primary RSA the success rate was 82-85%, which is in the same range as for leukocyte therapy. In contrast, IVIG was successful in only 40% of secondary aborters. We conclude that IVIG can be an effective treatment for prevention of primary RSA. Compared to leukocyte therapy the risks of transmission of infections and of HLA immunization can be avoided.
Abortion, Habitual↗