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Biomedical subjects

J Mendlewicz

Publications and source records attributed to J Mendlewicz.

At least 19 recordsLinked to original sources
PubMed1997

No association between bipolar affective disorder and a serotonin receptor (5-HT2A) polymorphism.

The serotonergic system is implicated in the pathogenesis of affective disorders. In particular, the role of the postsynaptic 5-hydroxytryptamine (serotonin) type 2 receptor (5-HT2) has been documented by several studies. The 5-HT2A receptor gene located on chromosome 13 (13q14-21) can be considered a candidate gene for bipolar affective disorder (BPAD). We tested association between a 5-HT2A receptor DNA variant and BPAD using a case-control design. Eighty-three BPAD patients and 129 unrelated normal controls, carefully matched for sex and geographical origin, were studied. Allele and genotype frequencies as well as homo-heterozygote distribution at the 5-HT2A receptor polymorphism were compared between the two groups. No significant allelic or genotypic associations were observed. There was no significant difference for homo-heterozygote distribution between the two groups. These preliminary results may indicate that in our sample the 5-HT2 receptor polymorphism studied is unlikely to play a role in the genetic susceptibility to BPAD.

Adult↗
PubMed1997

Clinical and psychosocial predictors of recurrence in recovered bipolar and unipolar depressives: a one-year controlled prospective study.

Unipolar and bipolar patients with a chronic illness pattern were investigated to evaluate the relevance of clinical and psychosocial risk factors to predict subsequent recurrence. Self-esteem, social adjustment, social support and attributional style were assessed in 27 recovered bipolar patients, 24 recovered unipolar patients maintained on lithium or antidepressant prophylaxis and 26 healthy controls. They were further interviewed every 2 months in a 1-year period in order to diagnose affective episodes according to Research Diagnostic Criteria. Survival analyses and Cox's regressions demonstrated that being a unipolar patient and showing poor social adjustment were the strongest predictors of the occurrence of affective episodes. Self-esteem, social support, attributional style and clinical characteristics, such as age at illness onset, number of previous episodes or of previous hospitalizations and presence of affective disorder in first-degree relatives, were not found to be risk factors for further recurrence. This study stresses the importance of social adjustment in evaluating the outcome of affectively ill patients maintained on medication prophylaxis.

Age of Onset↗
PubMed1997

Distribution of delta activity across nonrapid eye movement sleep episodes in healthy young men.

The distribution of delta activity across successive nonrapid eye movement (NREM) sleep episodes and its night-to-night stability across three consecutive nights were investigated by studying delta power with spectral analysis in 31 healthy young men. Repeated-measures analysis of variance (ANOVA) with polynomial contrast was applied to grouped data of absolute delta power and three indexes: (1) the rate of delta power per NREM episode to its duration, 2) the standardized rate for the last NREM episode, and 3) the logarithm of the standardized rate. A significant linear decrease across NREM episodes was observed for each variable in each successive night. In addition, using night as a second within-subjects factor, no night effect was observed. Yet, the subsequent analysis of the logarithmic data yielded greater F values in all three nights' data as well as a linear function that accounted for a greater proportion of total variance than the analysis of the nonlogarithmic data. Since a linear decline for the logarithm of a variable implies an exponential distribution for that variable, we conclude that delta activity is distributed exponentially across NREM episodes, and this finding shows a remarkable night-to-night stability.

Adolescent↗
PubMed1997

Depression in the community: the first pan-European study DEPRES (Depression Research in European Society).

DEPRESS (Depression Research in European Society) is the first large pan-European survey of depression in the community. A total of 13359 of the 78463 adults who participated in screening interviews across six countries were identified as suffering from depression, a 6-month prevalence of 17%. Major depression accounted for 6.9% of the cases of depression and minor depression for 1.8%. Depressed subjects in both these categories perceived that their working or social lives were substantially impaired by depressive symptoms. The remaining 8.3% of depressed subjects considered that their functional impairment was not substantial. A significant proportion of sufferers from depression (43%) failed to seek treatment for their depressive symptoms. Of those who did seek help (57%), most consulted a primary care physician, the frequency of consultation increasing with the severity of depression. Sufferers from major depression imposed the greatest demand on healthcare resources, making almost three times as many visits to their GP or family doctor as non-sufferers (4.4 vs 1.5 visits over 6 months). More than two-thirds of depressed subjects (69%) were not prescribed any treatment and when drug therapy was prescribed (31%), only 25% of these subjects were given antidepressant drugs. The number of days of work lost due to illness increased with the severity of depression. Major depression had most impact on productive work, with sufferers losing four times as many working days over 6 months as non-sufferers. The results of the DEPRES survey confirm the high prevalence of depression in the community and the burden imposed on the individual sufferer in terms of impaired quality of life and on society in terms of healthcare utilization and lost productivity.

Adult↗
PubMed1996

Association study of bipolar disorder with candidate genes involved in catecholamine neurotransmission: DRD2, DRD3, DAT1, and TH genes.

Despite strong evidence for genetic involvement in the etiology of affective disorders (from twin adoption and family studies), linkage and association methodologies are still exploring the nature of genetic factors in these diseases. Interesting testable hypotheses have been described, including candidate genes involved in catecholamine neurotransmission. We studied 69 bipolar patients and 69 matched controls (for age, sex, and geographical origin) for association and linkage disequilibrium with DNA markers at the following genes: the tyrosine hydroxylase gene, dopamine transporter gene, and dopamine D2 and D3 receptor genes. Association and linkage disequilibrium were excluded between bipolar affective disorder and these four candidate genes in our sample.

Adult↗
PubMed1996

TRH stimulation and dexamethasone suppression in borderline personality disorder.

The link between borderline personality disorder (BPD) and affective disorders is controversial. The dexamethasone suppression test (DST) and the thyrotropin-releasing hormone (TRH) stimulation test, which are useful in the study of affective illness, might help to elucidate this possible link. This report assessed these endocrine tests in a sample of 20 borderline patients without a concomitant diagnosis of major depression (but showing depressive symptoms) in comparison to a group of sex- and age-matched patients with major depressive disorder (MDD) without BPD. Only 5 of our BPD patients were DST nonsuppressors compared to 13 MDD patients at a threshold of 50 micrograms/L. With a threshold of delta max TSH < 5 microU/mL following TRH, 1 BPD patient showed a blunted TSH response compared to 9 MDD patients. BPD patients displayed significantly less perturbed tests. These results show no evidence of an endocrine biological link between BPD and the MDD. The depressive symptoms observed in BPD patients might not have the same biological substrates as those found in patients with MDD.

Adult↗
PubMed1996

Neuroendocrine and sleep variables in major depressed inpatients: role of severity.

To evaluate the reliability of the endogenous concept of depressive illness according to the Newcastle Endogenous Depression Diagnostic Index (NEDDI), 155 major depressive inpatients with NEDDI scores > or = 6 (endogenous) were matched for gender and age (+/- 5 years) to 155 major depressive inpatients with NEDDI scores < 6 (nonendogenous). When sleep polygraphic variables, neuroendocrine parameters (dexamethasone suppression and thyrotropin-releasing hormone tests), and various clinical variables (unipolar/bipolar status, psychotic/nonpsychotic subtype, and severity of the depressive episode) were examined, statistically significant differences between endogenous and nonendogenous patients emerged for three variables: the thyroid-stimulating hormone response to the thyrotropin-releasing hormone test, the dexamethasone suppression test response at 16:00 h, and the percentage of time awake during the night. However, when the effects of age and severity of depression were controlled, those differences disappeared.

Adult↗
PubMed1996

Linkage analysis of families with bipolar illness and chromosome 18 markers.

Linkage of bipolar (BP) illness with chromosome 18 markers located at 18p11 was recently reported. A possible role for chromosome 18 in the etiology of BP illness was implicated previously by the finding in three unrelated patients of a ring chromosome with breakpoints and deleted segments at 18pter-p11 and 18q23-qter. To test the potential importance of a gene defect on chromosome 18 in our material, we examined linkage with chromosome 18 markers in two families with multiple patients with BP illness or BP spectrum disorders. fourteen simple tandem repeat polymorphisms were used located in the chromosomal region 18p11 to 18q23 and separated by distances of approximately 10 cM on the genetic map. In one family linkage to chromosome 18 could not be excluded. Linkage and segregation analysis in the family suggests that the 12-cM region between D18S51 and D18S61 located at 18q21.33-q23 may contain a candidate gene for BP illness.

Adolescent↗
PubMed1996

Sex difference in 5HT2 receptor in the living human brain.

Serotonergic mechanisms are involved in gender-related behaviors and psychiatric conditions like aggression, eating disorders, depression, impulsivity or suicide. We studied gender differences in the living human brain type-2 serotonin receptor (5HT2r). Twenty-two healthy age-matched men and women were investigated using positron emission tomography and the selective radiotracer, 18F-labeled altanserin. Binding was quantified using a non-linear least-squares minimization procedure. We found significantly higher 5HT2r binding capacity in men than in women, especially in the frontal and cingulate cortices. Distinct liability for men and women to suffer from some psychiatric disorders responding to serotonergic agents may be related to differences in brain serotonin receptors.

Adult↗
PubMed1996

Interregional correlation of cerebral glucose metabolism in unmedicated schizophrenia.

To investigate metabolic relationships between different brain regions in schizophrenia, we measured regional brain metabolism using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) in 15 unmedicated schizophrenic patients and 15 healthy subjects. We analyzed correlations between glucose metabolism data of multiple brain regions using factorial analysis and correlation coefficient comparisons. Absolute regional intercorrelations in schizophrenic brains were found to be significantly stronger than in controls, in relationship to the greater variability of metabolic rates in schizophrenic patients. Variability of normalized metabolic rates and regional intercorrelations were not significantly different between schizophrenic patients and control subjects. We conclude that a global metabolic factor accounts for the variability of metabolic data in untreated schizophrenia.

Adult↗
PubMed1996

A linkage study between bipolar disorder and genes involved in dopaminergic and GABAergic neurotransmission.

Neurobiological studies indicate a dysregulation of the dopaminergic and GABAergic neurotransmission in bipolar disorder. We examined two large families segregating bipolar disorder, for linkage with the genes encoding dopamine beta-hydroxylase, the dopamine transporter DAT1, the dopamine D2, D3 and D5 receptors, and the alpha-1, alpha-5 and beta-1 subunits of the GABAA receptor. Under at least one diagnostic model one of the two families provided evidence to exclude linkage for the DAT1, DRD2, DRD3, DRD5, DBH, GABRA1 and GABARB1 genes but could not exclude the GABRA5 locus. A second family excluded only the GABRA1 and GABRA5 loci at zero recombination and could not formally reject linkage at the DBH, DRD2, DRD3, DRD5, DAT1 and GABARB1 loci. Further analyses at these loci are warranted.

Bipolar Disorder↗
PubMed1996

Psychosocial predictors of major affective recurrences in bipolar disorder: a 4-year longitudinal study of patients on prophylactic treatment.

A total of 21 recovered bipolar patients on prophylactic treatment were prospectively followed up for a period of 1 year. Data for major recurrences were retrospectively collected for an additional 3-year period. During the entire 4-year period, over half of the patients (52%) had no major affective recurrences. Eight patients experienced a major depressive episode, while only two experienced a manic one. Psychosocial and clinical variables were assessed at entry to the study. The effect of these variables on the subsequent 4-year illness course was analysed using survivorship curves. The results show that the following psychosocial variables significantly predicted the occurrence of a major affective episode: low level of social support, maladjustment in social and leisure activities, and poor quality of relationships with extended family. In contrast, clinical variables which characterize illness history were not significantly associated with major recurrences.

Adult↗
PubMed1996

Sleep EEG analysis by linear prediction: frequency changes of slow-wave activity within NREM and REM sleep episodes in healthy men.

The linear prediction method was applied to obtain a power spectra estimate of sleep EEG in 10 healthy young men. In order to analyze frequency changes of the slow-wave activity (EEG power in the delta band, 0.05-2.88 Hz), the delta mean frequency was computed for each 20-second sleep epoch. A mean delta mean frequency was calculated for each sleep stage in each individual. Our observations indicate that the delta mean frequency decreases during NREM periods and increases mainly at the onset of the REM episodes. This finding, in parallel with the detailed analysis of slow-wave power variations, leads to an additional description of sleep characteristics during transitions between the NREM-REM sleep episodes.

Adult↗
PubMed1996

Life events and primary affective disorders. A one year prospective study.

BACKGROUND: Unipolar and bipolar patients with a chronic illness pattern were investigated to determine whether they experienced a higher number of life events prior to the onset of recurrent affective episodes. METHOD: The study participants consisted of 27 recovered bipolar patients, 24 recovered unipolar patients and 26 healthy control subjects. Life events and psychiatric status were assessed by bimonthly interviews over the period of one year using the Inventory for Recent Life Events and the Research Diagnostic Criteria. RESULTS: In both unipolar and bipolar patients, analyses revealed no significant differences in the number of life events experienced, irrespective of whether the patients had presented with a depressive episode of at least minor intensity during the study (all P > 0.1). Specifically, an increase in marital problems was observed in bipolar patients prior to the onset of recurrent hypomanic and manic episodes (P = 0.06). CONCLUSION: The causal association between life events and the onset of depression, shown to be relevant in non-chronically depressed subjects, does not apply in chronic affective disorders. In addition, our results suggest that marital events have an impact on the onset of recurrent hypomanic and manic episodes.

Adult↗
PubMed1995

Altered frontostriatal relationship in unmedicated schizophrenic patients.

Positron emission tomography with [18F]-fluoro-2-deoxy-D-glucose as tracer was used to investigate frontal glucose metabolism in 15 unmedicated schizophrenic patients and 15 healthy subjects under resting conditions. Although no difference in absolute frontal cerebral metabolic rates of glucose (CMRglu) were found between schizophrenic patients and control subjects, relative measures significantly differentiated the two groups. Whole frontal metabolism and frontocaudate ratio were significantly decreased in both hemispheres in the patients. The results confirm the existence of hypofrontality in unmedicated schizophrenia and indicate disturbances in metabolic relationships between the frontal cortex and the striatum in this disorder.

Adult↗
PubMed1995

Efficacy of the 'clonidine REM suppression test (CREST)' to separate patients with major depression from controls; a comparison with three currently proposed biological markers of depression.

We have shown that clonidine, infused i.v. during the second non-REM period, was significantly less REM sleep suppressant in depressed patients than in control subjects. We have named this procedure the 'clonidine REM suppression test (CREST)'. In this report, we compare in the same sample (15 patients with primary major affective illness, 10 normal controls, 15 patients with minor depression and 15 patients with generalized anxiety) the efficacy of the CREST to separate the major depressed patients from the control subjects with the efficacy of three currently proposed biological markers of depression, i.e., the latency of REM sleep, the dexamethasone suppression test and the clonidine growth hormone stimulation test. We found that the CREST had the highest efficacy and suggest that further studies with independent and larger samples of patients and controls are needed to confirm those preliminary results and establish if the CREST could provide a new biological marker of major affective disorders.

Adult↗