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Biomedical subjects

J Angst

Publications and source records attributed to J Angst.

At least 19 recordsLinked to original sources
PubMed1997

Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis.

The effects of the indolehallucinogen psilocybin, a mixed 5-HT2 and 5-HT1 agonist, on regional cerebral glucose metabolism were investigated in 10 healthy volunteers with PET and [F-18]-fluorodeoxyglucose (FDG) prior to and following a 15- or 20-mg dose of psilocybin. Psychotomimetic doses of psilocybin were found to produce a global increase in cerebral metabolic rate of glucose (CMRglu) with significant and most marked increases in the frontomedial and frontolateral cortex (24.3%), anterior cingulate (24.9%), and temporomedial cortex (25.3%). Somewhat smaller increases of CMRglu were found in the basal ganglia (18.5%), and the smallest increases were found in the sensorimotor (14.7%) and occipital cortex (14.4%). The increases of CMRglu in the prefrontal cortex, anterior cingulate, temporomedial cortex, and putamen correlated positively with psychotic symptom formation, in particular with hallucinatory ego disintegration. The present data suggest that excessive 5-HT2 receptor activation results in a hyperfrontal metablic pattern that parallels comparable metabolic findings associated with acute psychotic episodes in chronic schizophrenics and contrasts with the hypofrontality in chronic schizophrenic patients.

Adult↗
PubMed1997

Metabolic hyperfrontality and psychopathology in the ketamine model of psychosis using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG).

To date, the ketamine/PCP model of psychosis has been proposed to be one of the best pharmacological models to mimic schizophrenic psychosis in healthy volunteers, since ketamine can induce both positive and negative symptoms of schizophrenia. At subanesthetic doses, ketamine has been reported to primarily block N-methyl-D-aspartate (NMDA) receptor complex giving support to a glutamate deficiency hypothesis in schizophrenia. Positron emission tomography was used to study ketamine-induced psychotic symptom formation in relation to cerebral metabolic alterations in healthy volunteers. Our study shows that NMDA receptor blockade results in a hyperfrontal metabolic pattern. Increased metabolic activity in the frontomedial and anterior cingulate cortex correlated positively with psychotic symptom formation, in particular with ego pathology. Analysis of correlations between syndrome scores and metabolic rate of glucose (CMRglu) or metabolic gradients (ratios) revealed that each psychopathological syndrome was associated with a number of metabolic alterations in cortical and subcortical brain regions, suggesting that not a single brain region, but distributed neuronal networks are involved in acute psychotic symptom formation.

Adult↗
PubMed1997

Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET).

Until recently, racemic ketamine (S-ketamine/R-ketamine = 50:50) has been used to study NMDA receptor hypofunction in relation to pathophysiological models of schizophrenia. Ketamine given to normal humans in subanesthetic doses produces a model psychosis including both positive and negative symptoms of schizophrenia. More recently it has been shown that at subanesthetic doses the pure (S)- and (R)-ketamine enantiomeres interact differently with the NMDA and sigma receptor sites in human brain. It was found that (S)-ketamine binds with a 3-4 time higher affinity to the PCP binding site of the NMDA receptor than (R)-ketamine, and that at these concentrations (R)-ketamine interacts also weakly with the sigma receptor sites, where (S)-ketamine binds only negligibly. To further investigate the role of NMDA-receptor mediated neurotransmission in schizophrenic psychosis, the effects of pure (S)- and (R)-ketamine enantiomeres on brain energy metabolism in normal humans using positron emission tomography and [18F]fluorodeoxyglucose (FDG) are reported here. Psychotomimetic doses of (S)-ketamine increased cerebral metabolic rates of glucose (CMRglu) markedly in the frontal cortex including the anterior cingulate, parietal and left sensorimotor cortex, and in the thalamus. The metabolic changes in the frontal and left temporal cortex correlated with ego-disintegration and hallucinatory phenomena. Equimolar doses of (R)-ketamine tended to decrease CMRglu across brain regions and significantly suppressed CMRglu in the temporomedial cortex and left insula. (R)-ketamine did not produce psychotic symptoms, but a state of relaxation. The (S)-ketamine-induced metabolic hyperfrontality appears to parallel similar metabolic findings in acute psychotic schizophrenic patients and encourages further investigations of glutamatergic disturbances in schizophrenia.

Adult↗
PubMed1996

The Zurich Study: XXII. Epidemiology of gastrointestinal complaints and comorbidity with anxiety and depression.

A representative cohort of Swiss adults recruited at age 20 years and interviewed at ages 23, 28 and 30 years was studied regarding the symptomatology, prevalence and longitudinal course of functional gastrointestinal symptoms and their association with psychiatric syndromes. A functional gastrointestinal complaint was identified if a proband reported symptoms at least eight times in the past year or for a duration of at least 2 weeks without medical explanation and with a moderate degree of distress. Of the population, 9.4-17.7% was found to suffer from functional stomach complaints and 4.9-16% from functional intestinal complaints. Women reported functional gastrointestinal complaints two to three times more often than men, and increasingly so with age. The overlap of stomach and intestinal complaints was modest with 2.0-6.7%. Cross sectionally, functional stomach complaints were significantly associated with major depression (DSM-III-R), recurrent brief depression (RBD), subthreshold RBD and dysthymia, and with subthreshold panic disorder, agoraphobia, social phobia and recurrent brief anxiety. Functional intestinal complaints showed a consistently significant association with RBD, dysthymia, major depression, subthreshold RBD, panic disorder, subthreshold panic disorder, agoraphobia, simple and social phobia and generalized anxiety disorder. Individuals who at younger ages suffered from functional gastrointestinal complaints did not show an increased risk for a subsequent development of an anxiety or depressive disorder. Functional gastrointestinal complaints reflect an unspecific concomitant vegetative disturbance common to depression and anxiety; they do not reflect a risk factor for the development of a specific anxiety or depressive disorder.

Adult↗
PubMed1996

Delayed onset of action of antidepressant drugs? Survey of results of Zurich meta-analyses.

The onset of action of antidepressant drugs was investigated on the basis of two independent, multicenter, double-blind studies, comparing amitriptyline (N = 120), oxaprotiline (N = 120), imipramine (N = 506) and moclobemide (N = 580) with placebo (N = 189/+191). Highly significant differences between the active drugs and placebo were found with respect to the total number of improvers and the total number of responders. In addition, significant differences between treatment modalities showed up in both the percentage rate and the time distribution of premature withdrawals. However, among improvers, the distribution of time spans to onset of improvement was found to be independent of treatment modality, indicated by virtually identical cumulative percentages of improvers over the whole observation period. This picture of treatment-independent improvement rates was essentially the same for the HAMD, HAMA and ZUNG assessments, except for a significant time lag between observerratings and self-ratings. Specifically, our analyses revealed no evidence for a delayed onset of action of various antidepressants with large biochemical and pharmacological differences when compared to placebo. The early onset of improvement was highly predictive of later outcome: on average, 70% of patients showing improvement within the first 14 days became responders. Differences between active treatments and placebo emerged within the first five days and reached a point of maximum distinction around day 14. After this time point, differences between treatment modalities remained constant until the end of the observation period. Not more than 20-25% of patients were, on average, "true" drug responders, thus suggesting that the therapeutic qualities of antidepressants do not lie in the suppression of symptoms, but rather relate to their ability to elicit and maintain certain conditions which enable recovery in a subgroup of patients who would otherwise remain nonresponders.

Adolescent↗
PubMed1996

Moclobemide: a paradigm of research in clinical psychopharmacology.

The pre-clinical development of moclobemide is an example of broad research combined with serendipity. Moclobemide was first hypothesized as being an antilipaemic or antibiotic, but the screenings were negative. The search for its antidepressant qualities, based on anticholinergic tests, also proved negative and moclobemide was then suspected of being an antipsychotic before its specific and reversible monoamine oxidase (MAO)-A inhibition qualities were detected. After the establishment of its lack of relevant interference with tyramine pressure response, clinical trials were launched in 1977. In the first stage, multiple, small open and double-blind studies were carried out. Two decisive, large, multicentre, double-blind studies were later performed in Latin America and Austria. Further trials have confirmed the broad antidepressant activity of reversible monoamine oxidase inhibitors (RIMA), which is not confined to any one subtype of depression and which show good tolerability and low toxicity. Since moclobemide has been available on the market, extensive meta-analyses of a large data set provided a series of methodological results: factor structure of the Hamilton Depression Scale (HAMD), optimal criteria of efficacy, predictors of response, onset of action for antidepressants and placebo.

Antidepressive Agents↗
PubMed1996

Quality of life in anxiety and social phobia.

Most studies on anxiety including social phobia have measured social adjustment behavior rather than quality of life (i.e. the subjective perception of the patient of his or her illness in relation to different domains). These social adjustment studies have found panic disorders to be more disabling than social phobia. However, quality of life was measured in terms of subjective well-being or satisfaction, and the Zürich study showed that patients with social phobia had less well-being in domains of friends, partner and childhood memories than patients with other anxiety or mood disorders. It is concluded that shyness has a great impact on quality of life.

Anxiety Disorders↗
PubMed1996

Recovery from depression: risk or reality?

Depression is a serious condition associated with a high rate of recurrence in all populations of depressed patients. Research studies in the past have focused more on the criteria for onset of depressive disorder than on consistent criteria for outcome. However, the issue of concern to the patient is whether their depression is a lifelong condition or a condition from which they can reasonably expect to make a complete recovery. The issues surrounding recovery from depression are reviewed in the following article. The lifetime prognosis of depression is examined with reference to the Zürich follow-up study, and outcome criteria and the importance of assessing recovery in terms of quality of life as well as symptomatic improvement are considered. The relevance of clinical trial results to the clinical management of depression is also addressed.

Depressive Disorder↗
PubMed1996

Comorbidity of mood disorders: a longitudinal prospective study.

From the Zurich cohort study (n = 591), the association of major depressive episodes and recurrent brief depression (RBD) with other psychiatric disorders is presented cross-sectionally at age 28 and 30 years, and over ten years (age 20 to 30 years). Longitudinally, the odds ratios of major depression are highest with dysthymia (4.4), generalised anxiety disorder (4.4), panic disorder (2.7), hypomania and agoraphobia (2.6), and social phobia (2.4). There is a significant association with cannabis consumption and smoking. Follow-up data over nine years are available for 41 patients with a major depressive disorder (MDD) and 62 with RBD: approximately 20% of MDD patients did not receive a diagnosis during follow-up. Major depression reoccurred in 32%, became bipolar in 24%, or developed into RBD in 24%. RBD remitted in 41%, reoccurred in 35%, turned into major depression in 22%, and became bipolar in only 7%. Longitudinally, MDD and RBD show a symmetrical diagnostic change in a quarter of the cases. There is no substantial development of MDD or RBD into minor depression or generalised anxiety disorder. Thirteen per cent of those with RBD later developed panic disorder.

Acute Disease↗
PubMed1996

Comorbidity and boundaries of affective disorders with anxiety disorders and substance misuse: results of an international task force.

Associations between affective disorders, anxiety disorders, and substance use disorders were examined in epidemiological studies conducted in Germany, Switzerland, Puerto Rico, and the mainland US. There was a remarkable degree of similarity across studies in the magnitude and type of specific disorders associated with the affective disorders. Comorbidity with affective disorders was greater for the anxiety disorders than for substance misuse. Panic disorder was the subtype of anxiety that was most highly comorbid with depression. Social phobia was the specific phobic type with the strongest association with the affective disorders. The magnitude of associations between substance misuse and affective disorders generally was quite low and less consistent across sites. No major differences were found in the patterns of comorbidity by gender or age group, affective subtype or prevalence period. The onset of anxiety disorders generally preceded that of depression, whereas alcohol misuse was equally likely to pre-or post-date the onset of affective disorders. Finally, comorbidity was associated with an elevation in treatment rates across all sites, confirming Berkson's paradox on an international level.

Adolescent↗
PubMed1995

Therapeutic efficacy of antidepressants in agitated anxious depression--a meta-analysis of moclobemide studies.

The results of the meta-analysis of studies comparing the efficacy of moclobemide, imipramine and so-called sedative antidepressants (amitriptyline, mianserin and maprotiline) in 2416 patients are described. The results demonstrated that in agitated-anxious depressive patients (defined by HAMD factor score or HAMD item 9) a nonsedative, reversible MAO-A inhibitor moclobemide has about equal efficacy as imipramine or sedative antidepressants. All antidepressants were clearly superior to placebo, irrespective of the outcome measures applied (> 50% HAMD decrease, CGI improvement). The efficacy of antidepressants in agitated patients was unrelated to the severity of agitation and did not appear to be inferior to the efficacy in nonagitated patients. Comedication with benzodiazepines had no impact on overall efficacy of either moclobemide or other antidepressants in this patient population. Previous treatment with antidepressants, however, always negatively influenced the outcome with trial drugs, e.g., reduced their efficacy. Placebo response in agitated depressives appeared generally to be low (20-30%) and was clearly reduced with increased severity of agitation, irrespectively of how the agitation was defined.

Adult↗
PubMed1995

Social phobia.

Explore the source record for details and available documents.

Humans↗
PubMed1995

Comorbidity and social phobia: evidence from clinical, epidemiologic, and genetic studies.

This paper reviews evidence from clinical, epidemiologic, and family studies regarding the association between social phobia and other syndromes. Social phobia is strongly associated with other anxiety disorders, substance abuse, and affective disorders in both clinical and community samples. An average of 80% of social phobics identified in community samples meet diagnostic criteria for another lifetime condition. Social phobia is most strongly associated with other subtypes of anxiety disorders, with an average of 50% of social phobics in the community reporting a concomitant anxiety disorder including another phobic disorder, generalized anxiety, or panic disorder. Approximately 20% of subjects in the community meet lifetime criteria for a major depressive disorder. The onset of social phobia generally precedes that of all other disorders, with the exception of simple phobia. Both clinical severity and treated prevalence are consistently greater among social phobics with comorbid disorders. The results of family and twin studies reveal that shared etiologic factors explain a substantial proportion of the comorbidity between social phobia and depression, whereas the association between social phobia and alcoholism derives from a nonfamilial causal relationship between the two conditions. Clinical and phenomenologic implications of these findings are discussed.

Adult↗
PubMed1995

Depression in old age. Is there a real decrease in prevalence? A review.

The discrepancy between the constancy or increase of the prevalence of depressive symptoms and dysphoria in old age on one hand, and the decrease in the prevalence of the DSM-III diagnoses of major depression and dysthymia on the other, is discussed in light of the most frequent explanatory hypotheses such as memory defects, interpretation of depressive as somatic symptoms, higher risk of institutionalization as well as higher mortality of depressives and a mitigated course of depression in old age. We conclude that higher mortality, mitigation and the rarity of true late-onset depression are arguments for a real decline in prevalence, which occurs in accordance with the decline in all psychiatric disorders that are connected with emotional upheavals and substance ingestion. On the other hand, the connection of depressive states with somatic illness is strengthened, and according to preliminary validation studies, clinically relevant depressive states not reaching the threshold of DSM-III diagnoses may be typical for the depressive psychopathology of old age.

Adolescent↗
PubMed1995

The epidemiology of depressive disorders.

The Zürich cohort study of a community sample identified, up to age 35, a lifetime prevalence rate for DSM mania/hypomania of 5.5%, half of these cases also met the criteria for major depressive episodes. The lifetime prevalence rates obtained for major depressive disorder were 17.85% and the rate for all depressive subgroups including dysthymia, minor depression, recurrent brief depression and major depression was 35.4%. Data on the validity of the diagnostic subgroups suggest that these high prevalence rates are based on clinically relevant case definitions.

Adult↗