To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
Daily-life stress sensitivity is associated with depression, but prospective data are lacking.
To examine associations between baseline ecological daily-life stress sensitivity and later depression, and to identify genetic and non-genetic factors moderating the transition from stress sensitivity to depression.
Daily-life stress sensitivity was assessed at baseline in twins (n = 502). One baseline and four follow-up measurements of depressive symptoms and negative life events were collected, as well as interview-based diagnoses at baseline and last follow-up. Hypothesised genetic markers were determined.
Baseline stress sensitivity was associated with increased depressive symptoms at follow-up and risk of major depressive disorder. Both genetic liability and major life events moderated the probability of transition from stress sensitivity to depression.
Onset of depression is attributable to pre-onset ecological measurements of stress sensitivity, particularly where genetic liability is high and individuals have reached a stage where the influence of competing environmental causes is low.
A bias to develop negative affect in response to daily life stressors may be an important depression endophenotype, but remains difficult to assess.
To assess this mood bias endophenotype, uncontaminated by current mood, in the course of daily life.
The experience samping method was used to collect multiple appraisals of daily life event-related stress and negative affect in 279 female twin pairs. Cross-twin, cross-trait associations between daily life mood bias and DSM – IV depression were conducted.
Probands whose co-twins were diagnosed with lifetime depression showed a stronger mood bias to stress than those with co-twins without such a diagnosis, independent of probands' current depressive symptoms and to a greater extent in monozygotic twins than in dizygotic twins.
Genetic liability to depression is in part expressed as the tendency to display negative affect in response to minor stressors in daily life. This trait may represent a true depression endophenotype.
It has been established that thyrotropin-releasing hormone (TRH) affects several aspects of immunoreactivity, e.g. production of proinflammatory cytokines. It has been shown that TRH enhances the therapeutic efficiency of classical tricyclic antidepressants. Proinflammatory cytokines may play a role in the etiology of depression, whereas the therapeutic efficacy of antidepressants may be related to their negative immunoregulatory effects.
In order to verify the hypothesis that TRH-induced increase of therapeutic efficiency of classical tricyclic antidepressants results from synergistic inhibitory effects of these agents on the secretion of proinflammatory cytokines, we determine the effect of imipramine or fluoxetine with and without TRH on the production of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) by stimulated human whole blood cells.
Diluted whole blood of 17 volunteers was incubated with imipramine or fluoxetine (both in doses of 10−5 M) with or without TRH (in a dose of 10−5 M). The supernatants were collected 24 h later for the assay of TNF-α and after 72 h for the assays of IFN-γ and IL-10. The three cytokines were assayed by ELISA methods.
A significant decrease in production of IFN-γ was observed in cells stimulated with mitogens and co-incubated with imipramine or fluoxetine and TRH. Under the same conditions, TRH alone did not change the production of these cytokines, whereas imipramine alone significantly decreases IFN-γ production, and fluoxetine alone significantly decreases IFN-γ and TNF-α production.
Although a significant decrease in IFN-γ production was observed after joint application of TRH and antidepressants, our data did not support the above-mentioned hypothesis. Indeed, we did not observe synergistic inhibitory effects of these agents on the secretion of proinflammatory cytokines.
Email your librarian or administrator to recommend adding this to your organisation's collection.