The association between hippocampal volume and life events in healthy twins.

Hippocampal volume deficits have been linked to life stress. However, the degree to which genes and environment influence the association between hippocampal volume and life events is largely unknown. In total, 123 healthy twins from monozygotic and dizygotic twin pairs underwent magnetic resonance imaging (MRI), and 57 healthy twins were interviewed with the Life Events and Difficulties Schedule (LEDS), with an overlap of 54 twins undergoing both MRI and the life events interview. Hippocampal volumes were segmented with Freesurfer software. Data were analyzed with OpenMx software. Smaller hippocampal volume was associated with higher severe life event load (rph = -0.39), where shared environmental factors influencing both measures fully explained the association. Hippocampal volume was not associated with total or mild life event load. Hippocampal volume showed high heritability (range, h(2) : 57%-81%) whereas life event measures were influenced by shared (c(2) ) and unique (e(2) ) environmental factors only (range, c(2) :40%-64%, e(2) : 36%-60%). The results suggested that shared environmental factors influenced the relationship between smaller hippocampal volume and severe (but not mild) stress. This indicated that particularly severe life events that were shared between twins were associated with smaller hippocampal volume. Furthermore, it is suggested to distinguish between mild and severe life events in life event research. © 2016 Wiley Periodicals, Inc.

Contribution of genes and unique environment to cross-sectional and longitudinal measures of subcortical volumes in bipolar disorder.

The influence of genes and environment on the association between bipolar disorder (BD) and volumes of subcortical brain regions involved in emotion processing has rarely been studied. Furthermore, as far as we know, longitudinal twin studies of subcortical brain volume change in BD have not been carried out at all. In this study, we focused on the genetic and environmental contributions to cross-sectional and longitudinal measures of subcortical brain volumes in BD. A total of 99 twins from monozygotic and dizygotic pairs concordant or discordant for BD and 129 twins from monozygotic and dizygotic healthy control pairs underwent magnetic resonance imaging at baseline. Longitudinal assessment was carried out in 48 twins from monozygotic and dizygotic patient pairs and 52 twins from monozygotic and dizygotic control pairs. Subcortical volume measures were obtained with Freesurfer software and analyzed with structural equation modeling software OpenMx. At baseline, BD was phenotypically and genetically associated with smaller volumes of the thalamus, putamen and nucleus accumbens. BD was not associated with subcortical brain volume change over time in any of the examined regions. Heritability of subcortical volumes at baseline was high, whereas subcortical volume change had low heritability. Genes contributing to BD showed overlap with those associated with smaller volumes of the thalamus, putamen and nucleus accumbens at baseline. Further evaluation of genetic contributions to abnormalities in subcortical brain regions assumed to be involved in emotion processing is recommended.

The influence of life events on first and recurrent admissions in bipolar disorder.

BACKGROUND: Life events play an important role in the onset and course of bipolar disorder. We will test the influence of life events on first and recurrent admissions in bipolar disorder and their interaction to test the kindling hypothesis. METHODS: We collected information about life events and admissions across the life span in 51 bipolar patients. We constructed four models to explore the decay of life event effects on admissions. To test their interaction, we used the Andersen-Gill model. RESULTS: The relationship between life events and admissions was best described with a model in which the effects of life events gradually decayed by 25% per year. Both life event load and recurrent admissions significantly increased the risk of both first and subsequent admissions. No significant interaction between life event load and number of admissions was found. CONCLUSIONS: Life events increase the risk of both first and recurrent admissions in bipolar disorder. We found no significant interaction between life events and admissions, but the effect of life events on admissions decreases after the first admission which is in line with the kindling hypothesis.

Relationship between clinical features and inflammation-related monocyte gene expression in bipolar disorder - towards a better understanding of psychoimmunological interactions.

OBJECTIVES: Existing and previously published datasets were examined for associations between illness and treatment characteristics and monocyte pro-inflammatory gene expression in patients with bipolar disorder (BD). We hypothesized a priori that increased monocyte pro-inflammatory gene expression would be found more frequently in patients with a lifetime history of psychotic symptoms. METHODS: Monocyte quantitative polymerase chain reaction and symptom data from 64 patients with BD were collected from three Dutch studies. Regression analyses were performed to analyze the various associations between pro-inflammatory gene expression and clinical features, from which feature-expression heat maps were drawn. RESULTS: No associations were found between pro-inflammatory gene expression and lifetime psychotic symptoms, whereas a positive association was identified between subcluster 2 genes and manic symptoms. For several subcluster 1a genes, a negative association was found with age at onset. For most subcluster 2 genes, a positive association was found with the duration of illness. Current use of antidepressants and of anti-epileptic agents was associated with subcluster 2 gene expression, and current use of lithium and antipsychotic agents with subcluster 1a gene expression. CONCLUSIONS: Our hypothesis that lifetime psychotic features would be associated with pro-inflammatory monocyte gene expression was not confirmed. In an explorative analysis we found: (i) a possible relationship between pro-inflammatory gene expression and manic symptomatology; (ii) a differential immune activation related to age at onset and duration of illness; and (iii) support for the concept of an immune suppressive action of some of the mood-regulating medications.

Auditory verbal hallucinations and cognitive functioning in healthy individuals.

Auditory verbal hallucinations (AVH) are a characteristic symptom in schizophrenia, and also occur in the general, non-clinical population. In schizophrenia patients, several specific cognitive deficits, such as in speech processing, working memory, source memory, attention, inhibition, episodic memory and self-monitoring have been associated with auditory verbal hallucinations. Such associations are interesting, as they may identify specific cognitive traits that constitute a predisposition for AVH. However, it is difficult to disentangle a specific relation with AVH in patients with schizophrenia, as so many other factors can affect the performance on cognitive tests. Examining the cognitive profile of healthy individuals experiencing AVH may reveal a more direct association between AVH and aberrant cognitive functioning in a specific domain. For the current study, performance in executive functioning, memory (both short- and long-term), processing speed, spatial ability, lexical access, abstract reasoning, language and intelligence performance was compared between 101 healthy individuals with AVH and 101 healthy controls, matched for gender, age, handedness and education. Although performance of both groups was within the normal range, not clinically impaired, significant differences between the groups were found in the verbal domain as well as in executive functioning. Performance on all other cognitive domains was similar in both groups. The predisposition to experience AVH is associated with lower performance in executive functioning and aberrant language performance. This association might be related to difficulties in the inhibition of irrelevant verbal information.