Angela Heinrich

Longer telomere length in patients with schizophrenia

Previous studies have reported an association between shorter leukocyte telomere length and schizophrenia (SCZ). The aim of the present study was to replicate this finding in a large sample of SCZ patients (n=539) and population-based controls (n=519). In addition, the possible influence of SCZ severity on telomere length - as measured by age of onset, mode of onset, and course of the disorder - was investigated. Telomere length was negatively associated with age in both patients and controls. This is a consistently reported phenomenon, related to the problem of DNA end-replication. However, in contrast to previous findings, SCZ patients displayed longer telomeres compared to controls (p=0.015). No association was found with any SCZ-severity subphenotype. Interestingly, recent studies have reported associations between longer leukocyte telomere length and both smaller hippocampal volume, and poorer episodic memory performance. Both phenotypes are common in patients with SCZ. Further studies are warranted to investigate whether the present association between SCZ and increased telomere length was driven by such associations, or rather by association with the clinical disease per se or other associated phenotypes, endophenotypes or lifestyle factors.

Effects of static magnetic fields on cognition, vital signs, and sensory perception: A meta-analysis

To evaluate whether cognitive processes, sensory perception, and vital signs might be influenced by static magnetic fields in magnetic resonance imaging (MRI), which could pose a risk for health personnel and patients, we conducted a meta‐analysis of studies that examined effects of static magnetic fields. Studies covering the time from 1992 to 2007 were selected. Cohens d effects sizes were used and combined in different categories of neuropsychology (reaction time, visual processing, eye‐hand coordination, and working memory). Additionally, effects of static magnetic fields on sensory perception and vital signs were analyzed. In the category “neuropsychology,” only effects on the visual system were homogeneous, showing a statistically significant impairment as a result of exposure to static magnetic fields (d = −0.415). Vital signs were not affected and effects on sensory perceptions included an increase of dizziness and vertigo, primarily caused by movement during static magnetic field gradient exposures. The number of studies dealing with this topic is very small and the experimental set‐up of some of the analyzed studies makes it difficult to accurately determine the effects of static magnetic fields by themselves, excluding nonspecific factors. The implications of these results for MRI lead to suggestions for improvement in research designs. J. Magn. Reson. Imaging 2011;.

Cognition and Sensation in Very High Static Magnetic Fields: A Randomized Case-Crossover Study with Different Field Strengths

PURPOSE To establish the extent to which representative cognitive functions in subjects undergoing magnetic resonance (MR) imaging are acutely impaired by static magnetic fields of varying field strengths. MATERIALS AND METHODS This study was approved by the local ethics committee, and informed consent was obtained from all subjects. In this single-blind case-crossover study, 41 healthy subjects underwent an extensive neuropsychologic examination while in MR units of differing field strengths (1.5, 3.0, and 7.0 T), including a mock imager with no magnetic field as a control condition. Subjects were blinded to field strength. Tests were performed while subjects were lying still in the MR unit and while the examination table was moved. The tests covered a representative set of cognitive functions, such as memory, eye-hand coordination, attention, reaction time, and visual discrimination. Subjective sensory perceptions were also assessed. Effects were analyzed with a repeated-measures analysis of variance; the within-subject factors were field strength (0, 1.5, 3.0, and 7.0 T) and state (static, dynamic). RESULTS Static magnetic fields were not found to have a significant effect on cognitive function at any field strength. However, sensory perceptions did vary according to field strength. Dizziness, nystagmus, phosphenes, and head ringing were related to the strength of the static magnetic field. CONCLUSION Static magnetic fields as high as 7.0 T did not have a significant effect on cognition.

Prediction of alcohol drinking in adolescents: personality-traits, behavior, brain responses, and genetic variations in the context of reward sensitivity

Adolescence is a time that can set the course of alcohol abuse later in life. Sensitivity to reward on multiple levels is a major factor in this development. We examined 736 adolescents from the IMAGEN longitudinal study for alcohol drinking during early (mean age=14.37) and again later (mean age=16.45) adolescence. Conducting structural equation modeling we evaluated the contribution of reward-related personality traits, behavior, brain responses and candidate genes. Personality seems to be most important in explaining alcohol drinking in early adolescence. However, genetic variations in ANKK1 (rs1800497) and HOMER1 (rs7713917) play an equal role in predicting alcohol drinking two years later and are most important in predicting the increase in alcohol consumption. We hypothesize that the initiation of alcohol use may be driven more strongly by personality while the transition to increased alcohol use is more genetically influenced.

A mechanism-oriented approach to psychopathology: The role of Pavlovian conditioning

The Research Domain Criteria Project suggests to base the classification of mental disorders on dimensions of observable behavior and neurobiological measures of these functions rather than on symptom-based descriptive categorical diagnoses. We suggest a mechanistic approach that focuses on the role of learning as a core mechanism that can be studied in animals and humans. We review human studies on neurobiological, psychophysiological, and behavioral correlates of Pavlovian associative learning and delineate commonalities and differences across disorders. In addition to the hedonic value, the learning phase (i.e. habituation, acquisition, extinction, extinction recall), the role of stimulus properties (i.e., cue and context), and event timing (e.g. delay and trace conditioning) were considered. We address how core behavioral and psychophysiological indicators of conditioning, such as contingency ratings and skin conductance responses or startle modulation, respectively, are altered. We also discuss plastic changes in core brain regions and the interaction of brain regions in inhibitory and excitatory circuits. We also address the translation of findings pertaining to classical conditioning and its affiliated processes into the development of new behavioral and pharmacological treatments for mental disorders, and discuss productive avenues for future studies.

From gene to brain to behavior: schizophrenia-associated variation in AMBRA1 alters impulsivity-related traits

Recently, genome‐wide association between schizophrenia and an intronic variant in AMBRA1 (rs11819869) was reported. Additionally, in a reverse genetic approach in adult healthy subjects, risk allele carriers showed a higher medial prefrontal cortex blood oxygen level‐dependent (BOLD) response during a flanker task examining motor inhibition as an aspect of impulsivity. To test whether this finding can be expanded to further aspects of impulsivity, we analysed the effects of the rs11819869 genotype on impulsivity‐related traits on a behavioral, temperament and neural level in a large sample of healthy adolescents. We consider this reverse genetic approach specifically suited for use in a healthy adolescent sample, as these individuals comprise those who will eventually develop mental disorders in which impulsivity is implicated. Healthy adolescents from the IMAGEN study were included in the neuropsychological analysis (n = 848) and a functional magnetic resonance imaging (fMRI) task (n = 512). Various aspects of impulsivity were assessed using the Temperament and Character Inventory‐Revised, the Substance Use Risk Profile Scale, the Cambridge Cognition Neuropsychological Test Automated Battery, and the Stop Signal Task (SST) in the fMRI paradigm. On a behavioral level, increased delay aversion was observed in risk allele carriers. Furthermore, risk allele carriers showed a higher BOLD response in an orbito‐frontal target region during the SST, which declined to trend status after Family Wise Error correction. Our findings support the hypothesis that the schizophrenia‐related risk variant of rs11819869 is involved in various aspects of impulsivity, and that this involvement occurs on a behavioral as well as an imaging genetics level.

The risk variant in ODZ4 for bipolar disorder impacts on amygdala activation during reward processing

OBJECTIVES Bipolar disorder is a severe mood disorder, which normally begins during adolescence or early adulthood and has a heritability of up to 80%. The largest genome-wide association analysis of bipolar disorder recently identified a new genome-wide associated variant in OZD4 (rs12576775). The aim of the present study was to further elucidate the role of this risk variant in the disease process using an imaging genetics approach. As increased amygdala and striatal responses during the processing of reward and emotion are characteristic for bipolar disorder patients, it was tested whether the risk variant has an influence on this endophenotype in healthy adolescents. METHODS We examined the impact of the risk variant rs12576775 on functional magnetic resonance imaging data in an adolescent sample (N = 485). Differential activation between carriers of the risk allele (G-allele) and homozygous A-allele carriers in the amygdala and the striatum during a modification of the monetary incentive delay task (examining reward) and a face task (examining emotion) was analyzed. RESULTS Carriers of the risk allele showed an increased blood oxygen level-dependent response in the amygdala during reward sensitivity (p = 0.05) and reward expectation (p < 0.05) but not during the face task. No significant group differences were found in the striatum during both reward and emotion processing. CONCLUSION Our results indicate that the ODZ4 risk variant influences reward processing in the amygdala. Alterations in the processing of emotion may have different underlying mechanisms and need to be further examined.

A cross-over study of effects on the hypothalamus-pituitary-adrenal (HPA) axis and the sympathoadrenergic system in magnetic field strength exposure from 0 to 7 T.

The concept of stress is relevant to magnetic resonance imaging (MRI) examination in various ways. First, levels of stress to staff and patients have not been quantified in ultra-high magnetic fields. Second, research is increasingly interested in experimentally defining regional brain activity during stress. It is therefore important to know whether exposure to the ultra-high static magnetic fields per se might also lead to neurohormonal responses in the hypothalamus–pituitary–adrenal axis and the sympathoadrenal systems. In the present blinded case cross-over study with 41 healthy participants, we measured cortisol not only before and after but also during static magnetic field exposure in MRI scanners. Measures of catecholamines before and after exposure were also part of the study protocol. Using three different field strengths (1.5, 3 and 7 T) and a mock scanner (0 T), we examined whether not only the MRI procedure but also the static magnetic field per se has an influence on the neuroendocrine responses. We found no significant differences in the course of cortisol or catecholamine concentrations between the different static magnetic fields. Our study suggests that the results of MRI studies using stress-paradigms are not influenced by the static magnetic field itself.

Women are more strongly affected by dizziness in static magnetic fields of magnetic resonance imaging scanners.

Increasing field strengths in MRI necessitate the examination of potential side effects. Previously reported results have been contradictory, possibly caused by imbalanced samples. We aimed to examine whether special groups of people are more prone to develop side effects that might have led to contradictory results in previous studies. We examined the occurrence of sensory side effects in static magnetic fields of MRI scanners of 1.5, 3, and 7 T and a mock scanner in 41 healthy participants. The contribution of field strength, sex, age, and attention to bodily processes, and stress hormone levels to the sensation of dizziness was examined in separate univariate analyses and in a joint analysis that included all variables. Field strength and sex were significant factors in the joint analysis (P=0.001), with women being more strongly affected than men by dizziness in higher static magnetic fields. This effect was not mediated by the other variables such as attention to bodily symptoms or stress hormones. Further research needs to elucidate the underlying factors of increased dizziness in women in static magnetic fields in MRI. We hypothesize that imbalanced samples of earlier studies might be one reason for previous contradictory results on the side effects of static magnetic fields.

The role of the cannabinoid receptor in adolescents' processing of facial expressions.

The processing of emotional faces is an important prerequisite for adequate social interactions in daily life, and might thus specifically be altered in adolescence, a period marked by significant changes in social emotional processing. Previous research has shown that the cannabinoid receptor CB1R is associated with longer gaze duration and increased brain responses in the striatum to happy faces in adults, yet, for adolescents, it is not clear whether an association between CBR1 and face processing exists. In the present study we investigated genetic effects of the two CB1R polymorphisms, rs1049353 and rs806377, on the processing of emotional faces in healthy adolescents. They participated in functional magnetic resonance imaging during a Faces Task, watching blocks of video clips with angry and neutral facial expressions, and completed a Morphed Faces Task in the laboratory where they looked at different facial expressions that switched from anger to fear or sadness or from happiness to fear or sadness, and labelled them according to these four emotional expressions. A‐allele versus GG‐carriers in rs1049353 displayed earlier recognition of facial expressions changing from anger to sadness or fear, but not for expressions changing from happiness to sadness or fear, and higher brain responses to angry, but not neutral, faces in the amygdala and insula. For rs806377 no significant effects emerged. This suggests that rs1049353 is involved in the processing of negative facial expressions with relation to anger in adolescence. These findings add to our understanding of social emotion‐related mechanisms in this life period.