Katalin Dohrmann

Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor

Prenatal exposure to maternal stress can have lifelong implications for psychological function, such as behavioral problems and even the development of mental illness. Previous research suggests that this is due to transgenerational epigenetic programming of genes operating in the hypothalamic–pituitary–adrenal axis, such as the glucocorticoid receptor (GR). However, it is not known whether intrauterine exposure to maternal stress affects the epigenetic state of these genes beyond infancy. Here, we analyze the methylation status of the GR gene in mothers and their children, at 10–19 years after birth. We combine these data with a retrospective evaluation of maternal exposure to intimate partner violence (IPV). Methylation of the mothers GR gene was not affected by IPV. For the first time, we show that methylation status of the GR gene of adolescent children is influenced by their mothers experience of IPV during pregnancy. As these sustained epigenetic modifications are established in utero, we consider this to be a plausible mechanism by which prenatal stress may program adult psychosocial function.

Tinnitus perception and distress is related to abnormal spontaneous brain activity as measured by magnetoencephalography

Background The neurophysiological mechanisms underlying tinnitus perception are not well understood. Surprisingly, there have been no group studies comparing abnormalities in ongoing, spontaneous neuronal activity in individuals with and without tinnitus perception. Methods and Findings Here, we show that the spontaneous neuronal activity of a group of individuals with tinnitus (n = 17) is characterised by a marked reduction in alpha (8–12 Hz) power together with an enhancement in delta (1.5–4 Hz) as compared to a normal hearing control group (n = 16). This pattern was especially pronounced for temporal regions. Moreover, correlations with tinnitus-related distress revealed strong associations with this abnormal spontaneous activity pattern, particularly in right temporal and left frontal areas. Overall, effects were stronger for the alpha than for the delta frequency band. A data stream of 5 min, recorded with a whole-head neuromagnetometer under a resting condition, was sufficient to extract the marked differences. Conclusions Despite some limitations, there are arguments that the regional pattern of abnormal spontaneous activity we found could reflect a tinnitus-related cortical network. This finding, which suggests that a neurofeedback approach could reduce the adverse effects of this disturbing condition, could have important implications for the treatment of tinnitus.

The Neural Code of Auditory Phantom Perception

Tinnitus is defined by an auditory perception in the absence of an external source of sound. This condition provides the distinctive possibility of extracting neural coding of perceptual representation. Previously, we had established that tinnitus is characterized by enhanced magnetic slow-wave activity (∼4 Hz) in perisylvian or putatively auditory regions. Because of works linking high-frequency oscillations to conscious sensory perception and positive symptoms in a variety of disorders, we examined gamma band activity during brief periods of marked enhancement of slow-wave activity. These periods were extracted from 5 min of resting spontaneous magnetoencephalography activity in 26 tinnitus and 21 control subjects. Results revealed the following, particularly within a frequency range of 50–60 Hz: (1) Both groups showed significant increases in gamma band activity after onset of slow waves. (2) Gamma is more prominent in tinnitus subjects than in controls. (3) Activity at ∼55 Hz determines the laterality of the tinnitus perception. Based on present and previous results, we have concluded that cochlear damage, or similar types of deafferentation from peripheral input, triggers reorganization in the central auditory system. This produces permanent alterations in the ongoing oscillatory dynamics at the higher layers of the auditory hierarchical stream. The change results in enhanced slow-wave activity reflecting altered corticothalamic and corticolimbic interplay. Such enhancement facilitates and sustains gamma activity as a neural code of phantom perception, in this case auditory.

High-frequency tinnitus without hearing loss does not mean absence of deafferentation

A broad consensus within the neuroscience of tinnitus holds that this audiologic condition is triggered by central deafferentation, mostly due to cochlear damage. The absence of audiometrically detectable hearing loss however poses a challenge to this rather generalizing assumption. The aim of this study was therefore to scrutinize cochlear functioning in a sample of tinnitus subjects audiometrically matched to a normal hearing control group. Two tests were applied: the Threshold Equalizing Noise (TEN) test and a pitch scaling task. To perform well on both tasks relatively normal functioning of inner hair cells is a requirement. In the TEN test the tinnitus group revealed a circumscribed increment of thresholds partially overlapping with the tinnitus spectrum. Abnormal slopes were observed in the pitch scaling task which indicated that tinnitus subjects, when presented with a high-frequency stimulus, relied heavily on input derived from lower-frequency inner hair cells (off-frequency listening). In total both results argue for the presence of a deafferentation also in tinnitus subjects with audiometrically normal thresholds and therefore favour the deafferentation assumption posed by most neuroscientific theories.

The relevance of spontaneous activity for the coding of the tinnitus sensation

In this chapter we will present support for the hypothesis that synchronous neuronal activity of cell assemblies within the auditory cortex could be the underlying neural code of tinnitus. Such synchronous activity is reflected in the ongoing oscillatory activation pattern that can be recorded non-invasively using MEG and EEG techniques. We conclude that such an oscillatory model of tinnitus can explain many different observations regarding tinnitus.

Neurofeedback for treating tinnitus.

Many individuals with tinnitus have abnormal oscillatory brain activity. Led by this finding, we have developed a way to normalize such pathological activity by neurofeedback techniques (Weisz et al. (2005). PLoS Med., 2: e153). This is achieved mainly through enhancement of tau activity, i.e., oscillatory activity produced in perisylvian regions within the alpha frequency range (8-12 Hz) and concomitant reduction in delta power range (0.5-4 Hz). This activity is recorded from electrodes placed on the frontal scalp. We have found that modification of the tau-to-delta ratio significantly reduces tinnitus intensity. Participants who successfully modified their oscillatory pattern profited from the treatment to the extent that the tinnitus sensation became completely abolished. Overall, this neurofeedback training was significantly superiorin reducing tinnitus-related distress than frequency discrimination training.

Are experiences of family and of organized violence predictors of aggression and violent behavior? A study with unaccompanied refugee minors

Background There is strong support for familial abuse as a risk factor for later delinquency and violent offending, whereas empirical evidence about the contribution of experienced organized violence to the cycle of violence is less clear. Nevertheless not all abused children do become violent offenders. This raises the question of which factors influence these childrens risk of future aggressive behavior. Recent evidence suggests that the trait of appetitive aggression plays an important role in the prediction of aggressive behavior. Objective The focus of the study is to investigate whether exposures to 1) organized; and 2) family violence equally contribute to aggressive behavior and how this is related to a trait of appetitive aggression. Furthermore it is of interest to uncover how the severity of posttraumatic stress disorder (PTSD) symptoms modulates associations between violent experiences and aggression. Method To answer these questions, we investigated unaccompanied refugee minors who had been exposed to varying levels of both violence types. Using structured interviews, experiences of organized and familial violence, self-committed aggressive acts, the trait of appetitive aggression, and PTSD symptoms were assessed in 49 volunteers. Results A sequential regression analysis revealed that the trait of appetitive aggression and experienced family violence were independent and significant predictors of self-committed aggressive acts, altogether accounting for 70% of the variance. Exposure to organized violence, however, was not significantly associated with aggressive acts or appetitive aggression. PTSD symptom severity was not correlated with measures of aggression but with the exposure to familial and organized violence. Conclusions Results suggest that in addition to the impact of family violence, an elevated trait of appetitive aggression plays a crucial role in aggressive behavior and should be considered in psychotherapeutic treatment.

Relations Between Traumatic Stress, Dimensions of Impulsivity, and Reactive and Appetitive Aggression in Individuals With Refugee Status.

Objective: Traumatic stressors and other forms of adversities, especially when experienced during childhood, shape aggressive behavior. Effects of differential dimensions of impulsivity on the relationship between psychological trauma, reactive aggression (defensive survival response to threat), and appetitive aggression (the pleasure of attacking and fighting) have not yet been assessed. Method: Using structural equation modeling, we sought to uncover precursors of reactive and appetitive aggression investigating a sample of 94 adult individuals with refugee status. We were interested in direct effects of childhood maltreatment and posttraumatic stress disorder (PTSD) and indirect effects via impulsivity dimensions. Results: For reactive aggression there was a direct link between childhood maltreatment and (a) PTSD symptoms and (b) marginal sensation seeking. Childhood maltreatment and sensation seeking best predicted appetitive aggression. There was no evidence for indirect effects of impulsivity. Conclusions: Fear-driven response to perceived threat based on inadequate cognitive appraisal is assumed to cause pathological reactive aggression, whereas excessive appetitive aggression can be explained by repeated experiences of thrill and excitement during violent acts. Prevention of early traumatic stress and adversities seems key to breaking the cycle of violence.

Brain activity and tinnitus

June 2005 | Volume 2 | Issue 6 | e195 | e198 As mothers get older and assisted conception becomes more common in developed countries, the incidence of multiple births—primarily of nonidentical siblings, but also of identical ones—has dramatically increased. Multiple pregnancies are high-risk pregnancies, with preterm delivery and monochorionicity (shared placenta) the major problems. Consequently, efforts are underway to optimize the management of these pregnancies. While identical (monozygotic) twins are much less common than dizygotic ones, monozygotic twinning events are increased after induced ovulation and in vitro fertilization. Monozygotic twins can be diamniotic dichorionic (two amniotic sacs, two placentas), monoamniotic monochorionic (one amniotic sac, one placenta), or diamniotic monochorionic (two amniotic sacs, one placenta). The last type accounts for approximately twothirds of all monozygotic twins. Monochorionic twins are at higher risk because they share a common placenta; they are primarily at risk from circulation abnormalities like twin–twin transfusion syndrome (the smaller twin [donor] does not get enough blood while the larger twin [recipient] becomes volume overloaded) and intrauterine growth restriction. However, the majority of diamniotic monochorionic twin pregnancies do not develop such complications. Nicholas Fisk and colleagues have studied records of 151 seemingly uncomplicated diamniotic monochorionic pregnancies and found a surprisingly high rate of fetal death: ten unexpected intrauterine deaths occurred in seven of the 151 pregnancies with no prior signs of complications. All deaths occurred within two weeks of a normal scan, at a median gestational age of 34 weeks and 1 day. The authors conclude that “despite intensive fetal surveillance, structurally normal monochorionic diamniotic twin pregnancies without twin–twin transfusion syndrome and intrauterine growth restriction are complicated by a high rate of intrauterine death.” As the deaths occurred predominantly after 32 weeks’ gestation, the authors suggest that the prospective risk for fetal death in these pregnancies might be eliminated by elective preterm delivery after 32 weeks. In an accompanying Perspective (DOI: 10.1371/journal.pmed.0020180), Jane Cleary-Goldman and Mary D’Alton agree that, despite the limitations of the study (its retrospective nature, small numbers, and lack of dichorionic controls), it highlights a critical question for obstetricians, namely, “when is the ideal gestational age to deliver apparently uncomplicated monochorionic twins?” As Cleary-Goldman and D’Alton discuss, at 32 weeks of gestation many of the risks associated with prematurity have abated, but the remaining ones are not negligible. Until larger prospective observational studies have been conducted, balancing these risks remains challenging.