Endometriosis, psychiatric comorbidities and neuroimaging: Estimating the odds of an endometriosis brain.

Endometriosis is a chronic pain disorder that affects young women, impairing their physical, mental and social well-being. Apart from personal suffering, it imposes a significant economic burden on the healthcare system. We analyzed studies reporting comorbid mental disorders in endometriosis based on the ICD/DSM criteria, discussing them in the context of available neuroimaging studies. We postulate that at least one-third of endometriosis patients suffer from mental disorders (mostly depression or anxiety) and require psychiatric or psychotherapeutic support. According to three neuroimaging studies involving patients with endometriosis, brain regions related not only to pain processing but also to emotion, cognition, self-regulation and reward likely constitute the so-called "endometriosis brain". It is not clear, however, whether the neurobiological changes seen in these patients are caused by chronic pain, mental comorbidities or endometriosis itself. Given the paucity of high-quality data on mental comorbidities and neurobiological correlates in endometriosis, further research is needed.

Pandemic-induced increase in adjustment disorders among postpartum women in Germany.

BACKGROUND: The current paper analyzed the effect of the pandemic-induced lockdown on maternal mental health during the first 12 postpartum weeks in Germany. METHODS: In this cohort study, we compared the participants' anamnestic backgrounds and the results of psychological tests, measuring stress levels, depressive symptoms and attachment. The 327 participants were divided into two groups with one representing the "pre-COVID" sample and the other the "lockdown" sample. We performed multiple comparisons, investigating the distribution of diagnoses and the correlating risk profiles between the two cohorts. RESULTS: Our analysis showed a significant difference between the two cohorts, with a 13.2% increase in the prevalence of adjustment disorders (AD), but not postpartum depression (PPD), in the first 12 weeks postpartum. However, during the pandemic, women with AD had fewer risk factors compared to their pre-pandemic counterparts. In the "lockdown" cohort, a tendency toward higher stress and lower mother-child attachment was observed in AD. CONCLUSIONS: In sum, we observed some negative impact of the pandemic on maternal mental health. The lockdown might have contributed to an increase in the number of cases involving AD in the postpartum period. The prevalence of PPD (ca. 6-10%), on the other hand, was not affected by the lockdown. Thus, the effect of COVID-19 on maternal mental health might not, after all, have been as severe as assumed at the beginning of the pandemic.

A short-term musical training affects implicit emotion regulation only in behaviour but not in brain activity.

BACKGROUND: In everyday life, negative emotions can be implicitly regulated by positive stimuli, without any conscious cognitive engagement; however, the effects of such implicit regulation on mood and related neuro-mechanisms, remain poorly investigated in literature. Yet, improving implicit emotional regulation could reduce psychological burden and therefore be clinically relevant for treating psychiatric disorders with strong affective symptomatology. RESULTS: Music training reduced the negative emotional state elicited by negative odours. However, such change was not reflected at the brain level. CONCLUSIONS: In a context of affective rivalry a musical training enhances implicit regulatory processes. Our findings offer a first base for future studies on implicit emotion regulation in clinical populations.

Neuroanatomical Correlates of Social Intelligence Measured by the Guilford Test.

Social interactions are a crucial aspect of human behaviour. Numerous neurophysiological studies have focused on socio-cognitive processes associated with the so-called theory of mind-the ability to attribute mental states to oneself and others. Theory of mind is closely related to social intelligence defined as a set of abilities that facilitate effective social interactions. Social intelligence encompasses multiple theory of mind components and can be measured by the Four Factor Test of Social Intelligence (the Guilford-Sullivan test). However, it is unclear whether the differences in social intelligence are reflected in structural brain differences. During the experiment, 48 healthy right-handed individuals completed the Guilford-Sullivan test. T1-weighted structural MRI images were obtained for all participants. Voxel-based morphometry analysis was performed to reveal grey matter volume differences between the two groups (24 subjects in each)-with high social intelligence scores and with low social intelligence scores, respectively. Participants with high social intelligence scores had larger grey matter volumes of the bilateral caudate. The obtained results suggest the caudate nucleus involvement in the neural system of socio-cognitive processes, reflected by its structural characteristics.

[Big data approaches in psychiatry: examples in depression research]. / Big-Data-Ansätze in der Psychiatrie: Beispiele aus der Depressionsforschung.

BACKGROUND: The exploration and therapy of depression is aggravated by heterogeneous etiological mechanisms and various comorbidities. With the growing trend towards big data in psychiatry, research and therapy can increasingly target the individual patient. This novel objective requires special methods of analysis. OBJECTIVE: The possibilities and challenges of the application of big data approaches in depression are examined in closer detail. MATERIAL AND METHODS: Examples are given to illustrate the possibilities of big data approaches in depression research. Modern machine learning methods are compared to traditional statistical methods in terms of their potential in applications to depression. RESULTS: Big data approaches are particularly suited to the analysis of detailed observational data, the prediction of single data points or several clinical variables and the identification of endophenotypes. A current challenge lies in the transfer of results into the clinical treatment of patients with depression. CONCLUSION: Big data approaches enable biological subtypes in depression to be identified and predictions in individual patients to be made. They have enormous potential for prevention, early diagnosis, treatment choice and prognosis of depression as well as for treatment development.

Serotonergic modulation of resting state default mode network connectivity in healthy women.

The default mode network (DMN) plays a central role in intrinsic thought processes. Altered DMN connectivity has been linked to diminished cerebral serotonin synthesis. Diminished brain serotonin synthesis is further associated with a lack of impulse control and various psychiatric disorders. Here, we investigated the serotonergic modulation of intrinsic functional connectivity (FC) within the DMN in healthy adult females, controlling for the menstrual cycle phase. Eighteen healthy women in the follicular phase (aged 20-31 years) participated in a double-blind controlled cross-over study of serotonin depletion. Acute tryptophan depletion (ATD) and a balanced amino acid load (BAL), used as the control condition, were applied on two separate days of assessment. Neural resting state data using functional magnetic resonance imaging (fMRI) and individual trait impulsivity scores were obtained. ATD compared with BAL significantly reduced FC with the DMN in the precuneus (associated with self-referential thinking) and enhanced FC with the DMN in the frontal cortex (associated with cognitive reasoning). Connectivity differences with the DMN between BAL and ATD in the precentral gyrus were significantly correlated with the magnitude of serotonin depletion. Right medial frontal gyrus and left superior frontal gyrus connectivity differences with the DMN were inversely correlated with trait impulsivity. These findings partially deviate from previous findings obtained in males and underline the importance of gender-specific studies and controlling for menstrual cycle to further elucidate the mechanism of ATD-induced changes within intrinsic thought processes.

[Gender-inclusive care of victims of violence : The model project "Gender Gewaltkonzept" at the University Hospital Aachen]. / Gendergerechte Versorgung von Gewaltopfern : Das Modellprojekt "Gender Gewaltkonzept" an der Uniklinik Aachen.

Violence is a topic of great social relevance, frequently causing tremendous health consequences for those affected and high consequential costs for health care and the national economy. The established consulting and assistance services are usually restricted to offers for ambulant supply, mainly from private agencies or societies. As a result, there is no identification and care for patients who have experienced violence and who are treated in hospital. Another deficiency is the identification and care of male victims of violence. Despite wide-ranging offers of assistance, only very few gender-specific consulting and support services have been available to date.Therefore, the model project "Gender Gewaltkonzept" was initiated at Aachen University Hospital to assess the prevalence of violence and the potential consequences of the violence experienced on the patients' health. In addition, we investigated whether males and females are in need of different supply requirements.Based on the results of the project "Gender Gewaltkonzept" so far, and on prevalence estimates proving that there is a high rate of violent experiences in both males and females, this overview is aimed at presenting the aid and protection concepts available for victims of violence, in addition to the existing deficiencies of the care system. We present approaches to resolving these deficiencies to be able to establish all-encompassing gender-appropriate support for victims of violence.

In a sweet mood? Effects of experimental modulation of blood glucose levels on mood-induction during fMRI.

Glucose is the primary source of energy for the human brain. Previous literature has shown that varying blood glucose levels may have a strong impact on behaviour, subjective mood, and the intensity of the BOLD signal measured in fMRI. Therefore, blood glucose levels varying even within the normal range may interact with cognitive and emotional processing as well as BOLD signal. Here, in a placebo-controlled, double-blind crossover study on 20 healthy women, we show that overnight fasting, compared to an elevated glucose condition, influences brain activation and the affective state during mood induction. Results indicate that our brain may compensate for low glucose levels during fasting by stronger recruitment of the brain areas relevant to the task at hand. Additionally, we systematically tested the effect of prior cognitive effort on behavioural and neural patterns and found that elevated activation is only associated with maintained performance as long as no prior cognitively challenging task is administered. Prior cognitive effort leads to deteriorated performance and a further increase in emotion-associated brain activation in the pregenual anterior and posterior cingulate, the superior frontal gyrus, and the pre-SMA. These results are in line with the strength model of self-regulation. Our results corroborate the strength model of self-regulation and extend it to affect regulation processes. Additionally, our observations suggest that experimentally controlling for fasting state or glucose levels may be beneficial, especially when studying processes that involve self-regulation.

Neural network of cognitive emotion regulation--an ALE meta-analysis and MACM analysis.

Cognitive regulation of emotions is a fundamental prerequisite for intact social functioning which impacts on both well being and psychopathology. The neural underpinnings of this process have been studied intensively in recent years, without, however, a general consensus. We here quantitatively summarize the published literature on cognitive emotion regulation using activation likelihood estimation in fMRI and PET (23 studies/479 subjects). In addition, we assessed the particular functional contribution of identified regions and their interactions using quantitative functional inference and meta-analytic connectivity modeling, respectively. In doing so, we developed a model for the core brain network involved in emotion regulation of emotional reactivity. According to this, the superior temporal gyrus, angular gyrus and (pre) supplementary motor area should be involved in execution of regulation initiated by frontal areas. The dorsolateral prefrontal cortex may be related to regulation of cognitive processes such as attention, while the ventrolateral prefrontal cortex may not necessarily reflect the regulatory process per se, but signals salience and therefore the need to regulate. We also identified a cluster in the anterior middle cingulate cortex as a region, which is anatomically and functionally in an ideal position to influence behavior and subcortical structures related to affect generation. Hence this area may play a central, integrative role in emotion regulation. By focusing on regions commonly active across multiple studies, this proposed model should provide important a priori information for the assessment of dysregulated emotion regulation in psychiatric disorders.

[Simultaneous EEG-fMRI measurements: insights in applications and challenges]. / Simultane EEG-fMRT-Messungen : Ein Einblick in Anwendungsmöglichkeiten und Herausforderungen.

BACKGROUND: The following article presents an introduction to simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) measurements which have undergone a huge development during the last few years. OBJECTIVES: The idea behind combining both non-invasive methods is to join the excellent temporal resolution of EEG (ms) together with the superior spatial resolution of fMRI (mm). In this article the status quo of the method and perspectives regarding multimodal imaging are discussed. MATERIAL AND METHODS: Simultaneous EEG-fMRI measurements are affected by scanner and cardioballistic artifacts. We present common artifact subtraction methods in order to achieve a feasible data quality and outline what to consider when planning and recording EEG and fMRI simultaneously. Moreover, we discuss different analysis strategies. RESULTS: Combined EEG-fMRI measurements have already increased our knowledge about the underlying relationships between the blood oxygenation level-dependent (BOLD) response and the EEG signal and are applied to answer widespread research questions. Simultaneous measurements are an essential part of multimodal imaging in investigating the underlying processing mechanisms of the brain as well as in advancing our understanding of neuropsychiatric diseases. CONCLUSIONS: Current developments in multimodal imaging focus on the combination of electrophysiological and MRI parameters within ultra-high field MRI as well as on positron emission tomography (PET) in a trimodal approach.

The scent of salience--is there olfactory-trigeminal conditioning in humans?

Pavlovian fear conditioning has been thoroughly studied in the visual, auditory and somatosensory domain, but evidence is scarce with regard to the chemosensory modality. Under the assumption that Pavlovian conditioning relies on the supra-modal mechanism of salience attribution, the present study was set out to attest the existence of chemosensory aversive conditioning in humans as a specific instance of salience attribution. fMRI was performed in 29 healthy subjects during a differential aversive conditioning paradigm. Two odors (rose, vanillin) served as conditioned stimuli (CS), one of which (CS+) was intermittently coupled with intranasally administered CO2. On the neural level, a robust differential response to the CS+ emerged in frontal, temporal, occipito-parietal and subcortical brain regions, including the amygdala. These changes were paralleled by the development of a CS+-specific connectivity profile of the anterior midcingulate cortex (aMCC), which is a key structure for processing salience information in order to guide adaptive response selection. Increased coupling could be found between key nodes of the salience network (anterior insula, neo-cerebellum) and sensorimotor areas, representing putative input and output structures of the aMCC for exerting adaptive motor control. In contrast, behavioral and skin conductance responses did not show significant effects of conditioning, which has been attributed to contingency unawareness. These findings imply substantial similarities of conditioning involving chemosensory and other sensory modalities, and suggest that salience attribution and adaptive control represent a general, modality-independent principle underlying Pavlovian conditioning.

Influence of acute tryptophan depletion on verbal declarative episodic memory in young adult females.

Diminished synthesis of the neurotransmitter serotonin (5-HT) in the brain has been linked to disturbed memory processes. The present study investigated the effects of diminished central nervous 5-HT synthesis as achieved by an acute dietary tryptophan depletion (ATD) on verbal declarative episodic memory in young women while controlling for the effects of female sex hormones. Eighteen healthy females (aged 20-31 years) participated in a within-subject repeated measures study, with two separate days of assessment spaced at least one individual menstrual cycle apart. On one day, participants were subjected to ATD, thus lowering central nervous 5-HT synthesis. The other day participants received a tryptophan-balanced amino acid load (BAL = control condition). The study was randomized, counterbalanced and double blind in terms of ATD/BAL administration. Measurements took place in the early follicular phase of the participants' menstrual cycle. Estrogen, FSH and LH levels were assessed at baseline. Verbal declarative episodic memory was assessed using a structured word-learning task. Short-term memory, as indexed by immediate recall, was reduced after ATD intake, whereas delayed recall and recognition after a 25-min delay did not show any differences after intake of ATD or BAL. In young women, verbal short-term memory function was more vulnerable to ATD than consolidation processes. In light of the possible interplay between female sex hormones and 5-HT, further studies comparing different menstrual cycle phases are needed.

Endocrine stress response in pregnancy and 12 weeks postpartum - Exploring risk factors for postpartum depression.

Pregnancy and the postpartum period are characterized by physiological alterations in cortisol and cortisone levels. In the present study, we sought to explore the risk factors for postpartum depression (PPD) and self-remitting postpartum adjustment disorder (AD) and whether cortisol/cortisone metabolism might have any bearing on them. Hair samples from 196 participants (mean age = 31.44, SD = 4.71) were collected at two time points (1-6 days after childbirth and 12 weeks postpartum) to determine the cumulative hair cortisol (HCC) and hair cortisone (HCNC) exposure in the third trimester and during the 12 weeks postpartum. Compared to the non-depressed group (ND, n = 141), more women in the AD (n = 28) and PPD (n = 27) groups had a personal or family history of depression and more stressful life events. Compared to ND and PPD, more women in the AD group had birth-related complications with their children being more often transferred to a pediatric ward. The factors associated with PPD were found to include being unmarried and having a lower household income, less support at home, more subjectively perceived stress after childbirth and lower maternal sensitivity. The natural decrease in HCC concentration from the third trimester to 12 weeks postpartum was significant only in the ND and AD groups, but not in PPD. In summary, prolonged subjectively perceived postpartum stress associated with living situations may contribute to the development of PPD while birth- and child-related complications are likely to trigger brief episodes of AD. Only in ND and AD, the pregnancy-related physiological changes in glucocorticoid levels return to the pre-pregnancy baseline after 12 weeks. Our observations point to the difference between the ND and PPD groups in glucocorticoid metabolism-related postpartum adjustment, which may be a factor in the development of PPD.

[Functional magnetic resonance imaging in psychiatry and psychotherapy]. / Funktionelle Magnetresonanztomographie in der Psychiatrie und Psychotherapie.

technical improvements, functional magnetic resonance imaging (fMRI) has become the most popular and versatile imaging method in psychiatric research. The scope of this manuscript is to briefly introduce the basics of MR physics, the blood oxygenation level-dependent (BOLD) contrast as well as the principles of MR study design and functional data analysis. The presentation of exemplary studies on emotion recognition and empathy in schizophrenia patients will highlight the importance of MR methods in psychiatry. Finally, we will demonstrate insights into new developments that will further boost MR techniques in clinical research and will help to gain more insight into dysfunctional neural networks underlying cognitive and emotional deficits in psychiatric patients. Moreover, some techniques such as neurofeedback seem promising for evaluation of therapy effects on a behavioral and neural level.

[Evaluation of diagnostic and therapeutic services in German university hospitals for adults with autism spectrum disorder (ASD)]. / Evaluation diagnostischer und therapeutischer Angebote deutscher Universitätskliniken für Patienten mit Autismus-Spektrum-Störungen (ASD) im Erwachsenenalter.

INTRODUCTION: Autism spectrum disorders (ASD), are pervasive developmental disorders, which are defined by qualitative impairment in reciprocal social interaction and communication as well as by stereotyped repetitive behaviour. Newer epidemiological studies report a prevalence of 1 %. However, parents and self-help organisations report a considerable lack of diagnostic services, especially in the university hospital setting. In order to receive funding for adequate treatment at an "autism therapy centre", a Consultant psychiatrist has to diagnose ASD. METHODS: We assessed the diagnostic and therapeutic facilities for adults with ASD by sending out questionnaires to 33 German university hospitals. Furthermore, we evaluated the demographic data of the first 74 patients that presented at the specialist clinic for adults with ASD at the Department for Psychiatry and Psychotherapy, RWTH Aachen University. RESULTS: At the time of the evaluation, only 9 university hospitals in Germany offered a specialist clinic for diagnostics and/or treatment for adults with ASD. A comorbid psychiatric disorder was diagnosed in 52.9 % of the patients presenting at the specialist clinic for adult ASD. These were mostly mental retardation and affective disorders. The most common differential diagnosis for the patients presenting at the service were affective and personality disorders. CONCLUSION: There is still great need of specialist services at university hospitals in Germany for adults with ASD, although more services have been established over the past few years. Over half of the patients with ASD had other psychiatric comorbid disorders, which were mostly mental retardation and affective disorders. The most common differential diagnosis for patients presenting at the clinics were personality disorders and depression.

[Functional magnetic resonance tomography in patients with schizophrenia: neural correlates of symptoms, cognition and emotion]. / Funktionelle MRT bei Patienten mit Schizophrenie: Neurale Korrelate von Symptomen, Kognition und Emotion.

In patients with schizophrenia, numerous mental processes are impaired, which can be related to brain systems using functional imaging methods (e.g. functional magnetic resonance imaging; fMRI). In this review the methodological and conceptual background of fMRI will first be discussed. Secondly, the cerebral networks involved in important symptoms of schizophrenia such as hallucinations, delusions and formal thought disorders will be outlined. Furthermore, the pathways of the central nervous system involved in cognitive dysfunction in patients with schizophrenia will be described also in the dependence on genotype and medicinal status. Functional imaging methods provide psychiatry and psychotherapy with the unique opportunity to correlate mental processes and dysfunctions with neural networks.

Cumulative cortisol exposure in the third trimester correlates with postpartum mothers' neural response to emotional interference.

Prolonged stress affects the central nervous system, rendering individuals vulnerable to a wide range of mental health disorders. 76 healthy postpartum mothers were studied by means of functional magnetic resonance imaging within 6 days of childbirth. The subjects were required to perform the emotional Stroop task involving happy and anxious word-face combinations. Hair samples were collected to determine cumulative hair cortisol concentration (HCC) in the third trimester. HCC was found to be negatively correlated with the recruitment of the dorsal anterior cingulate cortex (ACC) and the midcingulate cortex (MCC). In response to the emotional interference of only anxious target faces, a negative correlation was seen between HCC and the bilateral orbitofrontal cortex, extending to the rostral ACC and the MCC. Women with lower HCC recruited brain areas relevant to emotional cognitive control, indicating that lower HCC helps preserve conflict monitoring and resolution capacities and thus benefits mental health in pregnancy.

Immediate and delayed neuroendocrine responses to social exclusion in males and females.

Social exclusion is a complex phenomenon, with wide-ranging immediate and delayed effects on well-being, hormone levels, brain activation and motivational behavior. Building upon previous work, the current fMRI study investigated affective, endocrine and neural responses to social exclusion in a more naturalistic Cyberball task in 40 males and 40 females. As expected, social exclusion elicited well-documented affective and neural responses, i.e., increased anger and distress, as well as increased exclusion-related activation of the anterior insula, the posterior-medial frontal cortex and the orbitofrontal cortex. Cortisol and testosterone decreased over the course of the experiment, whereas progesterone showed no changes. Hormone levels were not correlated with subjective affect, but they were related to exclusion-induced neural responses. Exclusion-related activation in frontal areas was associated with decreases in cortisol and increases in testosterone until recovery. Given that results were largely independent of sex, the current findings have important implications regarding between-sex vs. within-sex variations and the conceptualization of state vs. trait neuroendocrine functions in social neuroscience.

Prolonged fasting impairs neural reactivity to visual stimulation.

Previous literature has shown that hypoglycemia influences the intensity of the BOLD signal. A similar but smaller effect may also be elicited by low normal blood glucose levels in healthy individuals. This may not only confound the BOLD signal measured in fMRI, but also more generally interact with cognitive processing, and thus indirectly influence fMRI results. Here we show in a placebo-controlled, crossover, double-blind study on 40 healthy subjects, that overnight fasting and low normal levels of glucose contrasted to an activated, elevated glucose condition have an impact on brain activation during basal visual stimulation. Additionally, functional connectivity of the visual cortex shows a strengthened association with higher-order attention-related brain areas in an elevated blood glucose condition compared to the fasting condition. In a fasting state visual brain areas show stronger coupling to the inferior temporal gyrus. Results demonstrate that prolonged overnight fasting leads to a diminished BOLD signal in higher-order occipital processing areas when compared to an elevated blood glucose condition. Additionally, functional connectivity patterns underscore the modulatory influence of fasting on visual brain networks. Patterns of brain activation and functional connectivity associated with a broad range of attentional processes are affected by maturation and aging and associated with psychiatric disease and intoxication. Thus, we conclude that prolonged fasting may decrease fMRI design sensitivity in any task involving attentional processes when fasting status or blood glucose is not controlled.

Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: intersubject variability and probability maps.

Probabilistic maps of neocortical areas and subcortical fiber tracts, warped to a common reference brain, have been published using microscopic architectonic parcellations in ten human postmortem brains. The maps have been successfully applied as topographical references for the anatomical localization of activations observed in functional imaging studies. Here, for the first time, we present stereotaxic, probabilistic maps of the hippocampus, the amygdala and the entorhinal cortex and some of their subdivisions. Cytoarchitectonic mapping was performed in serial, cell-body stained histological sections. The positions and the extent of cytoarchitectonically defined structures were traced in digitized histological sections, 3-D reconstructed and warped to the reference space of the MNI single subject brain using both linear and non-linear elastic tools of alignment. The probability maps and volumes of all structures were calculated. The precise localization of the borders of the mapped regions cannot be predicted consistently by macroanatomical landmarks. Many borders, e.g. between the subiculum and entorhinal cortex, subiculum and Cornu ammonis, and amygdala and hippocampus, do not match sulcal landmarks such as the bottom of a sulcus. Only microscopic observation enables the precise localization of the borders of these brain regions. The superposition of the cytoarchitectonic maps in the common spatial reference system shows a considerably lower degree of intersubject variability in size and position of the allocortical structures and nuclei than the previously delineated neocortical areas. For the first time, the present observations provide cytoarchitectonically verified maps of the human amygdala, hippocampus and entorhinal cortex, which take into account the stereotaxic position of the brain structures as well as intersubject variability. We believe that these maps are efficient tools for the precise microstructural localization of fMRI, PET and anatomical MR data, both in healthy and pathologically altered brains.