Electrophysiological evidence of an attentional bias towards appetitive and aversive words in adults with attention-deficit/hyperactivity disorder.

OBJECTIVE: Emotional dysregulation has emerged as a core symptom domain in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the pathophysiological underpinnings remain poorly understood. This study investigated attentional biases to positive and negative emotional words as possible contributing mechanisms. METHODS: Event-related potentials (ERPSs) and behavioral attention bias indices were recorded from 39 adult patients with ADHD and 41 healthy controls during a verbal dot-probe task with positive-neutral, negative-neutral, and neutral-neutral word pairs. RESULTS: Cue-locked N2pc amplitudes indicated a significant attentional bias towards emotional words in patients with ADHD and healthy controls. In healthy controls, the bias was only significant in positive trials. In patients, the bias was associated with ADHD severity and self-reported poor emotion regulation skills. ADHD patients also exhibited reduced target-locked P1 amplitudes and inferior behavioral performance compared with healthy controls. CONCLUSIONS: Our findings provide evidence of an attention bias to positive and negative emotional stimuli in adult patients with ADHD and adverse effects of emotional stimuli on task performance. SIGNIFICANCE: An attentional bias to emotional stimuli might contribute to emotional reactivity and dysregulation in adult patients with ADHD.

[Traumatology in the elderly : Multimodal prevention of delirium and use of augmentation techniques]. / Alterstraumatologie : Multimodale Delirprävention und Verwendung von Augmentationstechniken.

Recent data show that 20-80% of surgery patients are affected by delirium during inpatient clinical treatment. The medical consequences are often dramatic and include a 20 times higher mortality and treatment expenses of the medical unit increase considerably. At the University Hospital of Münster a multimodal and interdisciplinary concept for prevention and management of delirium was developed: all patients older than 65 years admitted for surgery are screened by a specialized team for the risk of developing delirium and treated by members of the team if there is a risk of delirium. Studies proved that by this multimodal approach the incidence of delirium was lowered and therefore the quality of medical care improved.When surgical treatment of fractures in the elderly is required, limited bone quality as well as pre-existing implants can complicate the procedure. Secondary loss of reduction after osteosynthesis and avulsion of the implant in particular must be prevented. Augmentation of the osteosynthetic implant with bone cement can increase the bone-implant interface and therefore stability can be improved. Additional intraoperative 3D imaging can be necessary depending on the localization of the fracture. In biomechanical studies we could prove greater stability in the osteosynthesis of osteoporotic fractures of the distal femur when using additional bone cement; therefore, the use of bone cement is an important tool, which helps to prevent complications in the surgical treatment of fractures in the elderly. Nevertheless, special implants and technical skills are required and some safety aspects should be considered.

Deficient interference control during working memory updating in adults with ADHD: An event-related potential study.

OBJECTIVE: Little is known about the underlying mechanisms of poor working memory (WM) performance of adults with attention deficit hyperactivity disorder (ADHD). This study investigates interference and load effects during WM updating by use of event-related potentials. METHOD: Forty ADHD patients and 41 controls performed verbal n-back tasks under conditions of low and high WM load. Intrusion probes, i.e., lures, were implemented to challenge interference control abilities during WM processing. RESULTS: Stimulus-dependent N200 amplitude modulation and behavioral performance in lure trials were reduced in adults with ADHD compared to healthy controls. Also, P300 amplitudes tended to be less sensitive to WM load in patients with ADHD. CONCLUSION: Our findings provide electrophysiological evidence for inaccurate discrimination of stimulus categories. Particularly, deficient interference control may lead to overt WM deficits in adult subjects with ADHD. SIGNIFICANCE: The current findings contribute to a deeper understanding of the neural substrates of executive dysfunction in adult ADHD, focusing on the domain of WM.

Multimodal imaging of a tescalcin (TESC)-regulating polymorphism (rs7294919)-specific effects on hippocampal gray matter structure.

In two large genome-wide association studies, an intergenic single-nucleotide polymorphism (SNP; rs7294919) involved in TESC gene regulation has been associated with hippocampus volume. Further characterization of neurobiological effects of the TESC gene is warranted using multimodal brain-wide structural and functional imaging. Voxel-based morphometry (VBM8) was used in two large, well-characterized samples of healthy individuals of West-European ancestry (Münster sample, N=503; SHIP-TREND, N=721) to analyze associations between rs7294919 and local gray matter volume. In subsamples, white matter fiber structure was investigated using diffusion tensor imaging (DTI) and limbic responsiveness was measured by means of functional magnetic resonance imaging (fMRI) during facial emotion processing (N=220 and N=264, respectively). Furthermore, gene x environment (G × E) interaction and gene x gene interaction with SNPs from genes previously found to be associated with hippocampal size (FKBP5, Reelin, IL-6, TNF-α, BDNF and 5-HTTLPR/rs25531) were explored. We demonstrated highly significant effects of rs7294919 on hippocampal gray matter volumes in both samples. In whole-brain analyses, no other brain areas except the hippocampal formation and adjacent temporal structures were associated with rs7294919. There were no genotype effects on DTI and fMRI results, including functional connectivity measures. No G × E interaction with childhood maltreatment was found in both samples. However, an interaction between rs7294919 and rs2299403 in the Reelin gene was found that withstood correction for multiple comparisons. We conclude that rs7294919 exerts highly robust and regionally specific effects on hippocampal gray matter structures, but not on other neuropsychiatrically relevant imaging markers. The biological interaction between TESC and RELN pointing to a neurodevelopmental origin of the observed findings warrants further mechanistic investigations.

[High-functioning autism spectrum disorders in adulthood]. / Autismusspektrumstörungen mit hohem Funktionsniveau im Erwachsenenalter.

The prevalence of autism spectrum disorders in the general population is approximately 1 %. Some individuals with high-functioning autism graduate from regular schools without autism having been diagnosed and problems only occur when the demands for social competence increase. Then patients often present with secondary psychiatric symptoms, such as depression, anxiety or interpersonal problems. At this time, typical autistic features, such as social interaction deficits, restricted interests and stereotypic behavior can be camouflaged by high compensatory skills, particularly in highly intelligent patients. Therefore, missed or wrong diagnoses are frequent. Interviews, questionnaires and neuropsychological tests might be used to support the diagnosis. In cases where there is evidence for a secondary cause of autistic symptoms, somatic disorders should be excluded. Pharmacological treatment should be symptom-oriented. Individualized psychotherapeutic approaches are becoming increasingly more available; however, pragmatic solutions often need to be deployed.

Identification of a biological signature for schizophrenia in serum.

Biomarkers are now used in many areas of medicine but are still lacking for psychiatric conditions such as schizophrenia (SCZ). We have used a multiplex molecular profiling approach to measure serum concentrations of 181 proteins and small molecules in 250 first and recent onset SCZ, 35 major depressive disorder (MDD), 32 euthymic bipolar disorder (BPD), 45 Asperger syndrome and 280 control subjects. Preliminary analysis resulted in identification of a signature comprised of 34 analytes in a cohort of closely matched SCZ (n=71) and control (n=59) subjects. Partial least squares discriminant analysis using this signature gave a separation of 60-75% of SCZ subjects from controls across five independent cohorts. The same analysis also gave a separation of ~50% of MDD patients and 10-20% of BPD and Asperger syndrome subjects from controls. These results demonstrate for the first time that a biological signature for SCZ can be identified in blood serum. This study lays the groundwork for development of a diagnostic test that can be used as an aid for distinguishing SCZ subjects from healthy controls and from those affected by related psychiatric illnesses with overlapping symptoms.

Neuropeptide S receptor gene -- converging evidence for a role in panic disorder.

Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In this study, a multilevel approach was applied to further elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn¹°7Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case-control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli.

Automatic brain response to facial emotion as a function of implicitly and explicitly measured extraversion.

Extraversion/introversion is a basic dimension of personality that describes individual differences in social behavior and sensory sensitivity. Previous neuroimaging research exclusively relied on self reports for assessing personality traits. In recent years, implicit measures of personality have been developed that aim at assessing the implicit self-concept of personality and complement self report instruments which are thought to measure aspects of the explicit self-concept of personality. In the present study functional magnetic resonance imaging was used to examine automatic brain reactivity to facial expression as a function of both implicitly and explicitly measured extraversion in 30 healthy women. Sad, happy, and neutral faces were presented for 33 ms masked by neutral faces beside a no face control condition. Subjects evaluated the briefly shown neutral mask faces. The Implicit Association Test (IAT) and the NEO Five-Factor Inventory (NEO-FFI) were applied as measures of extraversion which were not correlated in our sample. IAT extraversion was negatively correlated with automatic reactivity of the caudate head, thalamus, and inferior frontal cortex to sad faces. NEO-FFI extraversion was negatively correlated with response of the inferior frontal cortex and putamen to sad faces. For masked happy faces, an inverse correlation of the IAT effect for extraversion with activation of the caudate head and superior parietal lobule was observed. NEO-FFI extraversion was inversely correlated with the response of the thalamus to happy faces. Neither NEO-FFI extraversion nor IAT effect were significantly related to brain response to masked neutral faces (compared to the no face condition). Taken together, a specific heightened responsivity of the fronto-striatal-thalamic circuit to facial emotions which are arousing stimuli might underlie introverts' preference for avoiding social interactions. Research on the neurobiology of extraversion could benefit from the application of implicit in addition to explicit measurement instruments when automatic neural responses are investigated.

[Theory of mind in schizophrenia: clinical aspects and empirical research]. / Theory of Mind bei Schizophrenien: Klinische und wissenschaftliche Aspekte.

The term Theory of Mind (ToM) refers to the capacity to infer one's own and other persons' mental states. A substantial body of research has highlighted impaired ToM in a variety of neuropsychiatric disorders, including schizophrenia. There is good empirical evidence that ToM is specifically impaired in schizophrenia and that many psychotic symptoms--for instance, delusions of alien control and persecution--may best be understood in light of a disturbed capacity in patients to relate their own intentions to executing behavior, and to monitor others' intentions. However, it is still under debate if impaired ToM in schizophrenia is a state- or trait marker and whether patients could benefit from cognitive training in this domain. Recently, research has not only emphasized social cognitive deficits in patients, but has also focussed on interactions between ToM with language and other cognitive functions. Furthermore, interest in subprocesses of social cognition in psychotic spectrum disorders (e. g. schizotypy) is growing. The aim of this article is to line out clinical aspects of disturbed social cognition, to clarify terms used in this context as well as to present the latest research approaches into social cognition deficits.

The functional anatomy of semantic retrieval is influenced by gender, menstrual cycle, and sex hormones.

This study examines the neurobiology of semantic retrieval and describes the influence of gender, menstrual cycle, and sex hormones on semantic networks. Healthy right-handed subjects (12 men, 12 women) were investigated with 3T-fMRI during synonym generation. Behavioral performance and sex hormone levels were assessed. Women were examined during the early follicular and midluteal cycle phase. The activation pattern in all groups involved left frontal and temporal as well as bilateral medial frontal, cingulate, occipital, basal ganglia, and cerebellar regions. Men showed greater left frontal activation than women in both menstrual cycle phases. Women yielded high correlations of left prefrontal activation with estradiol in the midluteal phase and with progesterone in both phases. Testosterone levels correlated highly with left prefrontal activation in all three groups. In all, we describe a cerebral network involved in semantic processing and demonstrate that it is significantly affected by gender and sex steroid hormones.

Functional anatomy of visuo-spatial working memory during mental rotation is influenced by sex, menstrual cycle, and sex steroid hormones.

Recent observations indicate that sex and level of steroid hormones may influence cortical networks associated with specific cognitive functions, in particular visuo-spatial abilities. The present study probed the influence of sex, menstrual cycle, and sex steroid hormones on 3D mental rotation and brain function using 3-T fMRI. Twelve healthy women and 12 men were investigated. Menstrual cycle and hormone levels were assessed. The early follicular and midluteal phase of the menstrual cycle were chosen to examine short-term cyclical changes. Parietal and frontal areas were activated during mental rotation in both sexes. Significant differences between men and women were revealed in both phases of menstrual cycle. In men we observed a significant correlation of activation levels with testosterone levels in the left parietal lobe (BA 40). In women, a cycle-dependent correlation pattern was observed for testosterone: brain activation correlated with this male hormone only during the early follicular phase. In both cycle phases females' brain activation was significantly correlated with estradiol in frontal and parietal areas. Our study provides evidence that fMRI-related activity during performance of cognitive tasks varies across sex and phases of the menstrual cycle. The variation might be partly explained by better task performance in men, but our results indicate that further explanations like basic neuronal or neurovascular effects modulated by steroid hormones must be considered. Both estradiol and testosterone levels may influence fMRI signals of cognitive tasks, which should affect selection of subjects for future fMRI studies.

Complicated grief after traumatic loss: a 14-month follow up study.

The traumatic loss of an unborn child after TOP due to fetal malformation and/or severe chromosomal disorders in late pregnancy is a major life-event and a potential source of serious psychological problems for those women. To obtain information on the course of grief following a traumatic loss, 62 women who had undergone TOP between the 15th and 32nd gestational week were investigated in a longitudinal study design and compared with 65 women after spontaneous delivery of a full-term healthy child. Grief, posttraumatic stress, depression, anxiety and psychiatric disorders were evaluated 14 days, 6 months and 14 months after the event, implementing validated self-report and clinician rated instruments. Compared to women after spontaneous delivery, women after induced TOP were significantly more stressed regarding all psychological outcomes at all three measuring points. Especially, 14 months after TOP 13.7% of the women fulfilled all criteria of a complicated grief diagnoses following Horowitz et al. (1997, Am J Psychiat 154:7904-7910). 16.7% were diagnosed as having a manifest psychiatric disorder according to DSM-IV. All in all, 25% of these women were critically affected by the traumatic loss. TOP for fetal anomaly is to be seen as a major life event, which causes complicated grief reactions and psychiatric disorders for a substantial number of women.

Serotonergic genes modulate amygdala activity in major depression.

Serotonergic genes have been implicated in the pathogenesis of depression probably via their influence on neural activity during emotion processing. This study used an imaging genomics approach to investigate amygdala activity in major depression as a function of common functional polymorphisms in the serotonin transporter gene (5-HTTLPR) and the serotonin receptor 1A gene (5-HT(1A)-1019C/G). In 27 medicated patients with major depression, amygdala responses to happy, sad and angry faces were assessed using functional magnetic resonance imaging at 3 Tesla. Patients were genotyped for the 5-HT(1A)-1019C/G and the 5-HTTLPR polymorphism, including the newly described 5-HTT-rs25531 single nucleotide polymorphism. Risk allele carriers for either gene showed significantly increased bilateral amygdala activation in response to emotional stimuli, implicating an additive effect of both genotypes. Our data suggest that the genetic susceptibility for major depression might be transported via dysfunctional neural activity in brain regions critical for emotion processing.

Trauma and grief 2-7 years after termination of pregnancy because of fetal anomalies--a pilot study.

The aim of the study was to obtain information on the long-term posttraumatic stress response and grief several years after termination of pregnancy due to fetal malformation. We investigated 83 women who had undergone termination of pregnancy between 1995 and 1999 and compared them with 60 women 14 days after termination of pregnancy and 65 women after the spontaneous delivery of a full-term healthy child. Women 2-7 years after termination of pregnancy were expected to show a significantly lower degree of traumatic experience and grief than women 14 days after termination of pregnancy. Contrary to the hypothesis, however, the results showed no significant intergroup differences with respect to the degree of traumatic experience. With the exception of one subscale (fear of loss), this also applied to the grief reported by the women. However, both groups differed significantly in their posttraumatic stress response from women who had given spontaneous birth to a full-term healthy child. The results indicate that termination of pregnancy is to be seen as an emotionally traumatic major life event which leads to severe posttraumatic stress response and intense grief reactions that are still detectable some years later.

Maternal posttraumatic stress response after the birth of a very low-birth-weight infant.

OBJECTIVE: For parents, the premature birth of a child represents a traumatic event for which they are poorly prepared. To date, the focus of scientific interest has been on maternal psychological stress responses, such as anxiety and depression, or on appropriate coping mechanisms, whereas only scant attention has been paid to the traumatic aspect of the maternal experience after very low-birth-weight (VLBW) birth. The present study is the first to investigate the posttraumatic stress response of mothers after the birth of a VLBW infant in a prospective longitudinal study. METHODS: Fifty mothers of VLBW infants were examined at four measuring time points (1-3 days pp, 14 days pp and 6 and 14 months pp) with respect to posttraumatic symptoms [Impact of Event Scale (IES-R)], psychiatric diagnosis (SKID I for DSM-IV) and the extent of depression [Beck Depression Inventory (BDI) and Montgomery Asberg Depression Scale (MADRS)] and anxiety [State-Trait Anxiety Inventory (STAI) and Hamilton Anxiety Scale (HAMA)]. The control group comprised a group of 30 mothers after the uncomplicated spontaneous birth of a healthy child. RESULTS: At all four measuring timepoints (except 6 months pp), the mothers of the premature infants recorded significantly higher values for traumatic experience and depressive symptoms and anxiety compared with the controls. In contrast to the mothers in the control group, the mothers of the premature infants displayed no significant reduction in posttraumatic symptoms (IES-total), even 14 months after birth. CONCLUSION: The results indicate that the situation of a mother who has given birth to a VLBW infant is a complex, with long-term traumatic event necessitating ongoing emotional support extending beyond the period immediately after the birth.

N-acetylaspartate levels of left frontal cortex are associated with verbal intelligence in women but not in men: a proton magnetic resonance spectroscopy study.

The left frontal cortex plays an important role in executive function and complex language processing inclusive of spoken language. The purpose of this work was to assess metabolite levels in the left and right prefrontal cortex and left anterior cingulum by proton magnetic resonance spectroscopy and relate results to verbal intelligence (Wechsler Adult Intelligence Scale revised) in a sample of college-educated healthy volunteers (dorsolateral prefrontal cortex [DLPFC]: n=52, 23 females, and left anterior cingulum: n=62, 22 females; age range: 20-75 years). In women only, N-acetylaspartate in the DLPFC and in the left anterior cingulate cortex was positively correlated with vocabulary scores. Our data support the hypothesis of existing gender differences regarding the involvement of the left frontal cortex in verbal processing as reflected in different correlations of specific metabolites with verbal scores.

Incidental learning of food and emotional words in women with anorexia nervosa.

Prior research suggests that anorexic patients show a memory bias for fattening foods when they are processed in depth or with reference to the self. The present study examined whether anorexic subjects exhibit a bias for fattening foods when these are presented as task-irrelevant distractor stimuli. It also investigated whether anorexic patients pay less attention to emotion stimuli. A sequential word-word evaluation task was administered to 11 inpatients with anorexia nervosa and 11 non-dieting normal subjects. There were four types of distractor words: high caloric foods, positive, negative, and neutral. Anorexic patients recalled no more food words but fewer neutral and positive words than normal subjects. The present data suggest that, compared to healthy young women, anorexic patients show no memory bias for fattening foods when these data are presented as peripheral environmental information. Anorexic patients are perceptually no less sensitive to negative emotional information than normal subjects.

Grief after termination of pregnancy due to fetal malformation.

Termination of pregnancy for fetal malformation is a traumatic event which any woman finds hard to withstand and which entails the risk of severe and complicated grieving. This paper presents three cases illustrating the trauma and coping mechanisms. Grieving continued for over 6 months in all cases and included pathological anxiety and depression. We offer advice and counselling to such women.

Metabolic changes within the left dorsolateral prefrontal cortex occurring with electroconvulsive therapy in patients with treatment resistant unipolar depression.

BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) is involved in the pathophysiology of major depression. In particular, metabolic (functional hypometabolism) and structural alterations have been described. In this study metabolic changes within the DLPFC of severely depressed patients before and after electroconvulsive therapy (ECT) were evaluated by proton STEAM spectroscopy (1H-MRS). METHOD: Twelve severely depressed patients with a diagnosis of major depressive episode, unipolar with melancholic features (DSM-IV), were enrolled, and the left dorsolateral prefrontal cortex (DLPFC) was investigated before and after unilateral ECT by 1H-MRS. Three of the four non-responding patients were remeasured a third time after a combined ECT/antidepressant pharmacotherapy. The results were compared with 12 age- and gender-matched controls. RESULTS: In depressed patients reduced glutamate/glutamine (Glx) levels were measured pre-ECT; Glx concentrations correlated negatively with severity of depression. After successful treatment, Glx increased significantly and levels no longer differed from those of age-matched controls. CONCLUSIONS: Our results indicate that major depressive disorder is accompanied by state-dependent metabolic alterations, especially in glutamate/glutamine metabolism, which can be reversed by successful ECT.