Deficient inhibitory processing in trait anxiety: Evidence from context-dependent fear learning, extinction recall and renewal.

BACKGROUND: Impaired fear inhibition has been described as a hallmark of pathological anxiety. We aimed at further characterizing the relation between fear inhibition and anxiety by extending previous work to contextual safety stimuli as well as to dimensional scores of trait anxiety in a large sample. METHODS: We employed a validated paradigm for context-dependent fear acquisition/extinction (day 1) and retrieval/expression (day 2) in 377 healthy individuals. This large sample size allowed the employment of a dimensional rather than binary approach with respect to individual differences in trait anxiety. RESULTS: We observed a positive correlation on day 1 between trait anxiety with all CSs that possess an inherent inhibitory component, conveyed either by reliable non-reinforcement of a specific CS in a dangerous context (safe cue) or by the context itself (i.e., safe context). No correlation however was observed for a CS that possesses excitatory (threatening) properties only. These results were observed during fear learning (day 1) for US expectancy and fear ratings but not for SCRs. No such pattern was evident during fear and extinction retrieval/expression (day 2). CONCLUSION: We provide further evidence that high trait anxiety is associated with the inability to take immediate advantage of environmental safety cues (cued and contextual), which might represent a promising trans-diagnostic marker for different anxiety disorders. Consequently, the incorporation of methods to optimize inhibitory learning in current cognitive behavioral therapy (CBT) treatments might open up a promising avenue for precision medicine in anxiety disorders. LIMITATIONS: We did not include patients diagnosed with anxiety disorders.

Maternal interpersonal affiliation is associated with adolescents' brain structure and reward processing.

Considerable animal and human research has been dedicated to the effects of parenting on structural brain development, focusing on hippocampal and prefrontal areas. Conversely, although functional imaging studies suggest that the neural reward circuitry is involved in parental affection, little is known about mothers' interpersonal qualities in relation to their children's brain structure and function. Moreover, gender differences concerning the effect of maternal qualities have rarely been investigated systematically. In 63 adolescents, we assessed structural and functional magnetic resonance imaging as well as interpersonal affiliation in their mothers. This allowed us to associate maternal affiliation with gray matter density and neural responses during different phases of the well-established Monetary Incentive Delay task. Maternal affiliation was positively associated with hippocampal and orbitofrontal gray matter density. Moreover, in the feedback of reward hit as compared with reward miss, an association with caudate activation was found. Although no significant gender effects were observed in these associations, during reward feedback as compared with baseline, maternal affiliation was significantly associated with ventral striatal and caudate activation only in females. Our findings demonstrate that maternal interpersonal affiliation is related to alterations in both the brain structure and reward-related activation in healthy adolescents. Importantly, the pattern is in line with typical findings in depression and post-traumatic stress disorder, suggesting that a lack of maternal affiliation might have a role in the genesis of mental disorders.

Boys do it the right way: sex-dependent amygdala lateralization during face processing in adolescents.

Previous studies have observed a sex-dependent lateralization of amygdala activation related to emotional memory. Specifically, it was shown that the activity of the right amygdala correlates significantly stronger with memory for images judged as arousing in men than in women, and that there is a significantly stronger relationship in women than in men between activity of the left amygdala and memory for arousing images. Using a large sample of 235 male adolescents and 235 females matched for age and handedness, we investigated the sex-specific lateralization of amygdala activation during an emotional face perception fMRI task. Performing a formal sex by hemisphere analysis, we observed in males a significantly stronger right amygdala activation as compared to females. Our results indicate that adolescents display a sex-dependent lateralization of amygdala activation that is also present in basic processes of emotional perception. This finding suggests a sex-dependent development of human emotion processing and may further implicate possible etiological pathways for mental disorders most frequent in adolescent males (i.e., conduct disorder).

[Functional magnetic resonance imaging and antipsychotics. Overview and own data]. / Funktionelle Magnetresonanztomographie und Antipsychotika. Uberblick und eigene Daten.

Recently, there has been growing interest in using functional magnetic resonance imaging (fMRI) for the evaluation of psychopharmacological drugs. fMRI studies in healthy human volunteers and psychiatric patients focus on cerebral activity following acute drug administration (single challenge) and on adaptive effects on neural networks due to long-term medication. In our own fMRI studies, the effects of olanzapine or amisulpride in never treated or medication-free schizophrenic patients using robust motor, visual, and acoustic tasks was longitudinally examined. In agreement with previous reports in the literature it could be shown that, in contrast to traditional neuroleptics, atypical drugs do not decrease the activation of the sensorimotor cortex but rather normalize the reduced frontoparietal activation as well as the neuropsychological test results. This encourages the assumption that atypical antipsychotics seem to support the recovery or normalization of frontoparietal brain dysfunction in schizophrenia. However, with these new opportunities additional methodological considerations and limitations emerge.

[Depression and modern neuroimaging]. / Depression und moderne Bildgebung - Eine Ubersicht des aktuellen Forschungsstandes zur Anwendung bildgebender Verfahren bei depressiven Störungen -

Modern neuroimaging like PET, SPECT, MR-Volumetry, functional MRI and MR-Spectroscopy has effectively advanced research on aetiology, pathogenesis and therapy options of depressive disorders. This review highlights the status of current research on this topic. Consistent with morphological findings, which report alterations in regions of emotionally relevant networks of the brain in depressive disorders, findings of functional studies point to changes in the basal ganglia, the frontal cortex and the limbic system involving the hippocampus and the amygdala. During processing of emotional cues depressive patients show different activation patterns in the regions of the frontal lobe and the amygdala. In our study of a subgroup we were also able to show deficits in processing cues independently from the emotional quality of the stimulus - especially in posterior-parietal and prefrontal areas. In healthy subjects affective modulation correlates with an ordered interaction of ventral-limbic and dorsal-neocortical regions of the brain, which become unbalanced in depressive disorders. In the future, modern neuroimaging will open promising fields of research, which aim at the identification of valid neurofunctional subgroups of the heterogeneous affective disorders and the development of more adjusted and efficient therapy strategies.

[Neuropsychiatric aspects of Huntington chorea. Presentation of 2 cases and review of the literature]. / Neuropsychiatrische Aspekte der Chorea Huntington. Vorstellung zweier Fälle und Literaturübersicht.

Huntington's disease (HD) is an autosomal, dominant, inherited disorder of the central nervous system with characteristic neurodegenerative alterations in the basal ganglia and cortex. Dependent on the individual CAG expansion load, disease onset occurs between the third or fourth decade of life, entailing an invariably lethal progression within 10 to 20 years. Although the clinical picture is characterized equally by cognitive and psychiatric disturbances, the apparent neurodegenerative alterations and presentation as a choreatic movement disorder account for the traditional link of Huntington's disease to the field of neurology. In contrast to the traditionally emphasized core features of chorea and dementia, recent empirical evidence points to the frequent emergence of nonchoreatic motor signs and subtle cognitive and psychiatric complaints, especially in asymptomatic gene carriers and early disease stages. The case studies presented here emphasize the spectrum of neuropsychiatric phenomena associated with HD and illustrate the resulting difficulties of differential diagnosis in clinical settings. Furthermore, current scientific knowledge of HD pleiotrophy is reviewed and the diagnostic power of specific neuropsychological approaches is explained.

Prediction of treatment response to rivastigmine in Alzheimer's dementia.

OBJECTIVES: To predict the treatment response to rivastigmine in patients with Alzheimer's dementia using neuropsychological and EEG data. METHODS: A neuropsychological examination and a quantitative EEG study were done in 20 patients with Alzheimer's dementia before initiating treatment with rivastigmine. After one week of treatment a second EEG examination was done. Therapeutic efficacy was determined six months after treatment initiation. Treatment response was defined as improvement in short term memory after six months of rivastigmine treatment. RESULTS: For the group of patients as a whole, there was a significant improvement in short term memory and orientation during rivastigmine treatment. The mini-mental state score improved from 20.2 to 21.7 (NS). In the EEG, theta power decreased significantly after one week of treatment. Treatment responders had a greater decrease in theta power after one week of treatment and a better short term memory at baseline than non-responders. Decrease in theta power during rivastigmine treatment and baseline short term memory were good predictors of treatment response. CONCLUSIONS: Generally available neuropsychological and EEG data may be useful for predicting response to rivastigmine in patients with Alzheimer's disease.

Short-term effects of acetylcholinesterase inhibitor treatment on EEG and memory performance in Alzheimer patients: an open, controlled trial.

INTRODUCTION: Acetylcholinesterase inhibitor treatment enhances cholinergic neurotransmission and may thus partially reverse EEG slowing and memory impairment in Alzheimer patients within short time. METHODS: We studied the short-term effects of treatment with either rivastigmine or donepezil on EEG and memory performance in a group of 35 Alzheimer patients in an open, controlled design. RESULTS: Under a 1- or 2-week acetylcholinesterase inhibitor treatment, a decrease of global theta power and an improvement in the ADAS memory score were observed. However, compared to the control condition, only the theta power decrease remained significant and can be definitely considered a medication effect. DISCUSSION: EEG spectral analysis could be shown to rapidly reflect the cerebral cholinergic action of short-term acetylcholinesterase inhibitor treatment. Whether this action is related to the therapeutic efficacy of this type of drug must be determined in further longitudinal studies.

EEG coherence in Alzheimer's dementia.

In Alzheimer's dementia (AD) axonal disruption and cholinergic deficit lead to impaired cortical connectivity and to a decrease in EEG alpha coherence. The aim of the present study was to assess the usefulness of coherence parameters of the EEG for the diagnostics of AD. Quantitative EEG analyses were performed in 31 AD patients and 17 cognitively unimpaired depressive controls, both groups without psychopharmacological treatment. Differences between groups were examined and the diagnostic significance of EEG parameters was assessed by means of stepwise logistic regression analyses. In the AD patients global theta power was increased, left temporal alpha coherence and interhemispheric theta coherence were decreased. Left temporal alpha coherence and global theta power allowed an identification of AD patients with a sensitivity of 87% and a specificity of 77%. Quantitative analyses, especially the determination of left temporal alpha coherence, may enhance the usefulness of the EEG in the diagnostics of AD.

[Functional magnetic resonance imaging of psychopharmacological brain effects: an update]. / Funktionelle Kernspintomographie (fMRI) und Psychopharmakaeffekte: Eine Standortbestimmung.

Functional magnetic resonance imaging (fMRI) is well established for the examination of functional activity in the living brain. The method permits the development of functional activation maps during perceptual, cognitive and emotional efforts with a high temporal and spatial resolution. As of late there has been growing interest in using this technique to investigate regionally specific brain activity following the administration of drugs such as nicotine, cocaine, lorazepam, scopolamine, antipsychotics or antidepressants. Studies in experimental animals investigate signal changes associated with the administration of psychopharmacological substances in different brain areas using a high magnetising field (> 4 Tesla). FMRI-studies in healthy human volunteers and psychiatric patients focus on cerebral activity following acute drug administration (single challenge) and on adaptive effects of the CNS due to long- term medication. Their results provide insights into brain physiology and neuropharmacological mechanisms which are in turn relevant for preclinical pharmacological studies, responder analyses and for the investigation of pathogenetic models in psychiatric diseases. However, with these new opportunities, additional methodological considerations and limitations emerge. Besides the need of controlling motion artefacts, the influence of interfering psychological variables, an exact specification of the experimental design, a standardised analysis for data adjustment and technical limitations have to be considered. This article provides an overview of the underlying model of brain function, present applications, future possibilities and methodological limitations of fMRI for the understanding of human psychopharmacology.

Short-term rivastigmine treatment reduces EEG slow-wave power in Alzheimer patients.

The effects of a 5-day treatment with rivastigmine on the resting EEG power spectrum were studied in 15 mildly to moderately ill Alzheimer patients. In these patients, beta power was positively correlated with cognitive performance and negatively correlated with functional impairment. Rivastigmine produced a decrease in delta and theta power with no effect of hemisphere and electrode position. Delta power decrease reflects the cerebral cholinergic action of rivastigmine and may thus allow a quantitative assessment of its CNS effects.

Day-clinic treatment of late-life depression.

BACKGROUND: There are few studies evaluating treatment in gerontopsychiatric day-clinics. In this paper, data are presented on the outcome of day-clinic treatment in late-life depression. METHOD: Forty-four depressed elderly patients (mean Hamilton Depression Score: 17.6) were examined at admission and discharge for psychopathology, functioning in daily living, social situation, burden with medical disease and quality of life. RESULTS: At discharge, the patients showed a significant reduction in depressive symptoms, improvements in cognitive performance, social activities and contacts. However, a more detailed analysis revealed that only patients responding to treatment (n=20) improved in the respective parameters. Patients, who did not recover fully from depression (n=24), did not improve in any of these parameters. At admission, responders and nonresponders did not differ concerning quality of life. At discharge, responders were significantly more satisfied in 11 of 20 domains of life quality. A shorter life time duration of depressive disease and male sex were predictive for a remission of depression. Thus, it could be shown that a considerable number of patients suffering from late-life depression may be successfully treated in a gerontopsychiatric day-clinic and 45.5% fully recover from depression. CONCLUSIONS: The day-clinic setting meets the specific needs of patients suffering from late-life depression by maintaining them in the community, supporting their abilities for self-care and promoting social contacts. Treatment in a day-clinic may be recommended for many elderly depressed patients.

[Social status and life satisfaction of the elderly]. / Soziale Situation und Lebenszufriedenheit im Alter.

A rating instrument suited for a standardized evaluation of the social situation within a geriatric assessment is presented. The social dimensions "activities", "contacts", "living" and "finances" are screened by means of four to ten items and reflected by respective scores. The instrument was applied in a study group of 60 elderly persons of the general population and evaluated by means of life satisfaction measures. Positive correlations between the dimensions of the social situation and the respective domains of life satisfaction were found. Cut-offs, allowing the identification of patients, whose social situation is indicative for a low life satisfaction, are proposed.

[Anxiety as a concomitant symptom of depression in the elderly]. / Angst als Begleitsymptom der Altersdepression.

Anxiety is a symptom frequently encountered in elderly depressed patients. It is supposed to have an unfavourable prognostic impact. We studied the frequency of psychic anxiety and its relationship to demographic, social and clinical variables in a group of 54 elderly depressed patients admitted to a gerontopsychiatric day-clinic. Severity of depression, cognitive performance, functional level, social situation and life satisfaction were studied by means of standardized instruments. In about half of the patients studied, we found significant psychic anxiety. Compared to the other depressed patients, patients with anxiety suffered more frequently from cognitive impairment and were more dissatisfied with the acceptance of their disease by other persons. They more frequently lived together with other persons in one household. When leaving psychic anxiety out of consideration as a depressive symptom, the severity of depression was not different in patients with and without anxiety. Anxious patients were equally responsive to day-clinic treatment as non-anxious patients. However, duration of treatment was considerably increased. Thus, elderly depressed patients with anxiety show particular psychosocial and clinical features and require special attention in diagnostics and treatment.

[Outcome quality of gerontopsychiatric day-clinic treatment: changes in life-satisfaction:]. / Ergebnisqualität teilstationärer gerontopsychiatrischer Behandlung: Veränderungen der Lebenszufriedenheit.

OBJECTIVE: The variety of institutional treatments in psychiatry, as well as financial aspects make it necessary to evaluate these institutions for the quality of their medical care. At the Central Institute of Mental Health in Mannheim, the quality of treatment at the geronto-psychiatric day-clinic is assessed on the level of outcome quality. METHOD: The patients are examined at admission, at discharge, half a year and one year after discharge. Psychopathology, activities of daily living, social situation and quality of life are assessed by means of standardized instruments. RESULTS: Preliminary results show that at discharge, patients are less depressed, have achieved a higher level of social activities and contacts and that their quality of life improved in most domains. In some domains of quality of life improvement is highly correlated with the amelioration of depressive symptoms, in others not. CONCLUSION: Whether these effects of treatment will last, has to be studied in follow-up examinations.