Promoting stigma coping and empowerment in patients with schizophrenia and depression: results of a cluster-RCT.

There is a need for interventions supporting patients with mental health conditions in coping with stigma and discrimination. A psycho-educational group therapy module to promote stigma coping and empowerment (STEM) was developed and tested for efficacy in patients with schizophrenia or depression. 30 clinical centers participated in a cluster-randomized clinical trial, representing a broad spectrum of mental health care settings: in-patient (acute treatment, rehabilitation), out-patient, and day-hospitals. As randomized, patients in the intervention group clusters/centers received an illness-specific eight sessions standard psychoeducational group therapy plus three specific sessions on stigma coping and empowerment ('STEM'). In the control group clusters the same standard psychoeducational group therapy was extended to 11 sessions followed by one booster session in both conditions. In total, N = 462 patients were included in the analysis (N = 117 with schizophrenia spectrum disorders, ICD-10 F2x; N = 345 with depression, ICD-10 F31.3-F31.5, F32-F34, and F43.2). Clinical and stigma-related measures were assessed before and directly after treatment, as well as after 6 weeks, 6 months, and 12 months (M12). Primary outcome was improvement in quality of life (QoL) assessed with the WHO-QOL-BREF between pre-assessment and M12 analyzed by mixed models and adjusted for pre-treatment differences. Overall, QoL and secondary outcome measures (symptoms, functioning, compliance, internalized stigma, self-esteem, empowerment) improved significantly, but there was no significant difference between intervention and control group. The short STEM module has proven its practicability as an add-on in different settings in routine mental health care. The overall increase in empowerment in both, schizophrenia and depression, indicates patients' treatment benefit. However, factors contributing to improvement need to be explored.The study has been registered in the following trial registers. ClinicalTrials.gov: https://register.clinicaltrials.gov/ Registration number: NCT01655368. DRKS: https://www.drks.de/drks_web/ Registration number: DRKS00004217.

Incidental Memory Encoding Assessed with Signal Detection Theory and Functional Magnetic Resonance Imaging (fMRI).

In functional magnetic resonance imaging (fMRI) studies that apply a "subsequent memory" approach, successful encoding is indicated by increased fMRI activity during the encoding phase for hits vs. misses, in areas underlying memory encoding such as the hippocampal formation. Signal-detection theory (SDT) can be used to analyze memory-related fMRI activity as a function of the participant's memory trace strength (d(')). The goal of the present study was to use SDT to examine the relationship between fMRI activity during incidental encoding and participants' recognition performance. To implement a new approach, post-experimental group assignment into High- or Low Performers (HP or LP) was based on 29 healthy participants' recognition performance, assessed with SDT. The analyses focused on the interaction between the factors group (HP vs. LP) and recognition performance (hits vs. misses). A whole-brain analysis revealed increased activation for HP vs. LP during incidental encoding for remembered vs. forgotten items (hits > misses) in the insula/temporo-parietal junction (TPJ) and the fusiform gyrus (FFG). Parameter estimates in these regions exhibited a significant positive correlation with d('). As these brain regions are highly relevant for salience detection (insula), stimulus-driven attention (TPJ), and content-specific processing of mnemonic stimuli (FFG), we suggest that HPs' elevated memory performance was associated with enhanced attentional and content-specific sensory processing during the encoding phase. We provide first correlative evidence that encoding-related activity in content-specific sensory areas and content-independent attention and salience detection areas influences memory performance in a task with incidental encoding of facial stimuli. Based on our findings, we discuss whether the aforementioned group differences in brain activity during incidental encoding might constitute the basis of general differences in memory performance between HP and LP.

Empathy in individuals clinically at risk for psychosis: brain and behaviour.

BACKGROUND: Empathy is a basic human ability, and patients with schizophrenia show dysfunctional empathic abilities on the behavioural and neural level. AIMS: These dysfunctions may precede the onset of illness; thus, it seems mandatory to examine the empathic abilities in individuals at clinical high risk for psychosis. METHOD: Using functional magnetic resonance imaging, we measured 15 individuals at clinical high risk of psychosis (CHR group) and compared their empathy performance with 15 healthy volunteers and 15 patients with schizophrenia. RESULTS: Behavioural data analysis indicated no significant deficit in the CHR group. Functional data analysis revealed hyperactivation in a frontotemporoparietal network including the amygdala in the CHR group compared with the other two groups. CONCLUSIONS: Despite normal behavioural performance, the CHR group activated the neural empathy network differently and specifically showed hyperactivation in regions critical for emotion processing. This could suggest a compensatory mechanism reflecting emotional hypersensitivity or dysfunctional emotion regulation. Further investigations should clarify the role of these neural alterations for development and exacerbation of psychosis.

Neural correlates of the attention network test in schizophrenia.

Attentional deficits are prominent in schizophrenia, affecting nearly all cognitive functions. Human attention comprises three essential components: alerting, orienting and executive control. For the assessment of these functions, the attention network test (ANT) has been proposed and used in healthy controls and patients. In schizophrenia, the ANT has revealed behavioral deficits; however, the corresponding neural correlates have not been examined. In the present study, neural correlates of attention were investigated in 17 schizophrenia patients and 17 healthy controls using the ANT with fMRI. Behavioral deficits emerged in the alertness system with a reduced efficiency for temporal cues. In fMRI, changes were observed for all three domains-alerting, orienting and conflict-and revealed hyper- as well as hypoactivation in patients. Affected regions during alerting comprised a broad fronto-temporo-parieto-occipito-cerebellar network, while differences during orienting mainly tapped fronto-parietal regions and during conflict processing a thalamo-frontal-temporal occipital network including the postcentral regions. In general, hyperactivations were positively correlated with more severe psychopathologial symptoms.

Predicting acute affective symptoms after deep brain stimulation surgery in Parkinson's disease.

The current study aimed to investigate predictive markers for acute symptoms of depression and mania following deep brain stimulation (DBS) surgery of the subthalamic nucleus for the treatment of motor symptoms in Parkinson's disease (PD). Fourteen patients with PD (7 males) were included in a prospective longitudinal study. Neuropsychological tests, psychopathology scales and tests of motor functions were administered at several time points prior to and after neurosurgery. Pre-existing psychopathological and motor symptoms predicted postoperative affective side effects of DBS surgery. As these can easily be assessed, they should be considered along with other selection criteria for DBS surgery.

Neural correlates of emotion recognition in schizophrenia.

The following fMRI study aimed to characterize the neural correlates of explicit emotion discrimination in 17 patients with schizophrenia and 17 matched healthy controls. In patients, emotion recognition impairments were found to be paralleled by cerebral dysfunctions in the affective division of the anterior cingulate cortex, the bilateral dorsomedial prefrontal cortex, the right superior temporal gyrus and the right fusiform gyrus. While the patients' responses to emotional faces were characterized predominantly by hypoactivations, the neutral faces elicited hyperactivations mainly in the frontal and cingulate areas, and the basal ganglia, along with misattribution errors. The decreased activation in the fusiform face area during responses to both emotional and neutral stimuli may be indicative of general face processing deficits. Similar although less pronounced deficits have been observed in subjects at high risk of psychosis as well as in patients with early onset. In adult schizophrenia, the evidence of an imbalanced cerebral network appears early in the course of the illness, with the dysfunctions, as indicated by correlations here, becoming more pronounced in patients with longer illness duration.

Emotion-cognition interactions in schizophrenia.

OBJECTIVES: Negative emotion exerts a considerable influence on cognitive processes. This may have clinical implications in mental illnesses, such as schizophrenia, where negative emotions often prevail. Experimentally this influence can be studied by using olfactory emotion induction. METHODS: Fourteen schizophrenia patients and 14 healthy volunteers were investigated with functional magnetic resonance imaging with respect to the neural correlates of emotion-cognition interactions. Emotion was induced by odorants during an n-back working memory task. RESULTS: Similar detrimental effects of negative stimulation on working memory performance were observed in patients and control subjects. Among the neural correlates modulating this interaction a decreased activation emerged in patients in the anterior cingulate and the medial superior frontal cortex and increased activation in the medial orbitofrontal and middle frontal area. CONCLUSIONS: During emotion-cognition interaction hypoactivations were found in regions crucial for the monitoring/control of ongoing processes but also for emotion regulation. Decreased activations may reflect failure to adapt to higher task requirements. In contrast, increased activations could be indicative of a greater emotional response and irritation induced by the odour. These patterns may represent the neural correlates of an inefficient control of emotional influences on cognitive processes in patients with schizophrenia.

The interaction of working memory and emotion in persons clinically at risk for psychosis: an fMRI pilot study.

Subtle emotional and cognitive dysfunctions may already be apparent in individuals at risk for psychosis. However, there is a paucity of research on the neural correlates of the interaction of both domains. It remains unclear whether those correlates are already dysfunctional before a transition to psychosis. We used functional magnetic resonance imaging to examine the interaction of working memory and emotion in 12 persons clinically at high risk for psychosis (CHR) and 12 healthy subjects individually matched for age, gender and parental education. Participants performed an n-back task while negative or neutral emotion was induced by olfactory stimulation. Although healthy and psychosis-prone subjects did not differ in their working memory performance or the evaluation of the induced emotion, decreased activations were found in CHR subjects in the superior parietal lobe and the precuneus during working memory and in the insula during emotion induction. Looking at the interaction, CHR subjects, showed decreased activation in the right superior temporal gyrus, which correlated negatively with psychopathological scores. Decreased activation was also found in the thalamus. However, an increase of activation emerged in several cerebellar regions. Dysfunctions in areas associated with controlling whether incoming information is linked to emotional content and in the integration of multimodal information might lead to compensatory activations of cerebellar regions known to be involved in olfactory and working memory processes. Our study underlines that cerebral dysfunctions related to cognitive and emotional processes, as well as their interaction, can emerge in persons with CHR, even in absence of behavioral differences.

Brain imaging: on the way toward a therapeutic discipline.

Brain imaging has proven its importance as an essential tool of neuroscientific research, especially in psychiatry. Several of these methods at hand promise to enhance our understanding of function and dysfunction of neural processes and their disturbances in mental disorders in the near future. But the convincing success of imaging tools in research has not yet answered the demand to lead to new therapies or to new and useful tools in the diagnosis and treatment of single subjects. This article tries to point out how new methodological developments are promising to lead to a further step in this way. This therapeutic option is based on technical developments like high-field magnetic resonance imaging (MRI) or the further development of neurofeedback. This concept might make brain imaging such as realtime fMRI a therapeutic option at least in specialized institutions in the foreseeable future, especially since MR-scanners are already widely available nowadays.

Differential brain activation during facial emotion discrimination in first-episode schizophrenia.

BACKGROUND: Aberrant brain activation during facial emotion discrimination has been described in chronic schizophrenia, while little is known about early stages of the illness. The aim of the current study was to investigate valence-specific brain activation of emotion discrimination in first-episode schizophrenia. These patients provide the advantage of lacking the effects of long-term medication and chronic illness course and can hence further enhance the understanding of underlying psychopathological mechanisms. METHODS: Using event-related fMRI, we investigated 18 first-episode schizophrenia patients and 18 matched healthy subjects during an explicit emotion discrimination task presenting happy, sad and neutral monochromatic facial expressions. A repeated measure analysis of variance (ANOVA) with the factors Group (patients, healthy subjects), Gender and Emotion (happy, sad, neutral) was performed on behavioural and functional data. RESULTS: Behavioural performance did not differ between groups. Valence-independent hypoactivations in patients were observed for the anterior cingulate and orbitofrontal cortex while hyperactivations emerged in the posterior cingulate and the precuneus. Emotion-specific group differences were revealed in inferior parietal and orbitofrontal brain areas and the hippocampus. CONCLUSIONS: First-episode schizophrenia already affects areas involved in processing of both, emotions and primary facial information. Our study underlines the role of dysfunctional neural networks as the basis of disturbed social interactions in early schizophrenia.

Psychiatric symptoms in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder which is often reduced to a mere dysfunction of motor performance. Non-motor symptoms, however, are frequent impairments in PD and result in a major impact on the patients and their caregivers. The major neuropsychiatric comorbidities depression, anxiety, and psychotic symptoms are briefly discussed. Additionally, a brief outlook on deep brain stimulation and its effect on psychiatric symptoms is provided. Several studies did show that neuropsychiatric symptoms are underdiagnosed and consecutively treated inadequately. All in all more attention should be directed to the detection and treatment of psychiatric symptoms in PD patients in routine clinical settings.

Cerebral dysfunctions of emotion-cognition interactions in adolescent-onset schizophrenia.

OBJECTIVE: Schizophrenia is among the most severe of psychiatric disorders, leading to impairments of affective and cognitive abilities. These dysfunctions affect each other mutually. Adolescent-onset schizophrenia (AOS) constitutes a particularly severe form of the disorder. In this study, possible dysfunctions of the neural correlates underlying the interaction of negative emotion and working memory in AOS were investigated. METHOD: During functional magnetic resonance imaging, 12 patients with AOS and 12 non-AOS adolescents performed a verbal n-back task. Intermittently, negative and neutral emotions were induced by olfactory stimulation. Group differences in working memory, emotion, and their interaction were evaluated. RESULTS: In patients with AOS, lower performance sensitivity was observed, along with dorsolateral prefrontal, anterior cingulate, and inferior parietal hypoactivation during working memory demands. For negative versus neutral emotion induction, patients with AOS mainly showed increased brain activation compared with control subjects in widespread brain regions including the left orbitofrontal cortex and the medial frontal gyrus. Finally, during the interaction of emotion and cognition, altered patterns of activation in patients with AOS were found in the thalamocortical network, including the angular and the middle cingulate gyri extending to the precuneus. These activation differences were further decomposed by parameter estimates. CONCLUSIONS: Our results provide new insights into the neural correlates underlying the mutual influence of affective and cognitive symptoms in AOS. During the n-back task, areas typically associated with working memory performance were found hypoactivated in patients relative to the control subjects, including the dorsolateral prefrontal and parietal cortex and the anterior cingulate. However, patients with AOS mainly demonstrated increased activation in key areas of emotion processing, such as the left orbitofrontal cortex and medial frontal areas, during negative emotion induction. A dysfunctional thalamocortical network during the interaction mainly included regions involved in the integration of converging information--either on the subcortical (thalamus) or on a higher-order cortical level (comprising the angular gyrus). These findings point to dysfunctional emotion-cognition interactions in AOS, which may explain its poor prognosis.

Gender differences in the cognitive control of emotion: An fMRI study.

The interaction of emotion and cognition has become a topic of major interest. However, the influence of gender on the interplay between the two processes, along with its neural correlates have not been fully analysed so far. In this functional magnetic resonance imaging (fMRI) study we induced negative emotion using negative olfactory stimulation while male (n=21) and female (n=19) participants performed an n-back verbal working memory task. Based on findings indicating increased emotional reactivity in women, we expected the female participants to exhibit stronger activation in characteristically emotion-associated areas during the interaction of emotional and cognitive processing in comparison to the male participants. Both groups were found to be significantly impaired in their working memory performance by negative emotion induction. However, fMRI analysis revealed distinct differences in neuronal activation between groups. In men, cognitive performance under negative emotion induction was associated with extended activation patterns in mainly prefrontal and superior parietal regions. In women, the interaction between emotion and working memory yielded a significantly stronger response in the amygdala and the orbitofrontal cortex (OFC) compared to their male counterparts. Our data suggest that in women the interaction of verbal working memory and negative emotion is associated with relative hyperactivation in more emotion-associated areas whereas in men regions commonly regarded as important for cognition and cognitive control are activated. These results provide new insights in gender-specific cerebral mechanisms.

Stability of emotional dysfunctions? A long-term fMRI study in first-episode schizophrenia.

OBJECTIVE: Patients with schizophrenia are characterized by emotional symptoms such as flattened affect which are accompanied by cerebral dysfunctions. This study aimed at determining changes of mood-related neural correlates under standardized pharmacological therapy in first-episode schizophrenia. METHOD: Using fMRI in a longitudinal approach, 10 first-episode schizophrenia patients (6 males) and 10 healthy subjects (same education, gender and age) were investigated during sad and happy mood induction using facial expressions. Reassessments were carried out following 6 months of standardized antipsychotic treatment. Data analysis focussed on therapy-related changes in cerebral activation and on stable, therapy-independent group differences. RESULTS: According to self ratings, mood induction was successful in both groups and did not reveal time-dependent changes. Patients revealed stable hypoactivations in core brain regions of emotional processing like the anterior cingulate cortex, orbitofrontal and temporal areas as well as the hippocampus. Therapy-related signal increases in pre- and postcentral, inferior temporal and frontal areas were restricted to sadness. DISCUSSION: Stable dysfunctions which are unaffected by therapy and symptom improvement were found in cortico-limbic regions crucially involved in emotion processing. They presumably reflect patients' difficulties in emotion regulation and emotional memory processes. However, therapy-related activation changes were also observed and demonstrate efficacy of antipsychotic therapy on improving emotion functionality. They may represent an increased usage of autobiographic emotional memories and an improved strategy to experience an emotion by mirroring someone else's emotions.

The influence of olfactory-induced negative emotion on verbal working memory: individual differences in neurobehavioral findings.

The influence of emotion on cognition plays an important role in people's everyday life as well as in psychiatric and neurological disorders. The present study used fMRI to examine the neural correlates of cognitive-emotional interactions and its inter-individual differences. Twenty-one healthy males performed a 0-back/2-back task while negative or neutral emotion was induced by negative/neutral olfactory stimulation. Subjects revealed a differential effect of emotion on cognition; in 9 subjects, negative odor had a deteriorating influence on verbal working memory ("affected group", AG) while in 12 subjects, performance was not affected in a negative way ("unaffected group", UAG). Although no brain activation differences emerged during the working memory task, the interaction of working memory and emotion yielded significant differences between the AG and the UAG. The latter showed greater activation in the fronto-parieto-cerebellar working memory (WM) network including the precuneus while the AG demonstrated stronger activation in more "emotional" areas (mainly the temporal and medial frontal cortex) as well as compensatory activations in prefrontal regions known to be essential for the cognitive down-regulation of emotions. Hence, the UAG may have been better able to counteract the detrimental influence of negative stimulation during the 2-back task and to effectively sustain or even increase activation in the task-relevant WM network. Correlation analyses for the whole group supported this interpretation; reduced working memory performance during negative stimulation was accompanied by higher activation in the inferior frontal gyrus whereas less performance impairment was related to higher activation in the precuneus. Results confirm the importance of incorporating individual differences in emotion processing and its interaction with cognitive functions in neuroimaging.

Impairment in the specificity of emotion processing in schizophrenia.

OBJECTIVE: Deficits in emotion processing are a hallmark of schizophrenia, with consequences for social functioning and subjective well-being. However, their specificity and characteristics have not been ascertained psychometrically. The authors' purpose was to examine a differential deficit for processing emotional facets of the face compared to judgment of nonemotional features (age) and facial memory. The authors also sought to establish whether the deficit affects sensitivity or specificity of performance. METHOD: Participants were 20 patients with schizophrenia and 20 healthy subjects matched for age, gender, and parental education. The authors examined emotional discrimination abilities compared to age discrimination and recognition memory for faces with standardized faces displaying the universal emotions of happiness, sadness, anger, and fear. Percent correct in each condition and for each emotion were assessed as well as sensitivity (correct identification of a target emotion) and specificity (correct rejection of a nontarget emotion) for emotion recognition. RESULTS: Patients with schizophrenia were differentially impaired in the discrimination of emotional aspects of facial expressions compared to nonemotional aspects and memory. Within the emotional task, patients showed differential impairment in specificity and insensitivity to the emotion displayed. CONCLUSIONS: When identical stimuli were used across tasks, differential impairment was seen in patients with schizophrenia for processing emotional faces, although the nonemotional task proved harder for both groups. Impairment in the specificity of emotion identification may lead to misunderstanding of social communication and may underlie difficulties in social adjustment experienced by people with schizophrenia. Emotion discrimination tests could augment the neurobehavioral evaluation of patients.