Effects of an eating club for people with a psychotic disorder on personal recovery: Results of a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Many people with a psychotic disorder are coping with severe psychosocial limitations related to their illness. The current randomized controlled trial (RCT) investigates the effects of an eating club intervention (HospitalitY (HY)) aimed to improve personal and societal recovery. METHODS: In 15 biweekly sessions participants received individual home-based skill training and guided peer support sessions in groups of three participants from a trained nurse. A multi-center RCT was conducted (intended sample size: n = 84; n = 7 per block) in patients with a diagnosis of schizophrenia spectrum receiving community treatment. HospitalitY was compared to a Waiting List Control (WLC) condition at three time points (baseline, end-of-treatment (8 months) and follow-up (12 months)) using personal recovery as primary outcome and loneliness, social support, self-stigma, self-esteem, social skills, (social) functioning, independency competence, and psychopathology as secondary outcomes. Outcomes were evaluated with a mixed modeling statistical procedure. RESULTS: The HY-intervention had no significant effects on personal recovery or secondary outcomes. More attendance was associated with higher scores on social functioning. LIMITATIONS: With N = 43 participants included, power was insufficient. Seven HY-groups were started, from which three discontinued before the sixth meeting, one HY group stopped due the start of the COVID-19 pandemic. CONCLUSIONS: Despite a promising pilot study on feasibility, the current RCT did not show any effects of the HY intervention. A mixed qualitative-quantitative research methods might be more appropriate for researching the HospitalitY-intervention to investigate what social and cognitive processes are at play in this peer guided social intervention.

Facilitating Recovery of Daily Functioning in People With a Severe Mental Illness Who Need Longer-Term Intensive Psychiatric Services: Results From a Cluster Randomized Controlled Trial on Cognitive Adaptation Training Delivered by Nurses.

BACKGROUND: Feasible and effective interventions to improve daily functioning in people with a severe mental illness (SMI), such as schizophrenia, in need of longer-term rehabilitation are scarce. AIMS: We assessed the effectiveness of Cognitive Adaptation Training (CAT), a compensatory intervention to improve daily functioning, modified into a nursing intervention. METHOD: In this cluster randomized controlled trial, 12 nursing teams were randomized to CAT in addition to treatment as usual (CAT; n = 42) or TAU (n = 47). Daily functioning (primary outcome) was assessed every 3 months for 1 year. Additional follow-up assessments were performed for the CAT group in the second year. Secondary outcomes were assessed every 6 months. Data were analyzed using multilevel modeling. RESULTS: CAT participants improved significantly on daily functioning, executive functioning, and visual attention after 12 months compared to TAU. Improvements were maintained after 24 months. Improved executive functioning was related to improved daily functioning. Other secondary outcomes (quality of life, empowerment, negative symptoms) showed no significant effects. CONCLUSIONS: As a nursing intervention, CAT leads to maintained improvements in daily functioning, and may improve executive functioning and visual attention in people with SMI in need of longer-term intensive psychiatric care. Given the paucity of evidence-based interventions in this population, CAT can become a valuable addition to recovery-oriented care.

Peer support and skills training through an eating club for people with psychotic disorders: A feasibility study.

OBJECTIVE: The HospitalitY (HY) intervention is a novel recovery oriented intervention for people with psychotic disorders in which peer support and home-based skill training are combined in an eating club. A feasibility study was conducted to inform a subsequent randomised trial. METHODS: This study evaluated three eating clubs consisting of nine participants and three nurses. Semi-structured interviews and pre- and post-intervention measures (18 weeks) of personal recovery, quality of life and functioning were used to evaluate the intervention. Participants received individual skills training, guided by self-identified goals, while organising a dinner at their home. During each dinner, participants engaged in peer support, led by a nurse. RESULTS: In personal interviews participants reported positive effects on social support, loneliness, and self-esteem. Nurses reported that participants became more independent during the intervention. Participants were satisfied with the HY-intervention (attendance rate = 93%). All were able to organise a dinner for their peers with practical support from a nurse. Pre- and post -intervention measures did not show important improvements. LIMITATIONS: Outcome measures were not sensitive to change, likely due to a short intervention period (5 months) and a limited number of participants (N = 9). Using Goal Attainment Scaling to evaluate personal goals turned out to be unfeasible. CONCLUSIONS: The HY-intervention is feasible for participants with psychotic disorders. This study refined intervention and research design for the upcoming multicentre randomised controlled trial. We expect that the Experience Sampling Method will be more sensitive to changes in recovery outcomes than regular pre-post intervention measures.

The development and evaluation of a computerized decision aid for the treatment of psychotic disorders.

BACKGROUND: Routinely monitoring of symptoms and medical needs can improve the diagnostics and treatment of medical problems, including psychiatric. However, several studies show that few clinicians use Routine Outcome Monitoring (ROM) in their daily work. We describe the development and first evaluation of a ROM based computerized clinical decision aid, Treatment-E-Assist (TREAT) for the treatment of psychotic disorders. The goal is to generate personalized treatment recommendations, based on international guidelines combined with outcomes of mental and physical health acquired through ROM. We present a pilot study aimed to assess the feasibility of this computerized clinical decision aid in daily clinical practice by evaluating clinicians' experiences with the system. METHODS: Clinical decision algorithms were developed based on international schizophrenia treatment guidelines and the input of multidisciplinary expert panels from multiple psychiatric institutes. Yearly obtained diagnostic (ROM) information of patients was presented to treating clinicians combined with treatment suggestions generated by the algorithms of TREAT. In this pilot study 6 clinicians and 16 patients of Lentis Psychiatric Institute used the application. Clinicians were interviewed and asked to fill out self-report questionnaires evaluating their opinions about ROM and the effectiveness of TREAT. RESULTS: Six clinicians and 16 patients with psychotic disorders participated in the pilot study. The clinicians were psychiatrists, physicians and nurse-practitioners which all worked at least 8 years in mental health care of which at least 3 years treating patients with psychotic illnesses. All Clinicians found TREAT easy to use and would like to continue using the application. They reported that TREAT offered support in using diagnostic ROM information when drafting the treatment plans, by creating more awareness of current treatment options. CONCLUSION: This article presents a pilot study on the implementation of a computerized clinical decision aid linking routine outcome monitoring to clinical guidelines in order to generate personalized treatment advice. TREAT was found to be feasible for daily clinical practice and effective based on this first evaluation by clinicians. However, adjustments have to be made to the system and algorithms of the application. The ultimate goal is to provide appropriate evidence based care for patients with severe mental illnesses.

Aggression Regulation in Day Treatment of Eating Disorders: Two-Centre RCT of a Brief Body and Movement-Oriented Intervention.

OBJECTIVE: The objective is to evaluate a body and movement-oriented intervention on aggression regulation, specifically aimed towards reducing anger internalization in patients with an eating disorder. METHOD: Patients were randomized to treatment-as-usual (TAU) plus the intervention (n = 38) or to TAU only (n = 32). The intervention was delivered by a psychomotor therapist. TAU consisted of multidisciplinary day treatment (3-5 days per week during 3-9 months). Anger coping (Self-Expression and Control Scale) and eating pathology (Eating Disorder Examination-Self-report Questionnaire) were measured at baseline and follow-up. Differences between pre-intervention and post-intervention scores were tested by using repeated measures ANOVA. RESULTS: The intervention group showed a significantly larger decrease of anger internalization than the control group (η2 = 0.16, p = 0.001). Both groups showed a significant reduction in eating pathology, but differences between groups were not significant. DISCUSSION: A body and movement-oriented therapy seems a viable add-on for treating anger internalization in patients with an eating disorder. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Do routine outcome monitoring results translate to clinical practice? A cross-sectional study in patients with a psychotic disorder.

BACKGROUND: The use of Routine Outcome Monitoring (ROM) in mental health care has increased widely during the past decade. Little is known, however, on the implementation and applicability of ROM outcome in daily clinical practice. In the Netherlands, an extensive ROM-protocol for patients with psychotic disorders has been implemented over the last years (ROM-Phamous). The current study investigated to what extent ROM results translate to daily clinical practice. Therefore, we investigated whether clinical problems as identified with ROM were detected and used in the treatment of patients with psychotic disorders. METHODS: Out of the ROM database of 2010 (n = 1040), a random sample of 100 patients diagnosed with a psychotic disorder was drawn. ROM-data used in this study included a physical examination, laboratory tests, interviews and self-report questionnaires. Based on these data, the prevalence of positive and negative symptoms, psychosocial problems and cardiovascular risk factors was determined. Next, we investigated whether these problems, as identified with ROM, were reflected in the treatment plans of patients, as an indication of the use of ROM in clinical practice. RESULTS: The sample consisted of 63 males and 37 females. The mean age was 44 and the mean duration of illness was 17.7 years. The prevalence of positive and negative symptoms, psychosocial problems and cardiovascular risk factors ranged from 11 to 86 %. In the majority of cases, problems as identified with ROM were not reflected in the treatment plans of patients. CONCLUSIONS: We found a substantial discrepancy between the ROM measurements and the treatment plans, i.e. low rates of detection of symptoms, psychosocial problems and cardiovascular risk factors in the treatment plans, even though these problems were identified with ROM. The opposite occurred as well, where problems were reflected in the treatment plans but not identified with ROM. Thus, ROM and daily clinical practice appear to be two separate processes, whereas ideally they should be integrated. Strong efforts should be made to integrate ROM and consequent treatment activities. Such integration may help to provide patients with adequate and customized care and simultaneously minimize under- and over-treatment.

Effect of Aggression Regulation on Eating Disorder Pathology: RCT of a Brief Body and Movement Oriented Intervention.

OBJECTIVE: The objective of the study is to evaluate the effect of a brief body and movement oriented intervention on aggression regulation and eating disorder pathology for individuals with eating disorders. METHOD: In a first randomized controlled trial, 40 women were allocated to either the aggression regulation intervention plus supportive contact or a control condition of supportive contact only. The intervention was delivered by a psychomotor therapist. Participants completed questionnaires on anger coping and eating disorder pathology. Independent samples t-tests were performed on the difference between pre-treatment and post-treatment scores. RESULTS: Twenty-nine participants completed questionnaires at pre-intervention and post-intervention. The intervention resulted in a significantly greater improvement of anger coping, as well as of eating disorder pathology. DISCUSSION: Results indicate that body and movement-oriented aggression regulation may be a viable add-on for treating eating disorders. It tackles a difficult to treat emotion which may have a role in blocking the entire process of treating eating disorders.

Cognitive alexithymia is associated with the degree of risk for psychosis.

Alexithymia is a personality construct denoting emotion processing problems. It has been suggested to encompass two dimensions: a cognitive and affective dimension. The cognitive dimension is characterized by difficulties in identifying, verbalizing and analyzing emotions, while the affective dimension reflects the level of emotional arousal and imagination. Alexithymia has been previously proposed as a risk factor for developing psychosis. More specifically, the two alexithymia dimensions might be differentially related to the vulnerability for psychosis. Therefore, we examined the two dimensions of alexithymia, measured with the BVAQ in 94 siblings of patients with schizophrenia, 52 subjects at ultra-high risk (UHR) for developing psychosis, 38 patients with schizophrenia and 109 healthy controls. The results revealed that siblings and patients had higher levels of cognitive alexithymia compared to controls. In addition, subjects at UHR for psychosis had even higher levels of cognitive alexithymia compared to the siblings. The levels of affective alexithymia in siblings and patients were equal to controls. However, UHR individuals had significantly lower levels of affective alexithymia (i.e. higher levels of emotional arousal and fantasizing) compared to controls. Alexithymia was further related to subclinical levels of negative and depressive symptoms. These findings indicate that alexithymia varies parametrically with the degree of risk for psychosis. More specifically, a type-II alexithymia pattern, with high levels of cognitive alexithymia and normal or low levels of affective alexithymia, might be a vulnerability factor for psychosis.

Effectiveness and cost-effectiveness of cognitive adaptation training as a nursing intervention in long-term residential patients with severe mental illness: study protocol for a randomized controlled trial.

BACKGROUND: Despite the well-known importance of cognitive deficits for everyday functioning in patients with severe mental illness (SMI), evidence-based interventions directed at these problems are especially scarce for SMI patients in long-term clinical facilities. Cognitive adaptation Training (CAT) is a compensatory approach that aims at creating new routines in patients' living environments through the use of environmental supports. Previous studies on CAT showed that CAT is effective in improving everyday functioning in outpatients with schizophrenia. The aim of this study is to evaluate the effect of CAT as a nursing intervention in SMI patients who reside in long-term clinical facilities. METHODS/DESIGN: This is a multicenter cluster randomized controlled trial comparing CAT (intervention group) as a nursing intervention to treatment as usual (control group). The primary goal is to evaluate the effectiveness of CAT on everyday functioning. Secondary outcomes are quality of life, empowerment and apathy. Further, an economic evaluation will be performed. The study has a duration of one year, with four follow-up assessments at 15, 18, 21 and 24 months for the intervention group. DISCUSSION: There is a need for evidence-based interventions that contribute to the improvement of the functional recovery of long-term residential patients. If our hypotheses are confirmed, it may be recommended to include CAT in the guidelines for SMI care and to implement the method in standardized care. TRIAL REGISTRATION: Nederlands Trial Register (identifier: NTR3308 ). Date registered: 12 February 2012.

Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia.

BACKGROUND: Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies. METHODS: We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results. RESULTS: We included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings. LIMITATIONS: The main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites. CONCLUSION: These results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia.

Differential stigmatizing attitudes of healthcare professionals towards psychiatry and patients with mental health problems: something to worry about? A pilot study.

PURPOSE: This study compares stigmatizing attitudes of different healthcare professionals towards psychiatry and patients with mental health problems. METHODS: The Mental Illness Clinicians Attitude (MICA) questionnaire is used to assess stigmatizing attitudes in three groups: general practitioners (GPs, n = 55), mental healthcare professionals (MHCs, n = 67) and forensic psychiatric professionals (FPs, n = 53). RESULTS: A modest positive attitude towards psychiatry was found in the three groups (n = 176). Significant differences were found on the total MICA-score (p < 0.001). GPs scored significantly higher than the FPs and the latter scored significantly higher than the MHCs on all factors of the MICA. Most stigmatizing attitudes were found on professionals' views of health/social care field and mental illness and disclosure. Personal and work experience did not influence stigmatizing attitudes. CONCLUSIONS: Although all three groups have a relatively positive attitude using the MICA, there is room for improvement. Bias toward socially acceptable answers cannot be ruled out. Patients' view on stigmatizing attitudes of professionals may be a next step in stigma research in professionals.

Alexithymia influences brain activation during emotion perception but not regulation.

Alexithymia is a psychological construct that can be divided into a cognitive and affective dimension. The cognitive dimension is characterized by difficulties in identifying, verbalizing and analysing feelings. The affective dimension comprises reduced levels of emotional experience and imagination. Alexithymia is widely regarded to arise from an impairment of emotion regulation. This is the first functional magnetic resonance imaging (fMRI) study to critically evaluate this by investigating the neural correlates of emotion regulation as a function of alexithymia levels. The aim of the current study was to investigate the neural correlates underlying the two alexithymia dimensions during emotion perception and emotion regulation. Using fMRI, we scanned 51 healthy subjects while viewing, reappraising or suppressing negative emotional pictures. The results support the idea that cognitive alexithymia, but not affective alexithymia, is associated with lower activation in emotional attention and recognition networks during emotion perception. However, in contrast with several theories, no alexithymia-related differences were found during emotion regulation (neither reappraisal nor suppression). These findings suggest that alexithymia may result from an early emotion processing deficit rather than compromised frontal circuits subserving higher-order emotion regulation processes.

Neural correlates of emotion regulation in patients with schizophrenia and non-affected siblings.

BACKGROUND: Patients with schizophrenia often experience problems regulating their emotions. Non-affected relatives show similar difficulties, although to a lesser extent, and the neural basis of such difficulties remains to be elucidated. In the current paper we investigated whether schizophrenia patients, non-affected siblings and healthy controls (HC) exhibit differences in brain activation during emotion regulation. METHODS: All subjects (n = 20 per group) performed an emotion regulation task while they were in an fMRI scanner. The task contained two experimental conditions for the down-regulation of emotions (reappraise and suppress), in which IAPS pictures were used to generate a negative affect. We also assessed whether the groups differed in emotion regulation strategies used in daily life by means of the emotion regulation questionnaire (ERQ). RESULTS: Though the overall negative affect was higher for patients as well as for siblings compared to HC for all conditions, all groups reported decreased negative affect after both regulation conditions. Nonetheless, neuroimaging results showed hypoactivation relative to HC in VLPFC, insula, middle temporal gyrus, caudate and thalamus for patients when reappraising negative pictures. In siblings, the same pattern was evident as in patients, but only in cortical areas. CONCLUSIONS: Given that all groups performed similarly on the emotion regulation task, but differed in overall negative affect ratings and brain activation, our findings suggest reduced levels of emotion regulation processing in neural circuits in patients with schizophrenia. Notably, this also holds for siblings, albeit to a lesser extent, indicating that it may be part and parcel of a vulnerability for psychosis.

Dissociable morphometric profiles of the affective and cognitive dimensions of alexithymia.

Alexithymia ("no words for feelings") is a psychological construct that can be divided in a cognitive and affective dimension. The cognitive dimension reflects the ability to identify, verbalize and analyze feelings, whereas the affective dimension reflects the degree to which individuals get aroused by emotional stimuli and their ability to fantasize. These two alexithymia dimensions may differentially put individuals at risk to develop psychopathology. However, their neural correlates have rarely been investigated. The aim of the current study was to investigate whether the cognitive and affective alexithymia dimension are associated with unique anatomical profiles. Structural MRI scans of 57 participants (29 males; mean age: 34) were processed using a voxel-based morphometry (VBM) - Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra (DARTEL) approach. Multiple regression analyses were performed to examine the common and specific associations between gray and white matter volume and alexithymia subdimensions. The results revealed that the cognitive dimension was related to lower dorsal anterior cingulate volume. In contrast, the affective alexithymia was associated with lower gray matter volume in the medial orbitofrontal cortex (OFC) and lower white matter volume in the superior longitudinal fasciculus (SLF) near the angular gyrus. No relationship between corpus callosum volume and alexithymia was observed. These results are consistent with the idea that there are two separable neural systems underlying alexithymia. This finding might encourage future research into the link between specific alexithymia subtypes and the development of psychopathology.

Normal brain activation in schizophrenia patients during associative emotional learning.

Emotional deficits are among the core features of schizophrenia and both associative emotional learning and the related ability to verbalize emotions can be reduced. We investigated whether schizophrenia patients demonstrated impaired function of limbic and prefrontal areas during associative emotional learning. Patients and controls filled out an alexithymia questionnaire and performed an associative emotional learning task with positive, negative and neutral picture-word pairs during fMRI scanning. After scanning, they indicated for each pair whether they remembered it. We conducted standard GLM analysis and Independent Component Analysis (ICA). Both the GLM results and task-related ICA components were compared between groups. The alexithymia questionnaire indicated more cognitive-emotional processing difficulties in patients than controls, but equal experienced intensity of affective states. Patients remembered less picture-word pairs, irrespective of valence. GLM analysis showed significant visual, temporal, amygdalar/hippocampal, and prefrontal activation in all subjects. ICA identified a network of brain areas similar to GLM, mainly in response to negative stimuli. Neither analysis showed differences between patients and controls during learning. Although in previous studies schizophrenia patients showed abnormalities in both memory and emotion processing, neural circuits involved in cross-modal associative emotional learning may remain intact to a certain degree, which may have potential consequences for treatment.

When Broca goes uninformed: reduced information flow to Broca's area in schizophrenia patients with auditory hallucinations.

Auditory-verbal hallucinations (AVHs) are frequently associated with activation of the left superior temporal gyrus (including Wernicke's area), left inferior frontal gyrus (including Broca's area), and the right hemisphere homologs of both areas. It has been hypothesized that disconnectivity of both interhemispheric transfer and frontal and temporal areas may underlie hallucinations in schizophrenia. We investigated reduced information flow in this circuit for the first time using dynamic causal modeling, which allows for directional inference. A group of healthy subjects and 2 groups of schizophrenia patients-with and without AVH-performed a task requiring inner speech processing during functional brain scanning. We employed connectivity models between left hemispheric speech-processing areas and their right hemispheric homologs. Bayesian model averaging was used to estimate the connectivity strengths and evaluate group differences. Patients with AVH showed significantly reduced connectivity from Wernicke's to Broca's area (97% certainty) and a trend toward a reduction in connectivity from homologs of Broca's and Wernicke's areas to Broca's area (93% and 94% certainty). The connectivity magnitude in patients without hallucinations was found to be intermediate. Our results point toward a reduced input from temporal to frontal language areas in schizophrenia patients with AVH, suggesting that Broca's activity may be less constrained by perceptual information received from the temporal cortex. In addition, a lack of synchronization between Broca and its homolog may lead to the erroneous interpretation of emotional speech activity from the right hemisphere as coming from an external source.

Reduced connectivity in the self-processing network of schizophrenia patients with poor insight.

Lack of insight (unawareness of illness) is a common and clinically relevant feature of schizophrenia. Reduced levels of self-referential processing have been proposed as a mechanism underlying poor insight. The default mode network (DMN) has been implicated as a key node in the circuit for self-referential processing. We hypothesized that during resting state the DMN network would show decreased connectivity in schizophrenia patients with poor insight compared to patients with good insight. Patients with schizophrenia were recruited from mental health care centers in the north of the Netherlands and categorized in groups having good insight (n= 25) or poor insight (n = 19). All subjects underwent a resting state fMRI scan. A healthy control group (n = 30) was used as a reference. Functional connectivity of the anterior and posterior part of the DMN, identified using Independent Component Analysis, was compared between groups. Patients with poor insight showed lower connectivity of the ACC within the anterior DMN component and precuneus within the posterior DMN component compared to patients with good insight. Connectivity between the anterior and posterior part of the DMN was lower in patients than controls, and qualitatively different between the good and poor insight patient groups. As predicted, subjects with poor insight in psychosis showed decreased connectivity in DMN regions implicated in self-referential processing, although this concerned only part of the network. This finding is compatible with theories implying a role of reduced self-referential processing as a mechanism contributing to poor insight.

Altered resting state connectivity of the default mode network in alexithymia.

Alexithymia is a trait characterized by a diminished capacity to describe and distinguish emotions and to fantasize; it is associated with reduced introspection and problems in emotion processing. The default mode network (DMN) is a network of brain areas that is normally active during rest and involved in emotion processing and self-referential mental activity, including introspection. We hypothesized that connectivity of the DMN might be altered in alexithymia. Twenty alexithymic and 18 non-alexithymic healthy volunteers underwent a resting state fMRI scan. Independent component analysis was used to identify the DMN. Differences in connectivity strength were compared between groups. Within the DMN, alexithymic participants showed lower connectivity within areas of the DMN (medial frontal and temporal areas) as compared to non-alexithymic participants. In contrast, connectivity in the high-alexithymic participants was higher for the sensorimotor cortex, occipital areas and right lateral frontal cortex than in the low-alexithymic participants. These results suggest a diminished connectivity within the DMN of alexithymic participants, in brain areas that may also be involved in emotional awareness and self-referential processing. On the other hand, alexithymia was associated with stronger functional connections of the DMN with brain areas involved in sensory input and control of emotion.

Variation of the gene coding for DARPP-32 (PPP1R1B) and brain connectivity during associative emotional learning.

Associative emotional learning, which is important for the social emotional functioning of individuals and is often impaired in psychiatric illnesses, is in part mediated by dopamine and glutamate pathways in the brain. The protein DARPP-32 is involved in the regulation of dopaminergic and glutaminergic signaling. Consequently, it has been suggested that the haplotypic variants of the gene PPP1R1B that encodes DARPP-32 are associated with working memory and emotion processing. We hypothesized that PPP1R1B should have a significant influence on the network of brain regions involved in associative emotional learning that are rich in DARPP-32, namely the striatum, prefrontal cortex (comprising the medial frontal gyrus and inferior frontal gyrus (IFG)), amygdala and parahippocampal gyrus (PHG). Dynamic causal models were applied to functional MRI data to investigate how brain connectivity during an associative emotional learning task is affected by different single-nucleotide polymorphisms (SNPs) of PPP1R1B: rs879606, rs907094 and rs3764352. Compared to heterozygotes, homozygotes with GTA alleles displayed increased intrinsic connectivity between the IFG and PHG, as well as increased excitability of the PHG for negative emotional stimuli. We have also elucidated the directionality of these genetic influences. Our data suggest that homozygotes with GTA alleles involve stronger functional connections between brain areas in order to maintain activation of these regions. Homozygotes might engage a greater degree of motivational learning and integration of information to perform the emotional learning task correctly. We conclude that PPP1R1B is associated with the neural network involved in associative emotional learning.

Bidirectional information flow in frontoamygdalar circuits in humans: a dynamic causal modeling study of emotional associative learning.

Everyday language is replete with descriptions of emotional events that people have experienced and wish to share with others. Such descriptions presumably rely on pairings of affective words and visual information (such as events and pictures) that have been learnt throughout one's development. To study this kind of affective language learning in the brain, we used functional neuroimaging during associative learning of emotional words and pictures. Brain imaging revealed increased activation of both primary emotional areas such as the amygdala and of higher cognitive areas such as the inferior frontal gyrus (IFG) and medial frontal gyrus. The dynamic causal modeling with Bayesian model selection suggested that the IFG first receives the input and that the connections are bidirectional, suggesting that during such emotional picture-word pair learning, the frontal cortex drives the amygdala activation. Specifically, the interaction between the frontal regions and the amygdala was enhanced by active learning involving both negative and positive emotional stimuli as compared with neutral stimuli. This circuit (especially for negative stimuli) converges with emotion regulation circuits. The enhancement in the connectivity might be responsible for the emotional memory effect in this type of learning.