Papers by Mascha van 't Wout
Biological psychiatry, May 1, 2024
JAMA psychiatry, Mar 6, 2024
Biological Psychiatry, May 1, 2023
Frontiers in Human Neuroscience
IntroductionExposure-based psychotherapies for the treatment of anxiety- and fear-based disorders... more IntroductionExposure-based psychotherapies for the treatment of anxiety- and fear-based disorders rely on “corrective” associative learning. Namely the repeated confrontation with feared stimuli in the absence of negative outcomes allows the formation of new, corrected associations of safety, indicating that such stimuli no longer need to be avoided. Unfortunately, exposure-facilitated corrective learning tends to be bound by context and often poorly generalizes. One brain structure, the prefrontal cortex, is implicated in context-guided behavior and may be a relevant target for improving generalization of safety learning. Here, we tested whether inhibition of the left prefrontal cortex causally impaired updating of context-bound associations specifically or, alternatively, impaired updating of learned associations irrespective of contextual changes. Additionally, we tested whether prefrontal inhibition during corrective learning influenced subsequent generalization of associations ...
Journal of Visualized Experiments
Psychiatry Research, 2016
This study evaluated the influence of self-reported levels of depression on interpersonal strateg... more This study evaluated the influence of self-reported levels of depression on interpersonal strategic decision making when interacting with partners who differed in their predetermined tendency to cooperate in three separate computerized iterated Prisoner's Dilemma Games (iPDGs). Across 29 participants, cooperation was lowest when interacting with a predominantly defecting partner and highest when interacting with a predominantly cooperating partner. Greater depression severity was related to steadier and continued cooperation over trials with the cooperating partner, seeming to reflect a prosocial response tendency when interacting with this partner. With the unbiased partner, depression severity was associated with a more volatile response pattern in reaction to cooperation and defection by this partner. Severity of depression did not influence cooperation with a defecting partner or expectations about partner cooperation reported before the task began. Taken together, these data appear to show that in predominately positive interactions, as in the cooperating partner condition, depression is associated with less volatile, more consistent cooperation. When such clear feedback is absent, as in the unbiased partner condition, depression is associated with more volatile behavior. Nonetheless, participants were generally able to adapt their behavior accordingly in this dynamic interpersonal decision making context.
Applied Psychophysiology and Biofeedback, 2017
Interest in virtual reality (VR) as a clinical tool to augment posttraumatic stress (PTSD) treatm... more Interest in virtual reality (VR) as a clinical tool to augment posttraumatic stress (PTSD) treatment has grown substantially in recent years due to advances in VR technology. Moreover, its potential assisted use in the PTSD diagnostic process has been recognized. In this study we examined physiological responding, skin conductance, to a standardized presentation of non-personalized combat-related VR events (e.g. encountering enemy fire; explosions) as compared to non-combat classroom VR events in 19 Veterans with and 24 Veterans without combat-related PTSD who had been deployed to Iraq and Afghanistan. Veterans watched a total of 12 VR scenarios-six combat-related and six non-combat-related-with each scenario gradually increasing in emotional intensity by adding more VR events in addition to repeating prior VR events. Results show that Veterans with PTSD displayed larger skin conductance reactivity across VR combat events, but not for non-combat VR events, as compared to combat Veterans without PTSD. Nevertheless, Veterans with and without PTSD showed a similar reduction of emotional arousal to repeated presentation of the same VR combat events. Within the PTSD sample, the elevated level of VR combat-related arousal correlated marginally with severity of hyperarousal symptoms. This study confirms that the use of a non-personalized and standardized VR presentation successfully distinguishes Veterans with PTSD from those without on a measure of psychophysiological arousal to combat-related VR stimuli. The assessment of physiological reactivity during the repeated presentation of standardized, trauma-related VR events highlights its use for PTSD assessment as well as treatment.
Current Treatment Options in Psychiatry, 2017
Background: GPR52 is an orphan GPCR expressed primarily in the brain. Whereas in the striatum it ... more Background: GPR52 is an orphan GPCR expressed primarily in the brain. Whereas in the striatum it is co-expressed almost exclusively in neurons with D2 dopamine receptors, in the cortex it mainly co-expresses with D1 dopamine receptors on glutamatergic neurons. Since GPR52 is G-s coupled, GPR52 agonists are hypothesized to show anti-psychotic as well as pro-cognitive activity due to their action in the striatum and cortex, respectively, making GPR52 an interesting target for the treatment of schizophrenia. Methods: Compound potency was assessed by cAMP measurements from CHO cells overexpressing GPR52. To test GPR52 agonist influence cortical synaptic transmission, prefrontal cortical rat slices were stimulated in layer II and recorded in layer V. To demonstrate the GPR52 specificity of this stimulation, a GPR52 inverse agonist was used to block this effect. A social recognition task was used to assess if a GPR52 agonist showed pro-cognitive efficacy. Results: The tool GPR52 agonist assessed in these tasks has an EC50 of 6 nM and showed concentration dependent synaptic potentiation in the cortical slices. This potentiation was blocked by a GPR52 inverse agonist, demonstrating that this effect is specifically mediated by GPR52. Rats receiving the compound demonstrated a significant reduction of interaction time in the social recognition task after a 24 h interval, suggesting that the compound acts in a pro-cognitive manner. Conclusions: Taken together, these data show that GPR52 agonists potentiate synaptic transmission and show procognitive effects. These data therefore underscore that GPR52 agonists have potential for treatment of cognitive symptoms in schizophrenia.
PLOS ONE, 2016
Although deficits in facial affect processing have been reported in schizophrenia as well as in b... more Although deficits in facial affect processing have been reported in schizophrenia as well as in borderline personality disorder (BPD), these disorders have not yet been directly compared on facial affect labeling. Using degraded stimuli portraying neutral, angry, fearful and angry facial expressions, we hypothesized more errors in labeling negative facial expressions in patients with schizophrenia compared to healthy controls. Patients with BPD were expected to have difficulty in labeling neutral expressions and to display a bias towards a negative attribution when wrongly labeling neutral faces. Patients with schizophrenia (N = 57) and patients with BPD (N = 30) were compared to patients with somatoform disorder (SoD, a psychiatric control group; N = 25) and healthy control participants (N = 41) on facial affect labeling accuracy and type of misattributions. Patients with schizophrenia showed deficits in labeling angry and fearful expressions compared to the healthy control group and patients with BPD showed deficits in labeling neutral expressions compared to the healthy control group. Schizophrenia and BPD patients did not differ significantly from each other when labeling any of the facial expressions. Compared to SoD patients, schizophrenia patients showed deficits on fearful expressions, but BPD did not significantly differ from SoD patients on any of the facial expressions. With respect to the type of misattributions, BPD patients mistook neutral expressions more often for fearful expressions compared to schizophrenia patients and healthy controls, and less often for happy compared to schizophrenia patients. These findings suggest that although schizophrenia and BPD patients demonstrate different as well as similar facial affect labeling deficits, BPD may be associated with a tendency to detect negative affect in neutral expressions.
Psychiatry research, Jan 30, 2011
Studies that have investigated whether deficits in social cognition observed in schizophrenia are... more Studies that have investigated whether deficits in social cognition observed in schizophrenia are also present in schizotypal individuals have largely been inconclusive, and none of these studies have examined social interactive behavior. Here, we investigated interactive decision-making behavior in individuals differing in the amount of schizotypal symptoms using tasks derived from Game Theory. In total 1691 undergraduate students were screened with the Schizotypal Personality Questionnaire-Brief version. We selected 69 people distributed across the full schizotypal continuum to participate in Ultimatum and Dictator Games in which they played against human and non-human, computer partners. The results showed that higher levels of schizotypal symptoms, particularly positive and disorganized schizotypy, were related to proposing higher offers to all partners. Additionally, the amount of interpersonal schizotypal symptoms was associated with an increased acceptance rate of very unfair...
Schizophrenia research, 2004
Symptoms of psychosis have been proposed to form part of a continuous distribution of experiences... more Symptoms of psychosis have been proposed to form part of a continuous distribution of experiences in the general population rather than being an all-or-nothing phenomenon. Indeed, schizotypal signs have been reported in subjects from non-clinical samples. Emotional processing has been documented to be deficient in schizophrenia. In the present study, we tested the hypothesis whether putatively psychosis-prone subjects would show abnormalities in emotion processing. Based on the extremes of Launay-Slade Hallucination Scale (LSHS) ratings of 200 undergraduate students, two groups of subjects (total N=40) were selected. All 40 participants filled in the Schizotypal Personality Questionnaire (SPQ). We compared both groups on an alexithymia questionnaire and on four behavioral emotional information processing tasks. Hallucination-proneness was associated with an increased subjective emotional arousal and fantasy-proneness. Although no differences between the high and low group were obser...
Psychiatry Research, 2011
Studies of individuals at ultra high risk (UHR) for psychosis have revealed deviations in cogniti... more Studies of individuals at ultra high risk (UHR) for psychosis have revealed deviations in cognitive and neural development before the onset of psychosis. As affective impairments are among the core dysfunctions in psychotic disorders such as schizophrenia, this study assessed emotion processing and the relationship with social competence in adolescents at risk for psychosis. Thirty-four adolescents at UHR for psychosis and twenty-three non-clinical controls completed the Bermond-Vorst Alexithymia Questionnaire, a measure of emotion awareness. Social inadequacy was measured using the Dutch Personality Questionnaire. Schizophrenia spectrum psychopathology was assessed using self-report and clinical instruments. The Wechsler Adult Intelligence Scale (WAIS) was used to evaluate intellectual functioning. UHR adolescents showed difficulties in identifying and verbalizing their own emotions, independent of intelligence scores. Emotion awareness problems were related to social inadequacy and schizotypal traits in the high risk group. These findings suggest that UHR adolescents may have reduced emotion awareness, independent of intellectual functioning. The relationship with social inadequate behavior fits with the idea that emotion awareness is a prerequisite for the regulation of emotions in social contexts. In the search for early vulnerability markers of risk for psychosis, studying emotion processing besides cognitive abilities might increase our understanding of 'at risk' developmental pathways.
NeuroImage, 2012
Though emotions have been shown to have sometimes dramatic effects on decision-making, the neural... more Though emotions have been shown to have sometimes dramatic effects on decision-making, the neural mechanisms mediating these biases are relatively unexplored. Here, we investigated how incidental affect (i.e. emotional states unrelated to the decision at hand) may influence decisions, and how these biases are implemented in the brain. Nineteen adult participants made decisions which involved accepting or rejecting monetary offers from others in an Ultimatum Game while undergoing functional magnetic resonance imaging (fMRI). Prior to each set of decisions, participants watched a short video clip aimed at inducing either a sad or neutral emotional state. Results demonstrated that, as expected, sad participants rejected more unfair offers than those in the neutral condition. Neuroimaging analyses revealed that receiving unfair offers while in a sad mood elicited activity in brain areas related to aversive emotional states and somatosensory integration (anterior insula) and to cognitive conflict (anterior cingulate cortex). Sad participants also showed a diminished sensitivity in neural regions associated with reward processing (ventral striatum). Importantly, insular activation uniquely mediated the relationship between sadness and decision bias. This study is the first to reveal how subtle mood states can be integrated at the neural level to influence decision-making.
Journal of Nervous & Mental Disease, 2007
Although schizophrenia has often been associated with deficits in facial affect recognition, it i... more Although schizophrenia has often been associated with deficits in facial affect recognition, it is debated whether the recognition of specific emotions is affected and if these facial affect-processing deficits are related to symptomatology or other patient characteristics. The purpose of the present study was to explore whether particular patient characteristics are associated with the recognition of specific facial expressions in patients with schizophrenia. Sixty-four patients with a DSM-IV diagnosis of schizophrenia were assessed with a computerized test of degraded facial affect recognition. Linear regression analysis showed that, in particular, negative symptoms and male sex were associated with worse recognition of fearful faces. Furthermore, diagnosis of nonparanoid schizophrenia and later age of onset were associated with worse recognition of neutral faces. Findings are explained in the light of a neuroanatomical dysfunction accounting for both negative symptoms, such as reduced emotional expression and social-emotional dysfunction, for which men seem more vulnerable than women.
Frontiers in Psychology, 2013
In this study we aimed to investigate how awareness of bodily responses, referred to as interocep... more In this study we aimed to investigate how awareness of bodily responses, referred to as interoceptive awareness, influences decision-making in a social interactive context. Interoceptive awareness is thought to be crucial for adequate regulation of one's emotions. However, there is a dearth of studies that examine the association between interoceptive awareness and the ability to regulate emotions during interpersonal decision-making. Here, we quantified interoceptive awareness with a heartbeat detection task in which we measured the difference between subjective self-reports and an objective psychophysiological measurement of participant heart rates. Social decision-making was quantified using a tworound Ultimatum Game. Participants were asked to first reject or accept an unfair division of money proposed by a partner. In turn, participants could then make an offer on how to divide an amount of money with the same partner. Participants performed 20 rounds of the two-round Ultimatum Game twice, once during baseline condition and once while asked to reappraise emotional reactions when confronted with unfair offers from partners. Results showed that after reappraisal participants (1) accepted more unfair offers and (2) offered higher return divisions, as compared to baseline. With respect to interoceptive awareness, participants with better heartbeat detection scores tended to report less emotional involvement when they applied reappraisal while playing the Ultimatum Game. However, there was no reliably significant relationship between heartbeat detection and the acceptance of unfair offers. Similarly, heartbeat detection accuracy was not related to return offers made in the second round of the Ultimatum Game or the habitual use of emotion regulation. These preliminary findings suggest that the relationship between interoceptive awareness and behavioral changes due to emotion regulation in a social decision-making context appears to be complex.
Comprehensive Psychiatry, 2007
Alexithymia refers to difficulties in emotionalizing, fantasizing, verbalizing, identifying, and ... more Alexithymia refers to difficulties in emotionalizing, fantasizing, verbalizing, identifying, and analyzing emotions. The goal of this study was to investigate features of alexithymia in patients with schizophrenia. In addition, we investigated if alexithymia would be associated with vulnerability to schizophrenia, by studying unaffected first-degree relatives of schizophrenia patients. Furthermore, sex differences were taken into account. Forty-three patients with schizophrenia, 32 unaffected siblings, and 44 healthy control subjects were compared on the Bermond-Vorst Alexithymia Questionnaire. Results showed that male patients with schizophrenia, in particular, demonstrated a specific pattern of alexithymia, that is, difficulty identifying and verbalizing emotions, in the face of a higher subjective emotional arousal. Moreover, male siblings showed comparable problems in verbalizing their emotions as male patients. We suggest that these difficulties in aspects underlying affect regulation could account for the deficits in social functioning observed in schizophrenia and could contribute to a greater vulnerability for schizophrenia, in particular, for males.
Cognitive Neuropsychiatry, 2006
The accuracy of the Content should not be relied upon and should be independently verified with p... more The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content.
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Papers by Mascha van 't Wout