Investigating two mobile just-in-time adaptive interventions to foster psychological resilience: research protocol of the DynaM-INT study.

BACKGROUND: Stress-related disorders such as anxiety and depression are highly prevalent and cause a tremendous burden for affected individuals and society. In order to improve prevention strategies, knowledge regarding resilience mechanisms and ways to boost them is highly needed. In the Dynamic Modelling of Resilience - interventional multicenter study (DynaM-INT), we will conduct a large-scale feasibility and preliminary efficacy test for two mobile- and wearable-based just-in-time adaptive interventions (JITAIs), designed to target putative resilience mechanisms. Deep participant phenotyping at baseline serves to identify individual predictors for intervention success in terms of target engagement and stress resilience. METHODS: DynaM-INT aims to recruit N = 250 healthy but vulnerable young adults in the transition phase between adolescence and adulthood (18-27 years) across five research sites (Berlin, Mainz, Nijmegen, Tel Aviv, and Warsaw). Participants are included if they report at least three negative burdensome past life events and show increased levels of internalizing symptoms while not being affected by any major mental disorder. Participants are characterized in a multimodal baseline phase, which includes neuropsychological tests, neuroimaging, bio-samples, sociodemographic and psychological questionnaires, a video-recorded interview, as well as ecological momentary assessments (EMA) and ecological physiological assessments (EPA). Subsequently, participants are randomly assigned to one of two ecological momentary interventions (EMIs), targeting either positive cognitive reappraisal or reward sensitivity. During the following intervention phase, participants' stress responses are tracked using EMA and EPA, and JITAIs are triggered if an individually calibrated stress threshold is crossed. In a three-month-long follow-up phase, parts of the baseline characterization phase are repeated. Throughout the entire study, stressor exposure and mental health are regularly monitored to calculate stressor reactivity as a proxy for outcome resilience. The online monitoring questionnaires and the repetition of the baseline questionnaires also serve to assess target engagement. DISCUSSION: The DynaM-INT study intends to advance the field of resilience research by feasibility-testing two new mechanistically targeted JITAIs that aim at increasing individual stress resilience and identifying predictors for successful intervention response. Determining these predictors is an important step toward future randomized controlled trials to establish the efficacy of these interventions.

Loneliness during the Covid-19 pandemic in Germany: Impact of social factors and polygenic risk scores on interpersonal differences in loneliness and mental health.

OBJECTIVES: The outbreak of Covid-19 negatively affected mental health and increased loneliness. The subjective feeling of loneliness is influenced by genetic and social factors and has a negative impact on mental health. METHODS: From March 2020 to June 2021 loneliness was investigated in N = 517 individuals using monthly acquired questionnaire data and Latent Growth Curve Analysis. Associations of social factors and polygenic risk scores (PRSs, n = 361) with class membership were investigated. RESULTS: Three classes ("average", 40%; "not lonely", 38%; "elevated loneliness", 22%) were identified, that differ significantly regarding loneliness, mental dysfunction, and response to the lockdown phases. Individuals with a high PRS for neuroticism are more likely to belong to the "elevated loneliness" class, living with another person is a protective factor. CONCLUSION: As the "elevated loneliness" class was at the highest risk of mental dysfunction, our findings underscore the importance of identifying those individuals to implement counteractive measures.

The impact of physical fitness on resilience to modern life stress and the mediating role of general self-efficacy.

Substantial evidence shows that physical activity and fitness play a protective role in the development of stress related disorders. However, the beneficial effects of fitness for resilience to modern life stress are not fully understood. Potentially protective effects may be attributed to enhanced resilience via underlying psychosocial mechanisms such as self-efficacy expectations. This study investigated whether physical activity and fitness contribute to prospectively measured resilience and examined the mediating effect of general self-efficacy. 431 initially healthy adults participated in fitness assessments as part of a longitudinal-prospective study, designed to identify mechanisms of resilience. Self-efficacy and habitual activity were assessed in parallel to cardiorespiratory and muscular fitness, which were determined by a submaximal step-test, hand strength and standing long jump test. Resilience was indexed by stressor reactivity: mental health problems in relation to reported life events and daily hassles, monitored quarterly for nine months. Hierarchical linear regression models and bootstrapped mediation analyses were applied. We could show that muscular and self-perceived fitness were positively associated with stress resilience. Extending this finding, the muscular fitness-resilience relationship was partly mediated by self-efficacy expectations. In this context, self-efficacy expectations may act as one underlying psychological mechanism, with complementary benefits for the promotion of mental health. While physical activity and cardiorespiratory fitness did not predict resilience prospectively, we found muscular and self-perceived fitness to be significant prognostic parameters for stress resilience. Although there is still more need to identify specific fitness parameters in light of stress resilience, our study underscores the general relevance of fitness for stress-related disorders prevention.

Impact of COVID-19 lockdown on mental health in Germany: longitudinal observation of different mental health trajectories and protective factors.

The COVID-19 pandemic and resulting measures can be regarded as a global stressor. Cross-sectional studies showed rather negative impacts on people's mental health, while longitudinal studies considering pre-lockdown data are still scarce. The present study investigated the impact of COVID-19 related lockdown measures in a longitudinal German sample, assessed since 2017. During lockdown, 523 participants completed additional weekly online questionnaires on e.g., mental health, COVID-19-related and general stressor exposure. Predictors for and distinct trajectories of mental health outcomes were determined, using multilevel models and latent growth mixture models, respectively. Positive pandemic appraisal, social support, and adaptive cognitive emotion regulation were positively, whereas perceived stress, daily hassles, and feeling lonely negatively related to mental health outcomes in the entire sample. Three subgroups ("recovered," 9.0%; "resilient," 82.6%; "delayed dysfunction," 8.4%) with different mental health responses to initial lockdown measures were identified. Subgroups differed in perceived stress and COVID-19-specific positive appraisal. Although most participants remained mentally healthy, as observed in the resilient group, we also observed inter-individual differences. Participants' psychological state deteriorated over time in the delayed dysfunction group, putting them at risk for mental disorder development. Consequently, health services should especially identify and allocate resources to vulnerable individuals.

Longitudinal determination of resilience in humans to identify mechanisms of resilience to modern-life stressors: the longitudinal resilience assessment (LORA) study.

Resilience is the maintenance and/or quick recovery of mental health during and after periods of adversity. It is conceptualized to result from a dynamic process of successful adaptation to stressors. Up to now, a large number of resilience factors have been proposed, but the mechanisms underlying resilience are not yet understood. To shed light on the complex and time-varying processes of resilience that lead to a positive long-term outcome in the face of adversity, the Longitudinal Resilience Assessment (LORA) study has been established. In this study, 1191 healthy participants are followed up at 3- and 18-month intervals over a course of 4.5 years at two study centers in Germany. Baseline and 18-month visits entail multimodal phenotyping, including the assessment of mental health status, sociodemographic and lifestyle variables, resilience factors, life history, neuropsychological assessments (of proposed resilience mechanisms), and biomaterials (blood for genetic and epigenetic, stool for microbiome, and hair for cortisol analysis). At 3-monthly online assessments, subjects are monitored for subsequent exposure to stressors as well as mental health measures, which allows for a quantitative assessment of stressor-dependent changes in mental health as the main outcome. Descriptive analyses of mental health, number of stressors including major life events, daily hassles, perceived stress, and the ability to recover from stress are here presented for the baseline sample. The LORA study is unique in its design and will pave the way for a better understanding of resilience mechanisms in humans and for further development of interventions to successfully prevent stress-related disorder.

L-DOPA improves extinction memory retrieval after successful fear extinction.

RATIONALE: A promising strategy to prevent a return of fear after exposure-based therapy in anxiety disorders is to pharmacologically enhance the extinction memory consolidation presumed to occur after exposure. Accumulating evidence suggests that the effect of a number of pharmacological consolidation enhancers depends on a successful fear reduction during exposure. Here, we employed the dopamine precursor L-DOPA to clarify whether its documented potential to enhance extinction memory consolidation is dependent on successful fear extinction. METHODS: In two double-blind, randomized and placebo-controlled experiments (experiment 1: N = 79, experiment 2: N = 32) comprising fear conditioning (day 1), extinction followed by administration of 150 mg L-DOPA or placebo (day 2) and a memory test (day 3) in healthy male adults, conditioned responses were assessed as differential skin conductance responses. We tested whether the effect of L-DOPA on conditioned responses at test depended on conditioned responses at the end of extinction in an experiment with a short (10 trials, experiment 1) and long (25 trials, experiment 2) extinction session. RESULTS: In both experiments, the effect of L-DOPA was dependent on conditioned responses at the end of extinction. That is, post-extinction L-DOPA compared to placebo administration reduced conditioned responses at test only in participants showing a complete reduction of conditioned fear at the end of extinction. CONCLUSION: The results support the potential use of L-DOPA as a pharmacological adjunct to exposure treatment, but point towards a common boundary condition for pharmacological consolidation enhancers: a successful reduction of fear in the exposure session.

Author Correction: Dopamine-dependent prefrontal reactivations explain long-term benefit of fear extinction.

In the original version of this Article, the fourth sentence of the legend to Figure 1b incorrectly read "Note, that the group difference stemmed from significantly smaller CS+ evoked SCRs averaged across the whole test phase, but the speed of re-extinction did not differ significantly between drug groups (control analysis with stimulus (CS+, CS-) and trial (1-10) as within-, and group (placebo, L-DOPA) as between-subject factor: stimulus × group, F1,297 = 6.57, P = 0.02, partial η2 = 0.17; stimulus × trial × group, F1,297 = 1.32, P = 0.23; n = 35)". The correct version states "F1,33 = 6.58" instead of "F1,297 = 6.57", and "F9,297 = 1.32" instead of "F1,297 = 1.32". These errors have now been corrected in both the PDF and HTML versions of the Article. The correct values were used in the statistical analysis and the errors do not affect the conclusions.

Intimate stimuli result in fronto-parietal activation changes in anorexia nervosa.

BACKGROUND: Intimacy is a key psychological problem in anorexia nervosa (AN). Empirical evidence, including neurobiological underpinnings, is however, scarce. OBJECTIVE: In this study, we evaluated various emotional stimuli including intimate stimuli experienced in patients with AN and non-patients, as well as their cerebral response. METHODS: Functional magnetic resonance imaging was conducted using stimuli with positive, neutral, negative and intimate content. Participants (14 AN patients and 14 non-patients) alternated between passive viewing and explicit emotion regulation. RESULTS: Intimate stimuli were experienced less positively in AN patients compared to non-patients. AN patients showed decreased cerebral responses in superior parietal cortices in response to positive and intimate stimuli. Intimate stimuli led to stronger activation of the orbitofrontal cortex, and lower activation of the bilateral precuneus in AN patients. Orbitofrontal responses decreased in AN patients during explicit emotion regulation. CONCLUSIONS: These results show that intimate stimuli are of particular importance in AN patients, who show experiential differences compared to non-patients and altered activation of orbitofrontal and parietal brain structures. This supports that AN patients have difficulties with intimacy, attachment, self-referential processing and body perception. LEVEL OF EVIDENCE: Level III, case-control study.

Dopamine-dependent prefrontal reactivations explain long-term benefit of fear extinction.

Fear extinction does not prevent post-traumatic stress or have long-term therapeutic benefits in fear-related disorders unless extinction memories are easily retrieved at later encounters with the once-threatening stimulus. Previous research in rodents has pointed towards a role for spontaneous prefrontal activity occurring after extinction learning in stabilizing and consolidating extinction memories. In other memory domains spontaneous post-learning activity has been linked to dopamine. Here, we show that a neural activation pattern - evoked in the ventromedial prefrontal cortex (vmPFC) by the unexpected omission of the feared outcome during extinction learning - spontaneously reappears during postextinction rest. The number of spontaneous vmPFC pattern reactivations predicts extinction memory retrieval and vmPFC activation at test 24 h later. Critically, pharmacologically enhancing dopaminergic activity during extinction consolidation amplifies spontaneous vmPFC reactivations and correspondingly improves extinction memory retrieval at test. Hence, a spontaneous dopamine-dependent memory consolidation-based mechanism may underlie the long-term behavioral effects of fear extinction.

[Resilience trajectories-examples from longitudinal studies]. / Verläufe von Resilienz ­ Beispiele aus Längsschnittstudien.

BACKGROUND: According to current research concepts resilience can be defined as adaptation to past and ongoing exposure. Accordingly, adaptation to exposure is a dynamic process, which can be different in different population groups. Prospective longitudinal studies provide unique opportunities to investigate resilience processes. OBJECTIVES: The aim of this article is to define the concept of resilience, describe examples of longitudinal studies investigating resilience in children, adults and older individuals, exemplary describe four ongoing longitudinal resilience studies in which the authors of the article are participating and identify and analyze methodological challenges in empirical resilience research. MATERIAL AND METHODS: This study was based on a qualitative literature review of published prospective studies investigating resilience listed in PubMed and study protocols of the four longitudinal studies. RESULTS: The exemplarily described studies have shown that resilience processes are changeable in all age groups and subject to a variety of influencing factors. The specific and potentially age-associated types of alterations have so far been difficult to determine and need further clarification. DISCUSSION: In view of the dynamic course of resilience, prospective longitudinal studies are urgently needed. Prospective longitudinal studies have the potential to identify resilience mechanisms and predictors of the course of resilience in different population groups, such as children, adolescents, adults and older individuals. Furthermore, resilience research needs to develop an improved and precise assessment of exposure to stressors.

[Current concepts of resilience research]. / Aktuelle Konzepte der Resilienzforschung.

BACKGROUND: Stress-related mental disorders are the most prevalent and cost-intensive disorders of our time. On the other hand, the maintenance of mental health despite stressors, i. e. resilience, is a frequent phenomenon. Research on psychological resilience and its underlying mechanisms offers innovative possibilities for health promotion. It requires a consistent understanding of resilience and adequate methods of operationalization. OBJECTIVES: Modern concepts of the definition, operationalization and assessment of resilience as well as its implications for study designs in resilience research. MATERIAL AND METHODS: Analysis and discussion of current works and expert recommendations for the design of resilience research. RESULTS: Resilience research is undergoing a period of transition. Based on a new understanding of resilience as a dynamic and modifiable process, new approaches for operationalization and assessment were proposed. These include, for example, a transdiagnostic approach and the identification of resilience mechanisms, the consideration of stressor exposure in measuring the construct, and longitudinal cohort studies. CONCLUSIONS: In the upcoming decades, further profitable findings from current prospective longitudinal studies can be expected. One challenge for future resilience research consists in the continuous dissemination and implementation of the approaches described.

[Pharmacogenetics in psychiatry: state of the art]. / Pharmakogenetik in der Psychiatrie: eine Standortbestimmung.

In this article, the current literature on pharmacogenetics of antidepressants, antipsychotics and lithium are summarized by the section of Neurobiology and Genetics of the German Society of Psychiatry, Psychotherapy and Neurology (DGPPN). The publications of international expert groups and regulatory authorities are reviewed and discussed. In Germany, a statement on pharmacogenetics was also made by the gene diagnostics committee of the Ministry of Health. The DGPPN supports two recommendations: 1) to perform CYP2D6 genetic testing prior to prescription of tricyclic antidepressants and 2) to determine the HLA-B*1502 genotype in patients of Asian origin before using carbamazepine. The main obstacle for a broad application of pharmacogenetic tests in psychiatry remains the lack of large prospective studies, for both single gene-drug pair and cobinatorial pharmacogenetic tests, to evaluate the benefits of genetic testing. Psychiatrists, geneticists and funding agencies are encouraged to increase their efforts for the future benefit of psychiatric patients.

Intervention studies to foster resilience - A systematic review and proposal for a resilience framework in future intervention studies.

Psychological resilience refers to the phenomenon that many people are able to adapt to the challenges of life and maintain mental health despite exposure to adversity. This has stimulated research on training programs to foster psychological resilience. We evaluated concepts, methods and designs of 43 randomized controlled trials published between 1979 and 2014 which assessed the efficacy of such training programs and propose standards for future intervention research based on recent developments in the field. We found that concepts, methods and designs in current resilience intervention studies are of limited use to properly assess efficacy of interventions to foster resilience. Major problems are the use of definitions of resilience as trait or a composite of resilience factors, the use of unsuited assessment instruments, and inappropriate study designs. To overcome these challenges, we propose 1) an outcome-oriented definition of resilience, 2) an outcome-oriented assessment of resilience as change in mental health in relation to stressor load, and 3) methodological standards for suitable study designs of future intervention studies. Our proposals may contribute to an improved quality of resilience intervention studies and may stimulate further progress in this growing research field.

Alcohol Consumption in Healthy OPRM1 G Allele Carriers and Its Association with Impulsive Behavior.

AIMS: A link between alcohol use disorders (AUD) and impulsivity is well established. As there is evidence for the heritability of AUD, the investigation of the underlying genetic disposition for both conditions is an important issue. An association between AUD and a coding single nucleotide polymorphism (SNP) (rs1799971 encoding an Asn40Asp amino acid substitution, A118G) within the µ-opioid receptor 1 gene (OPRM1) has been reported. Therefore we tested the association between the OPRM1 A118G polymorphism and drinking as well as impulsive behavior in social drinkers. METHODS: A total of 214 healthy male social drinkers were recruited. Each participant was genotyped for the OPRM1 A118G variant. Alcohol use was assessed with items of the Alcohol Use Disorders Identification Test (AUDIT). Impulsivity was assessed using the UPPS impulsive behavior scale. For statistical analyses, we considered correlations, t-tests and ordinal regression models using SPSS V21. RESULTS: In total, 49 out of 214 participants were carriers of the OPRM1 118G allele. On average the OPRM1 118G carriers showed a slightly higher propensity for alcohol drinking. Higher drinking frequency among the G allele carriers was linked with higher urgency and perseveration subscores of impulsivity. CONCLUSION: Our results suggest a genetically influenced higher propensity for alcohol drinking among social drinkers carrying the 118G allele of the OPRM1 gene. The positive correlation between urgency and a higher drinking frequency among the OPRM1 118G hint towards a functional meaning of the opioid system in the regulation of impulsivity.

Transcranial sonography and [18F]fluorodeoxyglucose positron emission tomography for the differential diagnosis of parkinsonism: a head-to-head comparison.

BACKGROUND AND PURPOSE: Brain imaging with positron emission tomography using [(18) F]fluorodeoxyglucose (FDG-PET) and transcranial B-mode sonography (TCS) improves the differential diagnosis of parkinsonism. The diagnostic merits of these approaches in identifying and differentiating atypical parkinsonian syndromes (APS) are compared. METHODS: Data were included from 36 patients with clinically suspected APS who underwent PET and TCS. FDG-PET scans were analyzed by visual assessment (including voxel-based statistical maps) of a priori defined disease-specific metabolic patterns. Sonographers achieved diagnoses according to pre-defined criteria for echogenicities of the substantia nigra and lenticular nucleus, and third ventricle diameter. Patients with APS were identified and allocated to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). RESULTS: After a median follow-up period of 9 months, the final clinical diagnoses (reference standard) were Parkinson's disease, n = 15; MSA, n = 9; PSP, n = 7; and CBD, n = 5 (n = 21 APS in total). Six patients (4 APS) showed an insufficient bone window for TCS. In the remaining 30 patients, sensitivity/specificity for diagnosing APS were 82%/100% and 82%/85% for FDG-PET and TCS, respectively. Diagnostic accuracies did not differ between FDG-PET (90%) and TCS (83%; P = 0.69). Likewise, overall accuracy of subgroup classification (non-APS, MSA, PSP and CBD) did not differ between modalities (FDG-PET 87% and TCS 83%; P = 1.00). CONCLUSIONS: FDG-PET and TCS show comparable accuracies for differential diagnosis of neurodegenerative parkinsonism. This preliminary study supports the use of TCS and warrants further prospective validation.

Altered cingulate and amygdala response towards threat and safe cues in attention deficit hyperactivity disorder.

BACKGROUND: Emotional dysregulation is becoming increasingly recognized as an important feature of attention deficit hyperactivity disorder (ADHD). In this study, two experiments were conducted investigating the neural response to either verbally instructed fear (IF) or uninstructed (classically conditioned) fear (UF) using the skin conductance response (SCR) and functional magnetic resonance imaging (fMRI). METHOD: In the conditioning phase of the UF experiment (17 ADHD and 17 healthy controls), subjects experienced an unconditioned stimulus (UCS, unpleasant electrodermal stimulation) paired with a former neutral conditioned stimulus (CS+), whereas a control stimulus (CS-) was never paired with the UCS. In the subsequent test phase, only the CS+ and the CS- were presented. In the IF experiment (13 ADHD and 17 healthy controls), subjects were only told that an independently experienced UCS might occur together with the CS+ but not the CS- during testing. No UCS was presented. RESULTS: Groups did not detectably differ in SCR or neural responses to UF. In IF, ADHD patients showed a trend-line decreased SCR and significantly decreased activation of the dorsal anterior cingulate cortex (dACC), a region prominently involved in fear responding, to the CS+. This was accompanied by higher amygdala activation to the CS-. CONCLUSIONS: During IF, ADHD patients showed deficits in regions centrally involved in fear learning and expression in terms of diminished CS+-related dACC and increased CS--related amygdala signals. This suggests an impaired processing of verbally transmitted aversive information, which is central for conveying fear information in social contexts. This result extends the growing literature on emotional alterations in ADHD.

Differential effects of age on subcomponents of response inhibition.

Inhibitory deficits contribute to cognitive decline in the aging brain. Separating subcomponents of response inhibition may help to resolve contradictions in the existing literature. A total of 49 healthy participants underwent functional magnetic resonance imaging (fMRI) while performing a Go/no-go-, a Simon-, and a Stop-signal task. Regression analyses were conducted to identify correlations of age and activation patterns. Imaging results revealed a differential effect of age on subcomponents of response inhibition. In a simple Go/no-go task (no spatial discrimination), aging was associated with increased activation of the core inhibitory network and parietal areas. In the Simon task, which required spatial discrimination, increased activation in additional inhibitory control regions was present. However, in the Stop-signal task, the most demanding of the three tasks, aging was associated with decreased activation. This suggests that older adults increasingly recruit the inhibitory network and, with increasing load, additional inhibitory regions. However, if inhibitory load exceeds compensatory capacity, performance declines in concert with decreasing activation. Thus, the present findings may refine current theories of cognitive aging.

Disentangling common and specific neural subprocesses of response inhibition.

Response inhibition is disturbed in several disorders sharing impulse control deficits as a core symptom. Since response inhibition is a cognitively and neurally multifaceted function which has been shown to rely on differing neural subprocesses and neurotransmitter systems, further differentiation to define neurophysiological endophenotypes is essential. Response inhibition may involve at least three separable cognitive subcomponents, i.e. interference inhibition, action withholding, and action cancelation. Here, we introduce a novel paradigm - the Hybrid Response Inhibition task - to disentangle interference inhibition, action withholding and action cancelation and their neural subprocesses within one task setting during functional magnetic resonance imaging (fMRI). To validate the novel task, results were compared to a battery of separate, standard response inhibition tasks independently capturing these subcomponents and subprocesses. Across all subcomponents, mutual activation was present in the right inferior frontal cortex (rIFC), pre-supplementary motor area (pre-SMA) and parietal regions. Interference inhibition revealed stronger activation in pre-motor and parietal regions. Action cancelation resulted in stronger activation in fronto-striatal regions. Our results show that all subcomponents share a common neural network and thus all constitute different subprocesses of response inhibition. Subprocesses, however, differ to the degree of regional involvement: interference inhibition relies more pronouncedly on a fronto-parietal-pre-motor network suggesting its close relation to response selection processes. Action cancelation, in turn, is more strongly associated with the fronto-striatal pathway implicating it as a late subcomponent of response inhibition. The new paradigm reliably captures three putatively subsequent subprocesses of response inhibition and might be a promising tool to differentially assess disturbed neural networks in disorders showing impulse control deficits.

Frontostriatal activation in patients with obsessive-compulsive disorder before and after cognitive behavioral therapy.

BACKGROUND: Cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) is the psychotherapeutic treatment of choice for obsessive-compulsive disorder (OCD). However, little is known about the impact of CBT on frontostriatal dysfunctioning, known to be the neuronal correlate of OCD. METHOD: A probabilistic reversal learning (RL) task probing adaptive strategy switching capabilities was used in 10 unmedicated patients with OCD and 10 healthy controls during an event-related functional magnetic resonance imaging (fMRI) experiment. Patients were scanned before and after intensive CBT, controls twice at comparable intervals. RESULTS: Strategy change within the RL task involved activity in a broad frontal network in patients and controls. No significant differences between the groups or in group by time interactions were detected in a whole-brain analysis corrected for multiple comparisons. However, a reanalysis with a more lenient threshold revealed decreased responsiveness of the orbitofrontal cortex and right putamen during strategy change before treatment in patients compared with healthy subjects. A group by time effect was found in the caudate nucleus, demonstrating increased activity for patients over the course of time. Patients with greater clinical improvement, reflected by greater reductions in Yale-Brown Obsessive Compulsive Scale (YBOCS) scores, showed more stable activation in the pallidum. CONCLUSIONS: Although these findings are preliminary and need to be replicated in larger samples, they indicate a possible influence of psychotherapy on brain activity in core regions that have been shown to be directly involved both in acquisition of behavioral rules and stereotypes and in the pathophysiology of OCD, the caudate nucleus and the pallidum.