The Bergen 4-day treatment for panic disorder: adapting to COVID-19 restrictions with a hybrid approach of face-to-face and videoconference modalities.

BACKGROUND: The Bergen 4-day treatment (B4DT) is a concentrated exposure-based therapy that has been shown to be effective in the treatment of anxiety disorders. The current study sought to examine the effectiveness of B4DT for panic disorder (PD), when delivered with a combination of face-to-face sessions and videoconferencing. METHODS: Treatment was delivered to 50 patients from April 2020 to May 2021. Because of regulations during the pandemic, a significant portion of the treatment was conducted via videoconference. The primary outcome measure was the clinician-rated Panic Disorder Severity Scale (PDSS), and secondary measures included patient-rated symptoms of panic disorder, agoraphobia, generalized anxiety, depression, and treatment satisfaction. Changes in symptom levels over time were estimated using multilevel models. RESULTS: Patients showed a significant reduction in clinician-rated symptoms of panic disorder (Measured by PDSS) from before treatment to post treatment (d = 2.18) and 3-month follow-up (d = 2.01). At three months follow-up 62% of patients were classified as in remission, while 70% reported a clinically significant response. We also found a reduction in symptoms of depression and generalized anxiety, and the patients reported high satisfaction with the treatment. CONCLUSION: The current study suggests that B4DT delivered in a combination of videoconference and face-to-face meetings may be a useful treatment approach. As the study is uncontrolled, future studies should also include more strictly designed investigations.

Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive-Behavioral Therapy in Children With Obsessive-Compulsive Disorder.

OBJECTIVE: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

An fMRI study of cognitive planning before and after symptom provocation in pediatric obsessive-compulsive disorder.

BACKGROUND: Pediatric obsessive-compulsive disorder (OCD) has been associated with poorer planning in laboratory, school and home settings. It is unclear whether this impairment is a standalone cognitive issue or the result of OCD symptoms. No study has examined the influence of provoked distress on planning performance and neural correlates in pediatric OCD. METHODS: Before and after a symptom provocation task, youth with OCD (n = 23; 9 boys; mean age ± standard deviation 15.1 ± 2.6 years) and matched healthy controls (n = 23) completed the Tower of London task during functional MRI scanning. RESULTS: During planning, participants with OCD recruited the left superior frontal gyrus to a greater extent than healthy controls after symptom provocation (group × time point interaction; t 44 = 5.22, p < 0.001). In a seeded, region of interest-constrained, functional connectivity analysis, we identified greater connectivity between the left superior frontal gyrus and the right middle frontal gyrus, left precuneus and left inferior parietal lobule in participants with OCD than healthy controls. We also identified greater connectivity between the right amygdala and right medial frontal gyrus in patients with OCD than healthy controls, but only before symptom provocation. LIMITATIONS: The fixed-order design of the study and the number of participants taking medication (n = 20) should be noted. CONCLUSION: Participants with OCD demonstrated greater amygdalar-cortical connectivity before symptom provocation, while sustaining greater recruitment and connectivity of task-related planning areas throughout the task. These results suggest that brain activity and connectivity is altered after symptom provocation, in the absence of impaired planning performance.

Diffusion Tensor Imaging Before and 3 Months After Concentrated Exposure Response Prevention in Obsessive-Compulsive Disorder.

Background: Subtle differences in white matter microstructure have been found in obsessive-compulsive disorder (OCD) compared to controls using diffusion tensor imaging (DTI), but it is unclear if and how this change after treatment. The primary aim of this pre-registered study was to investigate white matter integrity between OCD patients and controls and changes after concentrated exposure and response prevention (ERP). Methods: Fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) and mean diffusivity (MD) were estimated using FMRIB Software Library (FSL). The images were registered to a study-specific template using a longitudinal pipeline based on full tensor information in DTI-TK. Voxel-based analysis was performed using tract-based spatial statistics (TBSS). Using SPSS, we compared the integrity in three bilateral regions of interest (ROI), the sagittal stratum, posterior thalamic radiation and cingulum, in 32 OCD patients and 30 matched healthy controls at baseline. Patients received a four-day concentrated ERP format. We investigated longitudinal changes in 26 OCD patients and 22 healthy controls at 3months follow-up using repeated-measures ANOVA. Exploratory t-tests were conducted for AD and MD. Secondary hypothesis used linear regression to investigate if baseline FA predict treatment outcome 3 months later, and if patients with illness onset before 18 years of age would show lower FA in sagittal stratum. Finally, we performed sensitivity analysis on medication and comorbidity influences on FA. Results: Three months after treatment, 77% of the patients were in remission. Contrary to our hypotheses, we did not find any significant differences in FA, RD, AD or MD between the groups before treatment, nor significant group by time effects in any of the ROI. None of the baseline FA measures significantly predicted treatment outcome. Illness onset before 18 years of age did not significantly predict FA in the sagittal stratum. Adjusting for medication or comorbid anxiety or mood disorder did not influence the results. Conclusions: Although concentrated ERP in OCD lead to high remission, we did not find significant long-term changes by DTI. Future studies will benefit from using larger sample sizes and multi-shell diffusion-weighted imaging when investigating white matter microstructure in OCD and underlying neurobiological mechanisms of treatment.

Disentangling Within- and Between-Person Effects During Response Inhibition in Obsessive-Compulsive Disorder.

Background: Obsessive-compulsive disorder (OCD) has been related to worse performance, abnormal brain activity, and functional connectivity during response inhibition. Whether these findings are indications of stable traits that contribute to the development of the disorder, or whether they are a result of the state severity of obsessions and anxiety, remains unclear since previous research mainly has employed cross-sectional designs. The present study aimed to assess longitudinal between- and within-person relationships between symptoms, task performance, right inferior frontal gyrus brain activation, and connectivity between the right amygdala and the right pre-supplementary motor area in 29 OCD patients before and after concentrated exposure and response prevention treatment. Method: Patients received exposure and response prevention delivered during 4 consecutive days, following the Bergen 4-day Treatment format. Patients performed a Stop Signal Task during 3T functional Magnetic Resonance Imaging the day before treatment, as well as 1 week and 3 months after treatment completion. Multilevel models were used to analyze disaggregated within- and between-person effects over time. Independent variables were scores on the symptom severity scales for OCD, anxiety, depression, and state distress during scanning. Dependent variables were reaction time for go trials, stop signal response time, task-related brain activation and connectivity. Results: A positive between-person effect was found for obsessive-compulsive, anxiety, and depressive symptom severity on go trial reaction time, indicating that patients with higher symptom scores on average respond slower during accurate go trials. We also found no significant between- or within-person relations between symptom severity and task-related activation or fronto-limbic connectivity. Conclusions: The between-person findings may point toward a general association between slower processing speed and symptom severity in OCD. Longitudinal studies should disaggregate between- and within-person effects to better understand variation over time.

Symptom dimensions in obsessive-compulsive disorder as predictors of neurobiology and treatment response.

PURPOSE OF REVIEW: Specific symptom dimensions of obsessive-compulsive disorder (OCD) have been suggested as an approach to reduce the heterogeneity of obsessive-compulsive disorder, predict treatment outcome, and relate to brain structure and function. Here, we review studies addressing these issues. RECENT FINDINGS: The contamination and symmetry/ordering dimensions have not been reliably associated with treatment outcome. Some studies found that greater severity of sexual/aggressive/religious symptoms predicted a worse outcome after cognitive behavioral therapy (CBT) and a better outcome after serotonin reuptake inhibitors (SRIs). Contamination symptoms have been related to increased amygdala and insula activation in a few studies, while sexual/aggressive/religious symptoms have also been related to more pronounced alterations in the function and structure of the amygdala. Increased pre-treatment limbic responsiveness has been related to better outcomes of CBT, but most imaging studies show important limitations and replication in large-scale studies is needed. We review possible reasons for the strong limbic involvement of the amygdala in patients with more sexual/aggressive/religious symptoms, in relation to their sensitivity to CBT. SUMMARY: Symptom dimensions may predict treatment outcome, and patients with sexual/religious/aggressive symptoms are at a greater risk of not starting or delaying treatment. This is likely partly due to more shame and perceived immorality which is also related to stronger amygdala response. Competently delivered CBT is likely to help these patients improve to the same degree as patients with other symptoms.

Emotional Processing in Obsessive-Compulsive Disorder: A Systematic Review and Meta-analysis of 25 Functional Neuroimaging Studies.

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) experience aversive emotions in response to obsessions, motivating avoidance and compulsive behaviors. However, there is considerable ambiguity regarding the brain circuitry involved in emotional processing in OCD, especially whether activation is altered in the amygdala. METHODS: We conducted a systematic literature review and performed a meta-analysis-seed-based d mapping-of 25 whole-brain neuroimaging studies (including 571 patients and 564 healthy control subjects) using functional magnetic resonance imaging or positron emission tomography, comparing brain activation of patients with OCD and healthy control subjects during presentation of emotionally valenced versus neutral stimuli. Meta-regressions were employed to investigate possible moderators. RESULTS: Patients with OCD, compared with healthy control subjects, showed increased activation in the bilateral amygdala, right putamen, orbitofrontal cortex extending into the anterior cingulate and ventromedial prefrontal cortex, and middle temporal and left inferior occipital cortices during emotional processing. Right amygdala hyperactivation was most pronounced in unmedicated patients. Symptom severity was related to increased activation in the orbitofrontal and anterior cingulate cortices and precuneus. Greater comorbidity with mood and anxiety disorders was associated with higher activation in the right amygdala, putamen, and insula as well as with lower activation in the left amygdala and right ventromedial prefrontal cortex. CONCLUSIONS: Patients with OCD show increased emotional processing-related activation in limbic, frontal, and temporal regions. Previous mixed evidence regarding the role of the amygdala in OCD has likely been influenced by patient characteristics (such as medication status) and low statistical power.

Parental socioeconomic status and child intellectual functioning in a Norwegian sample.

Socioeconomic status (SES) in childhood has been linked to cognitive function and future academic and occupational success in studies from several countries. However, previous Nordic studies have shown inconsistent results regarding the strength of this link. We therefore investigated the association between SES and cognitive functioning in a sample of 255 Norwegian children, including 151 typically developing children and 104 children with a psychiatric diagnosis. The third edition of the Wechsler Intelligence Scale for Children (WISC-III) to assess cognitive function was used. SES was defined from maternal and paternal education and family income of typically developing children and of a subsample of children with a psychiatric diagnosis. Multiple adjusted regression analyses were used to investigate the relation between SES and cognitive functioning. The analyses showed that SES explained a significant part of the variance of the full-scale WISC-III score and two WISC-III indices (Verbal Comprehension and Freedom from Distractibility). Overall, the strength of the relations was weaker than expected from reports from other non-Nordic countries. Parental education was the only significant individual predictor, suggesting that income was of minor importance as a predictor of cognitive functioning. Further studies should investigate how diverse political and socioeconomic contexts influence the relation between SES and cognitive functioning.

Neuroimaging of psychotherapy for obsessive-compulsive disorder: A systematic review.

The symptoms of obsessive-compulsive disorder (OCD) include intrusive thoughts, compulsive behavior, anxiety, and cognitive inflexibility, which are associated with dysfunction in dorsal and ventral corticostriato-thalamocortical (CSTC) circuits. Psychotherapy involving exposure and response prevention has been established as an effective treatment for the affective symptoms, but the impact on the underlying neural circuits is not clear. This systematic review used the Medline, Embase, and PsychINFO databases to investigate how successful therapy may affect neural substrates of OCD. Sixteen studies measuring neural changes after therapy were included in the review. The studies indicate that dysfunctions in neural function and structure are partly reversible and state-dependent for affective symptoms, which may also apply to cognitive symptoms. This is supported by post-treatment decreases of symptoms and activity in the ventral circuits during symptom provocation, as well as mainly increased activity in dorsal circuits during cognitive processing. These effects appear to be common to both psychotherapy and medication approaches. Although neural findings were not consistent across all studies, these findings indicate that people with OCD may experience functional, symptomatic, and neural recovery after successful treatment.

Neurobiology of cognitive remediation therapy for schizophrenia: a systematic review.

Cognitive impairment is an important aspect of schizophrenia, where cognitive remediation therapy (CRT) is a promising treatment for improving cognitive functioning. While neurobiological dysfunction in schizophrenia has been the target of much research, the neural substrate of cognitive remediation and recovery has not been thoroughly examined. The aim of the present article is to systematically review the evidence for neural changes after CRT for schizophrenia. The reviewed studies indicate that CRT affects several brain regions and circuits, including prefrontal, parietal, and limbic areas, both in terms of activity and structure. Changes in prefrontal areas are the most reported finding, fitting to previous evidence of dysfunction in this region. Two limitations of the current research are the few studies and the lack of knowledge on the mechanisms underlying neural and cognitive changes after treatment. Despite these limitations, the current evidence suggests that CRT is associated with both neurobiological and cognitive improvement. The evidence from these findings may shed light on both the neural substrate of cognitive impairment in schizophrenia, and how better treatment can be developed and applied.