Investigating brain structure and tDCS response in obsessive-compulsive disorder.

Obsessive-Compulsive Disorder (OCD) is characterized by intrusive thoughts and repetitive behaviors, with associated brain abnormalities in various regions. This study explores the correlation between neural biomarkers and the response to transcranial Direct Current Stimulation (tDCS) in OCD patients. Using structural MRI data from two tDCS trials involving 55 OCD patients and 28 controls, cortical thickness, and gray matter morphometry was analyzed. Findings revealed thicker precentral and paracentral areas in OCD patients, compared to control (p < 0.001). Correlations between cortical thickness and treatment response indicated a significant association between a thinner precentral area and reduced Yale-Brown Obsessive Compulsive Scale (YBOCS) scores (p = 0.02). While results highlight the complexity of treatment response predictors, this study sheds light on potential neural markers for tDCS response in OCD patients. Further investigations with larger datasets are warranted to better understand the underpinnings of these biomarkers and their implications for personalized treatment approaches.

Treating refractory obsessive compulsive disorder with cathodal transcranial direct current stimulation over the supplementary motor area: a large multisite randomized sham-controlled double-blind study.

Background: The present study evaluated the therapeutic efficacy and tolerability of 10 transcranial direct current stimulation (tDCS) sessions in treatment-resistance obsessive-compulsive disorder (OCD) patients using a multisite double-blind sham-controlled design. Methods: Eighty treatment-resistance outpatients suffering from obsessive-compulsive disorder were randomized to receive either active or sham transcranial direct current stimulation. The cathode was positioned over the supplementary motor area and the anode over the right supraorbital area. Patients were evaluated at baseline, end of treatment (day 14), one-month follow-up (day 45), and three-month follow-up (day 105) on the Yale-Brown Obsessive Compulsive Scale. Results: Although a significant interaction between time and treatment was observed, the primary endpoint-measuring the change in Yale-Brown obsessive compulsive scale scores after two weeks-was not achieved. Conversely, the secondary endpoint, which concerned the change in Yale-Brown obsessive compulsive scale scores after three months, was successfully met. It is important to note, however, that there were no significant differences in the percentage of responders and remitters at any of the post-treatment assessments. This suggests that the treatment may not have had a clinically relevant impact. Patients well received the transcranial direct current stimulation treatment, indicating its good tolerability. Conclusion: This is the largest controlled trial using transcranial direct current stimulation in treatment-resistance obsessive-compulsive disorder patients. Our results indicate the importance of studying the placebo effect in transcranial direct current stimulation and the necessity to consider a long follow-up time to best evaluate the effects of the intervention. Clinical trial registration: ClinicalTrials.gov, identifier NCT03304600.

Neurological soft signs as trait markers of a subset of patients with obsessive-compulsive disorder with low insight and altered cognitive abilities.

Neurological soft signs (NSS) are subtle motor control impairments that include involuntary movements and abnormalities of motor coordination, sensory integration and lateralization. They engage different brain networks, including the prefrontal networks that support the higher cognitive functions that are dysfunctional in obsessive-compulsive disorder (OCD). This study investigated the relationships between the presence of NSS and patients' severity of OCD symptoms, insight, and treatment resistance in a sample of 63 patients. Treatment-resistance was assessed considering all the treatments the patients received during the course of their disease. The four dimensions of OCD defined in the dimensional obsessive-compulsive scale were considered. Links between the patients' cognitive abilities and NSS were assessed using tests targeting specifically the core components of executive functions. As expected, OCD patients displayed more NSS than individually matched control participants. In OCD patients, high NSS scores were associated with poor insight and lower cognitive abilities. Multiple regression analysis identified worse visuospatial working memory, attentional control, and verbal fluency as predictive factors of high NSS scores among cognitive functions. Unexpectedly, the patients displaying symptoms in the contamination/washing dimension displayed less NSS than the other patients. In contrast, neither the severity of OCD symptoms nor long-range treatment resistance was significantly related to patients' NSS scores. Altogether, our findings suggest that high NSS scores may be a trait marker of a subset of OCD patients with low insight and particularly altered cognitive abilities who would not express the contamination/washing dimension of the pathology.

EEG microstate co-specificity in schizophrenia and obsessive-compulsive disorder.

The past 20 years of research on EEG microstates has yielded the hypothesis that the imbalance pattern in the temporal dynamics of microstates C (increased) and D (decreased) is specific to schizophrenia. A similar microstate imbalance has been recently found in obsessive-compulsive disorder (OCD). The aim of the present high-density EEG study was to examine whether this pathological microstate pattern is co-specific to schizophrenia and OCD. We compared microstate temporal dynamics using Bayesian analyses, transition probabilities analyses and the Topographic Electrophysiological State Source-Imaging method for source reconstruction in 24 OCD patients and 28 schizophrenia patients, respectively, free of comorbid psychotic and OCD symptoms, and 27 healthy controls. OCD and schizophrenia patients exhibited the same increased contribution of microstate C, decreased duration and contribution of microstate D and greater D → C transition probabilities, compared with controls. A Bayes factor of 4.424 for the contribution of microstate C, 4.600 and 3.824, respectively, for the duration and contribution of microstate D demonstrated that there was no difference in microstate patterns between the two disorders. Source reconstruction further showed undistinguishable dysregulations between the Salience Network (SN), associated with microstate C, and the Executive Control Network (ECN), associated with microstate D, and between the ECN and cognitive cortico-striato-thalamo-cortical (CSTC) loop in the two disorders. The ECN/CSTC loop dysconnectivity was slightly worsened in schizophrenia. Our findings provide substantial evidence for a common aetiological pathway in schizophrenia and OCD, i.e. microstate co-specificity, and same anomalies in salience and external attention processing, leading to co-expression of symptoms.

High treatment resistance is associated with lower performance in the Stroop test in patients with obsessive-compulsive disorder.

Around 50% of the patients with obsessive-compulsive disorder (OCD) are resistant to treatment, and patients with OCD show alterations in a broad range of cognitive abilities. The present study investigated the links between treatment-resistance, executive and working memory abilities, and the severity of OCD symptoms among 66 patients with OCD. The patients performed seven tests gauging their executive functions and working memory and filled in questionnaires for OCD severity and insight into their pathology. In addition, the executive and working memory abilities of a subset of these patients were compared with those of individually matched control participants. In contrast with previous studies, patients' treatment resistance was evaluated by considering the clinical outcomes of all the treatments that they received during the course of their disease. Higher treatment resistance was associated with lower performance in one particular executive test, the Stroop test, which assessed patients' ability to inhibit prepotent/automatic responses. Older age and more severe OCD symptoms were also associated with higher treatment resistance. Regardless of OCD severity, the patients displayed small to moderate deficits across most components of executive functions compared to control participants. Interestingly, patients with OCD took more time than control participants to perform speeded neuropsychological tests but never made more errors. Altogether, this study shows that the treatment-resistance of patients with OCD may be reliably quantified over the course of years and treatments using Pallanti and Quercioli's (2006) treatment resistance-related scales. The data suggest that the Stroop test could be used clinically to anticipate treatment outcomes in to-be-treated patients.

Microstates imbalance is associated with a functional dysregulation of the resting-state networks in obsessive-compulsive disorder: a high-density electrical neuroimaging study using the TESS method.

The dysfunctional patterns of microstates dynamics in obsessive-compulsive disorder (OCD) remain uncertain. Using high-density electrical neuroimaging (EEG) at rest, we explored microstates deterioration in OCD and whether abnormal microstates patterns are associated with a dysregulation of the resting-state networks interplay. We used EEG microstates analyses, TESS method for sources reconstruction, and General Linear Models to test for the effect of disease severity on neural responses. OCD patients exhibited an increased contribution and decreased duration of microstates C and D, respectively. Activity was decreased in the Salience Network (SN), associated with microstate C, but increased in the Default Mode Network (DMN) and Executive Control Network (ECN), respectively, associated with microstates E and D. The hyperactivity of the right angular gyrus in the ECN correlated with the symptoms severity. The imbalance between microstates C and D invalidates the hypothesis that this electrophysiological pattern is specific to psychosis. Demonstrating that the SN-ECN dysregulation manifests as abnormalities in microstates C and D, we confirm that the SN deterioration in OCD is accompanied by a failure of the DMN to deactivate and aberrant compensatory activation mechanisms in the ECN. These abnormalities explain typical OCD clinical features but also detachment from reality, shared with psychosis.

Baseline Clinical and Neuroimaging Biomarkers of Treatment Response to High-Frequency rTMS Over the Left DLPFC for Resistant Depression.

Background: Repetitive transcranial magnetic stimulation (rTMS) has proven to be an efficient treatment option for patients with treatment-resistant depression (TRD). However, the success rate of this method is still low, and the treatment outcome is unpredictable. The objective of this study was to explore clinical and structural neuroimaging factors as potential biomarkers of the efficacy of high-frequency (HF) rTMS (20 Hz) over the left dorso-lateral pre-frontal cortex (DLPFC). Methods: We analyzed the records of 131 patients with mood disorders who were treated with rTMS and were assessed at baseline at the end of the stimulation and at 1 month after the end of the treatment. The response is defined as a 50% decrease in the MADRS score between the first and the last assessment. Each of these patients underwent a T1 MRI scan of the brain, which was subsequently segmented with FreeSurfer. Whole-brain analyses [Query, Design, Estimate, Contrast (QDEC)] were conducted and corrected for multiple comparisons. Additionally, the responder status was also analyzed using binomial multivariate regression models. The explored variables were clinical and anatomical features of the rTMS target obtained from T1 MRI: target-scalp distance, DLPFC gray matter thickness, and various cortical measures of interest previously studied. Results: The results of a binomial multivariate regression model indicated that depression type (p = 0.025), gender (p = 0.010), and the severity of depression (p = 0.027) were found to be associated with response to rTMS. Additionally, the resistance stage showed a significant trend (p = 0.055). Whole-brain analyses on volume revealed that the average volume of the left part of the superior frontal and the caudal middle frontal regions is associated with the response status. Other MRI-based measures are not significantly associated with response to rTMS in our population. Conclusion: In this study, we investigated the clinical and neuroimaging biomarkers associated with responsiveness to high-frequency rTMS over the left DLPFC in a large sample of patients with TRD. Women, patients with bipolar depressive disorder (BDD), and patients who are less resistant to HF rTMS respond better. Responders present a lower volume of the left part of the superior frontal gyrus and the caudal middle frontal gyrus. These findings support further investigation into the use of clinical variables and structural MRI as possible biomarkers of rTMS treatment response.

Preliminary Evidence That the Short Allele of 5-HTTLPR Moderates the Association of Psychiatric Symptom Severity on Suicide Attempt: The Example in Obsessive-Compulsive Disorder.

Background: The severity of symptoms represents an important source of distress in patients with a psychiatric disease. However, the extent to which this endogenous stress factor interacts with genetic vulnerability factors for predicting suicide risks remains unclear. Methods: We evaluated whether the severity of symptoms interacts with a genetic vulnerability factor (the serotonin transporter gene-linked promoter region variation) in predicting the frequency of lifetime suicide attempts in patients with a psychiatric disease. Symptom severity and 5-HTTLPR polymorphism were collected from a sample of 95 patients with obsessive-compulsive disorder (OCD). Lifetime suicide attempt was the primary outcome, and antecedent of multiple suicide attempts was the secondary outcome. Results: The gene-by-symptoms interaction was associated with an excess risk of suicide attempts (OR = 4.39, 95CI[1.44, 13.38], p < 0.009) and of multiple suicide attempts (OR = 4.18, 95CI[1.04, 16.77], p = 0.043). Symptom severity (moderate, severe, or extreme) was associated with an approximately five-fold increase in the odds of a lifetime suicide attempt in patients carrying one or two copies of the short allele of 5-HTTLPR. No such relationship was found for patients carrying the long allele. Conclusion: This study provides preliminary evidence for the gene-by-stress interaction on suicide attempt when stress is operationalized as symptom severity. Progress in suicide research may come from efforts to investigate the gene-by-symptoms interaction hypothesis in a variety of diseases.

How do they add up? The interaction between the placebo and treatment effect: A systematic review.

AIM: The placebo effect and the specific effect are often thought to add up (additive model). Whether additivity holds can dramatically influence the external validity of a trial. This assumption of additivity was tested by Kleijnen et al in 1994 but the data produced since then have not been synthetized. In this review, we aimed to systematically review the literature to determine whether additivity held. METHODS: We searched Medline and PsychInfo up to 10 January 2019. Studies using the balanced placebo design (BPD), testing two different strengths of placebos, were included. The presence of interaction was evaluated by comparing each group in the BPD with analysis of variance or covariance. RESULTS: Thirty studies were included and the overall risk of bias was high: four found evidence of additivity and 16 studies found evidence of interaction (seven had evidence of positive additivity). CONCLUSION: Evidence of additivity between placebo and specific features of treatments was rare in included studies. We suggest interventions for placebo-sensitive ailments should be tested in trials designed to take interactions seriously once an exploratory RCTs has proven their efficacy with sufficient internal validity.

High-Frequency Neuronavigated rTMS in Auditory Verbal Hallucinations: A Pilot Double-Blind Controlled Study in Patients With Schizophrenia.

INTRODUCTION: Despite extensive testing, the efficacy of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of temporo-parietal targets for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia is still controversial, but promising results have been reported with both high-frequency and neuronavigated rTMS. Here, we report a double-blind sham-controlled study to assess the efficacy of high-frequency (20 Hz) rTMS applied over a precise anatomical site in the left temporal region using neuronavigation. METHODS: Fifty-nine of 74 randomized patients with schizophrenia or schizoaffective disorders (DSM-IV R) were treated with rTMS or sham treatment and fully evaluated over 4 weeks. The rTMS target was determined by morphological MRI at the crossing between the projection of the ascending branch of the left lateral sulcus and the superior temporal sulcus (STS). RESULTS: The primary outcome was response to treatment, defined as a 30% decrease of the Auditory Hallucinations Rating Scale (AHRS) frequency item, observed at 2 successive evaluations. While there was no difference in primary outcome between the treatment groups, the percentages of patients showing a decrease of more than 30% of AHRS score (secondary outcome) did differ between the active (34.6%) and sham groups (9.1%) (P = .016) at day 14. DISCUSSION: This controlled study reports negative results on the primary outcome but demonstrates a transient effect of 20 Hz rTMS guided by neuronavigation and targeted on an accurate anatomical site for the treatment of AVHs in schizophrenia patients.

Repetitive Transcranial Magnetic Stimulation to Supplementary Motor Area in Refractory Obsessive-Compulsive Disorder Treatment: a Sham-Controlled Trial.

BACKGROUND: Repetitive transcranial magnetic stimulation has been explored in patients with obsessive-compulsive disorder, but with negative or conflicting results. This randomized double-blind study was designed to assess the efficacy of 1-Hz repetitive transcranial magnetic stimulation over the presupplementary area. METHODS: Forty medication-resistant patients were assigned to 4 weeks of either active or sham repetitive transcranial magnetic stimulation targeting the presupplementary area with the help of a neuronavigation system. RESULTS: According to the Yale-Brown obsessive-compulsive scale, the baseline-week 4 evolution showed no significant differences between groups. Responder rates at week 4 were not different between groups (repetitive transcranial magnetic stimulation 10.5% vs sham 20%; P=.63). CONCLUSION: Low-frequency repetitive transcranial magnetic stimulation applied to the presupplementary area seems ineffective for the treatment of obsessive-compulsive disorder patients, at least in severe and drug-refractory cases such as those included in this study. Further research is required to determine profiles of responder patients and appropriate repetitive transcranial magnetic stimulation parameters for obsessive-compulsive disorder.

The relationship between insight and uncertainty in obsessive-compulsive disorder.

BACKGROUND: The aim of this study was to investigate the relationship between the levels of insight and checking-related uncertainty in patients with obsessive-compulsive disorder (OCD). SAMPLING AND METHODS: Twenty OCD patients with checking compulsions and without current comorbidity were recruited. We used an experimental paradigm that gave subjects the opportunity to check during a decision-making task, thereby allowing for the calculation of a response time index (RTI) as the 'uncertainty cost' during decision-making. The level of insight was assessed with the Brown Assessment of Beliefs Scale (BABS). RESULTS: Regression analyses indicated a significant positive correlation between RTI and BABS scores (r = 0.49). CONCLUSIONS: The level of insight is related to cognitive characteristics underlying OCD symptoms, in particular, checking-related uncertainty in checking OCD patients. STUDY LIMITATIONS: The absence of a comparison group and the low number of included patients are the main limitations of the present study.

Neurological soft signs in OCD patients with early age at onset, versus patients with schizophrenia and healthy subjects.

Compelling evidence suggests that both schizophrenia and obsessive compulsive disorder (OCD) are related to deviant neurodevelopment. Neurological soft signs (NSS) have been proposed to be a marker of abnormal brain development in schizophrenia. The purpose of this study is to examine whether NSS are also a marker in patients with OCD, in particular, in early-onset OCD. The authors included 162 subjects and compared patients with OCD, patients with schizophrenia (SCZ), and healthy control subjects. They were all examined for NSS (Krebs' Scale), extrapyramidal symptoms (Simpson-Angus Scale), and were rated on the Abnormal Involuntary Movements Scale (AIMS). The authors found no differences between NSS total scores and subscores in OCD versus controls, whereas total NSS, motor coordination, and motor integration were significantly lower in OCD than in SCZ. OCD patients with early-onset (before age 13) did not differ from those with later-onset OCD. These results support the idea that NSS, as determined by current scales, is relatively specific to schizophrenia, although they do not preclude the existence of a neurological dysfunction in OCD. Further studies are required to determine the type of neurological signs that could be useful trait-markers in the phenotypic characterization of subtype OCD.

Obsessive compulsive disorder in a patient with twiddler's syndrome.

Twiddler's or twist syndrome is the twisting of pulse generators around themselves. It may result from mechanical manipulation that can induce the malfunction of the device. In this case, twiddler's syndrome resulted from compulsive checking of the device. The implantable cardioverter-defibrillator (ICD) triggered the development of an obsessive compulsive disorder (OCD). Two invasive procedures were required to replace the ICD. Psychiatric intervention prevented the recurrence of twiddler's syndrome in this patient for more than 2 years. We believe that preimplant psychiatric assessment should be the rule.