Resting-state functional connectivity abnormalities in patients with obsessive–compulsive disorder and their healthy first-degree relatives

Background

Obsessive–compulsive disorder (OCD) is a common, heritable neuropsychiatric disorder, hypothetically underpinned by dysfunction of brain cortical–striatal–thalamic–cortical (CSTC) circuits; however, the extent of brain functional abnormalities in individuals with OCD is unclear, and the genetic basis of this disorder is poorly understood. We determined the whole brain functional connectivity patterns in patients with OCD and their healthy first-degree relatives.

Methods

We used resting-state fMRI to measure functional connectivity strength in patients with OCD, their healthy first-degree relatives and healthy controls. Whole brain functional networks were constructed by measuring the temporal correlations of all brain voxel pairs and further analyzed using a graph theory approach.

Results

We enrolled 39 patients with OCD, 20 healthy first-degree relatives and 39 healthy controls in our study. Compared with healthy controls, patients with OCD showed increased functional connectivity primarily within the CSTC circuits and decreased functional connectivity in the occipital cortex, temporal cortex and cerebellum. Moreover, patients with OCD and their first-degree relatives exhibited overlapping increased functional connectivity strength in the bilateral caudate nucleus, left orbitofrontal cortex (OFC) and left middle temporal gyrus.

Limitations

Potential confounding factors, such as medication use, heterogeneity in symptom clusters and comorbid disorders, may have impacted our findings.

Conclusion

Our preliminary results suggest that patients with OCD have abnormal resting-state functional connectivity that is not limited to CSTC circuits and involves abnormalities in additional large-scale brain systems, especially the limbic system. Moreover, resting-state functional connectivity strength abnormalities in the left OFC, bilateral caudate nucleus and left middle temporal gyrus may be neuroimaging endophenotypes for OCD.     

Suicidal ideation in patients with obsessive–compulsive disorder

The risk factors for suicidal behaviour in obsessive-compulsive disorder (OCD) have been less studied compared than in other anxiety disorders. In the present study, we examined the demographic and clinical correlates of current suicidal ideation (SI) in patients with OCD. Forty-four patients were grouped into those with (n = 23) and without current SI (n = 21) as assessed by the Scale for Suicidal Ideation. The Yale-Brown Obsessive–Compulsive Scale (Y-BOCS) was used to assess the obsessive–compulsive (OC) symptomatology. Following Bonferroni correction, only the severity of depression differed significantly between the two groups. The presence of major depression and aggressive obsessions, the level of hopelessness, and the severity of OC symptomatology were significant predictors of current SI in patients with OCD. The relatively low frequency of some comorbid Axis I disorders is based on small sample size and therefore may be vulnerable to type II error. We did not examine the relationship between the recent suicidal attempts and OCD. Also, we did not assess the effect of impulsivity in the occurrence of SI in patients with OCD. Associated depression, hopelessness, and aggressive obsessions might play an important role in the occurrence of SI in patients with OCD. However, future studies with a psychological autopsy design are required to systematically determine the presence for OCD among those who have completed suicide.     

Characterizing impulsivity profile in patients with obsessive–compulsive disorder

Objective. Impulsivity represents a key dimension in obsessive–compulsive disorder (OCD), in relation to outcome and course. It can be assessed through the Barratt Impulsiveness Scale (BIS), which explores three main areas: attentional, motor, and nonplanning. Present study was aimed to assess level of impulsivity in a sample of OCD patients, in comparison with healthy controls, using the BIS. Methods. Seventy-five OCD outpatients, 48 of them having psychiatric comorbidities and 70 healthy controls, were assessed through the BIS, and their scores were analyzed using Student's t-test for independent samples, on the basis of demographic and clinical characteristics. Results. BIS total scores were significantly higher (P: 0.01) in patients compared to controls, with no difference between pure and comorbid patients. Attentional impulsivity scores were significantly higher than controls in patients with pure (P < 0.001) and comorbid OCD (P < 0.001), without differences among them. Patients with multiple OC phenotypes showed higher, though statistically non significant, total and attentional scores, compared to single phenotype patients. In addition, patients with comorbid major depressive disorder had higher, though statistically non significant, total and attentional scores, compared to patients with comorbid bipolar disorder, generalized anxiety disorder, and other disorders. Conclusions. Present findings showed higher impulsivity levels in OCD patients versus controls, particularly in the attentional area, and ultimately suggest a potential cognitive implication.     

Accelerometer-determined physical activity and walking capacity in persons with Down syndrome,Williams syndrome and Prader–Willi syndrome

In this study we describe by use of accelerometers the total physical activity (PA), intensity pattern and walking capacity in 87 persons age 16–45 years with Down syndrome (DS), Williams syndrome (WS) and Prader–Willi syndrome (PWS). Participants were recruited from all over Norway, and lived either with their parents or in community residences with support.On average the participants generated 294 counts per minute (cpm) or 6712 steps per day, with most of the day spent in sedentary activity, 522 min/day, followed by 212 min/day in light PA, 71 min/day in lifestyle activity and 27 min/day in moderate-to-vigorous physical activity (MVPA). Inactivity was prevalent, as only 12% meet the current Nordic recommendations for PA.When compared, no differences for total physical activity or time in MVPA were observed between the three groups. However, participant with DS spent a mean of 73 min/day less and 43 min/day less in sedentary activities compared to participants with PWS and WS, respectively, (p = 0.011, 95% CI: ?10.9; ?80.1). In addition the DS-group spent a mean of 66 min/day more in light PA than the PWS-group and 41 min/day more than the WS-group, (p < 0.001, 95% CI: 29.3; 79.7). Participants with PWS spent on average 30 min/day less in lifestyle activities compared to both participants with DS and WS, (p < 0.001, 95% CI: ?14.2; ?45.4). No association between total PA and BMI were observed. Males were more active than females across all diagnoses. Males accumulated on average 85 counts per minutes more than females, (p = 0.002, 95% CI: 33.3; 136.7), 2137 more steps per day, (p = 0.002, 95% CI: 778; 3496). The mean walking capacity during six-minutes was 507 m (SD 112 m) for males and 466 m (SD 88 m) for females. Distance walked during testing decreased with 33.6 m when comparing normal or underweight participants to overweight participants, and 78.1 m when comparing overweight to obese participants (p < 0.001 95% CI: ?40.4; ?85.8). When adjusted for BMI no differences in walking capacity between the three genetic conditions were observed.     

Meta-analysis of cognitive functioning in patients with psychotic disorders and obsessive–compulsive symptoms

European Archives of Psychiatry and Clinical Neuroscience - Obsessive–compulsive symptoms (OCS) in psychotic disorders are associated with unfavorable outcomes, whether this extends to...     

Insight in adults with obsessive–compulsive disorder

The present study examined the clinical correlates of insight among adults with obsessive–compulsive disorder (OCD). One hundred and thirty treatment-seeking adults with a primary diagnosis of OCD, aged 18 to 68 years (mean 31.4 years) participated. Measures of clinical severity, obsessive–compulsive symptom dimensions, anxiety symptoms, depressive symptoms, and ability to resist and control OCD symptoms were obtained. Results indicated that poor insight was positively related to greater OCD symptom severity and poorer ability to resist and control OCD symptoms; this pattern of associations held when insight was examined continuously and categorically (i.e., high versus low insight). Insight was generally not associated with other clinical characteristics, except for a relationship with mental neutralizing behaviors. Insight did not mediate the relationship between the ability to resist and control OCD symptoms and obsessive–compulsive symptom severity. Overall, this study provides further information into the nature and role of insight in adults with OCD.     

Prader–Willi syndrome: From genetics to behaviour,with special focus on appetite treatments

Prader–Willi syndrome (PWS) is a neurodevelopmental disorder resulting from a deletion in the expression of the paternally derived alleles in the region of 15q11–q13. PWS has a prevalence rate of 1:10,000–1:30,000 and is characterized by marked endocrine abnormalities including growth hormone deficiency and raised ghrelin levels.The hyperphagic phenotype in PWS is established over a number of phases and is exacerbated by impaired satiety, low energy expenditure and intellectual difficulties including obsessive–compulsive disorder and/or autistic behaviours. Clinical management in PWS typically includes familial/carer restriction and close supervision of food intake. If the supervision of food is left unmanaged, morbid obesity eventuates, central to the risk of cardiorespiratory disorder. None of the current appetite management/intervention strategies for PWS include pharmacological treatment, though recent research shows some promise.We review the established aberrant genetics and the endocrine and neuronal attributes which may determine disturbed regulatory processes in PWS. Focusing on clinical trials for appetite behaviours in PWS, we define the effectiveness of pharmacological treatments with a view to initiating and focusing research towards possible targets for modulating appetite in PWS.     

A pro-inflammatory phenotype is associated with behavioural traits in children with Prader–Willi syndrome

European Child & Adolescent Psychiatry - Several lines of evidence indicate that immune-inflammatory alterations are widely observed in various mental disorders. Genetic syndromes with high...     

Disrupted pathways from frontal-parietal cortex to basal ganglia and cerebellum in patients with unmedicated obsessive compulsive disorder as observed by whole-brain resting-state effective connectivity analysis – a small sample pilot study

Brain Imaging and Behavior - To date, a systematic characterization of abnormalities in resting-state effective connectivity (rsEC) in obsessive–compulsive disorder (OCD) is lacking. The...     

Regional cerebral blood flow and abnormal eating behavior in Prader–Willi syndrome

Background: Prader–Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder and is generally regarded as a genetic model of obesity. Individuals with PWS exhibit behavioral symptoms including temper tantrums, rigid thinking, and compulsive behavior. The most striking feature of PWS is abnormal eating behavior, including hyperphagia, intense preoccupation with food, and incessant food seeking. To explore brain regions associated with the behavioral symptoms of PWS, we investigated differences in resting-state regional cerebral blood flow (rCBF) between individuals with PWS and healthy controls. Correlation analyses were also performed to examine the relationship between rCBF and altered eating behavior in PWS individuals. Methods: Twelve adults with PWS and 13 age- and gender-matched controls underwent resting-state single photon emission computerized tomography (SPECT) with N-isopropyl-p-[¹²³I] iodoamphetamine (IMP). The rCBF data were analyzed on a voxel-by-voxel basis using SPM5 software. Results: The results demonstrated that compared with controls, individuals with PWS had significantly lower rCBF in the right thalamus, left insular cortex, bilateral lingual gyrus, and bilateral cerebellum. They had significantly higher rCBF in the right inferior frontal gyrus, left middle/inferior frontal gyrus (anterior and posterior clusters), and bilateral angular gyrus. Additionally, rCBF in the left insula, which was significantly lower in PWS individuals, was negatively correlated with the eating behavior severity score. Conclusions: These results suggest that specific brain regions, particularly the left insula, may be partly responsible for the behavioral symptoms in PWS.     

Insight and alexithymia in adult outpatients with obsessive–compulsive disorder

Objective

To elucidate the relationships between insight and alexithymia in a sample of adult outpatients with obsessive–compulsive disorder (OCD).

Methods

112 adult outpatients with OCD were tested. Severity of OCD was assessed with the first 10–items of the Yale–Brown Obsessive Compulsive Scale (Y–BOCS) and score for item # 11 on the Y–BOCS was considered as a measure of insight. Alexithymia was measured with 20–item Toronto Alexithymia Scale (TAS–20). Additional measures were Maudsley Hospital Obsessive Compulsive Inventory (MOCI) and Montgomery Åsberg Depression Rating Scale (MADRS).

Results

Of the patients, 29.5% showed poor or no insight. Patients with poor or no insight were more alexithymic than patients with excellent, good and moderate insight. TAS–20 total score and subfactors positively correlated with score for item # 11 on the Y–BOCS, severity of OCD and MADRS scores. In stepwise regression model, MADRS scores, factor 3 of TAS–20 (Externally Oriented Thinking), somatic and hoarding–saving obsessions were significantly associated with lower insight.

Conclusions

Results show a relationship between poor or absent insight and high alexithymia levels in OCD patients.     

Brain structural correlates of sensory phenomena in patients with obsessive–compulsive disorder

Background

Sensory phenomena (SP) are uncomfortable feelings, including bodily sensations, sense of inner tension, “just-right” perceptions, feelings of incompleteness, or “urge-only” phenomena, which have been described to precede, trigger or accompany repetitive behaviours in individuals with obsessive–compulsive disorder (OCD). Sensory phenomena are also observed in individuals with tic disorders, and previous research suggests that sensorimotor cortex abnormalities underpin the presence of SP in such patients. However, to our knowledge, no studies have assessed the neural correlates of SP in patients with OCD.

Methods

We assessed the presence of SP using the University of São Paulo Sensory Phenomena Scale in patients with OCD and healthy controls from specialized units in São Paulo, Brazil, and Barcelona, Spain. All participants underwent a structural magnetic resonance examination, and brain images were examined using DARTEL voxel-based morphometry. We evaluated grey matter volume differences between patients with and without SP and healthy controls within the sensorimotor and premotor cortices.

Results

We included 106 patients with OCD and 87 controls in our study. Patients with SP (67% of the sample) showed grey matter volume increases in the left sensorimotor cortex in comparison to patients without SP and bilateral sensorimotor cortex grey matter volume increases in comparison to controls. No differences were observed between patients without SP and controls.

Limitations

Most patients were medicated. Participant recruitment and image acquisition were performed in 2 different centres.

Conclusion

We have identified a structural correlate of SP in patients with OCD involving grey matter volume increases within the sensorimotor cortex; this finding is in agreement with those of tic disorder studies showing that abnormal activity and volume increases within this region are associated with the urges preceding tic onset.     

Impaired theory of mind and symptoms of Autism Spectrum Disorder in children with Prader–Willi syndrome

In order to evaluate the social cognitive functioning in children with Prader–Willi syndrome (PWS), Theory of Mind (ToM) and symptoms of Autism Spectrum Disorder were evaluated. Sixty-six children with PWS aged 7–17 years were tested using the Theory of Mind test-R and the Diagnostic Interview for Social Communication disorders. We tested the correlation between Total ToM Standard Deviation Score (Total ToM SDS) and genetic subtype of paternal deletion or maternal uniparental disomy, and total IQ, verbal IQ and performal IQ. Prevalence and symptoms of Autism Spectrum Disorder were assessed. Median (interquartile range) of total ToM SDS of those aged 7–17 years was ?3.84 (?5.73, ?1.57). Their Total ToM SDS correlated with total IQ (β = 0.662, p < 0.001, adj.R² = 0.407), in particular with verbal IQ (β = 0.502, p = 0.001, adj.R² = 0.409), but not with performal IQ (β = 0.241, p > 0.05, adj.R² = 0.259). No difference in Total ToM SDS was found between children with deletion and maternal uniparental disomy (β = ?0.143, p > 0.05, adj.R² = ?0.016). Compared to the reference group of healthy children aged 7–12 years, children with PWS in the same age group had a median ToM developmental delay of 4 (3–5) years. One third of children with PWS scored positive for Autism Spectrum Disorder. Most prominent aberrations in Autism Spectrum Disorder were focused on maladaptive behavior. Our findings demonstrate a markedly reduced level of social cognitive functioning, which has consequences for the approach of children with PWS, i.e. adjustment to the child's level of social cognitive functioning.     

Subjective quality of life of patients with obsessive–compulsive disorder

BACKGROUND: Obsessive-compulsive disorder (OCD) is the fourth most frequent diagnosis in psychiatry. Patients with OCD suffer from obsessive thinking and compulsive behavior, which impact their everyday life negatively. OBJECTIVE: Subjective quality of life (QoL) in patients with OCD was examined and compared to the general German population and to patients with schizophrenia. METHODS: Seventy-five patients, aged 21-72, with OCD (ICD 10 F42.0-F42.2) were recruited from the outpatient clinic for anxiety disorders at the Department of Psychiatry of the University of Leipzig. By means of the WHOQOL-BREF, QoL was assessed in patients with OCD in a representative sample of patients with schizophrenia and in a sample of the general population of Saxony/Germany. RESULTS: Compared with the general population, QoL in patients with OCDs was lower in all domains of the WHOQOL-BREF. Unexpectedly, QoL in patients with OCDs was lower in the domains "psychological well-being" and "social relationships" when compared with schizophrenia patients. CONCLUSIONS: OCD has a substantial adverse effect on patients' subjective QoL, which may be even greater than the adverse effect of schizophrenia. Therefore, it will be necessary to include interventions in the treatment of OCD aimed at improving residual deficits in psychosocial functioning and QoL.     

Are trauma and dissociation related to treatment resistance in patients with obsessive–compulsive disorder?

Objective

Previous research has indicated a relation between obsessive–compulsive disorder (OCD), childhood traumatic experiences and higher levels of dissociation that appears to relate to negative treatment outcome for OCD. The aim of the present study is to investigate whether childhood trauma and dissociation are related to severity of OCD in adulthood. We also intend to examine the association between treatment resistance, dissociation, and each form of trauma.

Methods

Participants included 120 individuals diagnosed with OCD; 58 (48.3 %) of them met the criteria for treatment-resistant OCD (resistant group), whereas the other 62 (51.7 %) were labeled as responder group. The intensity of obsessions and compulsions was evaluated using Yale-brown obsessive–compulsive scale (Y-BOCS). All patients were assessed with the traumatic experiences checklist, dissociative experiences scale, beck depression inventory, and beck anxiety inventory.

Results

Controlling for clinical variables, resistant group had significantly higher general OCD severity, anxiety, depression, trauma, and dissociation scores than the responders. Correlation analyses indicated that Y-BOCS scores were significantly related to severity of dissociation, anxiety, depression, and traumatic experiences. In a logistic regression analysis with treatment resistance as a dependent variable, high dissociation levels, long duration of illness, and poor insight emerged as relevant predictors, but gender, levels of anxiety, depression, and traumatic experiences did not.

Conclusions

Our results suggest that dissociation may be a predictor of poorer treatment outcome in patients with OCD; therefore, a better understanding of the mechanisms that underlie this phenomenon may be useful. Future longitudinal studies are warranted to verify if this variable represents predictive factors of treatment non-response.     

Analysis of NREM sleep in children with Prader–Willi syndrome and the effect of growth hormone treatment

ObjectivesOnly few studies are available in the literature on sleep in children with Prader–Willi syndrome (PWS) and one single study analyzed the cyclic alternating pattern (CAP) in young adults with PWS, showing that patients with a higher proportion of A1 subtypes presented less severe GH deficiency. The aims of our study were to evaluate CAP in children with PWS compared to an age-matched control group and to evaluate the differences between PWS children with (GH+) and without (GH?) GH therapy.MethodsLaboratory polysomnographic sleep recordings were obtained from 30 children with PWS (17 GH? and 13 GH+ patients) and 15 age-matched normal controls.ResultsCompared to controls, PWS children had a reduction of sleep efficiency, of sleep stage 2 and of REM sleep. GH? PWS patients showed a global decrease in total CAP rate during S1 and S2 but not in SWS. In GH+ PWS patients, SWS CAP rate and A1 index were increased vs. GH? children.DiscussionThe decrease in total CAP rate and all A subtypes might suggest the presence of a decreased NREM sleep instability in our PWS children and can be considered to be in agreement with the reported generalized hypoarousal state of PWS subjects. GH therapy is likely to increase CAP rate and A1 index during SWS in PWS patients.     

Experimental functional analysis of severe skin-picking behavior in Prader–Willi syndrome

Skin picking is an extremely distressing and treatment resistant behavior commonly shown by individuals with Prader–Willi syndrome (PWS). However, with the exception of a limited number of published single-case and survey studies, little is known about the environmental determinants of skin picking in this population. In this study, functional analyses were conducted with thirteen individuals with PWS, aged 6–23 years, who engaged in severe skin-picking behavior. In addition to the conditions typically employed in a functional analysis (i.e., alone, attention, play, demand), we included an ignore condition to examine potential effects of stimulus control by the presence of an adult. Twelve participants engaged in skin picking during the functional analysis, with the highest levels occurring in the alone and ignore conditions for eight participants, suggesting that skin picking in these participants was maintained by automatic reinforcement. For the remaining four participants, an undifferentiated pattern of low-rate skin picking was observed across conditions. These data confirm previous studies indicating that skin picking in PWS may be maintained most often by automatically produced sensory consequences. There were no associations between demographic characteristics of the participants (e.g., sex, age, IQ or BMI) and levels of skin picking observed in the functional analysis. Additional investigations are needed to identify the nature of the sensory consequences produced during episodes of skin picking in PWS. Behavioral interventions designed to extinguish or compete with the potential sensory consequences arising from skin picking in PWS are also warranted.     

Preschool children with obsessive–compulsive disorder and fluoxetine treatment

Obsessive–compulsive disorder (OCD) is an anxiety disorder which can substantially disable children’s ability to function at home and school. Clinicians frequently rely on knowledge about symptoms that can be examined early in treatment to determine future treatment effectiveness. However, OCD in preschoolers has also received little attention in literature. To the best of our knowledge, there is only one retrospective chart review and one case report in the literature for preschool cases treated with SSRIs. Therefore, the effect of fluoxetine on preschool children was imprecisely understood. The aim of this case report was to examine the efficacy and safety of fluoxetine treatment for pediatric OCD. Four preschool children with OCD completed an 8-week fluoxetine (up to 20 mg) trial. We diagnosed OCD according to Diagnostic and statistical manual of mental disorders, 4th edition, text revision (DSM-IV-TR) criteria and symptoms of OCD were assessed with the Childrens’ Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Initial and post-treatment symptom severity and improvement were assessed by using the severity (S) and improvement (I) scales of Clinical Global Impressions Scale (CGI). The CY-BOCS total, obsessions and compulsions subscale scores and CGI-S scores were significantly improved for all of the cases at the end of the eighth week. In this case report four preschool children, with severe OCD and resistant to the previous non-psychopharmacologic treatment responded well to fluoxetine monotherapy. On the other hand, the usage of SSRIs in preschool children remains highly controversial, due to the lack of data on safety and efficacy.