Effect of behavior therapy for Tourette's disorder on psychiatric symptoms and functioning in adults.

BACKGROUND: Although behavior therapy reduces tic severity, it is unknown whether it improves co-occurring psychiatric symptoms and functional outcomes for adults with Tourette's disorder (TD). This information is essential for effective treatment planning. This study examined the effects of behavior therapy on psychiatric symptoms and functional outcomes in older adolescents and adults with TD. METHOD: A total of 122 individuals with TD or a chronic tic disorder participated in a clinical trial comparing behavior therapy to psychoeducation and supportive therapy. At baseline, posttreatment, and follow-up visits, participants completed assessments of tic severity, co-occurring symptoms (inattention, impulsiveness, hyperactivity, anger, anxiety, depression, obsessions, and compulsions), and psychosocial functioning. We compared changes in tic severity, psychiatric symptoms, and functional outcomes using repeated measure and one-way analysis of variance. RESULTS: At posttreatment, participants receiving behavior therapy reported greater reductions in obsessions compared to participants in supportive therapy ($\eta _p^2 $ = 0.04, p = 0.04). Across treatments, a positive treatment response on the Clinical Global Impression of Improvement scale was associated with a reduced disruption in family life ($\eta _p^2 $ = 0.05, p = 0.02) and improved functioning in a parental role ($\eta _p^2 $ = 0.37, p = 0.02). Participants who responded positively to eight sessions of behavior therapy had an improvement in tic severity ($\eta _p^2 $ = 0.75, p < 0.001), inattention ($\eta _p^2 $ = 0.48, p < 0.02), and functioning ($\eta _p^2 $ = 0.39-0.42, p < 0.03-0.04) at the 6-month follow-up. CONCLUSION: Behavior therapy has a therapeutic benefit for co-occurring obsessive symptoms in the short-term, and reduces tic severity and disability in adults with TD over time. Additional treatments may be necessary to address co-occurring symptoms and improve functional outcomes.

Nigrostriatal and Mesolimbic D2/3 Receptor Expression in Parkinson's Disease Patients with Compulsive Reward-Driven Behaviors.

The nigrostriatal and mesocorticolimbic dopamine networks regulate reward-driven behavior. Regional alterations to mesolimbic dopamine D2/3 receptor expression are described in drug-seeking and addiction disorders. Parkinson's disease (PD) patients are frequently prescribed D2-like dopamine agonist (DAgonist) therapy for motor symptoms, yet a proportion develop clinically significant behavioral addictions characterized by impulsive and compulsive behaviors (ICBs). Until now, changes in D2/3 receptor binding in both striatal and extrastriatal regions have not been concurrently quantified in this population. We identified 35 human PD patients (both male and female) receiving DAgonist therapy, with (n = 17) and without (n = 18) ICBs, matched for age, disease duration, disease severity, and dose of dopamine therapy. In the off-dopamine state, all completed PET imaging with [18F]fallypride, a high affinity D2-like receptor ligand that can measure striatal and extrastriatal D2/3 nondisplaceable binding potential (BPND). Striatal differences between ICB+/ICB- patients localized to the ventral striatum and putamen, where ICB+ subjects had reduced BPND In this group, self-reported severity of ICB symptoms positively correlated with midbrain D2/3 receptor BPND Group differences in regional D2/3 BPND relationships were also notable: ICB+ (but not ICB-) patients expressed positive correlations between midbrain and caudate, putamen, globus pallidus, and amygdala BPNDs. These findings support the hypothesis that compulsive behaviors in PD are associated with reduced ventral and dorsal striatal D2/3 expression, similar to changes in comparable behavioral disorders. The data also suggest that relatively preserved ventral midbrain dopaminergic projections throughout nigrostriatal and mesolimbic networks are characteristic of ICB+ patients, and may account for differential DAgonist therapeutic response.SIGNIFICANCE STATEMENT The biologic determinants of compulsive reward-based behaviors have broad clinical relevance, from addiction to neurodegenerative disorders. Here, we address biomolecular distinctions in Parkinson's disease patients with impulsive compulsive behaviors (ICBs). This is the first study to image a large cohort of ICB+ patients using positron emission tomography with [18F]fallypride, allowing quantification of D2/3 receptors throughout the mesocorticolimbic network. We demonstrate widespread differences in dopaminergic networks, including (1) D2-like receptor distinctions in the ventral striatum and putamen, and (2) a preservation of widespread dopaminergic projections emerging from the midbrain, which is associated with the severity of compulsive behaviors. This clearly illustrates the roles of D2/3 receptors and medication effects in maladaptive behaviors, and localizes them specifically to nigrostriatal and extrastriatal regions.

Forced person-following: a new type of stimulus-bound behavior.

We report a new type of stimulus-bound behavior, denoted forced person-following, which we documented for a patient with hypoxic encephalopathy following a suicide attempt with carbon monoxide poisoning. The patient's brain was damaged in the bilateral frontal, parietal, and temporal lobes and in the basal ganglia. The patient was compelled to follow any person who came into his sight and would continue to do so until the person went out of his sight. The patient also exhibited certain primitive reflexes. The forced person-following exhibited by our patient appears to be a consequence of stimulus-bound behavior due to frontal lobe dysfunction and, to a lesser degree, severe cognitive dysfunctions, e.g., visuospatial deficits, which are related to damage in posterior cortices. The unique behavior exhibited by this patient might contribute to our understanding of innate human behavior.

A high-refined carbohydrate diet facilitates compulsive-like behavior in mice through the nitric oxide pathway.

Obesity is characterized by abnormal adipose tissue expansion and is associated with chronic inflammation. Obesity itself may induce several comorbidities, including psychiatric disorders. It has been previously demonstrated that proinflammatory cytokines are able to up-regulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) release, which both have a role in compulsive related behaviors. OBJECTIVE: To evaluate whether acute or chronic consumption of a high-refined carbohydrate-containing (HC) diet will modify burying-behavior in the Marble Burying Test (MBT) through augmentation of NO signaling in the striatum, a brain region related to the reward system. Further, we also verified the effects of chronic consumption of a HC diet on the reinforcing effects induced by cocaine in the Conditioned Place Preference (CPP) test. METHODS: Male BALB/c mice received a standard diet (control diet) or a HC diet for 3 days or 12 weeks. RESULTS: An increase in burying behavior occurred in the MBT after chronic consumption of a HC diet that was associated with an increase of nitrite levels in the striatum. The pre-treatment with Aminoguanidine (50 mg/kg), a preferential inhibitor of iNOS, prevented such alterations. Additionally, a chronic HC diet also induced a higher expression of iNOS in this region and higher glutamate release from striatal synaptosomes. Neither statistical differences were observed in the expression levels of the neuronal isoform of NOS nor in microglia number and activation. Finally, the reinforcing effects induced by cocaine (15 mg/kg, i.p.) during the expression of the conditioned response in the CPP test were not different between the chronically HC diet fed mice and the control group. However, HC diet-feeding mice presented impairment of cocaine-preference extinction. CONCLUSION: Altogether, our results suggest that the chronic consumption of a HC diet induces compulsive-like behavior through a mechanism possibly associated with NO activation in the striatum.

Gilles de la Tourette syndrome as a paradigmatic neuropsychiatric disorder.

Gilles de la Tourette syndrome is a chronic and complex tic disorder accompanied by specific behavioral problems in the majority of patients. With its multifaceted interplay between motion and emotion, this condition is a paradigmatic example of the science and art of clinical neuropsychiatry. This review article encompasses the clinical phenomenology of motor and vocal tics and associated sensory experiences (premonitory urges), as well as the behavioral spectrum of the most common comorbidities, including obsessive-compulsive disorder, attention-deficit and hyperactivity disorder, affective symptoms, and impulsivity. Knowledge of the contributions of both tics and behavioral problems to patients' health-related quality of life across the lifespan should assist treating clinicians in formulating a targeted management plan. Although the exact pathophysiology of Gilles de la Tourette syndrome remains elusive, research into therapeutic interventions has expanded the range of available interventions across multiple domains. A thorough understanding of the neurology and psychiatry of this condition is of key importance to meet the needs of this patient population, from the formulation of an accurate diagnosis to the implementation of effective treatment strategies.

Personality and Alexithymic Disparity in Obsessive-Compulsive Disorder Based on Washing and Checking.

The aim of this study was to investigate pathway relationship of personality characteristics and alexithymic traits in OCD symptoms of obsession, and compulsive behavior of washing and checking. Two-hundred and seventy patients diagnosed with OCD were consecutively recruited from the psychiatric outpatient department of a teaching hospital. Structural equation modeling showed those more neurotic, less extraverted and with higher levels of alexithymia difficulty identifying feelings (DIF), difficulty describing feelings (DDF) and externally oriented thinking (EOT) were more likely to develop obsessive thoughts. Those less extraverted was more prone to develop washing compulsions, and those more neurotic were more likely to develop checking compulsions. EOT was the only alexithymic trait to have no gender difference within this group of patients with OCDs. The different personality and alexithymic trait pathways found between OCD obsession, washing and checking symptoms provide support that they may be different subtypes within the OCD diagnosis. Obsession was associated with washing, but not checking. Furthermore, no gender difference was found between the obsession and compulsive symptoms. Extraversion and neuroticism can be used to differentiate washing and checking, and alexithymia to differentiate washing and obsessions. This should be taken into consideration for intervention targeting patients with different OCD symptoms.

Compulsive sexual behavior: Prefrontal and limbic volume and interactions.

BACKGROUND: Compulsive sexual behaviors (CSB) are relatively common and associated with significant personal and social dysfunction. The underlying neurobiology is still poorly understood. The present study examines brain volumes and resting state functional connectivity in CSB compared with matched healthy volunteers (HV). METHODS: Structural MRI (MPRAGE) data were collected in 92 subjects (23 CSB males and 69 age-matched male HV) and analyzed using voxel-based morphometry. Resting state functional MRI data using multi-echo planar sequence and independent components analysis (ME-ICA) were collected in 68 subjects (23 CSB subjects and 45 age-matched HV). RESULTS: CSB subjects showed greater left amygdala gray matter volumes (small volume corrected, Bonferroni adjusted P < 0.01) and reduced resting state functional connectivity between the left amygdala seed and bilateral dorsolateral prefrontal cortex (whole brain, cluster corrected FWE P < 0.05) compared with HV. CONCLUSIONS: CSB is associated with elevated volumes in limbic regions relevant to motivational salience and emotion processing, and impaired functional connectivity between prefrontal control regulatory and limbic regions. Future studies should aim to assess longitudinal measures to investigate whether these findings are risk factors that predate the onset of the behaviors or are consequences of the behaviors. Hum Brain Mapp 38:1182-1190, 2017. © 2016 Wiley Periodicals, Inc.

Childhood risk factors for lifetime bulimic or compulsive eating by age 30 years in a British national birth cohort.

OBJECTIVE: To examine whether previously identified childhood risk factors for bulimia or compulsive eating (BCE) predict self-reported lifetime BCE by age 30 years in a prospective birth cohort. METHOD: Using data from the 1970 British Cohort Study at birth, 5, and 10 years, associations between 22 putative childhood risk factors and self-reported lifetime BCE at 30 years were examined, adjusting for sex and socioeconomic status. RESULTS: Only female sex (odds ratio (OR): 9.2; 95% confidence interval (CI): 1.9-43.7; p = 0.005), low self-esteem (OR:2.9; 95%CI: 1.1-7.5; p = 0.03) and high maternal education (OR:5.4; 95%CI: 2.0-14.8; p = 0.001) were significantly associated with higher risk of BCE, whereas high SES at 10 years was significantly protective (OR:0.2; 95%CI: 0.1-0.8; p = 0.022) of BCE in fully adjusted multivariable logistic regression analysis. DISCUSSION: Our findings do not support a strong role for childhood weight status and eating behaviours in the development of bulimia and compulsive eating pathology, rather suggesting a focus on self esteem may have greater relative importance. Findings in relation to maternal education and SES need further exploration.

Adult-onset stereotypical motor behaviors.

Stereotypies have been defined as non-goal-directed movement patterns repeated continuously for a period of time in the same form and on multiple occasions, and which are typically distractible. Stereotypical motor behaviors are a common clinical feature of a variety of neurological conditions that affect cortical and subcortical functions, including autism, tardive dyskinesia, excessive dopaminergic treatment of Parkinson's disease and frontotemporal dementia. The main differential diagnosis of stereotypies includes tic disorders, motor mannerisms, compulsion and habit. The pathophysiology of stereotypies may involve the corticostriatal pathways, especially the orbitofrontal and anterior cingulated cortices. Because antipsychotics have long been used to manage stereotypical behaviours in mental retardation, stereotypies that present in isolation tend not to warrant pharmacological intervention, as the benefit-to-risk ratio is not great enough.

Preventing compulsory admission to psychiatric inpatient care using psycho-education and monitoring: feasibility and outcomes after 12 months.

The aim of this study was to evaluate an intervention programme for people with severe mental illness that targets the reduction in compulsory psychiatric admissions. In the current study, we examine the feasibility of retaining patients in this programme and compare outcomes over the first 12 months to those after treatment as usual (TAU). Study participants were recruited in four psychiatric hospitals in the Canton of Zurich, Switzerland. Patients were eligible if they had at least one compulsory admission during the past 24 months. Participants were assigned at random to the intervention or to the TAU group. The intervention programme consists of individualised psycho-education focusing on behaviours prior to illness-related crisis, crisis cards and, after discharge from the psychiatric hospital, a 24-month preventive monitoring. In total, 238 (of 756 approached) inpatients were included in the trial. After 12 months, 80 (67.2%) in the intervention group and 102 (85.7%) in the TAU group were still participating in the trial. Of these, 22.5% in the intervention group (35.3% TAU) had been compulsorily readmitted to psychiatry; results suggest a significantly lower number of compulsory readmissions per patient (0.3 intervention; 0.7 TAU). Dropouts are characterised by younger age and unemployment. This interim analysis suggests beneficial effects of this intervention for targeted psychiatric patients.

Alexithymia-an independent risk factor for impulsive-compulsive disorders in Parkinson's disease.

Impulsive-compulsive disorders (ICDs) are frequent side effects of dopaminergic medication in Parkinson's disease (PD). Alexithymia, a personality trait characterized by difficulties identifying and describing feelings and an externally oriented thinking style, has been linked to various impulse-control problems in the general population. In PD, the prevalence of alexithymia is approximately twice as high as in the general population. However, whether alexithymia is associated with ICDs in PD is currently unknown. We examined the relationship between self-reported ICDs and alexithymia in a sample of 91 PD patients (89 on dopaminergic medication). Additional self-report measures assessed impulsivity, depression, anxiety, behavioral inhibition/approach, and emotion-regulation strategies. We observed that alexithymia, and particularly difficulty identifying feelings and difficulty describing feelings, was significantly correlated with ICDs, even when controlling for impulsivity, anxiety, and depression. In addition, a group analysis revealed that PD patients with clinical and moderate levels of alexithymia had significantly more ICDs than non-alexithymic patients, suggesting that even moderately high alexithymia levels increase the risk for ICDs in PD. Our results identify alexithymia as an independent risk factor for ICDs in PD. Thus, the inclusion of alexithymia in the neuropsychiatric assessment of patients with PD may help identify patients at risk for ICDs.

Clomipramine in the treatment of compulsive behavior in frontotemporal dementia: a case series.

Compulsive behaviors in patients with behavioral variant frontotemporal dementia (bvFTD) occur frequently and are challenging to manage. We report three cases of probable bvFTD associated with compulsive behaviors that responded well to treatment with clomipramine at daily dosages varying from 20 to 175 mg. The titration approach involved an initial 10-mg dose that was subsequently increased in 10 mg increments on a weekly basis until symptom relief without intolerable side effects. Our case series supports the consideration for a therapeutic trial with clomipramine in bvFTD when compulsive behavior occurs in these patients. It also highlights the need for further research on pharmacological treatments in bvFTD.

Feed-forward mechanisms: addiction-like behavioral and molecular adaptations in overeating.

Food reward, not hunger, is the main driving force behind eating in the modern obesogenic environment. Palatable foods, generally calorie-dense and rich in sugar/fat, are thus readily overconsumed despite the resulting health consequences. Important advances have been made to explain mechanisms underlying excessive consumption as an immediate response to presentation of rewarding tastants. However, our understanding of long-term neural adaptations to food reward that oftentimes persist during even a prolonged absence of palatable food and contribute to the reinstatement of compulsive overeating of high-fat high-sugar diets, is much more limited. Here we discuss the evidence from animal and human studies for neural and molecular adaptations in both homeostatic and non-homeostatic appetite regulation that may underlie the formation of a "feed-forward" system, sensitive to palatable food and propelling the individual from a basic preference for palatable diets to food craving and compulsive, addiction-like eating behavior.

Clozapine as a potential treatment for refractory impulsive, compulsive, and punding behaviors in Parkinson's disease.

There have been emerging cases of medication refractory obsessions, impulsivity, compulsivity, and/or punding in Parkinson's disease. These cases have proven difficult to treat, even for the experienced clinician. We report several medication refractory cases with a positive response to treatment with clozapine.

Avoidance of swallowing saliva: a symptom related to aberrant basal ganglia functions?

We report two patients with avoidance of swallowing saliva despite intact swallowing functions. One, with mild, de novo Parkinson's disease, had a fear that his saliva was contaminated and would harm him. The other, with a history of CNS germinoma in remission for 3 years following chemotherapy, expectorated because his saliva was distasteful and disgusting. He had a lesion involving the left pallidum. Both appeared obsessed with the idea of saliva contamination and both expectorated compulsively, presenting obsessive-compulsive disorder (OCD) symptoms. OCD-like behavior may be induced in association with pathological conditions in which aberrant basal ganglia functions are present.

Dyskinesia and impulsive compulsive behaviour in Parkinson's disease are not related: Insights from a study with a wearable sensor.

INTRODUCTION: Previous studies have suggested an association between Impulsive Compulsive Behaviour (ICB) and dyskinesia in Parkinson's disease (PD). However, none of these studies have employed an objective home-based measure of dyskinesia. OBJECTIVES: To evaluate in advanced PD the relationship between ICB and dyskinesia, objectively measured with a wearable device. METHODS: In this cross-sectional study, ICB and other neuropsychiatric symptoms were assessed by means of structured clinical interview and specific screening instruments. Presence and severity of motor fluctuations and dyskinesia were rated with patient's and clinician's based rating instruments. Motor fluctuations and dyskinesia were also measured at home for 5-days using a validated wearable devise, the Parkinson's KinetiGraph™(PKG). RESULTS: We included 89 subjects with PD (29 females, 62 ± 7 years, disease duration 10.3 ± 4.5), of whom 36 (40%) had ICB. Patients with and without ICB did not differ by presence and severity of dyskinesia measured by clinical scales and PKG. There was no association between the presence of ICB and dyskinesia in the whole sample. CONCLUSION: Our data suggest that ICB and dyskinesia are common but unrelated disorders in advanced PD.

Are there ethnic differences in impulsive/compulsive behaviors in Parkinson's disease?

BACKGROUND AND PURPOSE: Recent studies have suggested increased prevalence of impulsive/compulsive behaviors (ICB) in patients with Parkinson's disease (PD) as compared to general population in different ethnic groups. The spectrum of these behaviors includes dopamine dysregulation syndrome (DDS), punding, pathological gambling (PG), hypersexuality (HS), binge eating (BE), and compulsive shopping (CS). METHODS: Two hundred and seventy-eight consecutive patients with idiopathic PD regularly followed-up at an outpatient clinic were interviewed and screened for the ICB between September 2008 and December 2008 using designated diagnostic criteria. All patients who screened positive for ICB or obsessive-compulsive disorder (OCD) were further confirmed by an experienced psychiatrist. RESULTS: Of all the studied patients, 15 patients confirmed to have ICB (lifetime prevalence: 5.60%), 3 (1.12%) were diagnosed to have DDS, 1 (0.37%) punding, 4 (1.49%) PG, 8 (2.99%) HS, 1 (0.37%) BE, 0 (0%) CS. OCD was found in one patient (0.37%). CONCLUSIONS: The prevalence of ICB is lower in Taiwan as compared with the Caucasians, with similar risk factors. The possible reasons include differences in ethnicity, environmental, cultural, and social factors as well as the dosage and selection of dopaminergic medications.