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Neurosurgery for intractable obsessive-compulsive disorder and depression: critical issues.

Intractable OCD and depression cause tremendous suffering in those affected and in their families. The impaired ability to function of those affected imposes a heavy burden on society as a whole. Existing data suggest that lesion procedures offer benefit to a large proportion (ranging from about 35%-70%) of patients with intractable OCD and depression. The literature also suggests that although serious long-term adverse events have occurred, these are relatively infrequent overall. Methodologic limitations of the earlier reports on any of these procedures were described previously in this article. The major academic centers conducting this work have since been obtaining systematic prospective data using modern assessment tools. Nevertheless, even with improved methodologies, more recent studies confront some remaining issues that have been difficult to overcome fully. First, the number of patients who have received any one procedure has been relatively small, constraining statistical power. This limits the ability of researchers to enhance patient selection based on clinical characteristics. This is important, because patients with intractable OCD and depression referred for neurosurgery have high rates of comorbid Axis I diagnoses, personality disorders, and functional impairments, which may have value in predicting response. Other features, such as age of onset, chronicity, and symptom subtypes, may be likewise useful. Another key factor in response may be postoperative management, which has varied most over time but also across patients enrolled in trials. As noted previously, randomized controlled trials of neurosurgical treatment for intractable psychiatric illness have not been reported, although one has been proposed for gamma knife capsulotomy in intractable OCD [23]. The development of deep brain stimulation has also made sham-controlled studies possible and also allows within-patient designs to be considered. Bearing these problems in mind, the literature does provide important guidance on a number of key points, including approaches to referral, patient selection, and the need for long-term prospective follow-up and postoperative management. Nevertheless, important gaps in knowledge remain in all these areas. Research is expected to narrow these gaps in a number of ways, including patient selection, optimizing the procedures themselves, and understanding the mechanisms of therapeutic action. Neuroimaging studies will play a key role in achieving these aims (see the article by Rauch in this issue). So will cross-species translational research on the anatomy and physiology of the pathways implicated in the pathophysiology and response to treatment in these disorders. Future research in psychiatric neurosurgery must proceed cautiously. A recent editorial statement of the OCD-DBS Collaborative Group [26] recommends a minimum set of standards for any multidisciplinary teams contemplating work in this domain. The rationale for those standards is found throughout this issue and is especially developed in the article by Fins. The need for safe and effective therapeutic options for people suffering with these severe illnesses is just as clear. The experience over the last several decades provides grounds for careful optimism that refined lesion procedures or reversible deep brain stimulation may relieve suffering and improve the lives of people with these devastating disorders.

Brain↗

Severity of obsessive-compulsive symptoms is related to self-directedness character trait in obsessive-compulsive disorder.

OBJECTIVE: The present study examined the psychobiological Temperament and Character model of personality on obsessive-compulsive disorder (OCD) patients, as well as the relation of temperament and/or character dimensions on the severity of obsessive-compulsive symptoms. METHODS: Fifty-four subjects diagnosed with OCD, were assessed with the Temperament and Character Inventory, the Yale-Brown Obsessive-Compulsive scale and the Hamilton Rating Scales for depression and anxiety. RESULTS: Compared with controls, OCD subjects displayed increased harm avoidance and lower self-directedness and cooperativeness. Low self-directedness and high Hamilton depression scores were associated with increased severity of obsessive-compulsive symptoms. CONCLUSION: The Temperament and Character profile of OCD patients characterized in the present study was in agreement with previous reports using the same personality model and can be linked to some of their behavioral features. Furthermore, our data provides support of the influence that some personality traits may have on the severity of OCD symptoms.

Adult↗

Is obsessive-compulsive disorder caused by a second-messenger imbalance?

Although the precise etiologic nature of obsessive-compulsive disorder (OCD), one of the most common psychiatric conditions, is unknown, several findings indicate involvement of the serotonin (5-HT) transporter. Apart from the specific effects of selective 5-HT reuptake inhibitors, other studies show decreased functionality of the platelet 5-HT transporter in OCD. In this report, the authors combine data from two independent studies of patients with OCD, showing both an increased activity of protein kinase type C (PKC) and a decreased activity of protein kinase type A (PKA). The authors propose a unifying hypothesis that OCD might be determined by an imbalance between PKC and PKA, with a prevalence of the former and, more generally, of the phosphoinositide over the cyclic adenosine monophosophate (cAMP) pathway. Should this hypothesis prove correct, the path would be open for new therapeutic interventions in the treatment of OCD.

Journal Article↗

Psychostimulant-induced behavior as an animal model of obsessive-compulsive disorder: an ethological approach to the form of compulsive rituals.

Rats treated chronically with the D2/D3 dopamine receptor agonist quinpirole show a pattern of behavior that meets a set of ethologically derived criteria of compulsive behavior in obsessive-compulsive disorder (OCD). Moreover, in both quinpirole-treated rats and OCD patients, the structure of compulsive rituals appear similar in being composed of relatively few motor acts that are organized in a flexible yet recurrent manner. In addition, the development of compulsive behavior in quinpirole-treated rats is attenuated by the OCD pharmacotherapeutic drug clomipramine. These similarities support the validity of quinpirole-treated rats as a psychostimulant-induced animal model of OCD. Considering that the induction of compulsive behavior in the rat model involves chronic hyperstimulation of dopamine receptors, this raises the possibility that dopaminergic mechanisms may play a role in OCD, at least in some subtypes of this disorder.

Animals↗

Insight in body dysmorphic disorder with and without comorbid obsessive-compulsive disorder.

INTRODUCTION: The aim of this study was to compare the level of insight in patients with body dysmorphic disorder (BDD) with and without comorbid obsessive-compulsive disorder (OCD), and to measure its possible relationships with clinical features. METHODS: Thirty outpatients affected by BDD, according to Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria, of whom 18 were also suffering from OCD, were included in the study. Clinical assessment was carried out by means of the Yale-Brown Obsessive-Compulsive Scale modified for BDD and a specially designed OCD Questionnaire. The level of insight was measured by means of the score at item 11 of the Yale-Brown Obsessive-Compulsive Scale modified for BDD. RESULTS: The insight resulted to be excellent in four cases, good in four, fair in five, poor in 15 and absent in two. Significant and positive correlations were observed between the level of insight and the following items: resistance to thoughts and to activities as well as to time spent on activities and control on activities related to the defect. The insight was significantly lower in patients affected by both BDD and OCD. CONCLUSION: The findings indicate that the majority of BDD patients in this study, and especially those with comorbid OCD, have a low degree of insight that is significantly correlated to symptoms specific of the disorder.

Adolescent↗

[Post-partum as a specific risk factor for the onset of obsessive-compulsive disorder: clinical-controlled study].

OBJECTIVE: The aim of this study is to evaluate the presence of triggering life-events for the onset of Obsessive-Compulsive Disorder in women (OCD). DESIGN: Clinical controlled study. SETTING: Service for depressive and anxiety disorders; Department of Neuroscience, Psychiatric Unit, University of Turin. METHODS: The study compares twenty-nine women with OCD (DSM-IV criteria) with twenty-nine healthy control women matched for demographic features and with twenty-nine women with Bulimia Nervosa (DSM-IV criteria) matched for age, age at onset, education and marital status. All patients were assessed with the Clinical Structured Interview for DSMIII-R (SCID) and with the Interview for Recent Life Event by Paykel. Moreover, OCD patients were assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and bulimic patients with the Eating Disorder Inventory (EDI). RESULTS: The study demonstrates that the only specific life event that is significantly associated with the onset of OCD is "having a new born child" No significant differences in frequency and severity of stressing life events were found in the three groups. CONCLUSIONS: The results confirms the findings of our previous study: post partum is the only risk factor for the onset of OCD in female population, compared to healthy control. Furthermore, this research points-out the importance and the specificity of this association showing that post partum is not a risk factor in all psychiatric disorders.

Adult↗

[Phenomenology of patients with early and adult onset obsessive-compulsive disorder].

OBJECTIVE: To evaluate potential differences in socio-demographic and clinical characteristics (obsessive-compulsive symptomatology, axis I and II comorbidity) between OCD adults with an early age at onset (< 18 years) and later onset, (> or = 18 yrs). DESIGN: Clinical controlled study. SETTING: Anxiety and Mood Disorders Unit, Department of Neuroscience, University of Turin. METHODS: We included 149 subjects with a principal diagnosis of OCD (DSM-IV) and a Y-BOCS total score > or = 16. All patients underwent a semistructured clinical interview aimed at investigating sociodemographic characteristics and clinical features of the disorder. Lifetime Axis I comorbidity, according to DSM-IV criteria, was investigated with a structured interview following Othmer & Othmer guidelines (1994; 1999). Personality disorders were assessed using the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II). RESULTS: 39 patients referred age at onset of OCD before 18 years (early-onset group) and 110 patients at 18 years or later (later-onset group). Significant differences were found between the two groups: early-onset subjects are characterized by a preponderance of males, a chronic course of illness and a strong association with Schizotypal Personality Disorder. DISCUSSION: When subtyping OCD according to age at onset we found significant differences which suggest a possible heterogeneity of the disorder. Our results seem to confirm that early-onset OCD may represent a more severe subgroup, with clinical characteristics such as the chronic course and the high association with Schizotypal PD which are significant in order to apply specific therapeutic strategies.

Adolescent↗

Procedural and declarative memory in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) has been associated with frontostriatal abnormality. This has led to the hypothesis that the disorder is characterized by abnormality of procedural memory. However, evidence for either procedural or declarative memory disturbance has been mixed, and few studies have directly assessed both of these forms of memory in the same patient group. In the present study, we assessed encoding and retrieval in declarative memory using the Rey Auditory Verbal Learning Test (RAVLT), and procedural memory using the Pursuit Rotor Task, in 27 adults with OCD and 29 matched healthy controls. Groups did not differ with respect to salient demographic characteristics or memory on the RAVLT. In contrast, patients with OCD performed significantly better than controls during the early, but not later trial blocks of the Pursuit Rotor Task. This pattern of results indicates intact encoding and retrieval in declarative memory, but abnormally enhanced procedural memory during the early course of learning in OCD. These findings may be consistent with striatal overactivation observed in neuroimaging studies of OCD, as well as the prominent role of the striatum during early stages of procedural memory.

Adolescent↗

Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS).

The evidence to date, both published and unpublished, which addresses the validity of the proposed unique subgroup of children with early and abrupt onset of obsessive--compulsive disorder (OCD) and/or tic disorders subsequent to streptococcal infections was reviewed. The aetiology of OCD and tic disorders is unknown, although it appears that both disorders may arise from a variety of genetic and environmental factors. Post-streptococcal autoimmunity has been postulated as one possible mechanism for some. The acronym PANDAS (for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been given to a subgroup of paediatric patients who meet five inclusionary criteria: presence of OCD and/or tic disorder, pre-pubertal symptom onset, sudden onset or episodic course of symptoms, temporal association between streptococcal infections and neuropsychiatric symptom exacerbations, and associated neurological abnormalities. The proposed model of pathophysiology provides for several unique treatment strategies, including the use of antibiotic prophylaxis to prevent streptococcal-triggered exacerbations, and the use of immunomodulatory interventions (such as intravenous immunoglobulin or therapeutic plasma exchange) in the treatment severe neuropsychiatric symptoms. For the latter study group, long-term (2--5 yr) follow-up revealed continued symptom improvement for the majority of patients, particularly when antibiotic prophylaxis had been effective in preventing recurrent streptococcal infections. In addition, the episodic nature of the subgroup's illness provides for opportunities to study brain structure and function during health and disease, as well as allowing for investigations of the aetiologic role of anti-neuronal antibodies and neuroimmune dysfunction in both OCD and tic disorders. Although much research remains to be done, an increasing body of evidence provides support for the postulate that OCD and tic disorders may arise from post-streptococcal autoimmunity. The unique clinical characteristics of the PANDAS subgroup, the presence of volumetric changes in the basal ganglia, and the dramatic response to immunomodulatory treatments, suggest that symptoms arise from a combination of local, regional and systemic dysfunction. Ongoing research is directed at understanding the nature of the abnormal immune response, as well as identifying at-risk children, in order to provide for novel strategies of prevention and treatment.

Age of Onset↗

Brain anatomy and chemistry may predict treatment response in paediatric obsessive--compulsive disorder.

Obsessive--compulsive disorder (OCD) is a severe, highly prevalent and often chronically disabling illness with frequent onset in childhood and adolescence. This underscores the importance of studying the illness during childhood near the onset of illness to minimize potential confounds of long-term illness duration and treatment intervention as well as to examine the developmental underpinnings of the illness. In this review, the authors focus on an integrated series of brain-imaging studies in paediatric OCD suggesting a reversible glutamatergically mediated thalamo-cortical--striatal dysfunction in OCD and their relevance for improved diagnosis and treatment of the condition. Developmental neurobiological models for OCD are presented and particular attention is devoted to evaluating neuroimaging studies designed to test these models and how they may help predict treatment response in paediatric OCD.

Adolescent↗

Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obsessive-compulsive disorder.

Potent serotonin (5-HT) reuptake inhibitors are the only drugs that consistently exert a therapeutic action in obsessive-compulsive disorder (OCD). Given that some hallucinogens were reported to exert an anti-OCD effect outlasting their psychotomimetic action, possible modifications of neuronal responsiveness to 5-HT by LSD were examined in two rat brain structures: one associated with OCD, the orbitofrontal cortex (OFC), and another linked to depression, the hippocampus. The effects of concurrent microiontophoretic application of LSD and 5-HT were examined on neuronal firing rate in the rat OFC and hippocampus under chloral hydrate anaesthesia. In order to determine whether LSD could also exert a modification of 5-HT neuronal responsiveness upon systemic administration, after a delay when hallucinosis is presumably no longer present, it was given once daily (100 microg/kg i.p.) for 4 d and the experiments were carried out 24 h after the last dose. LSD attenuated the firing activity of OFC neurons, and enhanced the inhibitory effect of 5-HT when concomitantly ejected on the same neurons. In the hippocampus, LSD also decreased firing rate by itself but decreased the inhibitory action of 5-HT. The inhibitory action of 5-HT was significantly greater in the OFC, but smaller in the hippocampus, when examined after subacute systemic administration of LSD. It is postulated that some hallucinogens could have a beneficial action in OCD by enhancing the responsiveness to 5-HT in the OFC, and not necessarily in direct relation to hallucinosis. The latter observation may have theoretical implications for the pharmacotherapy of OCD.

Action Potentials↗

Subtyping obsessive compulsive patients by depressive symptoms: a retrospective pilot study.

Depression is a frequent comorbid condition in obsessive compulsive disorder (OCD) patients and may impact upon treatment prognosis. Identification of OCD "subtypes" might ultimately aid in treatment decision-making as it has in other psychiatric disorders. A retrospective pilot study was performed examining depressive and OCD symptomatology by analyzing the relation between factor scores on the Beck Depression Inventory (BDI) and the Maudsley Inventory (MOCI) in 41 OCD patients. Total BDI score was significantly correlated with total MOCI score (r = .36, p < .02). Checking was correlated with Retarded depression (r = .30, p < .05). Doubting correlated with both Guilty depression (r = .48, p < .002) and Retarded depression (r = .37, p < .02). None of the canonical correlations were significant. At p < .08, the first canonical correlation approached significance. The data were interpreted cautiously as suggesting that some OCD patients may exhibit symptoms of Doubting together with Guilty depression and Retarded depression symptoms. These data need replication in a larger, prospective study design.

Adult↗

Single photon emission computed tomography (SPECT) in obsessive-compulsive disorder before and after treatment with inositol.

Inositol, a glucose isomer and second messenger precursor, regulates numerous cellular functions and has demonstrated efficacy in obsessive-compulsive disorder (OCD) through mechanisms that remain unclear. The effect of inositol treatment on brain function in OCD has not been studied to date. Fourteen OCD subjects underwent single photon emission computed tomography (SPECT) with Tc-99m HMPAO before and after 12 weeks of treatment with inositol. Whole brain voxel-wise SPM was used to assess differences in perfusion between responders and nonresponders before and after treatment as well as the effect of treatment for the group as a whole. There was 1) deactivation in OCD responders relative to nonresponders following treatment with inositol in the left superior temporal gyrus, middle frontal gyrus and precuneus, and the right paramedian post-central gyrus; 2) no significant regions of deactivation for the group as a whole posttreatment; and 3) a single cluster of higher perfusion in the left medial prefrontal region in responders compared to nonresponders at baseline. Significant reductions in the YBOCS and CGI-severity scores followed treatment. These data are only partly consistent with previous functional imaging work on OCD. They may support the idea that inositol effects a clinical response through alternate neuronal circuitry to the SSRIs and may complement animal work proposing an overlapping but distinct mechanism of action.

Cerebrovascular Circulation↗

[Comorbidity of compulsive disorders in childhood and adolescence].

OBJECTIVE: The cross-sectional comorbidity of child and adolescent inpatients with obsessive-compulsive disorder (OCD) was assessed. METHODS: The hospital records of all inpatients treated for OCD since 1976 (31 girls, 46 boys) were compared with data from a prospective epidemiological longitudinal study (90 girls, 84 boys) in two age cohorts (< 15 years; > or = 15 years) with regard to comorbid psychiatric diagnoses. Additionally, psychiatric Axis I diagnoses of patients with a supplementary diagnosis of compulsive symptoms (n = 45) were descriptively assessed in the client population. RESULTS: In the subgroup of OCD patients < 15 years, boys showed a higher incidence of tic disorders. OCD girls > or = 15 years showed a tendency toward more frequent comorbid affective disorders and a significant result regarding concurrent eating disorders. Eighteen of 27 female patients with supplementary compulsive symptoms requiring clinical intervention had an Axis I diagnosis of eating disorder. CONCLUSIONS: Due to different criteria of classification, diverging definitions of comorbidity and different age cohorts and samples, studies on comorbidity in OCD patients are difficult to compare. The frequency of comorbid psychiatric disorders may be over-estimated if the general prevalence of psychiatric disorders in terms of gender and age is not taken into account.

Adolescent↗

[Obsessive-compulsive disorders in children and adolescents--a review].

OBJECTIVE: Presented is a review of the literature on the medium- and long-term course of obsessive-compulsive disorder (OCD) with onset in childhood or adolescence. METHODS: Using the data bank MEDLINE, relevant studies published since 1983 were investigated. Older studies were included if their results complemented those of recent studies. RESULTS: Follow-up studies point to a rather unfavorable course of childhood OCD. At the time of follow-up investigations, 30% to 70% of the patients still suffered from obsessive-compulsive symptoms or had a diagnosis of OCD. Other clinical disorders were diagnosed in 20% to 95% of them. One to two thirds of former patients had received at least one diagnosis of a personality disorder. Multicomorbidity was common. Impairment of the patients' psychosocial adjustment especially affected relationships and sexuality. Most of the variables examined in childhood or adolescence had no significant predictive power as to the course of obsessive-compulsive disorders. CONCLUSIONS: Differences between the results of the follow-up studies can partly be explained by the different study designs employed. Results on the course of childhood OCD point to the high stability of the disorder and the accompanying rate of comorbidity. This has to be taken into account in the diagnosis (supplementary diagnosis of comorbid disorders and family diagnostics) and therapy of childhood OCD (offering long-term therapeutic advice and booster sessions, treatment of comorbid disorder, inclusion of the family).

Adolescent↗

[Compulsive phenomena in children with tic disorder and attention deficit-hyperactive disorder].

Tic disorders (TD), obsessive-compulsive disorders (OCD) and attention-deficit/hyperactivity disorder (ADHD) are often associated with deficits of impulse control and aggressive behavior. Tic disorders and OCD are closely related on epidemiological, psychopathological and neurobiological levels, whereas ADHD and OCD phenomena seem to be at opposite poles. Research evidence on the clinical significance of associated obsessive-compulsive behavior is reviewed and linked to our own new data. Thus the analyses of a worldwide database on Tourette's Syndrome (TS) (N = 4,833) showed that that the associated symptomatology of the OCD spectrum has to emphasized. In further investigations, premonitory sensorimotor phenomena reminiscent of OCD were more frequent in children with tic disorders as they grew older. Obsessive-compulsive behavior concomitant with TS was particularly associated with impulsive and aggressive behavior, as well as with depression and anxiety. The data suggest a reduced serotonergic transmission. Self-reports by children with ADHD, as opposed to those by their parents, mentioned a significantly higher quantitative degree of OC phenomena than those by children with TS. These findings suggest that OC symptoms in children with ADHD have so far been neglected in assessments by others. In summary, a complex psychopathological pattern of tic, OC behavior, impulsivity and internalizing symptomatology emerges that requires discriminating assessment and treatment.

Adolescent↗

[Severe early-childhood obsessive-compulsive disorder--case report on a 4-year-old girl].

OBJECTIVES: OCD is seldom diagnosed in children younger than six years of age. The present report deals with the diagnosis and therapy of OCD at a very early onset in childhood. METHODS: Reported is the case of a 4-year-old girl who was affected by severe compulsive behaviour, with marked impairment of her familial and extra-domestic social activities, including an inability to attend kindergarten. RESULTS: The girl was affected to an extreme extent by compulsive symptoms pertaining to symmetry and order, and suffered from severe psychological strain. Her symptoms improved markedly following behaviour therapy in an inpatient setting. Adjuvant medication was not necessary. Her parents were counselled intensively and included in the therapeutic process. She was able to return to her family, resuming activities appropriate for a child her age, and to attend kindergarten. CONCLUSIONS: OCD can develop in a child as early as at the age of four. For diagnostic procedure in cases of "very early onset", OCD criteria described by ICD-10 and DSM-IV can be applied. Behaviour therapy was effective even in this case of early manifestation of OCD. Particularly important is the inclusion of the parents in the therapeutic process.

Behavior Therapy↗

Patterns of changes in temperament and character inventory scales in subjects with obsessive-compulsive disorder following a 4-month treatment.

OBJECTIVE: The purpose of this study was to assess changes in the temperament and character patterns in subjects with obsessive-compulsive disorder (OCD) following the treatment for obsessive/compulsive and accompanying depressive symptoms. METHOD: Study subjects were 35 patients who met the DSM-IV criteria for OCD. All subjects were assessed with the Temperament and Character Inventory (TCI), the Yale-Brown Obsessive-Compulsive Scale, the Beck Depression Inventory, and the Beck Anxiety Inventory before and after a 4-month treatment. RESULTS: Harm Avoidance (HA) scores in OCD subjects before treatment significantly decreased after treatment. However, the Self-Directedness scores, which were significantly lower than healthy comparison subjects before treatment, did not change. In addition, Reward Dependence scores in OCD subjects, which were not significantly different from healthy comparison subjects before treatment, significantly increased after treatment. CONCLUSION: The TCI pattern of untreated OCD subjects (high HA and low Self-Directedness, relative to healthy comparison subjects) and the decrease of HA scores and no change in Self-Directedness scores following a successful treatment suggest that temperaments are more amenable to treatment than characters.

Adolescent↗