A proof-of-concept study applying machine learning methods to putative risk factors for eating disorders: results from the multi-centre European project on healthy eating.

BACKGROUND: Despite a wide range of proposed risk factors and theoretical models, prediction of eating disorder (ED) onset remains poor. This study undertook the first comparison of two machine learning (ML) approaches [penalised logistic regression (LASSO), and prediction rule ensembles (PREs)] to conventional logistic regression (LR) models to enhance prediction of ED onset and differential ED diagnoses from a range of putative risk factors. METHOD: Data were part of a European Project and comprised 1402 participants, 642 ED patients [52% with anorexia nervosa (AN) and 40% with bulimia nervosa (BN)] and 760 controls. The Cross-Cultural Risk Factor Questionnaire, which assesses retrospectively a range of sociocultural and psychological ED risk factors occurring before the age of 12 years (46 predictors in total), was used. RESULTS: All three statistical approaches had satisfactory model accuracy, with an average area under the curve (AUC) of 86% for predicting ED onset and 70% for predicting AN v. BN. Predictive performance was greatest for the two regression methods (LR and LASSO), although the PRE technique relied on fewer predictors with comparable accuracy. The individual risk factors differed depending on the outcome classification (EDs v. non-EDs and AN v. BN). CONCLUSIONS: Even though the conventional LR performed comparably to the ML approaches in terms of predictive accuracy, the ML methods produced more parsimonious predictive models. ML approaches offer a viable way to modify screening practices for ED risk that balance accuracy against participant burden.

Visuo-tactile shape perception in women with Anorexia Nervosa and healthy women with and without body concerns.

A key feature of Anorexia Nervosa is body image disturbances, the study of which has focused mainly on visual and attitudinal aspects, did not always contain homogeneous groups of patients, and/or did not evaluate body shape concerns of the control group. In this study, we used psychophysical methods to investigate the visual, tactile and bimodal perception of elliptical shapes in a group of patients with Anorexia Nervosa (AN) restricting type and two groups of healthy participants, which differed from each other by the presence of concerns about their own bodies. We used an experimental paradigm designed to test the hypothesis that the perceptual deficits in AN reflect an impairment in multisensory integration. The results showed that the discrimination thresholds of AN patients are larger than those of the two control groups. While all participants overestimated the width of the ellipses, this distortion was more pronounced in AN patients and, to a lesser extent, healthy women concerned about their bodies. All groups integrated visual and tactile information similarly in the bimodal conditions, which does not support the multi-modal integration impairment hypothesis. We interpret these results within an integrated model of perceptual deficits of Anorexia Nervosa based on a model of somatosensation that posits a link between object tactile perception and Mental Body Representations. Finally, we found that the participants' perceptual abilities were correlated with their clinical scores. This result should encourage further studies that aim at evaluating the potential of perceptual indexes as a tool to support clinical practices.

Genome-wide association study of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10(-6) and P=3.44 × 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P<0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.

Neurocognitive functioning in bulimia nervosa: the role of neuroendocrine, personality and clinical aspects.

BACKGROUND: Studies investigating neurocognitive impairment in subjects with eating disorders (EDs) have reported heterogeneous patterns of impairment and, in some instances, no dysfunction. The present study aimed to define the pattern of neurocognitive impairment in a large sample of bulimia nervosa (BN) patients and to demonstrate that neuroendocrine, personality and clinical characteristics influence neurocognitive performance in BN. METHOD: Attention/immediate memory, set shifting, perseveration, conditional and implicit learning were evaluated in 83 untreated female patients with BN and 77 healthy controls (HC). Cortisol and 17ß-estradiol plasma levels were assessed. Cloninger's Temperament and Character Inventory - Revised (TCI-R), the Bulimic Investigation Test Edinburgh (BITE) and the Montgomery-Asberg Depression Rating Scale (MADRS) were administered. RESULTS: No impairment of cognitive performance was found in subjects with BN compared with HC. Cortisol and 'Self-directedness' were associated with better performance on conditional learning whereas 17ß-estradiol had a negative influence on this domain; 'Reward dependence' was associated with worse performance on implicit learning; and depressive symptomatology influenced performance on the Wisconsin Card Sorting Test (WCST) negatively. CONCLUSIONS: No cognitive impairment was found in untreated patients with BN. Neuroendocrine, personality and clinical variables do influence neurocognitive functioning and might explain discrepancies in literature findings.

Dizziness, migrainous vertigo and psychiatric disorders.

OBJECTIVES: This study sought to establish the prevalence of vestibular disorders, migraine and definite migrainous vertigo in patients with psychiatric disorders who were referred for treatment of dizziness, without a lifetime history of vertigo. STUDY DESIGN: Retrospective study. SETTING: Out-patients in a university hospital. MATERIALS AND METHODS: Fifty-two dizzy patients with panic disorders and agoraphobia, 30 with panic disorders without agoraphobia, and 20 with depressive disorders underwent otoneurological screening with bithermal caloric stimulation. The prevalence of migraine and migrainous vertigo was assessed. The level of dizziness was evaluated using the Dizziness Handicap Inventory. RESULTS: Dizzy patients with panic disorders and agoraphobia had a significantly p = 0.05 regarding the prevalence of peripheral vestibular abnormalities in the group of subjects with PD and agoraphobia and in those with depressive disorders. Migraine was equally represented in the three groups, but panic disorder patients had a higher prevalence of migrainous vertigo definite migrainous vertigo. Almost all patients with a peripheral vestibular disorder had a final diagnosis of definite migrainous vertigo according to Neuhauser criteria. These patients had higher Dizziness Handicap Inventory scores. The Dizziness Handicap Inventory total score was higher in the subgroup of patients with panic disorders with agoraphobia also presenting unilateral reduced caloric responses or definite migrainous vertigo, compared with the subgroup of remaining subjects with panic disorders with agoraphobia (p < 0.001). CONCLUSIONS: Our data support the hypothesis that, in patients with panic disorders (and especially those with additional agoraphobia), dizziness may be linked to malfunction of the vestibular system. However, the data are not inconsistent with the hypothesis that migrainous vertigo is the most common pathophysiological mechanism for vestibular disorders.

Disorganization of anatomical connectivity in obsessive compulsive disorder: a multi-parameter diffusion tensor imaging study in a subpopulation of patients.

Obsessive-compulsive disorder (OCD) is thought to involve large-scale brain systems but the anatomical connectivity via association fibers has not been specifically investigated yet. We evaluated organization and directionality of the major fiber bundles in a subpopulation of OCD, including washers and checkers who presented decision making deficits, by measuring MRI parameters related to water self-diffusion (Fractional Anisotropy, FA) and fiber directionality (Principal Diffusion Direction, PDD) in 15 OCD and 16 control subjects. OCD patients showed significantly lower FA and altered PDD along the corpus callosum, cingulum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus bilaterally. The track-based analysis of the inferior fronto-occipital fasciculus confirmed a significant bilateral FA reduction. Lower FA values in the inferior fronto-occipital fasciculus, superior longitudinal fasciculus and corpus callosum correlated with symptom severity and neuropsychological performance. This multi-parameter MRI study revealed specific white matter abnormalities in OCD suggesting tract disorganization as main feature, reflected by local changes in fiber directionality. This altered anatomical connectivity might play a specific role in OCD pathophysiology.

Vestibular testing in patients with panic disorder and chronic dizziness.

In order to investigate the relationship between chronic dizziness and vestibular function in patients with panic disorder, in the present study neurotologic findings in 15 patients with panic disorder and chronic dizziness were compared with those in 15 patients with chronic dizziness, without panic disorder. All underwent neurotologic screening for spontaneous, positional and positioning nystagmus with head-shaking and head-thrust tests, an audiometric examination and electronystagmography with bithermal stimulation according to Freyss. A significantly higher number of patients with panic disorder and chronic dizziness showed pathological neurotologic findings in comparison to subjects with chronic dizziness only (9 and 2 patients, respectively; p < 0.05). Most patients with panic disorder showed signs of peripheral vestibular disorders. These results suggest that the complaint of dizziness in patients with panic disorder may be linked to a malfunction of the vestibular system and vestibular disorders may play a role in the pathophysiology of panic disorder. Possible mechanisms underlying this finding are discussed. In patients with panic disorder and chronic dizziness between panic attacks, a careful neurotologic examination is warranted.

Comparison of the treatment with paroxetine and reboxetine in panic disorder: a randomized, single-blind study.

INTRODUCTION: Serotonergic agents have greater effectiveness than noradrenergic ones in the treatment of Panic Disorder (PD). However preliminary studies suggested that reboxetine might be effective in the treatment of PD. We compared the effectiveness and tolerability of reboxetine and paroxetine in the treatment of PD. METHODS: Sixty-eight patients with PD were assigned to treatment groups in a single-blind, randomized design. Each patient was assessed at day 0 and 90 by the Panic Associated Symptoms Scale (PASS), the Sheehan Disability Scale (SDS) and the Fear Questionnaire (FQ). Side effects were also recorded. RESULTS: Reduction of PASS scores was significantly greater in the paroxetine group than in the reboxetine one. Vice versa we did not find any significant differences for other outcome measures. Sexual dysfunction and weight gain were significantly less frequent in the reboxetine group. CONCLUSIONS: The results showed a greater effect of paroxetine on panic attacks than reboxetine, while no differences for anticipatory anxiety and avoidance were found, suggesting a different role of noradrenaline and serotonin in the treatment of PD.

Citalopram concentrations and response in obsessive-compulsive disorder. Preliminary results.

OBJECTIVE: Citalopram, a highly potent SSRI, is effective in the treatment of depressive disorders and obsessive-compulsive disorder (OCD); however, very few studies have reported concentration-effect relationships for SSRIs. The aim of this study was to investigate the relationship between citalopram concentrations and clinical response in patients with OCD. METHODS AND STUDY DESIGN: Fifteen patients (aged 18-65 years) with a DSM-IV diagnosis of OCD were included in this open-label, single-blind study. Citalopram was started at a dosage of 20 mg/day; the dosage was increased to a maximum of 60 mg/day by the third week, on the basis of clinical need and tolerability. The dosage then remained unchanged until the end of the 10-week study. Clinical assessments were made at baseline, weekly for the first four weeks and then at weeks 6, 8 and 10. The assessment scales used were the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Clinical Global Impression Scale (CGI) and the Hamilton Depression Rating Scale (HDRS). Plasma citalopram concentrations were determined using a high performance liquid chromatography method after solid phase extraction. RESULTS: One patient was withdrawn from the study because of poor compliance. Of the 14 patients who completed the study, nine did not meet the treatment response criterion of an improvement of >25% from the baseline total Y-BOCS score and a score of < or =3 for the global improvement item of the CGI (these patients were termed non-responders), while five did (responders). There were no differences in the main demographic and baseline clinical variables between responders and non-responders. Steady-state citalopram concentrations were similar in the two groups, suggesting that the anti-obsessional effects of citalopram were not related to pharmacokinetic differences between responders and non-responders. There was no linear relationship between steady-state citalopram concentrations and response. The citalopram concentrations and Y-BOCS scores of individual responders obtained at baseline and various study timepoints showed a sigmoid relationship when analysed using the E(max) (maximum change in Y-BOCS score) model, with a mean EC(50) value (drug concentration that elicits 50% of the E(max)) of 152 microg/L, whereas a similar analysis of the non-responders generated a flat line. CONCLUSION: The results of this preliminary study suggest that plasma citalopram concentrations may be related to the clinical response in responders, but do not seem to account for the lack of clinical effect in non-responders. These data, as well as the usefulness of the model in relating plasma concentrations to response, even after repeated administration, need to be validated by further investigations.

Combined family trio and case-control analysis of the COMT Val158Met polymorphism in European patients with anorexia nervosa.

The high activity Val158 (H) allele of the dopamine-metabolizing enzyme catechol-O-methyltransferase (COMT) was associated with anorexia nervosa (AN) in a recent family trio-based study of patients from Israel. In an attempt to replicate this finding, we performed a combined family trio and case-control study in an European population from seven centers in six different countries (Austria, Germany, Great Britain, Italy [Milan], Italy [Florence], Slovenia, and Spain), together contributing a total of 372 family trios, 684 controls and 266 cases. TDT analyses of high (H) and low (L) alleles in family trios showed that H allele and L allele were each transmitted 101 times (chi(2) = 0, ns). Allele-wise case-control analysis using separate samples simply combined from the centers was also not significant, with the frequencies of the H allele 50% in cases and same in controls. Stratified analysis of data from all centers gave an odds ratio of 0.98 (Cornfield 95% confidence limits 0.78-1.24). Analysis by genotype was likewise not significant (overall chi(2) = 0.42). Because we were not able to support the primary hypothesis that Val158Met is a risk factor for AN, we did not perform secondary analysis of minimum body mass index (mBMI), age at onset or illness subtype (restricting or binge purging anorexia). Overall we found no support for the hypothesis that the Val158 allele of COMT gene is associated with AN in our combined European sample.

Human nuclear transcription factor gene CREM: genomic organization, mutation screening, and association analysis in panic disorder.

Panic disorder is an anxiety disorder with an estimated heritability of 48%. Variation in the gene of the nuclear transcription factor "cAMP-responsive element modulator" (CREM) might contribute to its pathogenesis. CREM knock-out mice exhibit significantly less anxiety behavior than wild-type mice and the alternative CREM gene product "inducible cAMP early repressor" (ICER) plays a pivotal role in the hypothalamo-pituitary-adrenal (HPA) axis, which is disturbed in panic disorder. We characterized the genomic organization of the human CREM gene and performed a systematic mutation screening by means of single stranded conformational analysis (SSCA) in a sample of 40 German patients with panic disorder (DSM-III-R). Four novel single nucleotide polymorphisms in CREM promoters P 1 and P 4, one trinucleotide (ATT)-repeat polymorphism in CREM promoter P 2-generating the ICER isoform-and a rare amino acid substitution in CREM exon glut 2 were identified. Association analysis in an extended sample of German patients (n = 88) revealed a significant excess of the shorter CREM P 2 promoter eight-repeat trinucleotide allele and of genotypes containing the eight-repeat trinucleotide allele in panic disorder (P = 0.02), in particular in panic disorder without agoraphobia (P = 0.001). A replication study in independent Italian (n = 76) and Spanish (n = 62) samples, however, failed to confirm this observation. This suggests that the CREM P 2 promoter trinucleotide polymorphism is not a major susceptibility factor in the pathogenesis of panic disorder. Functional analysis of the observed CREM P 2 promoter polymorphism as well as studies in independent panic disorder samples are necessary.

Obsessive-Compulsive Disorder, 5-HTTLPR polymorphism and treatment response.

Recently, a role for a functional polymorphism within the promoter region of the serotonin transporter gene (5-HTTLPR) in conferring susceptibility to Obsessive Compulsive Disorder (OCD) has been suggested. The aim of this study was to test the hypothesis that allelic variation of the 5-HTTLPR could be associated with OCD susceptibility or influence the drug response in OCD. One hundred and eighty-one OCD patients were recruited; 92 patients underwent a standardized treatment with fluvoxamine. No significant differences in allele/genotype distribution of the 5-HTTLPR were found between 191 controls and OCD. No differences in fluvoxamine response in the three genotypes groups in OCD were found, considering Yale-Brown Obsessive Compulsive Scale (YBOCS) total scores. Nevertheless, a significant time per genotype interaction was found for the YBOCS subtotal compulsion scores. Considering patients without tic disorder co-diagnosis, a significant time per genotype interaction for both YBOCS total scores and compulsion scores was found.

Simultaneous determination of clomipramine and its desmethyl and hydroxy metabolites in plasma of patients by high-performance liquid chromatography after solid-phase extraction.

Clomipramine (CMI) is a typical tricyclic antidepressant with a wide clinical spectrum, being used in major depressive, panic and obsessive-compulsive disorders. The relationship between clinical response and plasma levels of clomipramine and its N-desmethylated (N-desmethylclomipramine, DMCMI) and hydroxy-metabolites remains unclear. In particular, limited information is available on the correlation with clinical response in patients with obsessive-compulsive disorder (OCD). This study describes a new sensitive method to simultaneously determine CMI and its major N-desmethylated and hydroxy-metabolites present in human plasma by HPLC with a UV detector. After a solid-phase extraction from plasma (Isolute C2 columns) the separation of the compounds was performed on a Lichrospher CN column (250 x 4 mm, 5 microm with a 2-cm pre-column) by an eluent consisting of 10 mM K(2)HPO(4)-acetonitrile-methanol (35:25:40 v/v/v) at a flow of 1.5 ml/min. UV detector was set at 214 nm. The lower limit of quantification for all the analytes was at least 5 ng/ml. The coefficients of variation ranged between 2.0 and 4.9% with recovery rates between 97.0 and 100.3%. Linear regression analyses showed correlation coefficients between 0.98 and 0.99. This method is simple, fast and reliable with good specificity and sensitivity. Solid phase extraction is efficient and rapid, allowing the extraction of several plasma samples on the same day and may therefore be usefully and realistically applied in the clinical context. We thus investigated the relevance of plasma levels of CMI and its metabolites as a predictor of clinical outcome in a group of 15 patients with OCD.

The 5-HT(2A) -1438G/A polymorphism in anorexia nervosa: a combined analysis of 316 trios from six European centres.

Several case-control association studies have raised the possibility that the A allele of a -1438 G/A polymorphism in the type 2A serotonin receptor (HTR2A) gene may be a risk factor for anorexia nervosa. However the absence of linkage and the existence of negative association studies raise the possibility of false positive findings, resulting from population stratification or lack of statistical power. To address this controversy we recruited a sample of 316 patients with anorexia nervosa from six European centres, and utilised a family-based transmission disequilibrium (TDT) approach to analyse the HTR2A-1438 G/A polymorphism. Age at onset and minimal BMI were also taken into consideration in order to detect clinical heterogeneity or a quantitative trait effect. The TDT approach showed that the A allele was transmitted 133 times and not transmitted 148 times (McNemar chi(2) = 0.29, df = 1, P = 0.59). Also, the haplotype-based haplotype relative risk method showed no evidence for association of the A allele, in samples from each centre (chi(2) < 2.15, df = 1, P > 0.14) and in the total sample (chi(2) = 0.55, df = 1; P = 0.46). Furthermore, we found no evidence for heterogeneity of the A allele frequency between samples (chi(2) = 2.54, df = 4, P = 0.64), either according to minimal-BMI (F1/242 = 2.14, P = 0.45) or age at onset (F1/224 = 2.39; P = 0.12). QTL-TDT analyses also showed no direct role of the A allele on these traits. We thus found no evidence for a significant role of the 5-HT(2A) gene in anorexia nervosa. Previous results may have been exposed to stratification bias (which we controlled by the TDT method) and/or the risk of type 1 error (from which we were less exposed because of the sample size).

Decision-making heterogeneity in obsessive-compulsive disorder: ventromedial prefrontal cortex function predicts different treatment outcomes.

Certain clinical aspects of patients with Obsessive-Compulsive Disorder (OCD) appear similar to those of patients with damage to the ventromedial sector of the prefrontal cortex. The hypothesis for the involvement of the frontal region in OCD is also supported by neuropsychological findings. Building on this evidence, we assessed the performance of a group of 34 OCD patients on a measure indexing with orbitofrontal cortex functioning and compared it with the performance of two other subject groups, one consisting of 34 healthy control subjects and the other 16 patients with panic disorder. All study subjects performed a neuropsychological task, which is sensitive to frontal lobe dysfunction and simulating real-life decision-making. Significant differences were found between the neuropsychological profiles of the OCD and of other groups, pointing to a possible specificity of decision-making deficit in OCD. Comparison of the performance of the OCD patients grouped according to response to antiobsessive drug treatment showed that poor neuropsychological task performance predicted poor outcome of pharmacological treatment. Task behavior did not correlate with severity of illness or demographic characteristics of the subjects. Results support the role of the ventromedial prefrontal cortex in OCD.

A neural network approach to the outcome definition on first treatment with sertraline in a psychiatric population.

Therapy decision is one of the most important tasks clinicians have to perform in their clinical practice. The decision process requires taking into account many different factors. The Authors have proposed a neural computing approach for supporting clinical decision analysis. The mathematical model of artificial neural network (ANN) has been applied on a pool of clinical information gathered through case description freely filled by senior psychiatrists into 416 clinical charts. Sertraline, as drug for treatment, has been chosen since its clinical uses range from treatment of depression to that of many other psychiatric clinical conditions so that it has been thought to be a good candidate to this type of study. The ANN performance in forecasting successful and unsuccessful treatment cases showed an overall accuracy of classification of 97.35%. This result suggests a possible future application of this method to obtain a reliable prediction of a given psychiatric patient outcome during a specific psychopharmacological therapy, optimising the decisional making process.

Clinical predictors of drug response in obsessive-compulsive disorder.

The aim of this study was to evaluate which clinical variables might influence the antiobsessional response to proserotonergic drugs in a sample of patients with obsessive-compulsive disorder (OCD). One hundred fifty-nine patients with DSM-IV OCD underwent a 12-week standardized treatment with fluvoxamine, clomipramine, citalopram, or paroxetine. According to treatment response, defined as a reduction of the Yale-Brown Obsessive Compulsive Scale total score >35%, patients were divided into two groups. Ninety patients (56.6%) responded to treatment and 69 (43.4%) did not. Responders had a significantly higher frequency of positive family history for OCD (FH-OCD) in their first-degree relatives, whereas nonresponders had an earlier onset and a higher frequency of "poor insight" subtype and somatic obsessions. The predictive value of all these variables was tested by a stepwise logistic regression analysis that confirmed poor insight and FH-OCD to be the best predictors of poor and good drug treatment response, respectively. These preliminary findings need additional investigations toward a better definition of the genetic and biological heterogeneity of patients with OCD, and they underlie the importance of collecting the insight score and family history for psychiatric disorders in the pretreatment assessment.

Panic disorder: the role of the balance system.

Experimental evidences suggest that Panic Disorder (PD) is characterized by abnormalities in respiratory and vestibular functions. We studied balance system function in patients with PD and its relationships with CO(2) reactivity and clinical characteristics. Nineteen patients with PD with/without agoraphobia underwent static posturography and the 35% CO(2) challenge. The severity of clinical symptomatology was measured by standardized psychometric scales. Patients were free of psychotropic medications during the 2 weeks before the study. Different investigators blind to each other carried out the CO(2) challenge, static posturography and clinical assessment. Nineteen age and sex-matched healthy controls underwent static posturography. Body sway velocity and length were significantly higher in panic patients than in controls and patients showed high percentages of abnormal scores. Patients with two or more abnormal scores on static posturography were significantly more agoraphobic than those with less than two. Abnormal posturography scores under the eyes-opened was related to high anticipatory anxiety, whereas those under eyes-closed was related to phobic avoidance. Symptomatological reactivity to CO(2) was significantly correlated to abnormal functions of the balance system in the eyes-closed condition. Our findings suggest that (1) many patients with PD (5-42%) have abnormalities in their balance system function compared with healthy controls (0-5%), (2) symptomatological reactivity to CO(2) and balance system function in patients with PD are correlated only in the eyes-closed condition and (3) there is a significant link between agoraphobic avoidance and subclinical abnormal function of the balance system network.

A neuropsychological study of dissociation in cortical and subcortical functioning in obsessive-compulsive disorder by Tower of Hanoi task.

Several biological models of Obsessive-Compulsive Disorder (OCD) have focused on the roles frontal cortex and basal ganglia dysfunctions play in the expression of the disorder. From a neuropsychological point of view, previous reports have underlined the possible involvement of the prefrontal cortex in declarative functions and the basal ganglia in procedural ones. A possible dissociation of cortical and subcortical functioning has been studied using the Hanoi Tower Task to explore different neuropsychological aspects of problem-solving procedures. Our results indicate that differential cortical and subcortical dysfunctions could contribute to OCD pathophysiology and that procedural and declarative forms might be independent of each other.