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.

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.

Rest-activity circadian rhythm and sleep quality in patients with binge eating disorder.

Recent findings suggest that altered rest-activity circadian rhythms (RARs) are associated with a compromised health status. RARs abnormalities have been observed also in several pathological conditions, such as cardiovascular, neurological, and cancer diseases. Binge eating disorder (BED) is the most common eating disorder, with a prevalence of 3.5% in women and 2% in men. BED and its associate obesity and motor inactivity could induce RARs disruption and have negative consequences on health-related quality of life. However, the circadian RARs and sleep behavior in patients with BED has been so far assessed only by questionnaires. Therefore, the purpose of this study was to determine RARs and sleep parameters by actigraphy in patients with BED compared to a body mass index-matched control group (Ctrl). Sixteen participants (eight obese women with and eight obese women without BED diagnosis) were recruited to undergo 5-day monitoring period by actigraphy (MotionWatch 8®, CamNtech, Cambridge, UK) to evaluate RARs and sleep parameters. In order to determine the RARs, the actigraphic data were analyzed using the single cosinor method. The rhythmometric parameters of activity levels (MESOR, amplitude and acrophase) were then processed with the population mean cosinor. The Actiwatch Sleep Analysis Software (Cambridge Neurotecnology, Cambridge, UK) evaluated the sleep patterns. In each participant, we considered seven sleep parameters (sleep onset: S-on; sleep offset: S-off; sleep duration: SD; sleep latency: SL; movement and fragmentation index: MFI; immobility time: IT; sleep efficiency: SE) calculated over a period of five nights. The population mean cosinor applied to BED and Ctrl revealed the presence of a significant circadian rhythm in both groups (p < 0.001). The MESOR (170.0 vs 301.6 a.c., in BED and Ctrl, respectively; p < 0.01) and amplitude (157.66 vs 238.19 a.c., in BED and Ctrl, respectively p < 0.05) differed significantly between the two groups. Acrophase was not different between BED and Ctrl, as well as all sleep parameters. Both groups displayed a low level of sleep quality (SE 80.7% and 75.7% in BED and Ctrl, respectively). These data provided the first actigraphy-based evidence of RARs disruption and sleep behavior disorder in patients with BED. However, while sleep disorders could be reasonably ascribed to overweight/obesity and the related lower daily physical activity, RARs disruption in this pathology should be ascribed to factors other than reduced physical activity. The circadian timing approach can represent a novel potential tool in the treatment of patients with eating disorders. These data provide exploratory evidence of behavioral association in a small population of patients that, if confirmed in a wider number of subjects and across different populations, may lead to a revision and enhancement of interventions in BED patients.

Tryptophan depletion in obsessive-compulsive patients.

Twelve patients with obsessive-compulsive disorder were studied after the administration of a mixture of amino acids devoid of tryptophan (TRP) or a mixture containing all the essential amino acids, in a double-blind, crossover design. The TRP-free mixture caused a marked depletion of plasma TRP. After TRP decrease, mean ratings of obsessions and compulsions, measured by Visual Analogue Scales (VAS) ratings, did not worsen. In contrast with other reports in literature, TRP depletion also failed to alter mood in our subjects.

Low versus standard dose mCPP challenge in obsessive-compulsive patients.

In several reports, the acute oral administration of the partial serotonergic agonist meta-chlorophenylpiperazine (mCPP) in dose of 0. 5 mg/kg induced a significant worsening of obsessive-compulsive (OC) symptoms in a number of patients. The aim of our study was to test the 0.25 mg/kg mCPP dose, which was hypothesized to be more specific for OC symptoms and was until now tested only on healthy subjects. In a double-blind, controlled crossover study, 12 OC patients participated on three test days, receiving one of the following on each day: oral 0.5 mg/kg mCPP (standard dose), 0.25 mg/kg mCPP (low dose), or placebo. Behavioral ratings were obtained by means of Visual Analogue Scale (VAS) ratings. The low dose mCPP induced a significant worsening of OC symptoms in 50% (6/12) of the patients, whereas 8.3% (1/12) of the patients showed a worsening after the standard dose. On the other hand, only the standard dose mCPP induced a worsening, although not statistically significant, of anxiety ratings. Our data show that the 0.25 mg/kg dose mCPP induces a specific response in OC symptoms, with little anxiogenic effect. To confirm these preliminary data, future studies will be needed on larger samples and with more sensitive rating scales.

Predictive value of obsessive-compulsive personality disorder in antiobsessional pharmacological treatment.

Previous reports have stressed the implication of Personality Disorders as predictors of a poorer treatment outcome in Obsessive-Compulsive Disorder (OCD). The aim of this study was to see whether or not Obsessive-Compulsive Personality Disorder in Obsessive-Compulsive Disorder may be predictive for a poorer outcome to antiobsessive pro-serotonergic pharmacological treatment. For this purpose, 30 OCD patients were divided into two groups according to the presence or absence of Obsessive-Compulsive Personality Disorder. Ten-week standardized treatments with oral SRI drugs were given to look for different outcomes between the two groups in Obsessive-Compulsive symptom severity. At the end of the study we found that the presence of Obsessive-Compulsive Personality Disorder, along with the total number of Personality Disorders, did predict poorer response to pharmacological treatment in OCD.

Serum cholinesterase in obsessive-compulsive disorder.

Levels of serum cholinesterase (PsChe) were measured in 32 drug-free patients with obsessive-compulsive disorder (OCD) and 32 sex- and age-matched healthy normal volunteers. No significant differences between OCD patients and normal subjects were found in PsChe levels. A significant positive correlation between patients' PsChe levels and the severity of anxiety, as measured by the Hamilton Rating Scale for Anxiety, was found, in agreement with the hypothesis of a relationship between state anxiety and PsChe activity. In contrast to findings in other reports, PsChe levels significantly increased after 10 weeks of antiobsessional pharmacological treatment, underscoring the potential influence of drugs on PsChe activity.

Plasma tryptophan levels and tryptophan/neutral amino acid ratios in obsessive-compulsive patients with and without depression.

We have studied fasting plasma tryptophan (TRP) levels and tryptophan/large neutral amino acid (TRP/LNAA) ratios in 12 patients with obsessive-compulsive disorder (OCD) and 12 patients with OCD and a coexisting current diagnosis of major depressive disorder (OCD-MDD). Assessments were made at baseline and after 6 weeks of treatment with fluvoxamine. OCD-MDD patients had significantly lower baseline TRP levels and TRP/LNAA ratios than OCD patients. After 6 weeks of fluvoxamine treatment, OCD-MDD patients had significant increases in plasma TRP and TRP/LNAA ratio, whereas OCD patients had non-significant decreases. Our data suggest that a major depressive syndrome could be a state variable affecting the changes in plasma TRP and TRP/LNAA ratio in OCD patients.

Relationship between obsessive-compulsive personality disorder and obsessive-compulsive disorder.

This study investigated the presence of obsessive-compulsive personality disorder (OCPD) in a group of 277 patients (88 with obsessive-compulsive disorder [OCD], 58 with major depressive disorder [MDD], and 131 with panic disorder [Panic]) to test the specificity of the relationship between OCPD and OCD. OCPD is statistically significantly more frequent in patients with OCD than in those with Panic and MDD. The distribution of single criteria of OCPD in the three groups does not differ significantly. Discriminant analysis selects a list of items that provide a correct classification rate of 66% based on OCPD criteria selected by canonical function. OCD patients with and without OCPD do not differ in sex, age of onset, duration of illness, positive family history for Tics disorder/Tourette syndrome (TS), or morbidity risk for OCD.

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.

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.