Leonardo Quercioli

The Shorter PROMIS Questionnaire and the Internet Addiction Scale in the assessment of multiple addictions in a high-school population: prevalence and related disability.

OBJECTIVE Taking into account the importance of act prevention on the development of addictions, we assessed the presence of multiple addictions in an adolescent high-school population, also assessing the prevalence of Internet abuse and the impact on disability. INTRODUCTION Adolescence seems to be a critical period of addiction vulnerability, based on social but also neurobiological factors. The earlier onset of behavioral/substance dependence seems to predict greater addiction severity, morbidity, and multiple addictive disorders. METHODS Data were collected from a sample of 275 students in Florence, Italy, high schools through surveys distributed in classes. The sample had an average age of 16.67+/-1.85 years (52.4% males, 47.6% females). To assess multiple addiction we used the 16 subscales of the Shorter PROMIS Questionnaire, to assess Internet addiction prevalence we used the Internet Addiction Scale, and to quantify disability symptoms, we used the Sheehan Disability Scale. RESULTS Caffeine abuse, sex, relationship submissive, gambling, food starving, and food bingeing have raised highest scores. 5.4% of the students were found to be Internet addicted similar to other countries. Disability seemed strongly correlated to the subscale of alcohol, gambling, sex, tobacco, food starving and food bingeing, shopping, exercise, and Internet addiction. Gambling, sex, caffeine abuse, compulsive help dominant, work, Internet addiction, relationship dominant, and relationship submissive in this sample were strongly related to substance dependence. CONCLUSION Level of concerns unexpected compared to the level reported in other countries for the behavioral compulsions, have been highlighted. Behavioral addictions are multiple, a source of disability, and they are related to substance abuse. It has yet to be clarified if they are a temporary phenomenon occurring in adolescents or if they are a stable trait, accounting as marker for the development of substance abuse.

Sumatriptan, 5-HT1D receptors and obsessive-compulsive disorder

Background: After considering the effects of 5-HT receptor agonists with different binding profiles on the symptoms of obsessive-compulsive disorder (OCD), Zohar and Kindler hypothesized that the 5-HT1D receptor was implicated in this disorder’s pathophysiology. Methods: We explored the 5-HT1D hypothesis in a 5-day, random, double-blind, placebo-controlled trial of oral sumatriptan 100 mg/day in medication-free adults with OCD. We hypothesized that sumatriptan, a 5-HT1D agonist, would diminish 5-HT release, thereby worsening OCD symptoms. We further hypothesized that by beginning to desensitize 5-HT1D receptors, sumatriptan pretreatment would promote a faster response or an increased likelihood of response to subsequent treatment with a selective serotonin reuptake inhibitor. Results: The five sumatriptan subjects’ OCD symptom worsening, as measured by the Yale–Brown scale (↑ 17.6% (S.D. 14.6)), was significant when compared to the slight symptom decrease in the five placebo subjects (↓ 5.2% (S.D. 4.9), P<0.015). The sumatriptan group did not exhibit a faster response or greater likelihood of response to a 90-day, open label trial of paroxetine. Conclusions: Longer term studies of the effects of 5-HT1D agonists on OCD symptoms are indicated. Zolmitriptan, a potent 5-HT1D receptor agonist with better penetration of the blood–brain barrier, may be a preferred challenge agent.

Unilateral low frequency versus sequential bilateral repetitive transcranial magnetic stimulation: is simpler better for treatment of resistant depression?

Repetitive transcranial magnetic stimulation (rTMS) efficacy in the treatment of major depression has been shown in both low frequency right-sided and high frequency left-sided stimulation over the dorsolateral prefrontal cortex (DLPFC). The aim of the present investigation was to evaluate the hypothesis of an additive effect of bilateral stimulation compare to sequential to unilateral stimulation. Sixty patients with treatment-resistant depression were assigned to receive either low-frequency rTMS over the right DLPFC (140 s x 1 Hz) followed by controlateral sham (unilateral group, n=20), low frequency right DLPFC rTMS followed by left DLPFC high frequency rTMS (5 s x 10 Hz) (bilateral group, n=20), or bilateral sham (sham group, n=20) in a 3 weeks double-blind, randomized trial. The primary outcome variable was the score on Hamilton Depression Scale (HAM-D). Low frequency right-sided and sequential bilateral stimulation showed different antidepressant efficacy at 3 weeks and across the full duration of the study, only the unilateral method appearing significantly more effective than sham at the end of the trial, and correlated to the higher percent of remitters (30% of the group vs. 10% -bilateral- and 5% -sham). Unilateral stimulation, but not bilateral, showed higher antidepressant efficacy compared to sham stimulation. The data suggest that right-sided low frequency stimulation may be a first line treatment alternative in resistant depression. To confirm and extend these findings further studies require a longer follow-up period, supported by biological observation and replication.

Effects of clozapine on awareness of illness and cognition in schizophrenia

Awareness of illness is a crucial factor in schizophrenia, both for clinical management and psychopathological modeling. To date, there has been relatively little investigation of the influence of treatment with conventional versus atypical neuroleptics in relation to awareness and cognitive functions. The effect of clozapine treatment, compared with conventional neuroleptics, was studied in 22 schizophrenic patients in a crossover study. The P300 component of the event-related potential and scores on the Scale for Unawareness of Mental Disorder (SUMD), the Extrapyramidal Side Effects Scale (EPS), and Andreasens Scales for the Assessment of Positive (SAPS) and Negative Symptoms (SANS) were studied at time 1 (conventional neuroleptic treatment) and time 2 (after 6 months of treatment with clozapine, in patients who interrupted the previous conventional regimen). Significantly increased P300 amplitudes were associated with clozapine treatment, together with heightened insight and reduced involuntary movements. The results confirm the effectiveness of clozapine not only in enhancing neurocognitive function, but also in increasing awareness of illness in schizophrenic patients.

Citalopram for treatment-resistant obsessive-compulsive disorder

We investigated the comparative efficacy of citalopram vs. citalopram administered with clomipramine, in treatment-resistant obsessive-compulsive disorder (OCD). Sixteen adult outpatients participated in a 90-day, randomized, open-label trial. Eligible patients were aged 18 to 45 years, had moderate to severe DSM-III-R OCD of >/= one years duration, a baseline Yale-Brown scale (Y-BOCS) score of >/= 25 and no other active axis I diagnosis, and had failed adequate clomipramine and fluoxetine trials. The citalopram-plus-clomipramine group (n = 9) experienced a significantly larger percent decrease in mean Y-BOCS score by day 90 than the citalopram alone group (n = 7). Only one citalopram patient decreased her score by >/= 35%, and two by >/= 25%. All nine citalopram-plus-clomipramine patients experienced decreases of 35%. Side effects were mild to moderate in both groups. We also treated with citalopram six OCD patients who had not tolerated fluoxetine alone and clomipramine alone; three achieved Y-BOCS score decreases of >/= 35% at 90 days. Since citalopram does not significantly affect clomipramine metabolism, the improvement in the combined drug group is unlikely to have resulted from increased plasma clomipramine levels. Double-blind controlled trials are needed of citalopram in OCD, and of combining citalopram with clomipramine in treatment-resistant OCD.

Pulse loading versus gradual dosing of intravenous clomipramine in obsessive-compulsive disorder

OBJECTIVE We compared gradually increased to pulse loaded doses of open-label, intravenous clomipramine (CMI) in patients with obsessive-compulsive disorder (OCD). METHOD We treated adult outpatients with DSM-III-R OCD, who had no prior exposure to effective treatments. Pulse loading patients received 150 mg on day 1; 150 mg or 200 mg on day 2. Gradual dosing patients received 25 mg per day increased to 200 mg per day over 2 weeks and then continued for a mean of 43 days (n=40). After i.v. dosing, all patients received oral CMI; the total treatment period was 6 months. RESULTS Pulse loading completers (n=7) had a rapid, dramatic response (mean Y-BOCS score decrease of 32% five days after pulse-loading). At this point (day 7), completers in the gradual intravenous group (n=20) exhibited no mean change in Y-BOCS score. The pulse loading group reached both a 25% or greater and a 50% or greater decrease in Y-BOCS score statistically and clinically significantly faster than the gradual group. CONCLUSIONS Pulse-loaded intravenous CMI for the treatment of OCD deserves further study.

Eye movement abnormalities in anorexia nervosa

The aim of the present study is to investigate smooth pursuit eye movement and saccadic performance in anorexia nervosa during a restored weight period and to determine if functional links can be made between eye movement performance and clinical features. SPEM parameters were recorded for 28 female anorectic out-patients (DSM IV), who had a body weight loss of up to 20% of ideal body weight. Twenty-eight comparison subjects were also tested. Clinically, each patient was assessed using the Eating Disorder Inventory (EDI), the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Structured Interview for Personality Disorders (SCID II), the Symptom Checklist-90-Revised (SCL-90-R) and the Hamilton Scale for Depression (HRSD). The anorectic patients performed slightly worse than the comparison subjects on a number of SPEM measures. No relationship was found between SPEM impairment and a global severity index of psychopathology (SCL 90-R GSI) or depressive symptoms. Moreover, OCD symptoms and scores on some EDI scales (such as perfectionism) appear related to the severity of the eye movement alterations. The evidence of SPEM abnormalities in a subgroup of anorectic patients during the remitted state and the relationship of the abnormalities to obsessive-compulsive symptoms are discussed. Results are in agreement with the hypothesis regarding the persistence of neurophysiological as well as psychopathological traits of disorder in anorectic patients.

Basic symptoms and negative symptoms in the light of language impairment

The Frankfurter Beschwerde-Fragebogen (FBF), assessing basic symptoms (B-S), and the Scale for the Assessment of Negative Symptoms (SANS) were administered to 30 patients satisfying DSM-III-R criteria for the diagnosis of schizophrenia. Considering the relationship between BS and negative symptoms (N-S), we identified the key role of the impairment of receptive and expressive language for the correlation of these two orders of phenomena.

Low-Frequency rTMS over Right Dorsolateral Prefrontal Cortex in the Treatment of Resistant Depression: Cognitive Improvement Is Independent from Clinical Response, Resting Motor Threshold Is Related to Clinical Response

Background: Clinical studies have shown that repetitive transcranial magnetic stimulation (rTMS) is effective in a certain percentage of treatment-resistant depression (TRD). The left dorsolateral prefrontal cortex (DLPFC) 10 Hz rTMS stimulation received FDA approval in 2008, although different rTMS protocols have also shown their effectiveness in reducing depressive symptoms. We investigated the clinical, cognitive and neurophysiologic effects of a 3 weeks’ protocol of low-frequency rTMS applied over the right DLPFC in resistant depression. Methods: Twenty-eight patients with TRD (age range 28–55) received low-frequency rTMS (1 Hz) over the right DLPFC in a 3-week open trial. Hamilton scales for depression and anxiety, Corsi block-tapping test, phonemic verbal fluency, right and left resting motor thresholds were evaluated in each subject over the trial period. Results: At the end of the trial 42.9% of the subjects were considered as responders. A significant reduction of both HAMD (p < 0.001) and HAMA (p < 0.01) total scores was observed. At the 3rd week, the performances in Corsi test (p < 0.02) and phonemic verbal fluency (p = 0.065) were improved independently from depressive symptoms variation. At the end of the rTMS protocol, a significantly decreased left hemisphere resting motor threshold was registered (p < 0.01), while right hemisphere resting motor threshold did not show significant variation. Conclusion: Low-frequency rTMS over the right DLPFC appeared effective in 42.9% of depressive resistant subjects in this sample. A significant decrease in left hemisphere resting motor threshold was observed only in responders, while a trend for improvement in cognitive function has been found and appeared independent from clinical response.

Cognitive event-related potentials differentiate schizophrenia with obsessive- compulsive disorder (schizo-OCD) from OCD and schizophrenia without OC symptoms

Clinical and neurobiological evidence suggests that concurrent presentation of schizophrenia and obsessive-compulsive (schizo-OCD) symptoms represents a distinct clinical entity. Given that obsessive-compulsive disorder (OCD) and schizophrenia have been modeled as having different neurofunctional profiles, the overlap between them represents a heuristic challenge for cognitive and endophenotype research. Event-related potentials (ERPs) may be used to probe neurophysiological correlates of the cognitive, emotional and behavioral disturbances found in neuropsychiatric entities such as schizo-OCD. Here we measure ERPs during a discriminative response task (DRT) in patients presenting with the DSM-IV criteria for both schizophrenia and OCD. We also performed these measurements in patients with OCD without psychotic features, as well as in patients with schizophrenia without OC symptoms. Schizo-OCD patients showed a distinct ERP pattern, with abnormally increased target activation (akin to OCD patients, but unlike the pattern observed in schizophrenic patients) and reduced P300 amplitudes (akin to schizophrenic patients, but unlike OCD patients). Similar to the control subjects, schizo-OCD patients showed larger amplitudes in the non-target condition than in the target condition. These results suggest that schizo-OCD may not only be a distinct clinical entity from pure OCD and schizophrenia, but it may also be characterized by a distinguishable neurophysiologic pattern. Neurobiological underpinnings deserve further considerations and might drive to a definition of a distinctive endophenotype for schizo-OCD in the de-construction of the schizophrenia endophenotype.