From neurological soft signs to functional outcome in young individuals in treatment with secondary services for non-psychotic disorders: a path analysis.

BACKGROUND: Functional decline among patients with mental illness is not unique to individuals with psychotic disorders. Despite this, research on early predictors of functional outcome mainly focused on individuals thought to have an 'at risk mental state' (ARMS) for psychosis. There is evidence suggesting that certain early vulnerability markers, such as neurological soft signs (NSS), may explain variability in functional outcomes independent of the level of psychosis risk and the traditional diagnostic classification. METHOD: Structural equation modeling was applied to baseline data from a prospective longitudinal study of 138 young individuals in treatment with secondary services for non-psychotic disorders. We evaluated theoretically based models of pathways to functional outcome starting from NSS. The intervening variables were established according to previous evidence and drawn from two general categories: cognition (neuro- and social-) and negative symptoms (expressive and experiential). RESULTS: A final trimmed model was a single path running from NSS to neurocognition to experiential negative symptoms to outcome. It could not be improved by adding or dropping connections that would change the single path to multiple paths. The indirect effect from NSS to outcome was significant. The validity of the model was independent of the ARMS status and the psychiatric diagnosis. CONCLUSIONS: Our results provide evidence for a single pathway model in which the starting and intervening variables represent modifiable trans-diagnostic therapeutic targets to improve functional trajectories in young individuals with a recent-onset psychiatric diagnosis and different levels of psychosis risk.

Olanzapine-induced neutropenia in a patient with systemiclupus erythematosus: a role of FcγRIIIb polymorphism?

In this study, we report the case of a Chinese patient with systemic lupus erythematosus (SLE) who developed neutropenia after treatment by olanzapine for the SLE-related psychiatric symptoms. The relationship between agranulocytosis, SLE and olanzapine is still unknown. Fcγ receptor IIIb (FcγRIIIb) is a low-affinity receptor, constitutively expressed only by neutrophils; NA1 and NA2 have been identified as representing polymorphisms of FcγRIIIb. NA1 is associated with the incidence of autoimmune neutropenia and is particularly frequent in Asiatic ethnic groups. The Chinese patient resulted to be homozygous for NA1. We suggest that the presence of NA1 allele may be a predisposing factor to olanzapine-induced agranulocytosis in patients with SLE. Hence, the analysis of FcγRIIIb polymorphism should be investigated in other cases of antipsychotic-induced agranulocytosis.

Genetic association of HLA-DQB1 and HLA-DRB1 polymorphisms with alopecia areata in the Italian population.

BACKGROUND: Alopecia areata (AA) is a multifactorial disease characterized by hair loss especially from the scalp. As for other autoimmune conditions, the major histocompatibility complex (HLA) region is associated with AA susceptibility. OBJECTIVE: To provide evidence for the association of specific HLA-DQB1 and HLA-DRB1 alleles with AA in an Italian population, using a case-control approach. METHODS: We performed a case-control study to investigate whether HLA-DQB1 and -DRB1 alleles predispose to AA in the Italian population. HLA class II typing was performed in 85 patients with AA and 210 healthy controls from the same ethnic group. RESULTS: An increased frequency of DQB1*03, coding for DQ7 heterodimers, and a decreased rate of the DQB1*06 allele were observed in patients when compared with controls; the greatest and significant difference was in the group of cases with a more severe phenotype [AA>50% patients (more than 50% hair loss) vs. controls, P=4·5×10(-3) , P(c)=0·031, odds ratio (OR) 2·01, 95% confidence interval (CI) 1·22-3·31 and P=2·5×10(-3) , P(c)=0·017, OR 0·22, 95% CI 0·07-0·72, respectively]. DQB1*03, serologically related to DQ8 or coding for DQ9 molecules, was not associated with AA susceptibility. Out of all patients, 65·9% carried DQ7 heterodimers compared with 49·5% of the controls (P=7·3×10(-3) , OR 1·97, 95% CI 1·17-3·32) and DQ7 prevalence rose to 76·3% in patients with AA>50% (P=1·7×10(-3) , OR 3·28, 95% CI 1·48-7·27). No significant difference was found in the distribution of DRB1 variants or phenotypes among cases and controls. CONCLUSION: Our data show a correlation between the HLA-DQB1 locus and the occurrence of AA in Italy supporting DQB1*03(DQ7) as a predisposing allele for the disease and the relevance of the HLA genetic test in the clinical management of AA.

A systematic review on sleep alterations anticipating the onset of bipolar disorder.

BACKGROUND: Sleep alterations are frequent occurrence in Bipolar Disorder (BD), both in acute and interepisodic phases. Sleep alterations have been also described both long before BD onset, as aspecific risk syndromes, or as immediate prodromes of BD onset. The aim of the present study is to systematically review the relationship between sleep alterations anticipating for the full-blown onset of BD, both in general and according to specific polarities of onset. METHODS: A systematic literature research according to PRISMA statement and considering: 1. prospective studies about BD patients' offspring with sleep alterations who later developed BD. 2. prospective studies assessing patients with sleep disorders who later developed BD. 3. retrospective studies on BD patients where sleep alterations before BD onset of the disease were reported. RESULTS: A total of 16 studies were included in this review. Sleep disturbances may frequently appear 1 year before the onset of BD or more, often during childhood or adolescence. A decreased need for sleep may precede the onset of the illness, specially a manic episode, while insomnia appears to anticipate either a manic or a depressive episode. Hypersomnia seems to precede bipolar depressive episodes. CONCLUSIONS: Sleep alterations frequently appear long before the onset of BD, and appear to be related specifically to the polarity of the index episode. The detection and treatment of sleep alterations in special high risk populations may help achieving an earlier detection of the illness.

Psychosis prediction in secondary mental health services. A broad, comprehensive approach to the "at risk mental state" syndrome.

BACKGROUND: Accuracy of risk algorithms for psychosis prediction in "at risk mental state" (ARMS) samples may differ according to the recruitment setting. Standardized criteria used to detect ARMS individuals may lack specificity if the recruitment setting is a secondary mental health service. The authors tested a modified strategy to predict psychosis conversion in this setting by using a systematic selection of trait-markers of the psychosis prodrome in a sample with a heterogeneous ARMS status. METHODS: 138 non-psychotic outpatients (aged 17-31) were consecutively recruited in secondary mental health services and followed-up for up to 3 years (mean follow-up time, 2.2 years; SD=0.9). Baseline ARMS status, clinical, demographic, cognitive, and neurological soft signs measures were collected. Cox regression was used to derive a risk index. RESULTS: 48% individuals met ARMS criteria (ARMS-Positive, ARMS+). Conversion rate to psychosis was 21% for the overall sample, 34% for ARMS+, and 9% for ARMS-Negative (ARMS-). The final predictor model with a positive predictive validity of 80% consisted of four variables: Disorder of Thought Content, visuospatial/constructional deficits, sensory-integration, and theory-of-mind abnormalities. Removing Disorder of Thought Content from the model only slightly modified the predictive accuracy (-6.2%), but increased the sensitivity (+9.5%). CONCLUSIONS: These results suggest that in a secondary mental health setting the use of trait-markers of the psychosis prodrome may predict psychosis conversion with great accuracy despite the heterogeneity of the ARMS status. The use of the proposed predictive algorithm may enable a selective recruitment, potentially reducing duration of untreated psychosis and improving prognostic outcomes.

Effects of moclobemide on depressive symptoms and cognitive performance in a geriatric population: a controlled comparative study versus imipramine.

Moclobemide, a novel monoamine oxidase-A reversible inhibitor with demonstrated antidepressive efficacy, was administered double-blind versus imipramine to aged depressive subjects. The two drugs were given for 60 days in increasing doses up to 600 mg for moclobemide and 100 mg for imipramine. Fifteen patients received moclobemide and 15 received imipramine. Psychiatric conditions and symptoms were rated at 0, 7, 14, 30, 45, and 60 days after the beginning of the trial by means of the Scale for the Assessment of Psychoorganic Syndromes, Hamilton Rating Scale for Depression, Rome. Depression Inventory, Hamilton Anxiety Rating Scale, State-Trait Anxiety Inventory-X form, and the Clinical Global Impression Scale. Cognition was tested through the Benton visual retention test at days 0, 30, and 60 and the Digit Substitution Test of the Wechsler Adult Intelligence Scale at days 0 and 60. Side effects were assessed through the Dosage Record Emergent Symptoms at days 0, 7, 14, 30, 45, and 60. The dropout rate was significantly greater in the moclobemide group. Both drugs induced an improvement in depressive and anxious symptomatology, with moclobemide showing a faster onset. Furthermore, moclobemide showed an enhancing effect on cognition, which was not shown by imipramine. Such results indicate that moclobemide could prove to be the drug of choice in geriatric depression, given that cognitive effects are prominent in the aged.

Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: a comprehensive review.

Deep transcranial magnetic stimulation (TMS) is a technique of neuromodulation and neurostimulation based on the principle of electromagnetic induction of an electric field in the brain. The coil (H-coil) used in deep TMS is able to modulate cortical excitability up to a maximum depth of 6 cm and is therefore able not only to modulate the activity of the cerebral cortex but also the activity of deeper neural circuits. Deep TMS is largely used for the treatment of drug-resistant major depressive disorder (MDD) and is being tested to treat a very wide range of neurological, psychiatric and medical conditions. The aim of this review is to illustrate the biophysical principles of deep TMS, to explain the pathophysiological basis for its utilization in each psychiatric disorder (major depression, autism, bipolar depression, auditory hallucinations, negative symptoms of schizophrenia), to summarize the results presented thus far in the international scientific literature regarding the use of deep TMS in psychiatry, its side effects and its effects on cognitive functions.

Bradykinesia in patients with obsessive-compulsive disorder.

OBJECTIVE: To investigate the frequency of bradykinesia in patients with obsessive-compulsive disorder (OCD) and to see whether patients with OCD who also have bradykinesia display distinctive neuropsychological and neuropsychiatric features. METHODS: We studied 23 antipsychotic-free patients with OCD and 13 healthy controls. Bradykinesia was assessed with section III of the Unified Parkinson Disease Rating Scale. The Wechsler Adult Intelligent Scales-Revised (WAIS-R) was used to assess the Full Scale IQ and to measure visuospatial, visuoconstructional ability and psychomotor speed/mental slowness. RESULTS: Of the 23 patients with OCD studied, 8 (34%) had mild symptoms of bradykinesia. No relationship was found between bradykinesia and the sociodemographic variables assessed but this motor symptom was significantly associated with the severity of compulsions. Patients with bradykinesia differed from those without: they had a higher frequency of repeating compulsions, and lower IQ scores, performance scores, and WAIS-R subtest scores for similarities and picture completion. No significant differences were found between patients without bradykinesia and healthy controls in any test. CONCLUSIONS: Clinical assessment of motor symptoms in adult patients with OCD often discloses mild bradykinesia sometimes associated with repeating compulsions and poor WAIS-R performance scores.

Alexithymia as related to sex, age, and educational level: results of the Toronto Alexithymia Scale in 417 normal subjects.

The Toronto Alexithymia Scale (TAS) was administered to 417 normal subjects. Total TAS scores and scores of the four TAS factors were correlated with sex, age, and educational level. Age ranged from 21 to 64 years. The sample was subdivided into three groups according to age. TAS scores, both total and on single subfactors, were significantly greater in the higher age groups with respect to lower age groups. Subjects with a lower educational level scored higher on factors 1, 2, and 4 and had higher TAS total scores with respect to subjects with a higher educational level. As for sex, no significant differences in total TAS scores were obtained, but women scored higher at factor 1. Factor analysis of the TAS, performed on both the whole sample and the subgroups according to sex and age, confirmed the fair internal stability of the TAS.

Assessment of the efficacy of buspirone in patients affected by generalized anxiety disorder, shifting to buspirone from prior treatment with lorazepam: a placebo-controlled, double-blind study.

Forty-four patients with DSM-III-R generalized anxiety disorder participated in this double-blind, randomized study. Patients were on a benzodiazepine before the study and were stabilized on 3 to 5 mg/day lorazepam for 5 weeks (weeks 0 to 5). Thereafter, they were randomized to 15 mg/day buspirone or placebo for the following 6 weeks (weeks 6 to 11). During the first 2 weeks of double-blind, randomized treatment (weeks 6 to 7), lorazepam was tapered off. During weeks 12 to 13, patients received single-blind placebo. Assessment included the Hamilton Rating Scale for Anxiety, the State-Trait Anxiety Inventory, the Zung and Eddy Self-Rating Scale of Anxiety Symptoms, the Hamilton Rating Scale for Depression, and the Rome Depression Inventory, completed at weeks 0, 5, 6, 7, 8, 9, 11, and 13. Side effects were assessed through the Dosage Treatment Emergent Symptoms at the same times. The benzodiazepine-withdrawal syndrome was evaluated through a 27-symptom checklist (Clinical-Rated Benzodiazepine Withdrawal Symptom Schedule) at weeks 0, 5, 6, 7, 11, and 13. The results showed that buspirone was more effective than placebo and comparable to lorazepam. Buspirone-treated patients showed no rebound anxiety or benzodiazepine-withdrawal syndrome compared with placebo. Buspirone caused fewer side effects than lorazepam and was not different from placebo in this respect. Finally, buspirone maintained its anxiolytic effect for at least 2 weeks after the discontinuation of treatment.

Nonverbal behavior and alexithymic traits in normal subjects. Individual differences in encoding emotions.

The relationship between nonverbal behavior and emotional awareness, as measured by the Toronto Alexithymia Scale, was studied in 24 young volunteers free of medical and psychiatric disorders. Multiple regression analysis revealed that nonverbal behavior during psychiatric interview was a significant predictor of the Toronto Alexithymia Scale total score independent of situational depression and anxiety. Subjects who had difficulty identifying and describing their feelings showed a combination of poor nonverbal expressivity and frequent self-directed behavior patterns indicative of tension and anxiety. In addition, subjects with a tendency toward externally oriented thinking showed more avoidance behavior during the interview. The ethological data of this study support clinical observations, which suggest that alexithymic traits interfere with both processing of emotion and interpersonal behavior.

ACTH 1-17 and short-term memory, anxiety, heart rate, blood pressure.

The research investigated the effects of acute ACTH 1-17 administration on plasma cortisol, short-term memory, anxiety state, blood pressure and heart rate. In a double blind crossover design, healthy volunteers were serially evaluated at 5 min, 20 min, 40 min, 60 min after injection of ACTH 1-17 or placebo in separate sessions. Results show that ACTH 1-17 produced, in addition to an increase in plasma cortisol (5 min - 60 min), significant improvements in short-term memory (5 min), a reduction in anxiety (20 min and 40 min), and an increase in systolic (5 min and 20 min) and diastolic blood pressure (5 min). If confirmed by other studies, the short-term memory effect of ACTH 1-17 at 5 min after i.v. could suggest a central action of the peptide, and confirm the role of HPA axis as a modulator of performance and emotional arousal during acute environmental changes.

Cardiovascular reactivity of mitral valve prolapse patients during experimental stress exposure: evidence for a functional nature of cardiovascular symptoms.

We studied a group of 18 patients with mitral valve prolapse (MVP) and a group of 20 healthy controls. Subjects in both groups were subjected to a 1-h experimental stress exposure during which Holter-ECG monitoring was performed and was then continued for the following 24 h. MVP patients complained of significant cardiac palpitation during the stress session, but ECG examination did not reveal significant inter-group differences. However, the two groups did show statistically significant differences in some psychometric measurements (Toronto Alexithymia Scale, Anxiety Sensitivity Index, Fear Questionnaire, Beck Depression Inventory, and Harm Avoidance subscale of Tridimensional Personality Questionnaire) that underlie personality traits known to be important in the process fostering functional somatic symptoms, according to the somatosensory amplification model. As no objective signs of cardiac rhythm modification were found in MVP patients under stress, we postulate that the symptoms for which these patients were referred have a functional nature, and that there is no pathogenetic link with the underlying valvular defect.

[Controlled clinical study on the effect of quazepam versus triazolam in patients with sleep disorders]. / Studio clinico controllato dell'effetto del quazepam vs triazolam in pazienti con disturbi del sonno.

Quazepam (QZP), a new long half-life benzodiazepine, seems to have a more specific hypnotic activity and a "physiological" mechanism of action. This study assessed its clinical efficacy and any withdrawal symptoms occurring after the treatment with QZP and triazolam (TRZ). Sixty-five patients (mean age 41.4 yrs +/- 12.43 SD) with sleep disorders were included in the study. The patients were treated with placebo for 4 days (run-in period) and if no amelioration of insomnia was observed, were then randomly allocated to 15 mg QZP (33 patients) or TRZ (32 patients) for 8 weeks and finally placebo for another week. Sleep quality, efficiency, side-effects and withdrawal effects were assessed by specific rating scales. In comparing data obtained from the two treatments, the following conclusions were drawn: 1) both drugs showed a hypnoinductive efficacy but patients treated with QZP had significantly fewer night awakenings; 2) at the end of treatment only patients treated with TRZ had longer awakenings and rebound symptoms; 3) a lower withdrawal symptom incidence was observed in patients treated with QZP. Therefore, QZP seems to have a good hypnotic effect without inducing withdrawal symptoms. In contrast TRZ turned out to be a merely hypno-inducing drug presenting higher risks of rebound effects after withdrawal.