Evaluating the contribution of the gene TARDBP in Italian patients with amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVES: Genetic variants in the gene TARDBP, encoding TDP-43 protein, are associated with amyotrophic lateral sclerosis (ALS) in familial (fALS) and sporadic (sALS) cases. Objectives of this study were to assess the contribution of TARDBP in a large cohort of Italian ALS patients, to determine the TARDBP-associated clinical features and to look for genotype-phenotype correlation and penetrance of the mutations. METHODS: A total of 1992 Italian ALS patients (193 fALS and 1799 sALS) were enrolled in this study. Sanger sequencing of TARDBP gene was performed in patients and, when available, in patients' relatives. RESULTS: In total, 13 different rare variants were identified in 43 index cases (10 fALS and 33 sALS) with a cumulative mutational frequency of 2.2% (5.2% of fALS, 1.8% of sALS). The most prevalent variant was the p.A382T followed by the p.G294V. Cognitive impairment was detected in almost 30% of patients. While some variants, including the p.G294V and the p.G376D, were associated with restricted phenotypes, the p.A382T showed a marked clinical heterogeneity regarding age of onset, survival and association with cognitive impairment. Investigations in parents, when possible, showed that the variants were inherited from healthy carriers and never occurred de novo. CONCLUSIONS: In our cohort, TARDBP variants have a relevant frequency in Italian ALS patients and they are significantly associated with cognitive impairment. Clinical presentation is heterogeneous. Consistent genotype-phenotype correlations are limited to some mutations. A marked phenotypic variability characterizes the p.A382T variant, suggesting a multifactorial/oligogenic pathogenic mechanism.

[The case of Giorgia: a systemic cognitive postrationalist intervention]. / Il caso di Giorgia: un intervento cognitivista sistemico postrazionalista.

To describe and to explain a clinical case from a cognitive systemic perspective means to focus on "how" the different data were set in order and organized during the therapy. The theoretical and clinical experience that uses this approach is based upon the integration of two conceptual models: the cognitive postrationalist one and the relational systemic one. These two approaches are founded upon the concept of system. The first one addresses the internal dimension, focusing on something that is not directly observable, taking into account the development processes and the maintenance of identity, that is to say the self organization of personal meaning. On the other hand, the second approach considers the structure of relations, its path and boundary, focusing on the mode of communication. The cognitive systemic model springs out of the integration of these two different ways of observing our object of investigation, intending to better the knowledge of the individual and of its context. The essay describes a clinical case study along a processual systemic method, in every phase, beginning with the intervention on the individual's system, subsequently engaging the family's system and all the sub systems that are part of the subjective experience.

[Pilot study on nutritional and eating disorders in children and mood disorders: comorbidity or prodromal traits?] / Studio pilota sui disturbi della nutrizione e dell'alimentazione in età pediatrica e i disturbi dell'umore: comorbilità o tratti prodromici?

INTRODUCTION: Both children affected by nutritional and eating disorders (ED) and adults with bipolar disorder (BD) display symptoms of deficient emotional self-regulation, which can present in different forms. If we observe the clinical and developmental histories of individuals affected by EDs and BD, based on a cognitive systemic post-rationalist approach, we can hypothesise a continuum between the two disorders. The aim of this pilot study is to support the hypothesis - from an explanatory rather than a non-descriptive approach - that EDs and BD are the possible result of issues tied to biological and psychological self-regulation. When such an issue manifests during an individual's early stages through an eating disorder, it is more likely to result in an actual affective disorder, such as BD, during an individual's adult years. MATERIALS AND METHODS: The study examined a total of 51 patients affected by an ED between the ages of 8 and 18. At least one of the parents had been diagnosed with a mental disorder. All of the subjects completed the Child Behavior Checklist (CBCL) and the Eating Disorders Inventory (EDI) II. Each of the patients underwent a pediatric assessment using their BMI to establish the type of ED. The parents were divided into two groups: subjects with BD and subjects affected by other psychopathologies. RESULTS: Although the comparison between patients with EDs and parents with or without BD did not demonstrate a significant difference in any scale, it highlighted specific common characteristics between the disorder presented by the parent and the cognitive-emotional expressions of his or her child. In fact, the results indicate that the CBCL "problems of thought" scale explains much of the Impulsivity variance obtained by the EDI and that the CBCL "high withdrawal/depression" dependent factor highlighted a statistical significance for the EDI's "low interoceptive awareness" scale. CONCLUSIONS: The study presented limitations, especially with respect to the sample size examined, but it suggests a field that can be further explored to understand the reasons for a significance in the aspects related to contrasting emotional adjustments, impulsivity and depression/withdrawal, highlighting a connection with the parents' distinctive relational model.

Post-rationalist psychotherapy academy today:research and clinical practice.

The post-rationalist psychotherapy academy (non-classic cognitive approach) started at the end of the 80's with a series of consistent hypotheses. It is an academy which stems from contemporary psychotherapy and develops different areas, giving a strong contribution to theoretical and clinical psychotherapy. This academy has presented development as all other psychotherapy schools have, as well as the same difficulties and solutions. In this article, our aim is to show some tendencies that don't present an epistemological, theoretical, methodological and coherency, since these tendencies don't allow any confutation, which is the fundamental premise of Vittorio Guidano's academy. Finally, we stress how it's nowadays crucial in psychotherapy, to apply coherent methodological and conceptual positions based on the research.

Aripiprazole: initial clinical experience with 142 hospitalized psychiatric patients.

BACKGROUND: Aripiprazole is the first dopamine D2 receptor partial-agonist approved for treatment of schizophrenia. Its apparently benign adverse-effect profile encourages broader use in other disorders, especially to limit weight gain associated with other antipsychotic or antimanic agents. We considered the first 6 months of experience with aripiprazole in psychiatric inpatients with a range of disorders. METHODS: We analyzed data obtained from medical records of patients treated with aripiprazole who were hospitalized at McLean Hospital (for 19 +/- 18 days) between December 2002 and June 2003 to evaluate dosing, tolerability, and clinical effects of this new agent in patients diagnosed with DSM-IV psychotic, major affective, or other disorders. RESULTS: Out of a sample of 2766 adult inpatients (65.5% women), 142 were given aripiprazole (mean final daily dose, 16.1 +/- 6.2 mg, 0.20 +/- 0.09 mg/kg body weight) for major affective disorders (52%), primary psychotic disorders (40%), and dementia (8%). CGI ratings improved by 20% on average. Adverse effects were infrequent (15.5%), were three times more likely among women, and most often involved moderate behavioral activation or nausea, with no new episodes of mania. Of the patients who were given aripiprazole, 83% continued it at discharge. Many patients were obese when they were admitted, and obesity was associated with relatively low mg/kg doses of aripiprazole. CONCLUSIONS: Aripiprazole was used in a range of disorders and was generally well tolerated. Adverse effects may reflect its unique dopamine partial-agonist activity. Since aripiprazole is likely to be considered for obese patients, body weight should be considered in establishing adequate doses. Controlled trials of this antipsychotic agent in disorders other than schizophrenia are needed.

Antipsychotic drug use: McLean Hospital, 2002.

OBJECTIVE: Major changes in antipsychotic treatment in recent years encouraged a survey of inpatient practice in 2002, compared with earlier samples. METHODS: Based on records of a random sample of McLean Hospital inpatients prescribed antipsychotics in 2002, the study recorded DSM-IV discharge diagnosis, all psychotropic treatments and doses, initial, peak and final doses of all antipsychotics, clinical status at admission and discharge, and adverse effects reported. Results were compared with similar data from our earlier surveys. RESULTS: Subjects were 344 inpatients (n = 202 women, 59%), diagnosed with psychotic (n = 102, 30%), bipolar (n = 93, 27%), major depressive (n = 67, 19.5%), dementia (n = 19, 5.5%), substance-use (n = 28, 8%) or other psychiatric disorders (n = 35, 10%). Second-generation antipsychotics accounted for 88% of antipsychotic prescriptions; 17% of patients received > or = 2 antipsychotics and total CPZ-eq discharge does in 2002 averaged 291 +/- 305 mg/day (22% less than a 1998 peak). Doses were unrelated to age, but higher in men, among psychotic vs major affective disorder patients, and with greater illness-severity and longer hospitalization. There was a 3.3-fold increase in the simultaneous use of > or = 3 psychotropic agents since 1998. CONCLUSIONS: The use of second-generation antipsychotics dominates current inpatient practice. Total antipsychotic dosing has not increased recently, but the use of multiple psychotropics increased strikingly from 1998 to 2002.