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Introduction: Attention deficit hyperactivity disorder (ADHD) is characterized by a lack in self-regulation of behaviour, cognition and emotional response. Children with ADHD often experience emotional dysregulation (ED) defined as the inability to regulate emotions and to organize behaviours in response to emotional stimuli. Objectives: The present exploratory study aimed to evaluate possible peculiar sensitivity to emotional stimuli in children with ADHD and ED, revealed by behavioural performances and cortical hemodynamic characteristics measured with functional Near Infrared Spectroscopy (fNIRS). The relationship between haemodynamic activation during task and ADHD and ED symptoms was also investigated. Methods: Eighteen children with ADHD and ED, all drug naïve, and 25 typically developing (TD) peers, aged 6-16 years, underwent fNIRS while performing a visual emotional continuous performance task in which faces with relevant positive, negative and neutral content were presented. ADHD and ED symptoms were evaluated with Conners' parents rating scales (CPRS). Selected fNIRS sources and detectors see figure1 Results: Between groups comparisons revealed worse performances of ADHD children, with a statistically significant difference for positive blocks and total errors. fNIRS analysis showed higher activation inTDgroup, as measured by higher oxygenated-haemoglobin concentration changes, localized in right prefrontal cortex, regardless from the valence of the emotional stimuli. Correlations conducted between fNIRS activation and CPRS revealed several associations between hemodynamic changes in right prefrontal regions and inattention and hyperactivity, but not ED symptoms. Conclusions: Lack of self-regulation and ED impact on ADHD children ability to process emotional stimuli, as revealed by worse performances and haemodynamic peculiarities in right prefrontal cortex. [ABSTRACT FROM AUTHOR]

Objective: The relation of temperamental dimensions to somatization and panic disorders in women was investigated.Method: Eighteen patients with both panic and somatization disorders, 41 patients with panic disorder only, and 22 control subjects were compared on the Tridimensional Personality Questionnaire.Results: The patients with somatization and panic disorders had significantly higher Novelty Seeking values than both the patients with panic only and the control subjects. The only significant correlation was between the number of symptoms of somatization disorder and Novelty Seeking. The presence of other psychiatric conditions, comorbid with panic disorder in the patient group, did not affect significantly the temperamental variables.Conclusions: A temperamental disposition characterized by extraversion, impulsivity, as well as frequent exploratory activity and pursuit of novel and pleasurable activities may help differentiate women with both somatization and panic disorders from women with panic disorder only. [ABSTRACT FROM AUTHOR]

Our ability to study and valorize the lignin fraction of biomass is hampered by the fundamental and still unmet challenge of precisely quantifying native lignin's structural features. Here, we developed a rapid elevated-temperature 1 H- 13 C Heteronuclear Single-Quantum Coherence Zero (HSQC 0 ) NMR method that enables this precise quantification of native lignin structural characteristics even with whole plant cell wall (WPCW) NMR spectroscopy, overcoming fast spin relaxation in the gel phase. We also formulated a Gaussian fitting algorithm to perform automatic and reliable spectral integration. By combining HSQC 0 measurements with yield measurements following depolymerisation, we can confirm the combinatorial nature of radical coupling reactions during biosynthesis leading to a random sequential organization of linkages within a largely linear lignin chain. Such analyses illustrate how this analytical method can greatly facilitate the study of native lignin structure, which can then be used for fundamental studies or to understand lignin depolymerization methods like reductive catalytic fractionation or aldehyde-assisted fractionation., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Concerns over the sustainability and end-of-life properties of fossil-derived surfactants have driven interest in bio-based alternatives. Lignocellulosic biomass with its polar functional groups is an obvious feedstock for surfactant production but its use is limited by process complexity and low yield. Here, we present a simple two-step approach to prepare bio-based amphiphiles directly from hemicellulose and lignin at high yields (29 % w/w based on the total raw biomass and >80 % w/w of these two fractions). Acetal functionalization of xylan and lignin with fatty aldehydes during fractionation introduced hydrophobic segments and subsequent defunctionalization by hydrogenolysis of the xylose derivatives or acidic hydrolysis of the lignin derivatives produced amphiphiles. The resulting biodegradable xylose acetals and/or ethers, and lignin-based amphiphilic polymers both largely retained their original natural structures, but exhibited competitive or superior surface activity in water/oil systems compared to common bio-based surfactants., (© 2023 Wiley-VCH GmbH.)

Transmission of viruses through contact with contaminated surfaces is an important pathway for the spread of infections. Antiviral surface coatings are useful to minimize such risks. Current state-of-the-art approaches toward antiviral surface coatings either involve metal-based materials or complex synthetic polymers. These approaches, however, even if successful, will have to face great challenges when it comes to large-scale applications and their environmental sustainability. Here, an antiviral surface coating was prepared by spin-coating lignin, a natural biomass residue of the paper production industry. We show effective inactivation of herpes simplex virus type 2 (>99% after 30 min) on a surface coating that is low-cost and environmentally sustainable. The antiviral mechanism of the lignin surface was investigated and is attributed to reactive oxygen species generated upon oxidation of lignin phenols. This mechanism does not consume the surface coating (as opposed to the release of a specific antiviral agent) and does not require regeneration. The coating is stable in ambient conditions, as demonstrated in a 6 month aging study that did not reveal any decrease in antiviral activity. This research suggests that natural compounds may be used for the development of affordable and sustainable antiviral coatings., Competing Interests: The authors declare the following competing financial interest(s): S.B. and J.S.L. are inventors on a European patent application (EP19202957) that was submitted by EPFL and covers the isolation of different functionalized lignins via the aldehyde assisted fractionation process. J.S.L. is co-founder and part owner of Bloom Biorenewables Ltd that aims at commercializing the aldehyde assisted fractionation process., (© 2022 The Authors. Published by American Chemical Society.)

The amphiphilic chemical structure of native lignin, composed by a hydrophobic aromatic core and hydrophilic hydroxy groups, makes it a promising alternative for the development of bio-based surface-active compounds. However, the severe conditions traditionally needed during biomass fractionation make lignin prone to condensation and cause it to lose hydrophilic hydroxy groups in favour of the formation of C-C bonds, ultimately decreasing lignin's abilities to lower surface tension of water/oil mixtures. Therefore, it is often necessary to further functionalize lignin in additional synthetic steps in order to obtain a surfactant with suitable properties. In this work, multifunctional aldehyde-assisted fractionation with glyoxylic acid (GA) was used to prevent lignin condensation and simultaneously introduce a controlled amount of carboxylic acid on the lignin backbone for its further use as surfactant. After fully characterizing the extracted GA-lignin, its surface activity was measured in several water/oil systems at different pH values. Then, the stability of water/mineral oil emulsions was evaluated at different pH and over a course of 30 days by traditional photography and microscopy imaging. Further, the use of GA-lignin as a surfactant was investigated in the formulation of a cosmetic hand cream composed of industrially relevant ingredients. Contrary to industrial lignins such as Kraft lignin, GA-lignin did not alter the color or smell of the formulation. Finally, the surface activity of GA-lignin was compared with other lignin-based and fossil-based surfactants, showing that GA-lignin presented similar or better surface-active properties compared to some of the most commonly used surfactants. The overall results showed that GA-lignin, a biopolymer that can be made exclusively from renewable carbon, can successfully be extracted in one step from lignocellulosic biomass. This lignin can be used as an effective surfactant without further modification, and as such is a promising candidate for the development of new bio-based surface-active products., (© 2022 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Individual responses to methylphenidate (MPH) can significantly differ in children with attention-deficit/hyperactivity disorder (ADHD) in terms of the extent of clinical amelioration, optimal dosage needed, possible side effects, and short- and long-term duration of the benefits. In the present repeated-measures observational study, we undertook a proof-of-concept study to determine whether clustering analysis could be useful to characterize different clusters of responses to MPH in children with ADHD. We recruited 33 children with ADHD who underwent a comprehensive clinical, cognitive, and neurophysiological assessment before and after one month of MPH treatment. Symptomatology changes were assessed by parents and clinicians. The neuropsychological measures used comprised pen-and-paper and computerized tasks. Functional near-infrared spectroscopy was used to measure cortical hemodynamic activation during an attentional task. We developed an unsupervised machine learning algorithm to characterize the possible clusters of responses to MPH in our multimodal data. A symptomatology improvement was observed for both clinical and neuropsychological measures. Our model identified distinct clusters of amelioration that were related to symptom severity and visual-attentional performances. The present findings provide preliminary evidence that clustering analysis can potentially be useful in identifying different responses to MPH in children with ADHD, highlighting the importance of a personalized medicine approach within the clinical framework.

Lignin has emerged as an attractive alternative in the search for more eco-friendly and less costly materials for enzyme immobilization. In this work, the terephthalic aldehyde-stabilization of lignin is carried out during its extraction to develop a series of functionalized lignins with a range of reactive groups (epoxy, amine, aldehyde, metal chelates). This expands the immobilization to a pool of enzymes (carboxylase, dehydrogenase, transaminase) by different binding chemistries, affording immobilization yields of 64-100 %. As a proof of concept, a ω-transaminase reversibly immobilized on polyethyleneimine-lignin is integrated in a packed-bed reactor. The stability of the immobilized biocatalyst is tested in continuous-flow deamination reactions and maintains the same conversion for 100 cycles. These results outperform previous stability tests carried out with the enzyme covalently immobilized on methacrylic resins, with the advantage that the reversibility of the immobilized enzyme allows recycling and reuse of lignin beyond the enzyme inactivation. Additionally, an in-line system also based on lignin is added into the downstream process to separate the reaction products by catch-and-release. These results demonstrate a fully closed-loop sustainable flow-biocatalytic system based exclusively on lignin., (© 2021 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Background: PTSD in youth is more common and debilitating than it was previously thought. This untreated condition is highly correlated to critical mental health condition, such as depression, anxiety disruptive-behaviours, and substance use disorders. Despite the growing number of studies investigating Eye Movement Desensitization and Reprocessing (EMDR) treatment for posttraumatic stress disorder (PTSD) in childhood and adolescent, results have not been systematically revised since 2017. The aim of this work is to systematically reviewed all randomized controlled trials (RCTs) evaluating the effect of EMDR on PTSD symptoms in children and adolescent and asses whether EMDR therapy was effective to improve anxious and/or depressive symptoms., Methods: In a short series of articles, we will review the efficacy of EMDR on children and adolescent with PTSD and comorbid symptoms. The present brief review will focus on randomized controlled trials with an EMDR group condition compared to a control group published until January 2020., Results: eight studies (n = 150) met our inclusion criteria. Preliminary analyses showed that EMDR has a comparable efficacy to cognitive behavior therapy (CBT) in reducing PTSD, anxiety symptoms, depressive symptoms and was superior to waitlist/placebo condition. Moreover EMDR seems to be more effective in a shorter period of time., Conclusion: despite the small number of studies, the preliminary results suggest that EMDR therapy could be an effective treatment for children and adolescent with PTSD and anxious and/or depressive symptoms. Further research is needed to support these results., (Copyright © 2021. Published by Elsevier B.V.)

Background: Children with attention deficit hyperactivity disorder (ADHD) exhibit behavioral inhibition deficits, which often lead to emotional dysregulation (ED) affecting individual ability to control emotions and behavioral responses. In ADHD, ED is associated with poor outcomes and comorbidities, with both externalizing and internalizing disorders. This work aims to evaluate sensitivity to emotional stimuli in children with ADHD using functional Near Infrared Spectroscopy (fNIRS)., Methods: During frontal fNIRS recording, 20 children with ADHD and 25 typically developing (TD) peers performed a visual continuous performance task with stimuli of different emotional content (i.e., positive, negative, neutral, and control stimuli without emotional content). This is a cognitive task designed to evaluate the ability to recognize emotional stimuli and to deal with emotional interference., Results: The ADHD sample showed more variability in response time to stimuli and more false alarms compared to TD group. fNIRS data showed between-group differences in right prefrontal and frontal cortices, with wider hemoglobin concentration changes in the TD group, during positive, negative, and neutral conditions., Limitations: Owing to the limited possibility of near infrared light to penetrate tissue, fNIRS can only measure cortical activations, while it would be of interest to identify the subcortical areas linked to emotional processing, too., Conclusions: Findings suggest the presence of emotional processing deficits in children with ADHD, as suggested by poor performances on the e-CPT task, and of peculiar sensitivity to emotional stimuli, linked to atypical hemodynamics of right prefrontal and frontal areas., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting up to 5.3% of children and 2.5% of adults depending on the country considered. Current pharmacological treatments for ADHD are based on stimulant or non-stimulant medications, targeting dopaminergic and noradrenergic systems in the frontal cortex and dopaminergic system in the basal ganglia. These drugs are effective and safe for the majority of patients, whereas about 20% of treated patients do not tolerate current therapies or experience insufficient efficacy. The adequate treatment of ADHD is necessary to allow a proper social placement and prevent the acquisition of additional, more severe, comorbidities., Areas Covered: We conducted a review of the scientific literature and of unpublished/ongoing clinical trials to summarize the advances made in the last 10 years (2010-2020) for the pharmacological treatment of ADHD. We found many pharmacological mechanisms beyond dopaminergic and noradrenergic ones have been investigated in patients., Expert Opinion: Some emerging drugs for ADHD may be promising as add-on treatment especially in children, amantadine to enhance cognitive functions and tipepidine for hyperactivity/impulsivity. Stand-alone emerging treatments for ADHD include viloxazine and dasotraline, which will soon have more clinical data available to support market access requests.

Lignin depolymerization could provide an attractive renewable aromatic feedstock for the chemical industry. Past studies have suggested that lignin structural features such as ether content are correlated to lignin's upgradeability. An obstacle to the development of a conclusive causal relationship between lignin structure and upgradeability has been the difficulty to quantitatively measure lignin structural features. Here, we demonstrated that a modified HSQC-NMR method known as HSQC 0 can accurately quantify lignin functionalities in extracted lignin using several synthetic polymer models. We then prepared a range of isolated lignin samples with a wide range of ether contents (6-46%). By using a simple ether cleavage model, we were able to predict final depolymerization yields very accurately (<4% error), conclusively demonstrating the direct causal relationship between ether content and lignin activity. The accuracy of this model suggests that, unlike in native lignin, ether linkages no longer appear to be randomly distributed in isolated lignin., (This journal is © The Royal Society of Chemistry 2019.)

Objective: The practical effectiveness of second-generation antipsychotics in children and adolescents is an understudied issue. It is a crucial area of study, though, because such patients are often treated for long-lasting disorders., Methods: We carried out a 24-month (March 2012-March 2014) observational study on an unselected population of pediatric outpatients treated with risperidone, aripiprazole, olanzapine, or quetiapine aiming to (1) describe drug use, (2) compare post hoc the discontinuation rates due to specific causes and dose adjustments by Kaplan-Meier analyses between drugs, and (3) analyze predictors influencing these outcomes by Cox multivariate models., Results: Among 184 pediatric patients, 77% patients were prescribed risperidone, and 18% were prescribed aripiprazole. Olanzapine or quetiapine were scantly used; therefore, they were excluded from analyses. Risperidone was prevalent in younger, male patients with disruptive behavioral disorders; aripiprazole, in patients with tic disorders. Overall, discontinuations occurred mostly in the first 6 months, and, at 24 months, the discontinuation numbers were similar between users of risperidone and aripiprazole (41.5% vs 39.4%). In univariate analyses, dose reduction was higher for aripiprazole (P = .033). Multivariate analyses yielded the following predictors: for all-cause discontinuation, baseline severity (hazard ratio [HR] = 1.48, P = .001) and dose increase (HR = 3.55, P = .001); for patient-decided discontinuation, dose change (increase: HR = 6.43, P = .004; reduction: HR = 7.89, P = .049) and the presence of concomitant drugs (HR = 4.03, P = .034), while autistic patients discontinued less (HR = 0.23, P = .050); for clinician-decided discontinuation due to adverse drug reactions, baseline severity (HR = 1.96, P = .005) and dose increase (HR = 5.09, P = .016); for clinician-decided discontinuation due to inefficacy, baseline severity (HR = 2.88, P = .014) and the use of aripiprazole (HR = 5.55, P = .013); for dose increase, none; for dose reduction, the occurrence of adverse drug reactions (HR = 4.74, P = .046), while dose reduction was less probable in autistic patients (HR = 0.22, P = .042)., Conclusions: The findings of this study show a similarity between the overall effectiveness of risperidone and aripiprazole in a real-life pediatric outpatient setting., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Objective: Gap in knowledge on benefit/risk ratio of second generation antipsychotics (SGA) in the paediatric population represents a challenge for the scientific community. This study aims to analyse all suspected adverse drug reactions (ADRs) to SGA observed during the study period; compare the safety profiles of risperidone and aripiprazole; evaluate the effect of switching from risperidone to aripiprazole or to a first generation antipsychotic (FGA)., Methods: Prospective analysis of spontaneously reported ADRs concerning 184 paediatric outpatients between 2012 and 2014.; clinical outcomes of drug switch were evaluated., Results: Out of the 184 patients, 130 experienced at least one ADR; ADRs were usually not serious and more frequently associated with aripiprazole. Switching to aripiprazole was associated with better results than switching to FGAs in the Clinical Global Impression scale- Efficacy (CGI-E) scores (p = 0.018), Disturbed behaviour checklist-parents (DBC-P) self-absorption subscale (p = 0.010); only a trend for difference between changing to aripiprazole vs FGAs in the DBC-P total score (p = 0.054) and social relating subscale (p = 0.053) was observed., Conclusions: SGAs safety data were consistent with the ones already known; however, there is still a need to improve the knowledge in pharmacovigilance field among clinicians. Switching to aripiprazole may be a valid alternative to risperidone.

The synthesis of N-benzyl- and N-cyclohexylammonium resorcinarene trifluoroacetate (TFA) and triflate (OTf) salt receptors was investigated. Solid-state analysis by single-crystal X-ray diffraction revealed that the N-alkylammonium resorcinarene salts (NARSs) with different upper substituents had different cavity sizes and different affinities for anions. Anion-exchange experiments by mixing equimolar amounts of N-benzylammonium resorcinarene trifluoroacetate and N-cyclohexylammonium resorcinarene triflate, as well as N-benzylammonium resorcinarene triflate and N-cyclohexylammonium resorcinarene trifluoroacetate showed that the NARS with flexible benzyl groups preferred the larger OTf anion, whereas the rigid cyclohexyl groups preferred the smaller TFA anions. The anion-exchange processes were confirmed in the solid state by single-crystal and powder X-ray diffraction experiments and in the gas phase by electrospray ionization mass spectrometry., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: Available guidelines on therapeutic drug monitoring of second-generation antipsychotics were designed for adults; therefore, they cannot be transferred as such in pediatric patients, who may have different drug absorption, distribution, metabolism, and elimination. Moreover, available tools that guide dosing in neuropsychiatric pediatric patients are scant, leading to the possibility of reduced efficacy and/or increased risks of toxicity. Here we describe the results of observational therapeutic drug monitoring conducted in three pediatric neuropsychiatry units across Italy in 2012-2014, with the following aims: (1) to describe the distribution of plasma concentrations of second-generation antipsychotics in our pediatric patients and (2) to identify clinical covariates associated with plasma drug levels., Methods: Five hundred fifty-six plasma trough concentrations of the second-generation antipsychotics risperidone (plus 9-hydroxy-risperidone), aripiprazole, olanzapine, and quetiapine were measured from 172 pediatric outpatients overall. The distribution of drug concentrations was described and correlated with drug doses and clinical variables., Results: Risperidone plasma levels were lower than in adults (median 13.6 ng/ml), with a high inter-patient (78.9%) but lower intra-patient (34.2%) variability. In multiple regression analyses, risperidone plasma levels depended only on drug dose (p < 0.001). Aripiprazole plasma levels were similar to those described in adults (median 165.8 ng/ml) and were widely distributed, with an inter-patient variability of 81.1%, while the intra-patient variability was much lower (29.3%). Multiple regression analyses indicated that aripiprazole plasma levels were influenced by the daily doses (p < 0.001) and by the number of concomitant drugs (p < 0.01)., Conclusion: Our study described the distribution of plasma levels of SGAs in a real-life setting involving pediatric patients, significantly increasing the amount of available data for this fragile population. If confirmed in larger dataset, these data may contribute to the definition of optimal therapeutic window for risperidone and aripiprazole plasma levels in pediatric patients.

Objective: The EudraVigilance Pharmacovigilance system classifies the seriousness of adverse drug reactions (ADRs) based on the requirement of hospital care. To date, no systematic study has been conducted on the impact of non-serious ADRs, in terms of therapy continuation and course of the underlying disease. We analyzed a pediatric population receiving psychiatric care and subjected to drug treatment, to assess whether non-serious ADRs do or do not have a relevant clinical impact., Methods: Data from a 1 year period were collected, which included: Administered drugs, choices made to manage the ADRs, the long-term (6 month) effect of these interventions on the course of the reaction, and their impact on the drug treatment for the underlying pathology., Results: Observed ADRs were concordant with those previously described for the same drug classes, and mainly comprised alterations of behavior, mood, and sleep (53%) and excessive variations of appetite and body weight (39%). The type of drug influenced the management decision, as we found that drug discontinuation was the most frequent strategy employed to resolve ADRs, especially with drugs employed in the treatment of attention-deficit/hyperactivity disorders (63%, p<0.05), whereas management of antipsychotics mainly relied upon drug substitution (21%, p<0.01). Also, the type of ADR influenced the management decision, as alterations of behavior, mood, and sleep were seldom managed by maintaining the drug unchanged (10%, p<0.05), at variance with appetite/weight alteration ADRs (unchanged in 41%, p<0.01). Follow-up information revealed that drug discontinuation was most efficient at treating ADRs (no persistent ADRs, p<0.01), but had a severe impact on the course of the underlying psychiatric disease. Conversely, management of ADRs by maintaining the original drug even if at different dosage did not lead to an amelioration of the reactions; however, as it caused a significant clinical improvement (83%, p<0.04) that superseded the ADR in terms of clinical benefit., Conclusions: These data suggest that the best strategy to improve both ADR management and the clinical course of patients is to limit, whenever possible, changes to the original therapy. Optimization of the actual therapeutic regimes also might benefit from development of specific pharmacokinetic and pharmacodynamic monitoring programs.

Background: Panic attacks can be induced in persons with panic disorder by inhalation of carbon dioxide. Hypercapnia also elicits a reflex hyperventilation, which is controlled in part by cholinergic mechanisms. This study investigated whether the exaggerated response to carbon dioxide in panic disorder (PD) can be modulated by antagonists of muscarinic cholinergic receptors., Methods: Twelve patients with PD received biperiden hydrochloride (a muscarinic antagonist that crosses the blood-brain barrier), pirenzepine hydrochloride (a muscarinic antagonist that does not cross the blood-brain barrier), or placebo 2 hours before a 35% carbon dioxide-65% oxygen respiratory challenge (vs air as a placebo) on 3 separate days, in a double-blind, random crossover design., Results: According to patients' self-ratings of subjective anxiety, inhalation of the carbon dioxide/oxygen mixture provoked a significant and intense response after treatment with pirenzepine and placebo. After biperiden treatment, however, hypercapnia elicited a response profile similar to that elicited by air, whereby subjective anxiety remained similar to preinhalation levels., Conclusions: Consistent with the hypothesis of the study, a centrally active muscarinic antagonist can block the response to carbon dioxide commonly observed in subjects with PD.

Objective: Anticipation (i.e., the decrease in age at onset or the increase in severity of a disorder in successive generations) has recently been reappraised as a key to understanding the genetics of some familial illnesses. The purpose of this study was to search for possible anticipation in panic disorder., Method: Thirty-eight unilineal, multigenerational families with multiple directly interviewed members who had panic disorder were compared across two successive generations for 1) age at the first panic attack, 2) age at the onset of panic disorder, and 3) the highest degree of agoraphobia ever experienced, as a tentative index of severity of illness. Intergenerational pairwise comparisons were implemented according to four different sampling schemes: random pairs, random transmitting pairs, all possible pairs, and all possible transmitting pairs., Results: Life table analyses showed a significant decrease in the time before the first episode of panic and onset of panic disorder from the older to the younger generation. Evidence for anticipation was found for both indexes of onset in all four sampling schemes. No evidence of a generational effect on the index of severity of agoraphobia was found. Corrections for possible biases suggested that these results are not likely to be simple artifacts., Conclusions: Anticipation is supported in this specific set of families and, if it is confirmed by other studies, a role for trinucleotide repeat sequences may be considered to account for the familial aggregation of panic disorder.

Although recent diagnostic systems support the distinctiveness of panic disorder (PD) and somatization disorder, a high level of comorbidity of these two diagnoses has been reported, indicating a need for investigations with external validators. One hundred fifty-nine outpatients with DSM-III-R PD and 76 surgical controls were screened for lifetime presence of DSM-III-R somatization disorder, and the risks for some types of psychiatric disorders in their families were computed. In our sample, 23% of women and 5% of men with PD also had DSM-III-R somatization disorder did not differ from women with PD only in age at onset of panic, agoraphobia, childhood history of separation anxiety, or lifetime diagnoses of other disorders. Familial risks for PD, PD-agoraphobia, and alcohol dependence were significantly higher for families of women with PD and women with PD plus somatization disorder than for controls. The familial risks for antisocial personality (ASP) disorder (a familial indicator for the somatization disorder spectrum of liability, phenomenologically independent from both PD and somatization disorder) were significantly higher for families of women with PD plus somatization disorder than for families of women with PD only or for controls. Application of DSM-IV criteria for somatization disorder substantially decreased the comorbidity with PD. Our data suggest that somatization disorder is not simply a form of PD, and that the two disorders may coexist in the same subject without sharing a common genetic diathesis. Compared with DSM-III-R, DSM-IV criteria for somatization disorder appear to be simpler in structure and of less complicated application.

Objective: The authors investigated the relation of age at onset of panic disorder to liability to panic disorder and agoraphobia., Method: Two hundred thirty-one outpatients with panic disorder were compared with 131 surgical outpatients on demographic variables and familial risk of psychiatric disorders. The distribution of patients' ages at onset of panic disorder and several covariates were entered in a stepwise survival analysis., Results: The patients with panic disorder had a significantly higher rate of childhood separation anxiety disorder and higher familial risks of panic disorder/panic disorder with agoraphobia and alcoholism. A family history of panic disorder with agoraphobia and the presence of childhood separation anxiety disorder influenced age at onset of panic disorder., Conclusions: Age at onset of panic disorder may reflect genetic penetrance, and separation anxiety disorder may be an individual predictor of earlier onset of panic disorder.