Gabriele Masi

Symptomatology and comorbidity of generalized anxiety disorder in children and adolescents

This study investigated the symptomatology and comorbidity of generalized anxiety disorder (GAD) in a clinically referred sample of Italian children and adolescents as a function of age and gender. The sample consisted of 58 subjects (19 children and 39 adolescents), 23 males and 35 females screened from consecutively referred children and adolescents. This sample was divided into two groups of younger children (19 subjects, eight males and 11 females aged 7 to 12 years; mean age, 9.6) and adolescents (39 subjects, 15 males and 24 females aged 12 to 18 years; mean age, 14.9). Feelings of tension, apprehension, the need for reassurance, irritability, negative self-image, and physical complaints were reported in more than 70% of the subjects. Differences in the symptomatic profile between males and females were not significant. Children and adolescents did not show significant differences in the number of symptoms. The need for reassurance was significantly more frequent in children, and brooding was more frequent in adolescents. Other anxiety disorders were commonly comorbid with GAD. More than half of the patients with GAD showed a concurrent depressive disorder; no differences were found for comorbidity between children and adolescents, except for higher rates of separation anxiety disorder in children.

Open trial of risperidone in 24 young children with pervasive developmental disorders

OBJECTIVEnTo describe tolerability and efficacy of risperidone in very young children with pervasive developmental disorders.nnnMETHODnTwenty-four children aged 3.6 to 6.6 years (mean 4.6 years +/- 8 months) enrolled during 1999 and 2000 participated in a 16-week open-label trial with risperidone monotherapy. Outcome measures included the Childrens Psychiatric Rating Scale (CPRS), Childhood Autism Rating Scale (CARS), Clinical Global Impression-Improvement (CGI-I), and Childrens Global Assessment Scale (C-GAS).nnnRESULTSnTwo subjects did not complete the trial because of side effects. The optimal dose was 0.5 mg/day. After the treatment a 21% improvement in CPRS and a 14% improvement in CARS total scores was found. Items related to behavioral control (hyperactivity, fidgetiness, rhythmic motions) and affect regulation (lability of affect, angry affect) improved more than 25%. Based on improvement of at least 25% on the CPRS and a score of 1 or 2 on the CGI-I, eight subjects were considered responders. Functional impairment (C-GAS) improved more than 25%. Thirteen subjects (54%) were free of any side effects; in the other participants risperidone was well tolerated. Only three subjects had a weight gain greater than 10%.nnnCONCLUSIONSnLow-dose risperidone may positively affect symptoms in young autistic children, improving disruptive/hyperactive behavior and affective dysregulation. Further controlled studies in this age group are warranted.

Autism with seizures and intellectual disability: possible causative role of gain-of-function of the inwardly-rectifying K+ channel Kir4.1.

The inwardly-rectifying potassium channel Kir4.1 is a major player in the astrocyte-mediated regulation of [K(+)](o) in the brain, which is essential for normal neuronal activity and synaptic functioning. KCNJ10, encoding Kir4.1, has been recently linked to seizure susceptibility in humans and mice, and is a possible candidate gene for Autism Spectrum Disorders (ASD). In this study, we performed a mutational screening of KCNJ10 in 52 patients with epilepsy of unknown cause associated with impairment of either cognitive or communicative abilities, or both. Among them, 14 patients fitted the diagnostic criteria for ASD. We identified two heterozygous KCNJ10 mutations (p.R18Q and p.V84M) in three children (two unrelated families) with seizures, ASD, and intellectual disability. The mutations replaced amino acid residues that are highly conserved throughout evolution and were undetected in about 500 healthy chromosomes. The effects of mutations on channel activity were functionally assayed using a heterologous expression system. These studies indicated that the molecular mechanism contributing to the disorder relates to an increase in either surface-expression or conductance of the Kir4.1 channel. Unlike previous syndromic associations of genetic variants in KCNJ10, the pure neuropsychiatric phenotype in our patients suggests that the new mutations affect K(+) homeostasis mainly in the brain, by acting through gain-of-function defects. Dysfunction in astrocytic-dependent K(+) buffering may contribute to autism/epilepsy phenotype, by altering neuronal excitability and synaptic function, and may represent a new target for novel therapeutic approaches.

Separation anxiety disorder in children and adolescents: Epidemiology, diagnosis and management

This paper provides an overview of the phenomenology, longitudinal outcome data, assessment and management of separation anxiety disorder (SAD) in children and adolescents.SAD is qualitatively different from early worries, and is characterised by an abnormal reactivity to real or imagined separation from attachment figures, which significantly interferes with daily activities and developmental tasks. Different epidemiological studies indicate a prevalence of 4 to 5% in children and adolescents. In contrast to other anxiety disorders, 50 to 75% of children with SAD come from homes of low socioeconomic status. The severity of symptomatology ranges from anticipatory uneasiness to full-blown anxiety about separation, but children are usually brought to the clinician when SAD results in school refusal or somatic symptoms. School refusal is reported in about 75% of children with SAD, and SAD is reported to occur in up to 80% of children with school refusal. Longitudinal studies have suggested that childhood SAD may be a risk factor for other anxiety disorders, but whether this link is specific to, for example, panic disorder and agoraphobia, or whether SAD represents a general factor of vulnerability for a broad range of anxiety disorders is still debated.Most relevant data are reported on nonpharmacological treatments (psychoeducational, behavioural, cognitive-behavioural, family and psychodynamic), and these are the first choice approach in SAD. Controlled studies show efficacy of cognitive-behavioural therapy in children with anxiety disorders and specifically in SAD-school phobia, supporting this approach as the best proven treatment. Pharmacotherapy should be used in addition to behavioural or psychotherapeutic intervention when the child’s symptoms have failed to respond to those treatments, and he/she is significantly impaired by the symptoms. Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRI) have a good adverse effect profile and may be considered as first choice drugs in SAD. When different SSRIs fail to improve symptomatology, a trial with a tricyclic antidepressant (TCA) is indicated, with careful monitoring of cardiac functioning. Because of the adverse effect profile and the potential for abuse and dependence, benzodiazepines should be used only when a rapid reduction of symptomatology is needed, until the SSRI or the TCA have begun to be effective (few weeks). Buspirone should be considered in children who have not responded to other treatments. Further research is needed to confirm efficacy of newer antidepressants (venlafaxine, mirtazapine, nefazodone) in childhood anxiety disorders.

Panic disorder in clinically referred children and adolescents.

Prevalence, phenomenology, comorbidity, functional impairment and familial correlates of juvenile panic disorder (PD) are described in this study. A clinical interview (Diagnostic Interview for Children and Adolescents-Revised) was administered to 220 children and adolescents consecutively referred to a Division of Child Neurology and Psychiatry. 23 subjects (10.4%), aged 7 to 18 years, fulfilled DSM-IV criteria for PD. Reported panic symptoms are described, according to gender and chronological age. High comorbidity with generalized anxiety disorder (74%) and depression (52%) was noted. Agoraphobia (56%) and other phobias (56%) were significantly more frequent than in two control groups of subjects with generalized anxiety disorder and with depression. Antecedent and/or associated separation anxiety disorder was reported in 73% of the patients. Functional impairment, assessed with a specific diagnostic instrument (Childrens Global Assessment Scale) was significantly greater in PD patients than in depressed or anxious patients. 90% of patients had at least one parent with an anxiety disorder, 52% had one parent with depressive disorder, 33% had one parent with drug treated PD.

Assessment of Anxiety and Depression in Adolescents with Mental Retardation

This report examines the concurrent validity of different informant and self-report assessment instruments of psychopathology, both general and specific for anxiety and/or depression, in referred mentally retarded adolescents with a depressive and anxiety disorders, according to DSM IV criteria. A consecutive, unselected sample of 50 mildly and moderate mentally retarded adolescents (29 males and 21 females, aged 11.8 to 18 years, mean age 15.1) were assessed using standardized assessment techniques: Psychopathology Instrument for Mentally Retarded Adults (PIMRA) (informant version) (total score, affective and anxiety subscales), Child Behavior Checklist (CBCL) (informant version) (total score, internalizing and externalizing scores, anxiety-depression scale), Zung Self-Rating Depression Scale and Zung Self-Rating Anxiety Scale. Patterns of correlation among measures were calculated. PIMRA and CBCL total scores were closely intercorrelated. Internalizing and externalizing scores of CBCL were not intercorrelated, but they both correlated with CBCL and PIMRA total scores. Anxiety measures were positively correlated; they correlated with PIMRA and CBCL total scores, as well as with the internalizing score of CBCL. Depression measures were not correlated; their correlation with more general measures of psychopathology was weak. Clinical implications of these findings are discussed.

Risperidone Monotherapy in Preschool Children With Pervasive Developmental Disorders

The aim of this preliminary study was to examine the short-term efficacy and safety of the atypical antipsychotic risperidone in preschool autistic children. The sample consisted of 10 subjects (7 males and 3 females) aged 39/12 to 66/12 years (mean age 4.7 years). A 16-week open-label trial with risperidone monotherapy was initiated at a starting dose of 0.25 mg daily and was increased to a maximum dose of 0.50 mg (0.027 mg/kg daily). Outcome measures were the Childhood Autism Rating Scale, the Childrens Psychiatric Rating Scale, Clinical Global Impression (improvement score), and the Childrens Global Assessment of Functioning. Two subjects did not complete the trial because of side effects (tachycardia and flushes, fever and hyporexia). After the 16-week treatment, data from the eight children who completed the trial indicated a modest improvement in the Childhood Autism Rating Scale total score, Childrens Psychiatric Rating Scale total score, and Childrens Global Assessment of Functioning. According to the Clinical Global Impression, the global improvement score for four subjects was much improved or very much improved; the score for the other four children was minimally improved. None of the children exhibited behavioral deterioration. The side effects in the eight children were not severe. (J Child Neurol 2001;16:395-400).

A comparison of North American versus non-North American ADHD study populations.

Few large, prospective clinical studies in Europe have assessed the validity and applicability of research methods used to study ADHD in North America. To assess comparability of study populations, we examined baseline patient characteristics from a group of North American studies against those of a large European/African/Australian study. All studies used identical diagnostic assessments and inclusion criteria, with ADHD diagnosis and the presence of comorbid psychiatric conditions confirmed using the KSADS-PL. Raters were trained and assessed to ensure uniform diagnostic and symptom severity rating standards. Six hundred and four patients (mean age=10.2xa0years) enrolled in the non-North American study, and 665 patients (mean age=10.4xa0years) enrolled in the North American study. The proportion of girls was higher in the North American studies (29.2% vs. 10.4%, pxa0<xa00.001). In both groups, most patients had a positive family history of ADHD and previous stimulant treatment. Fewer had the inattentive subtype of ADHD, and mean severity was slightly higher in the non-North American study. Results demonstrate that, when a uniform set of rigorous, standardized diagnostic criteria are used by skilled clinicians, the patient populations identified are generally similar. This supports the practice of generalizing results from treatment studies across geographies.

Depressive Comorbidity in Children and Adolescents with Generalized Anxiety Disorder

Aim of this study is to examine the effect of depressive comorbidity in 108 children and adolescents with Generalized Anxiety Disorder (GAD). Fifty-five patients with GAD and depression were compared with 53 patients with GAD without depression. Age, gender and socioeconomic status did not differentiate the groups. Patients with comorbid depression had significantly more anxiety symptoms than patients without depression. Clinical presentation of GAD and pattern of comorbidity was similar in the two groups. Subjects with comorbid depression showed a more severe functional impairment, assessed with C-GAS. Data are discussed in the light of conceptualizations about the relationship between anxiety and depression.

Depression and School Functioning in Non-Referred Adolescents: A Pilot Study

Self-image and self-perceived competencies have been considered to be related to depression in childhood and adolescence. Data from literature points to school functioning as one of the most important factors in self-esteem and self-worth during adolescence. Academic self image, defined as the way adolescents represent themselves as students, directly affects the global self-image; for this reason it has important psychopathological implications. The major aim of this preliminary report is to specifically analyze the relationship between academic self-image (assessed with a specific questionnaire), and self-reported depressive symptoms (assessed with the Childrens Depression Inventory) in a school sample 150 adolescents. Our data indicate that the emotional beliefs about schooling and learning were significantly related to depressive symptomatology. Females scored higher in CDI and school anxiety. A real school failure did not affect the academic self image. These data seem to suggest that different components of the academic self-image can be differently associated with depressive feelings.