HP1BP3 expression determines maternal behavior and offspring survival.

Maternal care is an indispensable behavioral component necessary for survival and reproductive success in mammals, and postpartum maternal behavior is mediated by an incompletely understood complex interplay of signals including effects of epigenetic regulation. We approached this issue using our recently established mice with targeted deletion of heterochromatin protein 1 binding protein 3 (HP1BP3), which we found to be a novel epigenetic repressor with critical roles in postnatal growth. Here, we report a dramatic reduction in the survival of pups born to Hp1bp3(-/-) deficient mouse dams, which could be rescued by co-fostering with wild-type dams. Hp1bp3(-/-) females failed to retrieve both their own pups and foster pups in a pup retrieval test, and showed reduced anxiety-like behavior in the open-field and elevated-plus-maze tests. In contrast, Hp1bp3(-/-) females showed no deficits in behaviors often associated with impaired maternal care, including social behavior, depression, motor coordination and olfactory capability; and maintained unchanged anxiety-associated hallmarks such as cholinergic status and brain miRNA profiles. Collectively, our results suggest a novel role for HP1BP3 in regulating maternal and anxiety-related behavior in mice and call for exploring ways to manipulate this epigenetic process.

Validity of the age-of-onset criterion for ADHD: a report from the DSM-IV field trials.

OBJECTIVE: To examine the validity of the DSM-IV requirement of an age of onset of impairment due to symptoms before 7 years of age for the diagnosis of attention-deficit/hyperactivity disorder (ADHD). METHOD: The validity of this criterion was examined in a clinic sample of 380 youths aged 4 through 17 years by comparing youths who met symptom criteria for ADHD and either did or did not display impairment before age 7 years. RESULTS: Nearly all youths who met symptom criteria for the predominantly hyperactive-impulsive subtype also met the age of onset of impairment criterion, but 18% of youths who met symptom criteria for the combined type, and 43% of youths who met symptom criteria for the predominantly inattentive type, did not manifest impairment before 7 years. For the latter two subtypes, requiring impairment before age 7 years reduced the accuracy of identification of currently impaired cases of ADHD and reduced agreement with clinicians' judgments. CONCLUSIONS: These findings raise questions about the validity of the DSM-IV definition of age of onset of ADHD. Marked differences in the ages of onset of both symptoms and impairment for the three subtypes of ADHD support the validity of distinguishing among these subtypes in DSM-IV.

DSM-IV field trials for oppositional defiant disorder and conduct disorder in children and adolescents.

OBJECTIVE: The purpose of the field trials for oppositional defiant disorder and conduct disorder was to select valid diagnostic thresholds for these disorders and to compare the psychometric properties of DSM-IV criteria for oppositional defiant disorder and conduct disorder with previous DSM diagnostic formulations. METHOD: Structured diagnostic interviews, standardized clinician's validation diagnoses, and multiple measures of impairment were obtained for 440 clinic-referred children and adolescents aged 4-17 years. RESULTS: A diagnostic threshold of four symptoms of oppositional defiant disorder optimized identification of impaired children, improved agreement somewhat with the clinician's validation diagnosis, and had somewhat better test-retest agreement than DSM-III-R. In the case of conduct disorder, the optimal time window for ascertainment of symptoms was clarified. A diagnostic threshold of three symptoms of conduct disorder maximized accurate identification of impaired children and agreement with the clinician's validation diagnosis and resulted in slightly better test-retest agreement than DSM-III-R. Compared with the DSM-III-R definition, the DSM-IV definition of oppositional defiant disorder was somewhat more prevalent, but the prevalence of conduct disorder was essentially unchanged. CONCLUSIONS: DSM-IV definitions of oppositional defiant disorder and conduct disorder are somewhat better than DSM-III-R definitions in terms of internal consistency and test-retest agreement, and the validity of the DSM-IV definition of oppositional defiant disorder is slightly better than that of DSM-III-R.

DSM-IV field trials for the disruptive behavior disorders: symptom utility estimates.

OBJECTIVE: We tested the predictive utility of symptoms for proposed DSM-IV definitions of the disruptive behavior disorders using indices corrected for symptom and diagnosis base rates. METHOD: The field trials sample consisted of 440 clinic-referred youths who were consecutive referrals to a heterogeneous group of mental health clinics. Multiple informants were interviewed to determine the presence of symptoms and diagnoses. RESULTS: Some symptoms which were either not in DSM-III or DSM-III-R, or were modifications of DSM-III-R symptoms, had greater diagnostic efficiency than did several existing symptoms. Symptom utility estimates were generally similar for different ages and genders, although some interesting age and sex trends emerged for a few symptoms. CONCLUSIONS: The results supported the inclusion of more restricted definitions of "lying" and "truancy" to increase their association with a conduct disorder diagnosis and they supported the elimination of "swearing" in the oppositional defiant disorder criteria. In addition to their relevance for developing optimal criteria for DSM-IV, these results can aid DSM-IV users by providing a useful guide to the relative efficiency of individual symptoms based on data from a large heterogeneous clinic population.

The nosology of attention-deficit hyperactivity disorder.

This study examined five central issues regarding the classification of attention-deficit hyperactivity disorder (ADHD) in an epidemiologically derived sample of primary school children. A monothetic schema (DSM-III) differed from a polythetic-only schema (DSM-III-R) by having a higher frequency of comorbid conduct disorder. A pervasive model was too restrictive, identifying only the most severe disruptive or conduct disordered children. Raising the minimum threshold above eight symptoms (DSM-III-R) missed less disruptive children who nevertheless exhibit significant functional impairment. There was minimal support for the independence of a syndrome of attention deficit disorder without hyperactivity (DSM-III). Finally, ADHD patients commonly have other diagnoses, most frequently conduct disorder, oppositional defiant disorder, and anxiety disorder.

Predictors of length of stay of psychiatric adolescent inpatients.

This study reviewed 158 consecutive admissions to an inpatient adolescent psychiatric service for factors that determine length of hospitalization. Variables associated with length of stay included diagnostic category and the treatment variables of number and type of psychotropic medications prescribed. Patients with disruptive behavior disorders had the shortest hospitalizations, those with anxiety and affective disorders had stays of intermediate length, and patients with psychotic/organic disorders had the longest hospitalizations. Treatment with lithium, neuroleptics, or tricyclic antidepressants was associated with longer stays. Demographic variables and variables describing the social and family situation or level of dangerousness were not significantly associated with length of hospitalization.

Growth hormone response patterns in sexually or physically abused boys.

The ratio of growth hormone response to clonidine and L-dopa challenge was compared in 74 boys: 15 with purported physical abuse, 7 with purported sexual abuse, 13 normal controls, and 39 psychiatric controls. Sexually abused boys demonstrate a statistically significant elevated ratio of growth hormone response to clonidine versus response to L-dopa. Physically abused boys demonstrate lower clonidine/L-dopa growth hormone response ratios compared with controls. These effects widen with increasing physical development.

Growth hormone response to L-dopa and clonidine in autistic children.

Studies have shown abnormal pituitary hormone responses to neuroendocrine agonists in autistic subjects. Two probes (clonidine and L-Dopa) were used to investigate neuroendocrine responses through changes in growth hormone levels. Seven medication-free autistic subjects (ages 6.6 to 19.1) were evaluated and compared to 14 normal controls. Growth hormone was collected at 30-min intervals during the entire study. Clonidine was administered first (dose: 0.15 mgm2), and samples were collected for 180 min. L-Dopa was then administered (dose: 250 mg for subjects less than 70 lb and 500 mg for subjects greater than 70 lb), and samples were collected for 120 min. There was no difference in the amplitude of the clonidine or L-Dopa peak growth hormone responses in the control versus the autistic subjects. In the autistic subjects, the L-Dopa-stimulated growth hormone peak was delayed and the clonidine growth hormone peak was premature. A statistical difference with the control subjects was found when consideration was given to both the premature response of growth hormone to clonidine and the delayed response to L-Dopa (p = .01, Fisher's Exact Test). These findings suggest possible abnormalities of both dopaminergic and noradrenergic neurotransmission in subjects with autism.

Comparative studies of pharmacotherapy for school refusal.

Two studies compared alprazolam and imipramine in the treatment of school refusal. In an open label study (N = 17), two-thirds of the subjects completing a trial in both the alprazolam and imipramine groups showed moderate to marked global improvement in symptoms of anxiety and depression. In the double-blind, placebo-controlled study (N = 24), posttreatment scores calculated as change from baseline on the Anxiety Rating for Children were significantly different (p = .03) among the three treatment groups, with the active medication groups showing the most improvement. Additionally, on all depression rating scales, similar trends were evident with the alprazolam and imipramine groups demonstrating greater improvement than the placebo group. However, analyses of covariance (with pretreatment scores as the covariates) showed no significant differences among the three treatment groups on change in anxiety and depression scales. Thus, additional research is needed to determine whether trends in this study are explained by drug effect or baseline differences on rating scales.

Growth hormone dysregulation in children with major depressive disorder.

The growth hormone response to stimulation with oral clonidine and L-dopa was measured in 14 boys with major depressive disorder (MDD) and 15 normal boys. The six MDD boys who were prepubertal or in early puberty were significantly lower than the 10 normal subjects of this age in peak growth hormone response following clonidine administration (p = 0.029) and area under the curve for clonidine (p = 0.030) and L-dopa (p = 0.028). The eight later puberty MDD boys did not differ from the five later puberty normal boys on any measures.

Comorbidity of ADHD and reading disability among clinic-referred children.

Of a consecutive series of 115 boys diagnosed in a university outpatient clinic as ADHD, 39% also demonstrated a specific reading disability. Pure ADHD patients were compared with mixed ADHD + RD and normal controls on a battery of cognitive and attentional measures. The aim was to determine whether a distinct pattern of deficits would distinguish the groups. Both ADHD subgroups performed significantly worse than controls on measures of sequential memory and attentional tasks involving impulse control and planful organization. Only ADHD + RD boys differed from controls on measures or rapid word naming and vocabulary. The results are discussed within the framework of an automatic versus effortful information-processing model.

School phobia: patterns of family functioning.

Seventy-six families of children with school phobia were evaluated with the Family Assessment Measure. Mothers and fathers, as separate groups, rated clinically significant dysfunction in the parent-child relationship in the areas of role performance and values and norms. There were no significant differences between intact and single-parent families on ratings of family dysfunction. There was significantly less family dysfunction as rated by mothers and by children if the child had a diagnosis of pure anxiety disorder compared to families of school phobic children in other diagnostic categories.

Behavioral and cognitive subtypes of ADHD.

Attention-deficit hyperactivity symptoms are observed by teachers in 9.2% of a nonreferred elementary school population. Two subtypes of attention-deficit hyperactivity disorder (ADHD), a cognitive form and a behavioral form, are identified. The behavioral subtype includes about 80% of those identified and is characterized by distinct clinical phenomenology of inattention, impulsivity, and hyperactivity. These children can be described on a continuum of severity, with the most severe showing behavioral features indistinguishable from conduct disorder. Children with behavioral subtypes of ADHD do not exhibit the specific skill deficits on neuropsychological tests that are characteristic of reading disabled children. There is a second, less prevalent type of cognitive attention-deficit hyperactivity disorder constituting approximately 20% of ADHD children that includes severe academic underachievement along with inattention, impulsivity, and overactivity. Children with the cognitive subtype exhibit information processing deficits that involve inadequate encoding and retrieval of linguistic information, characteristic of reading disabilities.

Clinical effect of buspirone in autistic children.

Buspirone is a novel antianxiety agent with no chemical similarity to other psychotropic medications. Pharmacological effects include inhibition of serotonin neurons, decrease of striatal levels of serotonin and metabolites, and reduction in serotonin binding sites. Buspirone also has effects on dopamine, norepinephrine, and the GABA systems. To pursue an antiserotonergic treatment rationale for autistic disorder, an open-blind 4-week trial comparing buspirone to fenfluramine or methylphenidate was conducted. Hyperactivity was a target symptom in three children with improvement noted in two with buspirone. Behavioral toxicity was encountered in one of two autistic subjects treated with methylphenidate and very mild improvement in another subject on fenfluramine. An autistic child with obsessive ideation was unchanged. No adverse reaction to buspirone was encountered. Further investigation in a double-blind trial of buspirone is warranted for treatment of symptoms of autism, especially aggression and hyperactivity.

Self-reported anxiety in adolescents.

In a study of 988 adolescents, female gender, somatic complaints, history of physical and sexual abuse, poor grades, use of street drugs, and family history related to depression were among factors that differentiated adolescents reporting high anxiety from those reporting low anxiety.

Completed suicide in youth.

The purpose of this study was to collect descriptive information on a large number of children, adolescents and young adults who had committed suicide. The medical examiner's records for deaths of persons 25 and under from non-natural causes were reviewed; 656 youth suicides were identified. Children, adolescents and young adults who committed suicide were most likely to be older males with a current psychiatric disorder, usually an affective disorder or alcohol or drug abuse. Suicides appeared to be impulsive and triggered by age-normative precipitants. Sex, age and cohort differences are presented. Results are evaluated in light of previous research.