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The Collaborative Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (ADHD), the MTA, is the first multisite, cooperative agreement treatment study of children, and the largest psychiatric/psychological treatment trial ever conducted by the National Institute of Mental Health. It examines the effectiveness of Medication vs. Psychosocial treatment vs. their combination for treatment of ADHD and compares these experimental arms to each other and to routine community care. In a parallel group design, 579 (male and female) ADHD children, aged 7-9 years, 11 months, were randomly assigned to one of the four experimental arms, and then received 14 months of prescribed treatment (or community care) with periodic reassessments. After delineating the theoretical and empirical rationales for Psychosocial treatment of ADHD, we describe the MTA's Psychosocial Treatment strategy applied to all children in two of the four experimental arms (Psychosocial treatment alone; Combined treatment). Psychosocial treatment consisted of three major components: a Parent Training component, a two-part School Intervention component, and a child treatment component anchored in an intensive Summer Treatment Program. Components were selected based on evidence of treatment efficacy and because they address comprehensive symptom targets, settings, comorbidities, and functional domains. We delineate key conceptual and logistical issues faced by clinical researchers in design and implementation of Psychosocial research with examples of how these issues were addressed in the MTA study. [ABSTRACT FROM AUTHOR]

This special issue grew out of a workshop sponsored by the National Institute of Mental Health, the MacArthur Foundation, and the Child and Adolescent Psychosocial Interventions Consortium. The goals of the workshop are outlined. The contents of the special issue are then described: definitions of psychotherapy and its mechanisms of action, developmental issues in psychotherapy research, methodologies for the treatment of anxious youth, measurement of change in interventions, predicting the outcome of treatment, and advancing the efficacy and effectiveness of psychosocial treatments. Finally, some areas that need to be addressed in the future are discussed, such as process research, the effects of comorbidity on outcomes, intensity, and duration, and transferability of treatments. [ABSTRACT FROM AUTHOR]

Increased spontaneous fluctuations in skin conductance (SC) in adult schizophrenics have been associated with high expressed emotion (EE) in their relatives. This is the first study in children where parental EE, parental psychopathology, and autonomic activity, indexed by SC levels and reactivity, have been assessed. The subjects were children and adolescents with disruptive behaviour disorders (DBD, n = 35), a psychiatric contrast group with obsessive-compulsive disorders (OCD, n = 42) and normal controls (NC, n = 45). Children living in homes with two high-EE parents had higher SC activity during rest period and slower adaptation to relaxation. Fathers' EE and maternal psychiatric diagnosis were related to higher SC activity, especially for the OCD group. [ABSTRACT FROM AUTHOR]

Pericytes are vascular mural cells that contract and relax in response to vasoactive stimuli to regulate neurovascular coupling and cerebral blood flow. Pericytes are damaged and degenerate in Alzheimer's disease (AD). We previously showed that the level of the regulatory vasoconstrictor, endothelin-1 (EDN1), is elevated in AD cerebral cortex and upregulated by amyloid-beta (Aβ). We have used electrical impedance analysis to monitor the contractile and proliferative response of cultured human fetal and adult brain-derived pericytes to EDN1 in real-time. EDN1 caused transient, dose-dependent contraction of fetal and adult brain pericytes that was mediated by EDN1 type A receptors and increased the subsequent proliferation of fetal but not adult cells. The contractile responses to EDN1 were weaker in the adult pericytes. The EDN1-mediated contractile response of fetal pericytes was unchanged after exposure to Aβ 1 - 40 or Aβ 1 - 42 (0.1-10 μM) for 1 h but both contraction and subsequent relaxation were significantly impaired upon exposure to Aβ for 24 h. These data suggest that chronic exposure to Aβ interferes with EDN1-mediated pericyte contractility, potentially contributing to neurovascular uncoupling and reduced cerebral blood flow in AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hibbs, Love and Miners.)

Hyperactivity of the renin-angiotensin system (RAS) is associated with the pathogenesis of Alzheimer's disease (AD) believed to be mediated by angiotensin-II (Ang-II) activation of the angiotensin type 1 receptor (AT1R). We previously showed that angiotensin-converting enzyme-1 (ACE-1) activity, the rate-limiting enzyme in the production of Ang-II, is increased in human postmortem brain tissue in AD. Angiotensin-III (Ang-III) activates the AT1R and angiotensin type-2 receptor (AT2R), but its potential role in the pathophysiology of AD remains unexplored. We measured Ang-II and Ang-III levels by ELISA, and the levels and activities of aminopeptidase-A (AP-A) and aminopeptidase-N (AP-N) (responsible for the production and metabolism of Ang-III, respectively) in human postmortem brain tissue in the mid-frontal cortex (Brodmann area 9) in a cohort of AD (n = 90) and age-matched non-demented controls (n = 59), for which we had previous measurements of ACE-1 activity, Aβ level, and tau pathology (also in the mid-frontal cortex). We found that both Ang-II and Ang-III levels were significantly higher in AD compared to age-matched controls and that Ang-III, rather than Ang-II, was strongly associated with Aβ load and tau load. Levels of AP-A were significantly reduced in AD but AP-A enzyme activity was unchanged whereas AP-N activity was reduced in AD but AP-N protein level was unchanged. Together, these data indicate that the APA/Ang-III/APN/Ang-IV/AT4R pathway is dysregulated and that elevated Ang-III could contribute to the pathogenesis of AD.

Psychotherapy research improved its methodological rigor in the last half of the past century and as we begin a new millennium and a new generation of research it is important to evaluate its effectiveness. In this article the historical perspective of psychotherapy evaluation is reviewed, followed by the presentation of the Child Task Force criteria for evaluating psychotherapy outcomes. The results of the American Psychological Association Task Force review of well-established and probably efficacious treatments for depression, anxiety, disruptive behavior disorders and attention deficit hyperactivity for child and adolescent disorder are presented. Finally, the advantages and disadvantages of these very structured criteria for evaluating psychotherapy research with children and adolescents are discussed, and future directions are proposed.

Using a longitudinal sample of children, this study examined the relation between maternal Expressed Emotion (EE) and mother-child attachment disorganization at age 6 years. A nonclinical sample of 33 children (at ages 12 months and 18 months) from Berlin, Germany participated with their mothers in Ainsworth's Strange Situation. Thirty-two children were again observed with their mothers at age 6 years in a standard laboratory attachment observation. At the time of the 6-year assessment, maternal EE was assessed based on a Five-Minute Speech Sample. Mothers also completed the Life Events Questionnaire, a measure of family stress, and the Present State Examination, a measure of maternal depression. Maternal Expressed Emotion was significantly linked to mother-child attachment security at age 6 years. Further analyses revealed that High EE was most closely linked to the disorganized attachment pattern at age 6 years, an at-risk attachment pattern that has been associated with intrusive and hostile maternal behavior. The relationship was upheld when other relevant variables, including infant attachment disorganization and a measure of perceived family stress, were simultaneously considered. The study provides independent validation of Expressed Emotion as a measure of relationship quality in early childhood. It also provides a basis for the further investigation of the nature of the relation between maternal Expressed Emotion and attachment disorganization.

There has been a proliferation of treatment manuals in the past decade as part of an effort to operationalize treatment applications and standardize treatments across subjects, settings, and therapists. In this article we present the essential elements needed to develop manuals for the psychosocial and psychopharmacological treatments of child and adolescent disorders, using one modality or in multimodal treatment trials. We delineate how to integrate various treatment components for psychosocial and psychopharmacological manuals, as well as those for control conditions. We also examine the therapist variable as it concerns training and adherence to the structured or flexible scripted manuals. Finally, we discuss the advantages and disadvantages of manuals in terms of how they may affect outcome, recommending that treatments be both empirically grounded and clinically meaningful.

Using a multimethod multistage screening procedure, the authors interviewed 201 parents and their children with the Diagnostic Interview Schedule for Children (DISC 2.1). In addition, parents completed the Child Behavior Checklist (CBCL) and other survey measures, while their children completed self-report scales. Receiver operating characteristic (ROC) analyses were done to determine optimal cutpoints on the CBCL, referenced to DISC diagnostic "caseness." DISC diagnoses, DISC "stem" symptoms, CBCL scores, and CBCL ROC-outpoints were compared against "external validators," in order to determine the comparative advantages of each approach for assessing child psychopathology. Overall findings suggest that the controversies about "best" assessment strategies may be artificial: When both assessment approaches are compared using similar methods, they are reasonably comparable. However, highly specific diagnostic categories may show fewer relationships with external validators and may therefore need more systematic validational studies.

The recent efforts of the National Institute of Mental Health (NIMH) to encourage child and adolescent research are described, including the creation of the Child and Adolescent Psychosocial Interventions Research Consortium as a forum to identify, delineate, and examine research needs in psychosocial treatments. This is followed by a summary review of the contents of this special issue: history of psychotherapy research with children, developmental issues, diagnosis and assessment, ecological and cultural validity, laboratory versus clinic research outcomes, cognitive behavioral treatments for childhood disorders, nontraditional treatments, and overview and future directions. Finally, methodological issues that need to be addressed in future research are discussed, such as the developmental level of children in treatment research, issues of comorbidity, family involvement, and duration of treatment.

In order to examine their relationship to Expressed Emotion, family environment and marital relationships were measured in the parents of disruptive, obsessive-compulsive, and normal children. Satisfactory family and martial environment were found to be related to low Expressed Emotion, while achievement orientation in mothers and greater family conflict were found to be significantly related to high Expressed Emotion.

Psychotherapy research with children is based mainly on adult methodologies. Common issues include bias in recruitment of subjects, demographics, developmental concerns, and control group considerations. The advantages and drawbacks of various types of control groups, such as wait-list controls, and placebo conditions are discussed along with ethical issues. Instrument choice, validity and reliability, and standardization of procedures in conducting research are addressed. Finally, the therapist as a variable is reviewed, including selection and assignment of therapists, and therapist bias.

A 2-year prospective follow-up study of 100% (N = 29) of a sample of children and adolescents with disruptive behavior disorders found that the baseline lumbar cerebrospinal fluid monoamine metabolite concentration and autonomic nervous system activity predicted some subsequent outcomes. The 5-hydroxyindoleacetic acid concentration significantly predicted severity of physical aggression during follow-up. The skin conductance level significantly predicted institutionalization. Correlations were in predicted directions with lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and autonomic activity correlated with poor outcome. Moreover, in multivariate analyses, which included nonlaboratory measures as predictors, cerebrospinal fluid and autonomic measures still contributed significantly to the prediction. However, hypothesized predictions of cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations for suicide attempts and of low autonomic nervous system activity for arrests were not supported thus far. Patients are still at risk; consequently, these results must be considered preliminary. Nonetheless, the results suggest that further investigation of relationships between biological factors and outcome of children with disruptive behavior disorders is warranted.

Both high expressed emotion (EE) and psychiatric disorders were frequent in the parents of children and adolescents with disruptive behavior disorder (DBD, N = 34) and obsessive compulsive disorder (OCD, N = 49) compared to normal controls (NC, N = 41). Parental psychiatric diagnosis was significantly related to high-EE in fathers (p = .0002) and mothers (p = .0001) of all groups combined, and in parents of the ill groups (p = .03). Absence of diagnosis was associated with low-EE in fathers (p = .0006) and mothers (p = .04) of the controls. Psychiatric diagnosis was the only significant predictor for high-EE in fathers, while for mothers child's diagnosis was a stronger predictor.

About half of adults volunteering as normal control research subjects may be rejected because of significant psychopathology, but no parallel study has been done to date for pediatric subjects. Of 152 applicants (ages 6 to 18) for participation as paid normal controls, 44% were found ineligible and at least 31.8% of the child volunteers had probable or certain psychiatric disorders. Successive screenings, including rating scales and structured interviews, were necessary to obtain controls meeting a defined standard of psychiatric health. Careful scrutiny of child volunteers in biological psychiatric research is needed to assure meaningful comparisons.

Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid, a metabolite of serotonin, were measured in relation to aggression, impulsivity, and social functioning in 29 children and adolescents with disruptive behavior disorders. The cerebrospinal fluid 5-hydroxyindoleacetic acid level was low compared with that of age-, sex-, and race-matched patients with obsessive-compulsive disorder. Within the disruptive group, significant negative correlations with age-corrected 5-hydroxyindoleacetic acid level were seen for the child's report of aggression toward people and the expressed emotionality of the child toward his or her mother; other correlations of age-corrected 5-hydroxyindoleacetic acid level with measures of aggression were in the expected negative direction but did not reach statistical significance. Impulsivity per se and socioenvironmental factors were not significantly related to cerebrospinal fluid 5-hydroxyindoleacetic acid concentration.

Hostile, impulsive, and aggressive behaviors have been associated with decreased urinary free cortisol (UFC) output. This is the first study to assess 24-hour UFC output in disruptive behavior disorders. The UFC of 19 boys with attention deficit and/or conduct disorder was compared with that of 19 age, race, and IQ matched normal controls studied as inpatients. Continuous Performance Test scores showed greater impulsivity in the disruptive group. UFC output did not differ between groups. However, UFC and difficulty were positively correlated on the continuous performance test in the form of longer interstimulus intervals and longer reaction times.

A family study of psychiatric diagnoses was performed in 29 children of bipolar patients and 37 children of normal controls, ages 6-17. There were no differences in major or minor affective diagnoses between the patient and control groups, but there was an increase of non-specific diagnoses in the patient group. Using DSM-III criteria, 10% of patients' children and 14% of controls' children had had at least one episode of major depression. This suggests that major depression in children is not familially related to adult bipolar major affective disorder. The observed prevalence of depression in childhood is increased when both direct interview of children and interview of parents are performed.