Jonathan B. Jensen

Depression and Symptoms of Attention Deficit Disorder with Hyperactivity

Abstract Thirty-five boys, classified as major depressive disorder (MDD, N = 12), attention deficit disorder with hyperactivity (ADDH, N = 12), or normal (NL, N = 11) on the basis of structured clinical interviews were evaluated using the Child Depression Rating Scale (CDRS), Connors Parent Questionnaire (CPQ), and Jesness Inventory Manifest Aggression Scale (JIMAS). The MDD group scored significantly higher than the NL group on the CPQ indicating a higher than normal rate of externalizing behavioral symptoms for the MDD boys. Item analyses of JIMAS revealed that the MDD group positively endorsed criteria showing poor impulse control and stress intolerance significantly more often than the other two groups. Boys with MDD did not have features of ADDH, but may have oppositional disorder, whereas boys with ADDH may have dysthymia.

A comparative pilot study of second-generation antipsychotics in children and adolescents with schizophrenia-spectrum disorders.

OBJECTIVE There is a limited evidence base to guide treatment of children and adolescents with nonaffective psychoses because few comparative studies of first-line second-generation antipsychotics (SGAs) have been undertaken. To plan the design of a subsequent randomized controlled trial (RCT), the authors conducted this pilot study to demonstrate the feasibility of the treatment and measurement protocols. METHOD Thirty children and adolescents (20 males, 10 females), ages 10-18 years, who met unmodified Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for a schizophrenia-spectrum disorder (schizophrenia, schizoaffective, schizophreniform, psychotic disorder not otherwise specified) were randomized to receive 12 weeks of open-label, flexibly dosed treatment with either risperidone (mean [standard deviation, SD] dose = 3.4 mg [1.5]), olanzapine (mean [SD] dose = 14.0 mg [4.6]) or quetiapine (mean [SD] dose = 611 mg [253.4]). RESULTS Twenty one (70%) of 30 subjects completed the study. There was no overall statistically significant difference with regard to reduction in Positive and Negative Syndrome Scale (PANSS) total scores in treatment efficacy observed (F((2,24)) = 3.13, p = 0.06). However, the possibility of a large differential treatment effect with regard to change in PANSS total scores favoring risperidone relative to quetiapine (risperidone vs. quetiapine, d = 1.10 [95% confidence interval, CI, 0.09-2.01]) was suggested by the point estimate. CONCLUSIONS These preliminary data, viewed together with the extant literature, suggest that a future larger RCT with only two treatment arms may be warranted to establish whether there is a clinically significant differential treatment effect between risperidone and quetiapine for children and adolescents with nonaffective psychoses. Additional challenges and considerations for mounting a larger RCT are explored.

The dexamethasone suppression test in infantile autism.

The Dexamethasone Suppression Test was administered to 13 autistic children and adolescents. Following either 1 or 2 mg of dexamethasone, this test was found to have an overall sensitivity of 84.6% when nonsuppression is defined as levels of cortisol greater than 5 mg/dl. Infantile autism must be included as further evidence of the lack of DST specificity. The authors speculate that infantile autism and major depression may show an underlying abnormal substrate that may be mediated by serotonin and norepinephrine which are ineffective in shutting off cortisol secretion.

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.

Developmental and symptom specificity of hopelessness, cognitive errors, and attributional bias among clinic-referred youth.

The present study examined the unique and interactive relationships between age and indices of psychopathology (i.e., anxiety, aggression, and depression), with three types of maladaptive cognitions: hopelessness, negative cognitive errors, and attributional bias. Some negative cognitions were not unique to depression and were associated with broader psychopathology. Developmental considerations also influenced some negative cognitions or qualified the association between negative cognitions and depression.

Untoward effects of fenfluramine in autistic children

Several recent studies have described the benefits of fenfluramine for the symptomatic treatment of infantile autism. No large surveys of side effects of this drug have been reported in autistic children. To evaluate the untoward effects of fenfluramine in children with autism, 12 subjects were systematically studied. Medication was administered in a double-blind, placebo-controlled crossover study. Parents were trained in monitoring untoward effects. These observations were compiled in detailed daily notes. In addition, four cases describing unusual effects found in a sample of 170 patients treated with fenfluramine are also reported. In the initial 2 weeks of active drug listlessness, food refusal, and stomach upset were frequently seen. A different pattern of untoward effects was seen in the final 14 weeks of treatment. Irritability, agitation, and crying along with continued food refusal were noted. The subjects lost 2.1% of body weight during active drug phase, but there was a rebound weight gain during the subsequent placebo phase. A thorough understanding of fenfluramines side effects and adverse reactions is necessary so as to differentiate them from the multiple symptoms inherent in the syndrome of autism. (J Clin Psychopharmacol 1986;6:350–355)

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.

Clinical and neurocognitive course in early-onset psychosis: a longitudinal study of adolescents with schizophrenia-spectrum disorders*

Aim: Adolescents with psychotic disorders show deficits in IQ, attention, learning and memory, executive functioning, and processing speed that are related to important clinical variables including negative symptoms, adaptive functioning and academics. Previous studies have reported relatively consistent deficits with varying relationships to illness status and symptoms. The goals of this study were to examine these relationships in a larger sample at baseline, and also to examine the longitudinal course of these deficits in a smaller subset of adolescents.

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 <70 lb and 500 mg for subjects >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, Fishers Exact Test). These findings suggest possible abnormalities of both dopaminergic and noradrenergic neurotransmission in subjects with autism.

Age associations with neural processing of reward anticipation in adolescents with bipolar disorders

Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD) and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age) associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI) protocol using the Monetary Incentive Delay (MID) task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex). Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus), suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development.