David R. Rosenberg

Decrease in Caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine

OBJECTIVE To measure in vivo neurochemical changes in the caudate nucleus in pediatric obsessive-compulsive disorder (OCD) before and after treatment. METHOD Single-voxel proton magnetic resonance spectroscopic (1H-MRS) examinations of the left caudate were conducted in 11 psychotropic drug-naive children, aged 8 to 17 years, with OCD before and after 12 weeks of monotherapy with the selective serotonin reuptake inhibitor paroxetine (10-60 mg/day) and 11 healthy children aged 8 to 17 years. A different sample of 8 pediatric OCD patients and 8 healthy children had a 1H-MRS examination of occipital cortex. RESULTS Caudate glutamatergic concentrations (Glx) were significantly greater in treatment-naive OCD patients than in controls but declined significantly after paroxetine treatment to levels comparable with those of controls. Decrease in caudate Glx was associated with decrease in OCD symptom severity. Occipital Glx did not differ between OCD patients and controls. CONCLUSIONS These preliminary findings provide new evidence of Glx abnormalities in the caudate nucleus in pediatric OCD and suggest that paroxetine treatment may be mediated by a serotonergically modulated reduction in caudate Glx.

Magnetic resonance imaging and spectroscopy in offspring at risk for schizophrenia : Preliminary studies

1. Studies of first-degree relatives of persons with schizophrenia provide an opportunity to characterize risk factors for the development of this illness. In this report the authors will provide preliminary data from an ongoing study of neurobiological alterations in the offspring of schizophrenia patients. 2. A series of offspring of schizophrenic patients (OS) were compared with age and sex matched healthy controls (HC) without psychiatric history in first degree relatives on psychiatric, volumetric Magnetic Resonance Imaging (MRI) of whole brain and proton Magnetic Resonance Spectroscopy (1H MRS) evaluations of the ventral prefrontal cortex. 3. Compared with HC group, high risk subjects had reduced left amygdala volume, enlarged third ventricular volume, and smaller overall brain volume. 4. 1H MRS studies showed a trend for decreased NAA/choline ratios in the anterior cingulate region in the OS group as compared to HC subjects. 5. Follow-up studies of these subjects are needed to confirm the predictive value of these measures for future emergence of schizophrenia in subjects at risk for this illness.

Changes in the dopaminergic innervation of monkey prefrontal cortex during late postnatal development: A tyrosine hydroxylase immunohistochemical study

In this study, we used immunohistochemical techniques and antibodies against tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, to examine the relative density and laminar distribution of labeled axons in the prefrontal cortex (PFC) of preadolescent, adolescent and adult monkeys

Magnetic Resonance Imaging of Children Without Sedation: Preparation With Simulation

OBJECTIVE It was hypothesized that a scanner simulator that replicates the magnetic resonance imaging (MRI) environment could be used to prepare pediatric subjects for successful completion of a diagnostic-quality MRI examination without pharmacological sedation. METHOD Sixteen healthy children, 6 to 17 years of age, were matched for age and sex with 16 psychotropic medication-naive children with obsessive-compulsive disorder. Distress was measured throughout simulation and scanning procedures using heart rate and a self-report distress scale. Ten healthy children, 6 to 17 years of age, also underwent the same actual MRI scanning procedure but did not undergo the simulation scanning procedure. RESULTS Significant decreases in heart rate and self-reported distress level were observed in all subjects during the simulator session that were maintained to the end of the actual scanner experience. All subjects successfully completed MRI examinations without chemical restraint. Subjects who were not trained in the simulator had higher heart rates and self-reported distress levels in the actual scanner than did simulation-trained subjects. CONCLUSIONS Simulation without pharmacological sedation successfully prepared pediatric subjects in this pilot study for high-quality MRI studies. Subject preparation may be an alternative procedure to sedation for routine MRI examination in healthy and anxious children 6 years of age and older.

Eye-tracking dysfunction in offspring from the New York High-Risk Project: diagnostic specificity and the role of attention

Eye tracking abnormalities were studied in the offspring of schizophrenic, unipolar depressed and bipolar probands from the New York High-Risk Project to examine their familial specificity. Offspring of schizophrenic and depressed probands both had significant global performance deficits based on spectral purity measurements, but only the offspring of schizophrenic probands had an increased rate of intrusive anticipatory saccades. The greater specificity of high anticipatory saccade rate than global performance impairment suggests that this eye movement abnormality may provide a more specific biological marker of risk for schizophrenia than the global measure of eye tracking performance used in this study. Attention facilitation effectively normalized all performance deficits in the offspring of schizophrenic patients, suggesting that a problem sustaining focused visual attention may contribute to eye tracking deficits observed in the relatives of schizophrenic probands.

Dopamine Axons in Primate Prefrontal Cortex: Specificity of Distribution, Synaptic Targets, and Development

Publisher Summary The substantial specificity in innervation patterns, synaptic targets, and postnatal development exhibited by dopamine (DA) axons may provide insight into the role of these afferents in the functional architecture of the prefrontal cortex (PFC), in both normal and disease states. In addition, abnormalities in DA neurotransmission have been implicated in the pathophysiology of certain disorders, such as schizophrenia, that are associated with disturbances in the cognitive functions subserved by the PFC. The researchers have examined the regional and laminar innervation patterns of DA axons in monkey PFC, their synaptic targets, and their maturational changes during postnatal development. Within the monkey cerebral cortex, the distribution of DA transporter-immunoreactive (DAT-IR) axons differed substantially across cytoarchitectonic regions. In most areas, DAT-labeled axons in the PFC have been distributed in a bilaminar fashion, with the density of labeled axons greatest in the superficial layers (I-IIIa), intermediate in the deep layers (Vb-VI), and very low in the middle layers (IIIb-Va). This apparent specificity of the synaptic targets of DA axons has been further demonstrated by the fact that THpositive terminals do not form synapses with CR-containing dendrites in the superficial cortical layers of monkey PFC, although synaptic contacts between tyrosine hydroxylase-immunoreactive (TH-IR) terminals and GABA-labeled dendrites are clearly present in these layers The synaptic regulation of parvalbumin (PARV) -containing local circuit neurons by DA is particularly interesting, given the potent inhibitory control that these neurons may exert on pyramidal cells. These findings may reflect differences in the subcellular localization of TH and DAT and the different role that these two proteins play in the regulation of DA neurotransmission.

Eye tracking dysfunction in offspring from the New York high-risk project

Eye tracking abnormalities were studied in the offspring of schizophrenic, unipolar depressed and bipolar probands from the New York High-Risk Project to examine their familial specificity. Offspring of schizophrenic and depressed probands both had significant global performance deficits based on spectral purity measurements, but only the offspring of schizophrenic probands had an increased rate of intrusive anticipatory saccades. The greater specificity of high anticipatory saccade rate than global performance impairment suggests that this eye movement abnormality may provide a more specific biological marker of risk for schizophrenia than the global measure of eye tracking performance used in this study. Attention facilitation effectively normalized all performance deficits in the offspring of schizophrenic patients, suggesting that a problem sustaining focused visual attention may contribute to eye tracking deficits observed in the relatives of schizophrenic probands.

Depression in the Elderly

This paper examines the clinical presentation of, the biochemical abnormalities associated with, and the treatment of depressive disorders in late life. A comparison of geriatric depression (late-onse

Pharmacotherapy for Child and Adolescent Psychiatric Disorders

The book covers the emerging question of treating children who do not yet meet diagnostic criteria for psychosis, e.g, schizophrenia or bipolar disorder, but who are deemed to be at high risk. This is an active area of debate: such children are being treated in certain centers, while others reject this completely. The book addresses the antidepressant controversy, the placebo response and unique strategies for delineating this, and ways to optimize the differential between active medication and placebo. It reviews the impact of recent American Heart Association guidelines for monitoring children on stimulants and other psychotropics. It adheres closely to DSM-IV diagnostic criteria throughout. The book describes the use of newly approved drugs such as Lexapro for treating adolescent depression and the novel compound Intuniv. It covers the TADS and CAMS studies, which evaluated the use of SSRIs alone and in combination with cognitive behavioral therapy for adolescent depression. Other topics include treatment of bipolar disorders, the increasing popularity of generic equivalents, combination pharmacotherapy and the potential dangers of psychotropic medications.

Psychosis and idiopathic precocious puberty in two 7-year-old boys

The authors present case reports of psychosis and idiopathic precocious puberty (IPP) with tall stature in two 7-year-old boys. Other similarities in the two cases are discussed. Review of the literature revealed only one report regarding the role of accelerated sexual maturation in the clinical picture of psychoses in children and one case report of Pervasive Developmental Disorder and IPP in a 5-year-old girl. Possible mechanisms by which psychosis and IPP with tall stature may be related are discussed.