Neonatal maternal separation and enhancement of the hypoxic ventilatory response in rat: the role of GABAergic modulation within the paraventricular nucleus of the hypothalamus. (25/94)

Neonatal maternal separation (NMS) affects respiratory control development as adult male (but not female) rats previously subjected to NMS show a hypoxic ventilatory response 25% greater than controls. The paraventricular nucleus of the hypothalamus (PVN) is an important modulator of respiratory activity. In the present study, we hypothesized that in awake rats, altered GABAergic inhibition within the PVN contributes to the enhancement of hypoxic ventilatory response observed in rats previously subjected to NMS. During normoxia, the increase in minute ventilation following microinjection of bicuculline (1 mm) within the PVN is greater in NMS versus control rats. These data show that regulation of ventilatory activity related to tonic inhibition of the PVN is more important in NMS than control rats. Microinjection of GABA or muscimol (1 mM) attenuated the ventilatory response to hypoxia (12% O2) in NMS rats only. The higher efficiency of microinjections in NMS rats is supported by results from GABAA receptor autoradiography which revealed a 22% increase in GABAA receptor binding sites within the PVN of NMS rats versus controls. Despite this increase, however, NMS rats still show a larger hypoxic ventilatory response than controls, suggesting that within the PVN the larger number of GABAA receptors either compensate for (1) a deficient GABAergic modulation, (2) an increase in the efficacy of excitatory inputs converging onto this structure, or (3) both. Together, these results show that the life-long consequences of NMS are far reaching as they can compromise the development of vital homeostatic function in a way that may predispose to respiratory disorders.  (+info)

Developmental trajectories of anxiety disorders in offspring at high risk for panic disorder and major depression. (26/94)

The objective of this study was to evaluate the longitudinal course of psychiatric disorders in children of parents with and without panic disorder and major depression as they transition through the period of risk from early to late childhood. Over a 5-year follow-up, we compared the course of psychiatric disorders in offspring of parents with panic disorder, major depression, or neither disorder. Subjects consisted of 233 offspring (from 151 families) with baseline and follow-up assessments. Subjects were comprehensively assessed with structured diagnostic interviews. Anxiety disorders at baseline were used to predict anxiety disorders and major depression at follow-up using stepwise logistic regression. Separation anxiety disorder significantly increased the risk for the subsequent development of specific phobia, agoraphobia, panic disorder, and major depression, even after parental panic and depression were covaried. Agoraphobia significantly increased the risk for subsequent generalized anxiety disorder. These findings suggest that separation anxiety disorder is a major antecedent disorder for the development of panic disorder and a wide range of other psychopathological outcomes, and that it increases the risk for subsequent psychopathology even among children already at high familial risk for anxiety or mood disorder.  (+info)

Panic, suffocation false alarms, separation anxiety and endogenous opioids. (27/94)

This review paper presents an amplification of the suffocation false alarm theory (SFA) of spontaneous panic [Klein DF (1993). False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis. Arch Gen Psychiatry; 50:306-17.]. SFA postulates the existence of an evolved physiologic suffocation alarm system that monitors information about potential suffocation. Panic attacks maladaptively occur when the alarm is erroneously triggered. That panic is distinct from Cannon's emergency fear response and Selye's General Alarm Syndrome is shown by the prominence of intense air hunger during these attacks. Further, panic sufferers have chronic sighing abnormalities outside of the acute attack. Another basic physiologic distinction between fear and panic is the counter-intuitive lack of hypothalamic-pituitary-adrenal (HPA) activation in panic. Understanding panic as provoked by indicators of potential suffocation, such as fluctuations in pCO(2) and brain lactate, as well as environmental circumstances fits the observed respiratory abnormalities. However, that sudden loss, bereavement and childhood separation anxiety are also antecedents of "spontaneous" panic requires an integrative explanation. Because of the opioid system's central regulatory role in both disordered breathing and separation distress, we detail the role of opioidergic dysfunction in decreasing the suffocation alarm threshold. We present results from our laboratory where the naloxone-lactate challenge in normals produces supportive evidence for the endorphinergic defect hypothesis in the form of a distress episode of specific tidal volume hyperventilation paralleling challenge-produced and clinical panic.  (+info)

Diagnostic specificity and nonspecificity in the dimensions of preschool psychopathology. (28/94)

BACKGROUND: The appropriateness of the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) nosology for classifying preschool mental health disturbances continues to be debated. To inform this debate, we investigate whether preschool psychopathology shows differentiation along diagnostically specific lines when DSM-IV symptoms are aggregated statistically. METHODS: One thousand seventy-three parents of preschoolers aged 2-5 years attending a large pediatric clinic completed the Child Behavior Checklist 1.5-5. A stratified probability sample of 193 parents of high scorers and 114 parents of low scorers were interviewed with the Preschool Age Psychiatric Assessment (PAPA). Confirmatory factor analysis was performed on symptoms from seven DSM disorders. RESULTS: Comparison of competing models supported the differentiation of emotional syndromes into three factors: social phobia (SOC), separation anxiety (SAD), and depression/generalized anxiety (MDD/GAD), and the differentiation of disruptive syndromes into three factors: oppositional defiant/conduct syndrome (ODD/CD), hyperactivity/impulsivity, and inattention. Latent syndrome correlations were moderately high after accounting for symptom overlap and measurement error. CONCLUSIONS: Psychopathology appears to be differentiated among preschoolers much as it is among older children, and adolescents. We conclude that it is as reasonable to apply the DSM-IV nosology to preschoolers as it is to apply it to older individuals.  (+info)

The impact of maternal separation on adult mouse behaviour and on the total neuron number in the mouse hippocampus. (29/94)

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Postnatal life events affect the severity of asthmatic airway inflammation in the adult rat. (30/94)

Genetic and hygienic factors influence susceptibility to asthma. In autoimmune and inflammatory diseases, additional effects of the psychosocial environment have been demonstrated that might also play a role in asthma. In this study, the impact of different early postnatal stressors on an OVA-induced model of asthma was tested in adulthood. Fischer 344 rats were subjected to either repeated handling stimulation (HA), maternal separation (MS), or were left undisturbed in their first 4 wk of life. Behavioral differences were characterized at the age of 4 mo. At 5 mo of age, immunological cellular and serologic changes were investigated and experimental asthma was induced. Results show significantly increased exploratory behavior and reduced anxiety in HA rats compared with MS and controls. Without further behavioral or immunological challenges, HA animals exhibited an increased ex vivo NK cell cytotoxicity but no other obvious immunological differences. After induction of asthma, in contrast, MS animals exhibited proinflammatory effects in leukocyte subset composition including increased eosinophil numbers, whereas levels of IgE and the allergy-specific cytokine IL-13 were reduced compared with HA. There was a most remarkable increase of adrenocorticotropin in HA animals, comparing pre- to postchallenge plasma levels. These data demonstrate for the first time that early postnatal stimulative or adverse experiences exert long-lasting changes of the "neuroendocrinoimmune" interface in adulthood, resulting in either protective or aggravating mechanisms in allergic airway disease. Thus, in addition to genetic and hygienic factors, nongenetically acquired individual differences contribute to the pathobiology of asthma.  (+info)

Separation anxiety disorder in childhood as a risk factor for future mental illness. (31/94)

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Parental responses to positive and negative emotions in anxious and nonanxious children. (32/94)

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