Memory and language impairments are associated with anxiety disorder severity in childhood

Abstract Introduction Children with anxiety disorders have been suggested to possess deficits in verbal fluency, shifting and attention, with inconsistent results regarding working memory and its subcomponents. This study extends previous findings by analyzing the performance of children with anxiety disorders in a wide range of neuropsychological functions. Methods We evaluated 54 children with a primary diagnosis of an anxiety disorder according to diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) using subtests of a neuropsychological battery. The severity of anxiety disorders was assessed using the Pediatric Anxiety Rating Scale (PARS). We calculated the frequency of neuropsychological impairments (-1.5 standard deviation of the normative sample). Comparisons between groups were performed based on the severity of anxiety symptoms, as well as in the presence of one vs. more diagnoses of anxiety disorder. Results We found higher impairment in visuospatial working memory (23.1%), semantic memory (27.8%), oral language (35.4%) and word writing (44.4%) in anxious children. Moreover, children with higher anxiety severity presented lower performance in visuospatial working memory, inferential processing, word reading, writing comprehension, copied writing, and semantic verbal fluency (d = 0.49 to 0.96 [Cohen's d]). The higher the number of anxiety diagnoses, the lower the performance in episodic memory and oral and written language (d = 0.56 to 0.77). Conclusion Our data suggested the presence of memory (visuospatial working memory and semantic memory) and language deficits (oral and writing) in some children with an anxiety disorder. Severity and number of anxiety diagnoses were associated with lower performance in memory and language domains in childhood.

Hypothalamus-pituitary-adrenal axis imbalance and inflammation contribute to sex differences in separation- and restraint-induced depression.

Whether social contact contributes to the underlying mechanisms of depression and the observed sex differences is unclear. In this study, we subjected young male and female mice to separation- and restraint-induced stress for 4 weeks and assessed behaviors, neurotransmitter levels, hormones, and inflammatory cytokines. Results showed that, compared with controls, male mice exposed to stress displayed significant decreases in body weight and sucrose preference after 1 week. In the fourth week, they exhibited a higher degree of anxiety (open field test) and depressive-like behavior (forced swim test). Moreover, the males showed significant decreases in monoamine neurotransmitters, including norepinephrine and dopamine in striatum, and an increase in pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1ß in serum. In contrast, females showed persistent loss of weight during stress and displayed significant decreases in sucrose preference after stress. Importantly, the females but not males showed activation of the hypothalamus-pituitary-adrenal (HPA) axis, with significantly higher levels adrenocorticotropic hormone. Additionally, mRNA level of c-fos and AVP showed there was significant interaction between stress and sex. Finally, we conclude that an imbalance of the HPA axis and inflammation might be important contributors to sex differences in separation/restraint-induced depressive behavior and that changes might be mediated by c-fos and AVP.

Effects of adenoidectomy/adenotonsillectomy on ADHD symptoms and behavioral problems in children.

OBJECTIVES: In children, the most common reason of upper airway obstruction (UAO) is adenotonsillar hypertrophy. In literature, the adverse effects of UAO and obstructive sleep apnea syndrome on behavior and attention in children have been reported in several articles. However, the methods used for the evaluation of behavioral disorders have not been standardized in those studies. The aim of this study was to investigate the behavioral and attention characteristics of children before and after adenoidectomy/adenotonsillectomy using an internationally valid method. METHODS: A total of 41 patients, between 6 and 11 years of age and having a medical history of UAO for at least one year for which adenotonsillectomy procedure was indicated, were enrolled in the study. The patients were evaluated for signs of attention/behavioral disorders by a child-adolescent psychiatrist and Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children: Present and Lifetime Version (K-SADS-PL) and The Turgay DSM-IV-Based Child and Adolescent Disruptive Behavioral Disorders Screening and Rating Scale (T-DSM-IV-S), before and at the 6th month following the operation. RESULTS: In the preoperative period, a psychiatric disorder was identified by K-SADS-PL in 41.4% (n =1 7) of patients. Of these, 11 patients had attention deficit hyperactivity disorder (ADHD), 6 had enuresis nocturna, and 2 had separation anxiety disorder. Pre- and postoperative mean scores in T-DSM-IV-S parent scale were 31.3 ± 8.5 and 20.2 ± 10.3, respectively, and this difference was statistically significant (p < 0.001). CONCLUSION: The relationship of UAO and attention/behavioral disorders should be taken into consideration by child-adolescent psychiatrists together with ENT specialists and a multidisciplinary approach is important for the treatment team.

Neonatal stress affects the aging trajectory of female rats on the endocrine, temperature, and ventilatory responses to hypoxia.

Human and animal studies on sleep-disordered breathing and respiratory regulation show that the effects of sex hormones are heterogeneous. Because neonatal stress results in sex-specific disruption of the respiratory control in adult rats, we postulate that it might affect respiratory control modulation induced by ovarian steroids in female rats. The hypoxic ventilatory response (HVR) of adult female rats exposed to neonatal maternal separation (NMS) is ∼30% smaller than controls (24), but consequences of NMS on respiratory control in aging female rats are unknown. To address this issue, whole body plethysmography was used to evaluate the impact of NMS on the HVR (12% O2, 20 min) of middle-aged (MA; ∼57 wk old) female rats. Pups subjected to NMS were placed in an incubator 3 h/day for 10 consecutive days (P3 to P12). Controls were undisturbed. To determine whether the effects were related to sexual hormone decline or aging per se, experiments were repeated on bilaterally ovariectomized (OVX) young (∼12 wk old) adult female rats. OVX and MA both reduced the HVR significantly in control rats but had little effect on the HVR of NMS females. OVX (but not aging) reduced the anapyrexic response in both control and NMS animals. These results show that hormonal decline decreases the HVR of control animals, while leaving that of NMS female animals unaffected. This suggests that neonatal stress alters the interaction between sex hormone regulation and the development of body temperature, hormonal, and ventilatory responses to hypoxia.

Early life stress induces renal dysfunction in adult male rats but not female rats.

Maternal separation (MatSep) is a model of behavioral stress during early life. We reported that MatSep exacerbates ANG II-induced hypertension in adult male rats. The aims of this study were to determine whether exposure to MatSep in female rats sensitizes blood pressure to ANG II infusion similar to male MatSep rats and to elucidate renal mechanisms involved in the response in MatSep rats. Wistar Kyoto (WKY) pups were exposed to MatSep 3 h/day from days 2 to 14, while control rats remained with their mothers. ANG II-induced mean arterial pressure (MAP; telemetry) was enhanced in female MatSep rats compared with control female rats but delayed compared with male MatSep rats. Creatinine clearance (Ccr) was reduced in male MatSep rats compared with control rats at baseline and after ANG II infusion. ANG II infusion significantly increased T cells in the renal cortex and greater histological damage in the interstitial arteries of male MatSep rats compared with control male rats. Plasma testosterone was greater and estradiol was lower in male MatSep rats compared with control rats with ANG II infusion. ANG II infusion failed to increase blood pressure in orchidectomized male MatSep and control rats. Female MatSep and control rats had similar Ccr, histological renal analysis, and sex hormones at baseline and after ANG II infusion. These data indicate that during ANG II-induced hypertension, MatSep sensitizes the renal phenotype in male but not female rats.

Adult separation anxiety during pregnancy and its relationship to depression and anxiety.

AIMS: The current study, the first of its kind, investigated the overlap between adult separation anxiety (ASA) and the symptoms of depression and anxiety in the context of pregnancy. METHODS: Women attending an antenatal clinic were screened using the Adult Separation Anxiety Scale (ASA-27). As most perinatal clinics use the Edinburgh Depression Scale (EDS), this study explored the relationship between ASA and the anxiety and depression symptoms by comparing the ASA-27 scores with the scores on the EDS. A subsample including both screen positives and screen negatives on ASA-27 was clinically interviewed using the Mini International Neuropsychiatric Interview (MINI). RESULTS: Women with ASA were significantly more likely to be screened positive for depression (EDS total score) and anxiety (EDS-3A anxiety subscale) than those without ASA. The diagnosis of ASA disorder in this population had only a moderate but significant association with the diagnoses of generalized anxiety disorder [χ2 (1) = 25.9, P = 0.000, Φ = 0.443] and major depression [χ2 (1) = 16, P = 0.000, Φ = 0.348] made using the MINI. CONCLUSION: Adult separation anxiety warrants independent assessment in order to tailor appropriate interventions for the individual subtypes of anxiety in the perinatal period.

Trastorno de ansiedad por separación / Separation anxiety disorder and developmental separation anxiety

Anxiety disorders constitute the most common psychiatric diseases in children. These disorders predict an increase in the risk of later anxiety disorders, mayor depression and hospitalization for psychiatric pathology. The primary feature of Separation Anxiety Disorder is developmentally inappropriate anxiety sufficient to cause clinically significant distress or impairment when faced with separation from home or major attachment figures. Drugs that selectively inhibit serotonin reuptake, psychotherapy and parent education constitute effective treatments for children and adolescents with anxiety disorders. Pediatricians and other health care professionals are in a unique position to assist families in understanding the etiology, prevention and treatment of separation anxiety disorder. Early identification in pediatric primary care and effective management may help improve outcome. The objective of our review is to analyze clinical and therapeutic aspects of the Separation Anxiety Disorder and its differences with Separation Anxiety as an expression of the evolutionary emotional development in children.

Los trastornos por ansiedad son cuadros clínicos psiquiátricos frecuentes y predicen un riesgo aumentado de presentar posteriormente trastornos ansiosos y depresivos, además de hospitalizaciones por causa psiquiátrica. El trastorno por ansiedad de separación tiene como característica principal ansiedad excesiva e inapropiada para el desarrollo del niño, concerniente a su separación respecto de las personas con quienes está vinculado. El uso de fármacos, psicoterapia y apoyo parental son medidas terapéuticas eficaces. Los pediatras pueden ser los primeros profesionales que tomen contacto clínico con los niños y realicen la primera aproximación diagnóstica y terapéutica. El propósito de nuestra revisión es analizar aspectos clínicos y terapéuticos del trastorno de ansiedad por separación y sus diferencias con la ansiedad de separación propia del desarrollo emocional del niño.

Visceral hyperalgesia induced by neonatal maternal separation is associated with nerve growth factor-mediated central neuronal plasticity in rat spinal cord.

Neonatal maternal separation (NMS) has been shown to trigger alterations in neuroendocrine, neurochemical and sensory response to nociceptive stimuli along the brain-gut axis. These alterations may be the result of a cascade of events that are regulated by neurotrophic factors. Nerve growth factor (NGF), a member of the neurotrophin family, is essential for the development and maintenance of sensory neurons and for the formation of central pain circuitry. The present study aimed to investigate whether NMS causes changes in neuronal plasticity and the relationship of these changes in plasticity with the expression of NGF and its high affinity tyrosine kinase receptor A (TrkA) in the lumbosacral spinal cord in adult rats. Male Wistar rat pups were either subjected to 180 min daily of NMS or not handled (NH) for 13 consecutive days. The expression of NGF and TrkA was examined in NH and NMS rats with or without colorectal distention (CRD) as determined by Western blot analysis and immunohistochemistry. The present results of Western blot analysis indicated NMS and CRD have a significant effect on NGF protein level in the lumbosacral spinal cord of rats. Assessments of optical densities revealed that NMS enhanced TrkA-ir fiber densities in laminae I-III and laminae V-VI of rats in both conditions with or without CRD. Double immunofluorescence revealed that TrkA co-expressed with calcitonin gene-related peptide (CGRP) in afferent fibers, while no significant difference in terms of the intensity of TrkA-ir in these fibers was found among groups. Quantitative analysis of TrkA-ir neurons indicated a significant interactive effect of NMS and CRD on the mean number of TrkA-ir neurons in laminae V-VI of rats, in which significant difference was found between NMS+CRD and NH+CRD. Double immunofluorescence of TrkA and Fos showed that CRD has a significant effect on TrkA expression in Fos-positive neurons in laminae V-VI and lamina X of rats, while no significant difference was found between NMS+CRD and NH+CRD. These results demonstrate that NMS induced alterations in NGF protein level and TrkA expression in adult rat spinal cord and indicate that NGF is a crucial mediator for the changes in neuronal plasticity that occur in NMS-induced visceral hyperalgesia.

Factores de riesgo psicológico en el trastorno límite de personalidad / Psychological risk factors in borderline personality disorder

En este trabajo se revisan los factores de riesgo psicológico en los trastornos límite de personalidad. Se concluye que el desarrollo de la psicopatología de estos trastornos no puede ser explicada por un único factor psicológico de riesgo o por un grupo de factores psicológicos de riesgo. Probablemente hay muchas vías que conducen el trastorno límite de personalidad. Las historias de tráuma tienen un papel relevante en un subgrupo de pacientes, mientras que otros factores de riesgo psicológico pueden ser más importantes en otros casos

Stuttering as a complication of strabismus surgery.

Children may experience extremely high levels of psychological stress in the operating suite because of anxiety associated with the separation from their parents, the unfamiliar and intimidating environment, the presence of strangers in unusual attire (masks, caps, gowns), the act of being forcibly restrained, and the forceful pressing over the mouth and nose of an anesthetic mask which emits a foul-smelling gas and which seems to restrict breathing in a manner reminiscent of suffocation. High levels of anxiety can lead to regression in a child's mental development, including stuttering, which is a regression to an earlier speech pattern and failure to develop fluent speech. Two cases are reported in which children developed stuttering following inappropriate or abusive treatment by the anesthesia departments of the hospitals in which they had surgery for strabismus. Both patients were four-year-old boys.

Disorders of the gastrointestinal tract in children: consultation-liaison experience.

Disorders of the gastrointestinal tract are common in children. Fortunately, many are short-lived, related to infection, food intolerance, or specific etiology. Those that persist or recur require greater attention on the part of the physician and can require psychiatric consultation. The frequency of consultation will depend in large part on the psychosocial sophistication and philosophy of care of the referring physician. When consulted, the child psychiatrist can complement the medical care by examination in greater detail of the psychosocial environment of the child, the family, and by psychiatric evaluation of the child. Formulation of these factors may then point the way to more helpful management of the child and treatment. The most serious problems, such as regional ileitis and ulcerative colitis, require not only collaboration of pediatricians and child psychiatrist, but surgeons as well if patients are to receive optimum care.