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Aim: This study aimed to investigate whether separation anxiety (SA) constitutes a dimension related to age at onset of panic disorder (PD), in homogeneous subgroups of outpatients with PD, based on their age of onset and symptom severity., Methods: A sample of 232 outpatients with PD was assessed with the Panic Disorder Severity Scale (PDSS) and the Sheehan Disability Scale (SDS) for functional impairments. Separation anxiety was evaluated using structured interviews and questionnaires. We applied a K-Means Cluster Analysis based on the standardized "PD age of onset" and "the PDSS total score" to identify distinct but homogeneous groups., Results: We identified three groups of patients: group 1 ("PD early onset/severe", N = 97, 42%, onset 23.2 ± 6.7 years), group 2 ("PD early onset/not severe", N = 76, 33%, onset 23.4 ± 6.0 years) and group 3 ("PD adult onset/not severe", N = 59, 25%, onset 42.8 ± 7.0 years). Patients with early onset/severe PD had significantly higher scores on all SA measures than PD late-onset/not severe. Regression analyses showed that SA scores, but not PDSS scores, were predictive of impairment in SDS work/school, social life, and family functioning domains., Conclusions: Our data indicate a significant relationship between SA and PD with an earlier age of onset and an impact on individual functioning. This may have important implications for implementing preventive interventions targeting early risk factors for the subsequent onset of PD., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Background: Separation anxiety disorder may be important when considering risk of suicide. The aim of this study was to examine the association between both childhood and adult separation anxiety (disorder) and measures of suicide risk in a large cohort of outpatients with anxiety and mood disorders., Methods: The sample included 509 consecutive adult psychiatric outpatients with DSM-IV mood disorders or anxiety disorders as a principal diagnosis recruited at the Department of Psychiatry, University of Pisa, Italy, between 2015 and 2018. Suicide risk was evaluated by the Hamilton Depression Rating Scale (HDRS) item 3. Patients were classified in 2 groups: those with a score ≥ 1 and those with a score of 0 on HDRS item 3. Suicide risk was also evaluated by specific items within the Mood Spectrum, Self-Report (MOODS-SR), a questionnaire evaluating lifetime suicidal symptoms. Separation anxiety (disorder) was assessed based on the Structured Interview for Separation Anxiety Symptoms in Adulthood/Childhood (SCI-SAS-A/C), the Separation Anxiety Symptom Inventory (SASI), and the Adult Separation Anxiety Scale (ASA-27)., Results: Of the 509 patients, 97 had an HDRS item 3 score ≥ 1, and 412 had a score of 0. Adult separation anxiety disorder was more frequent among individuals who had suicidal thoughts (53.6%) than those who did not (39.6%) (P = .01). Dimensional separation anxiety symptoms on all scales were elevated in patients with suicidality when compared to patients without (SASI: P = .02; SCI-SAS-C: P < .001; SCI-SAS-A: P < .001; ASA-27: P = .002). Logistic regression found that adult separation anxiety disorder (odds ratio [OR] = 1.86, 95% CI = 1.16-2.97), major depression (OR = 7.13, 95% CI = 3.18-15.97), bipolar I disorder (8.15, 95% CI = 3.34-19.90), and bipolar II disorder (OR = 8.16, 95% CI = 3.50-19.05) predicted suicidal thoughts. Linear regression found that depression (P = .001) and ASA-27 separation anxiety (P = .001) significantly predicted lifetime suicide risk. Mediation analysis found that separation anxiety significantly mediated the association between depression and suicide risk., Conclusions: This study indicates a substantial role of separation anxiety in predicting suicidal thoughts, both as state-related symptoms (evaluated by HDRS item 3) and as longitudinal dimensional symptoms (as evaluated by MOODS-SR). Greater understanding of the influence of separation anxiety in patients with affective disorders may encourage personalized interventions for reducing suicide risk., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

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 1β 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., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Rejection hypersensitivity has been considered the core feature of patients with borderline personality disorder (BPD). However, little is known about the possible developmental mechanisms that might explain the association between rejection sensitivity and BPD features. The current study investigated the mediating roles of adult attachment, need to belong, and self-criticism in the association between rejection sensitivity and BPD features in 256 healthy adults. Results indicated that attachment anxiety, need to belong, and self-criticism mediated the association between rejection sensitivity and BPD features. However, attachment anxiety and self-criticism did not moderate the mediated association between rejection sensitivity and BPD features. The findings suggest that individuals with high rejection sensitivity are more likely to be anxiously attached to significant others, which might increase the desire to be accepted by others. To satisfy this elevated need to affiliate with others, these individuals might become more self-critical, which may contribute to high BPD features.

Panic disorder (PD) is an acute paroxysmal anxiety disorder with poorly understood pathophysiology. The dorsal periaqueductal gray (dPAG) is involved in the genesis of PD. However, the downstream neurofunctional changes of the dPAG during panic attacks have yet to be evaluated in vivo. In this study, optogenetic stimulation to the dPAG was performed to induce panic-like behaviors, and in vivo positron emission tomography (PET) imaging with 18 F-flurodeoxyglucose ( 18 F-FDG) was conducted to evaluate neurofunctional changes before and after the optogenetic stimulation. Compared with the baseline, post-optogenetic stimulation PET imaging demonstrated that the glucose metabolism significantly increased (P < 0.001) in dPAG, the cuneiform nucleus, the cerebellar lobule, the cingulate cortex, the alveus of the hippocampus, the primary visual cortex, the septohypothalamic nucleus, and the retrosplenial granular cortex but significantly decreased (P < 0.001) in the basal ganglia, the frontal cortex, the forceps minor corpus callosum, the primary somatosensory cortex, the primary motor cortex, the secondary visual cortex, and the dorsal lateral geniculate nucleus. Taken together, these data indicated that in vivo PET imaging can successfully detect downstream neurofunctional changes involved in the panic attacks after optogenetic stimulation to the dPAG.

Background: Behavioural and psychological symptoms of dementia (BPSD) cause great suffering in patients and their families. Phenomenology can help clarify the diagnosis and propose some new therapeutic responses using Daseinsanalyse. Separation issues understood using the phenomenological description of the melancholic type (MT) by Tellenbach may further shed light on our understanding of depression in dementia., Subject and Methods: In a 90-year-old woman presenting with advanced (Clinical Dementia Rating 3) mixed dementia and BPSD in the form of vocally disruptive behaviour (VDB), we discuss separation anxiety as the aetiopathogenic hypothesis. Depression and BPSD were assessed using the Neuropsychiatric Inventory, Cornell scale, and Montgomery-Åsberg Depression Rating Scale to confirm our second phenomenological diagnostic hypothesis, ie, melancholy. The Big Five Inventory scale filled in by a proxy was also used to evaluate the patient's premorbid personality. We then propose an explanatory frame of VDB and depression through the standard phenomenological assessment of its relation to time, space, self, and other., Results: Confirming MT, we found an inhibited temperament and low openness to experience in the patient, as well as a symbiotic relationship with a close relative (the other)., Conclusion: Separation anxiety may well explain the patient's MT expressed by VDB. Melancholic type and her symbiotic relationship led to a situation unbearable to the patient and her close relative unable to delegate care to a specialized team., Running Head: Phenomenology in vocally disruptive behaviour in dementia. We have found new explanations in similar clinical cases in dementia as follows. A patient presenting with vocally disruptive behaviour has a melancholic type, a behavioural-inhibited temperament, and marital violence in the past. Phenomenology may help explain this profile with neurobiological disorders. The life trajectory, from childhood into older age, must be taken into account to understand behavioural and psychological symptoms of dementia., (© 2018 John Wiley & Sons, Ltd.)

Objective: In the present study, we compared social anxiety disorder (SAD) patients with ( n  = 31) and without childhood and adulthood separation anxiety disorder (SeAD) ( n  = 50) with respect to suicidal behavior, avoidant personality disorder (AvPD), other anxiety disorders (ADs), and major depression as well as some sociodemographic variables. Methods: In assessment of patients, we used Structured Clinical Interview for Separation Anxiety Symptoms, childhood and adulthood Separation Anxiety Symptom Inventories, Liebowitz Social Anxiety Scale, The SCID-II Avoidant Personality Disorder Module, Beck Depression Inventory, and Beck Scale for Suicidal Ideation. Results: SAD patients with SeAD had higher comorbidity rates of AvPD, other lifetime ADs and panic disorder, and current major depression than those without SeAD. The current scores of SAD, depression, and suicide ideation and the mean number of AvPD symptoms were significantly higher in comorbid group compared to pure SAD subjects. The SAD and SeAD scores had significant associations with current depression, suicide ideations, and AvPD. The mean number of AvPD criteria and the current severity of depression were significantly associated with the comorbidity between SAD and SeAD. Conclusion: Our findings might indicate that the comorbidity of SeAD with SAD may increase the risk of the severity of AvPD and current depression.

The present study examined the incremental validity of persistent complex bereavement disorder (PCBD) symptoms using an on-line survey of 255 bereaved college students. A series of hierarchical multiple regression analyses examined the extent to which PCBD symptoms explained unique variance in different domains of life impairment, beyond symptoms of depression, posttraumatic stress, and separation anxiety. The results supported the incremental validity of PCBD symptoms for fear of future losses, sleep impairment, and work/social impairment. However, PCBD symptoms did not account for loneliness scores. These findings collectively support the validity and clinical utility of the DSM-5's PCBD construct.

Lower urinary tract dysfunction (LUTD) is a common problem in children and constitutes up to 40% of pediatric urology clinic visits. Improved diagnosis and interventions have been leading to better outcomes in many patients, whereas some children are left untreated or do not respond to the treatment successfully. In addition, many of these patients are lost by the pediatric urologists during their teenage years, and the outcome in later life largely remains unidentified. Studies suggest childhood LUTD is associated with subsequent adult urinary tract symptoms. However, whether and how early life LUTD attributes to urinary symptoms in those patients later in life remains to be elucidated. In the current study, we investigated the effects of early life voiding perturbation on bladder function using a neonatal maternal separation (NMS) protocol in mice. The NMS group displayed a delayed development of voluntary voiding behavior, a significant reduction of functional bladder capacity, and bladder overactivity compared with control mice later in life. In vitro evaluation of detrusor smooth muscle and molecular study showed a decrease in muscarinic contribution alongside an increase in purinergic contribution in detrusor contractility in NMS mice compared with control group. These results suggest that early life bladder dysfunction interfered with the normal maturation of the voluntary micturition control and facilitated LUTD in a later stage, which is at least partly attributed to an alteration of muscarinic and purinergic signaling in the urinary bladder.

Purpose of Review: In light of the apparent symptomatic resemblance of separation anxiety disorder (SAD) symptoms on the one hand and abandonment fears, anxiousness, and separation insecurity central to borderline personality disorder (BPD) on the other hand, a comprehensive overview of separation anxiety and related traits in BPD is provided., Recent Findings: Epidemiological, environmental, psychological, and neurobiological data connecting BPD to separation events, feelings of loneliness, insecure attachment styles, dimensional separation anxiety as well as SAD per se suggest a partly shared etiological pathway model underlying BPD and SAD. Differential diagnostic aspects and implications for treatment are discussed, highlighting separation anxiety as a promising transdiagnostic target for specific psychotherapeutic and pharmacological treatment approaches in BPD. This innovative angle on cross-disorder symptomatology might carry potential for novel preventive and therapeutic avenues in clinical practice by guiding the development of interventions specifically targeting separation anxiety and attachment-related issues in BPD.

Background: Saffron has antidepressant and anxiolytic effects in adults with mild-to-moderate depression. However, this is the first study examining its mood-related effects in teenagers., Methods: In this 8-week, randomised, double-blind, placebo-controlled study, youth aged 12-16 years, with mild-to-moderate anxiety or depressive symptoms were given tablets containing placebo or a saffron extract (affron ® , 14 mg b.i.d). The youth and parent versions of the Revised Child Anxiety and Depression Scale (RCADS) were used as outcome measures., Results: 80 participants were enrolled and 68 completed the study. Based on youth self-reports, affron ® was associated with greater improvements in overall internalising symptoms (p = 0.049), separation anxiety (p = 0.003), social phobia (p = 0.023), and depression (p = 0.016). Total internalising scores decreased by an average of 33% compared to 17% in the placebo group (p = 0.029). However, parental reports of improvements were inconsistent as mean improvements in RCADS scores were greater in the saffron group (40% vs 26%) (p = 0.026), although no other significant differences were identified. affron ® was well-tolerated and there was a trend of reduced headaches in participants on the active treatment., Limitations: The use of a self-report instrument, limited study duration, single treatment dose, and non-clinical sample used in this study limit the generalisability of study findings., Conclusion: The administration of a standardised saffron extract (affron ® ) for 8 weeks improved anxiety and depressive symptoms in youth with mild-to-moderate symptoms, at least from the perspective of the adolescent. However, these beneficial effects were inconsistently corroborated by parents., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Separation of newborn rats from their mothers induces visceral hypersensitivity and impaired epithelial secretory cell lineages when they are adults. Little is known about the mechanisms by which maternal separation causes visceral hypersensitivity or its relationship with defects in epithelial secretory cell lineages., Methods: We performed studies with C3H/HeN mice separated from their mothers as newborns and mice genetically engineered (Sox9 flox/flox -vil-cre on C57BL/6 background) to have deficiencies in Paneth cells. Paneth cell deficiency was assessed by lysozyme staining of ileum tissues and lysozyme activity in fecal samples. When mice were 50 days old, their abdominal response to colorectal distension was assessed by electromyography. Fecal samples were collected and microbiota were analyzed using Gut Low-Density Array quantitative polymerase chain reaction., Results: Mice with maternal separation developed visceral hypersensitivity and defects in Paneth cells, as reported from rats, compared with mice without maternal separation. Sox9 flox/flox -vil-Cre mice also had increased visceral hypersensitivity compared with control littermate Sox9 flox/flox mice. Fecal samples from mice with maternal separation and from Sox9 flox/flox -vil-cre mice had evidence for intestinal dysbiosis of the microbiota, characterized by expansion of Escherichia coli. Daily gavage of conventional C3H/HeN adult mice with 10 9 commensal E coli induced visceral hypersensitivity. Conversely, daily oral administration of lysozyme prevented expansion of E coli during maternal separation and visceral hypersensitivity., Conclusions: Mice with defects in Paneth cells (induced by maternal separation or genetically engineered) have intestinal expansion of E coli leading to visceral hypersensitivity. These findings provide evidence that Paneth cell function and intestinal dysbiosis are involved in visceral sensitivity., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The current study evaluated the possibility that greater negative mental health outcomes reported among gay, lesbian, and gender-atypical individuals, compared to gender-typical individuals, are present in childhood and persist into adulthood. Sex and sexual orientation differences in self-reported adulthood and recalled childhood indicators of depression and anxiety and their association with current and retrospectively reported gender (a)typicality were examined in a non-clinically recruited community sample of Canadian heterosexual men (n = 98), heterosexual women (n = 142), gay men (n = 289), and lesbian women (n = 69). Indicators of depression and anxiety were constructed based on diagnostic criteria for generalized anxiety disorder, major depression, agoraphobia, social anxiety disorder, panic disorder, obsessive-compulsive disorder, and specific phobias. Factor reduction analyses yielded three factors: (1) indicators of childhood separation anxiety, (2) indicators of childhood depression and anxiety, and (3) indicators of adulthood depression and anxiety. Lesbian women scored higher on childhood separation anxiety than all other groups. Heterosexual men scored lower on indicators of childhood separation anxiety than gay men and lower on indicators of childhood and adulthood depression and anxiety than all other groups. No other significant group differences were observed. Correlational analysis suggested that for men, but not for women, gender-atypical behavior was associated with negative mental health. The current study indicated that childhood should be considered a critical time period during which the noted sexual orientation-related mental health discrepancies manifest and that childhood gender atypicality is a key factor for understanding the emergence of such discrepancies.

Immigration often results in the separation of families, and in particular transnational parenting, which is the separation of mothers from children. Transnational mothers may have greater risks for poor mental health and behavioral conditions such as substance abuse, violence, sexual risk, and depression. This study was a secondary analysis of self-reported data from 425 Hispanic mothers (328 with no separations, 60 separated from an adult child, and 37 separated from a minor child) enrolled in a randomized trial of a sexual health group intervention in South Florida (USA). Separations were related to mother's age, years in the United States, family income, number of people living on income, acculturation to the United States, occupational/economic stress, immigration stress, and lifetime exposure to abuse. A follow-up analysis described the types of childhood or adulthood abuse experienced by mothers with separations. These findings provide new information for nurses about the experience of immigrant mothers.

The peculiarities in expression of transport proteins and the proteins implicated in the control of glycolysis by the cellular components of neurovascular units were examined in animals of different age under normal conditions and after modeled perinatal stress or hypoxic brain injury. In both cases, the specialties in expression of transport proteins in ontogenesis were revealed. The perinatal hypoxic brain injury resulted in up-regulation of MCT1, MCT4, and GLUT4 expression in endotheliocytes of hippocampal microvessels accompanied by transient elevation of HIF-1α and GSK3 expression.

US military deployments have become more frequent and lengthier in duration since 2003. Over half of US military members are married, and many also have children. The authors sought to understand the process of deployment from the perspective of the military family. After a thorough search of the literature, 21 primary research reports of 19 studies with an aggregate sample of 874 were analyzed using qualitative metasynthesis. The deployment process was experienced in four temporal domains. The military family as a whole shared the pre-deployment transition: all family members felt uncertain about the future, needed to complete tasks to "get ready" for deployment, and experienced a sense of distancing in preparation for the upcoming separation. The AD member went through the deployment transition independently, needing to "stay engaged" with the military mission, building a surrogate family and simultaneously trying to maintain connection with the family at home. In parallel, the home front family was going through a transposement transition, moving forward as an altered family unit, taking on new roles and responsibilities, and trying to simultaneously connect with the deployed member and find support from other military families. In post-deployment, the family went through the "reintegration" transition together, managing expectations, and readjusting family roles, all needing understanding and appreciation for their sacrifices during the recent separation. Effective family communication was important for military family well-being after deployment but unexpectedly challenging for many. Clinical, research, and policy recommendations are discussed., (© 2015 Wiley Periodicals, Inc. This article has been contributed to by a US Government employee and her work is in the public domain in the USA.)

Background: Separation anxiety among intellectually disabled (ID) persons with comorbid visual impairment could be rooted in a weak sense of person permanence. Technology-assisted Therapy for Separation Anxiety (TTSA) was used to address this problem., Aims: The primary aim was to determine whether technology alone or including caregivers was the best option, and whether TTSA decreased separation anxiety and challenging behaviour. Also, how the caregivers and the client experienced TTSA., Methods and Procedures: A pre-experimental, quantitative approach (AB1C1B2C2D) was used for this single-subject study. The frequency of the client's text messages was recorded daily. The variables were monitored with standardised instruments and caregivers rated the intensity and frequency of the client's anxious and challenging behaviour. The social validity was evaluated by means of questionnaires., Outcomes and Results: There was a significant decrease in the anxious and angry messages sent, and in anxious and challenging behaviour, in the phase in which the caregivers were included, compared with the phase in which technology alone was used. The client and the caregivers were positive about TTSA., Conclusion and Implication: Technology and the caregivers reactions reduces the anxiety and challenging behaviour. It might also aid the acquisition of the concept of person permanence., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Increasing literature has been focused on complicated grief (CG) and its distinctiveness from other potentially loss related mental disorders such as major depression (MD). In this regard, symptoms of separation distress seem to play a key role. The aim of this study was to compare the clinical features of CG to those of MD and of CG+MD, with particular attention to separation anxiety., Methods: Fifty patients with CG (26 with and 24 without MD) and 40 with MD were consecutively recruited. Assessments included: SCID-I/P, Inventory of Complicated Grief (ICG), Adult Separation Anxiety Symptom Questionnaire (ASA-27), Work and Social Adjustment Scale (WSAS), Mood Spectrum-Self Report (MOODS-SR)-lifetime version., Results: Patients with MD reported significantly higher ASA-27 scores than patients with CG either alone or with MD. In all groups, ASA-27 total scores were significantly correlated with the MOODS-SR total scores and with those of its depressive component and rhythmicity domain. No significant differences were reported in the WSAS scores., Limitations: Major limitations are the small sample size and the use of lifetime instruments., Conclusions: Our results suggest a correlation between adult separation anxiety symptoms and lifetime mood spectrum symptoms both in patients with CG and MD. Further studies are needed to better understand the role of adult separation anxiety in the development of these disorders and for their nosographic autonomy as well., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 the American Physiological Society.)

Aim: To investigate the pharmacological effect of TongXie-YaoFang (TXYF) formula and its underlying mechanisms., Methods: A neonatal maternal separation plus restraint stress (NMS + RS) model of diarrhea-predominant irritable bowel syndrome was developed by subjecting male Sprague-Dawley rats to daily maternal separation from postnatal days 2 to 21 plus restraint stress from days 50 to 59. Rats were randomly divided into two groups (NMS + RS and TXYF formula), and rats with no handling or separation were used as normal controls. Starting from postnatal day 60, rats were administered TXYF formula (9.84 g/100 g body weight) orally twice daily for 14 consecutive days, while the normal and NMS + RS groups were given distilled water. The distinctions of movement index (MI, area under the curve of contraction intensity/min, mg/min) and contraction frequency (CF, number of contractions/min, times/min) of isolated colonic longitudinal smooth muscle strips (CLSMs) in the three groups before and after treatment were observed with a Power Lab system. Different inhibitors were applied, and then 10(-4) mol/L acetylcholine chloride (Ach) was added to CLSMs to induce muscle contraction., Results: Before treatment, the MI of CLSMs in the NMS + RS and TXYF formula groups was similar and both higher than that in the normal group (545.49 ± 73.66 mg/min vs 245.76 ± 34.44 mg/min and 551.09 ± 54.29 mg/min vs 245.76 ± 34.44 mg/min, P < 0.01, respectively). After treatment, the MI in the TXYF formula group was lower than that in the NMS + RS group (261.39 ± 38.59 mg/min vs 533.9 ± 61.63 mg/min, P < 0.01). In the same way, the CF of CLSMs in the NMS + RS and TXYF formula groups was similar and both higher than that in the normal group (3.42 ± 0.25 times/min and 3.31 ± 0.21 vs 1.1 ± 0.17 times/min, P < 0.01) before treatment. After treatment, the CF in the TXYF formula group was lower than that in the NMS + RS group (1.42 ± 0.87 times/min vs 3.11 ± 0.82 times/min, P < 0.01) and similar to that in the normal group (1.42 ± 0.87 times/min vs 1.09 ± 0.13 times/min). When 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride and 4-aminopyridine were added to the bath and equilibrated for 30 min, respectively, and 10(-4) mol/L Ach was added to CLSMs to induce muscle contraction, MI of the CLSMs in the TXYF formula group was lower than that in the normal group (666 ± 36.32 mg/min vs 747.77 ± 49.47 mg/min, and 686.53 ± 39.17 mg/min vs 750.45 ± 29.39 mg/min; P < 0.01, respectively). The MI of CLSMs in the TXYF formula group was lower than that in the normal group after treatment with nifedipine (689.48 ± 30.84 mg/min vs 741.65 ± 32.41 mg/min; P < 0.05)., Conclusion: TXYF formula inhibits colon contraction in rats. This may be related to activation of specific potassium channels and inhibition of extracellular calcium internal flow.

Background: Anorexia nervosa is a primary psychiatric disorder, with non-negligible rates of mortality and morbidity. Some of the related alterations could participate in a vicious cycle limiting the recovery. Animal models mimicking various physiological alterations related to anorexia nervosa are necessary to provide better strategies of treatment., Aim: To explore physiological alterations and recovery in a long-term mouse model mimicking numerous consequences of severe anorexia nervosa., Methods: C57Bl/6 female mice were submitted to a separation-based anorexia protocol combining separation and time-restricted feeding for 10 weeks. Thereafter, mice were housed in standard conditions for 10 weeks. Body weight, food intake, body composition, plasma levels of leptin, adiponectin, IGF-1, blood levels of GH, reproductive function and glucose tolerance were followed. Gene expression of several markers of lipid and energy metabolism was assayed in adipose tissues., Results: Mimicking what is observed in anorexia nervosa patients, and despite a food intake close to that of control mice, separation-based anorexia mice displayed marked alterations in body weight, fat mass, lean mass, bone mass acquisition, reproductive function, GH/IGF-1 axis, and leptinemia. mRNA levels of markers of lipogenesis, lipolysis, and the brown-like adipocyte lineage in subcutaneous adipose tissue were also changed. All these alterations were corrected during the recovery phase, except for the hypoleptinemia that persisted despite the full recovery of fat mass., Conclusion: This study strongly supports the separation-based anorexia protocol as a valuable model of long-term negative energy balance state that closely mimics various symptoms observed in anorexia nervosa, including metabolic adaptations. Interestingly, during a recovery phase, mice showed a high capacity to normalize these parameters with the exception of plasma leptin levels. It will be interesting therefore to explore further the central and peripheral effects of the uncorrected hypoleptinemia during recovery from separation-based anorexia.

Plenty of evidence suggests that childhood separation anxiety (CSA) predisposes the subject to adult-onset panic disorder (PD). As well, panic is frequently comorbid with both anxiety and depression. The brain mechanisms whereby CSA predisposes to PD are but completely unknown in spite of the increasing evidence that panic attacks are mediated at midbrain's dorsal periaqueductal gray matter (DPAG). Accordingly, here we examined whether the neonatal social isolation (NSI), a model of CSA, facilitates panic-like behaviors produced by electrical stimulations of DPAG of rats as adults. Eventual changes in anxiety and depression were also assessed in the elevated plus-maze (EPM) and forced-swimming test (FST) respectively. Male pups were subjected to 3-h daily isolations from post-natal day 2 (PN2) until weaning (PN21) allotting half of litters in individual boxes inside a sound-attenuated chamber (NSI, n = 26) whilst siblings (sham-isolated rats, SHAM, n = 27) and dam were moved to another box in a separate room. Non-handled controls (CTRL, n = 18) remained undisturbed with dams until weaning. As adults, rats were implanted with electrodes into the DPAG (PN60) and subjected to sessions of intracranial stimulation (PN65), EPM (PN66) and FST (PN67-PN68). Groups were compared by Fisher's exact test (stimulation sites), likelihood ratio chi-square tests (stimulus-response threshold curves) and Bonferroni's post hoc t-tests (EPM and FST), for P<0.05. Notably, DPAG-evoked panic-like responses of immobility, exophthalmus, trotting, galloping and jumping were markedly facilitated in NSI rats relative to both SHAM and CTRL groups. Conversely, anxiety and depression scores either did not change or were even reduced in neonatally-handled groups relative to CTRL, respectively. Data are the first behavioral evidence in animals that early-life separation stress produces the selective facilitation of panic-like behaviors in adulthood. Most importantly, results implicate the DPAG not only in panic attacks but also in separation-anxious children's predispositions to the late development of PD.

The circadian system develops and changes in a gradual and programmed process over the lifespan. Early in life, maternal care represents an important zeitgeber and thus contributes to the development of circadian rhythmicity. Exposure to early life stress may affect circadian processes and induce a latent circadian disturbance evident after exposure to later life stress. Disturbance of the normal regulation of circadian rhythmicity is surmised to be an etiological factor in depression. We used postnatal maternal separation in rats to investigate how the early life environment might modify the circadian response to later life unpredictable and chronic stress. During postnatal days 2-14, male Wistar rats (n = 8 per group) were daily separated from their mothers for a period of either 180 min (long maternal separation; LMS) or 10 min (brief maternal separation; BMS). In adulthood, rats were exposed to chronic mild stress (CMS) for 4 weeks. Body temperature, locomotor activity and heart rate were measured and compared before and after CMS exposure. LMS offspring showed a delayed body temperature acrophase compared to BMS offspring. Otherwise, adult LMS and BMS offspring demonstrated similar diurnal rhythms of body temperature, locomotor activity and heart rate. Exposure to CMS provoked a stronger and longer lasting hypothermia in LMS rats than in BMS rats. The thermoregulatory response appears to be moderated by maternal care following reunion, an observation made in the LMS group only. The results show that early life stress (LMS) in an early developmental stage induced a thermoregulatory disturbance evident upon exposure to unpredictable adult life stressors.

Aberrant serotonin (5-HT) signalling and exposure to early life stress have both been suggested to play a role in anxiety- and impulsivity-related behaviours. However, whether congenital 5-HT deficiency × early life stress interactions influence the development of anxiety- or impulsivity-like behaviour has not been established. Here, we examined the effects of early life maternal separation (MS) stress on anxiety-like behaviour and behavioural disinhibition, a type of impulsivity-like behaviour, in wild-type (WT) and tryptophan hydroxylase 2 (Tph2) knock-in (Tph2KI) mice, which exhibit ~60-80% reductions in the levels of brain 5-HT due to a R439H mutation in Tph2. We also investigated the effects of 5-HT deficiency and early life stress on adult hippocampal neurogenesis, plasma corticosterone levels and several signal transduction pathways in the amygdala. We demonstrate that MS slightly increases anxiety-like behaviour in WT mice and induces behavioural disinhibition in Tph2KI animals. We also demonstrate that MS leads to a slight decrease in cell proliferation within the hippocampus and potentiates corticosterone responses to acute stress, but these effects are not affected by brain 5-HT deficiency. However, we show that 5-HT deficiency leads to significant alterations in SGK-1 and GSK3β signalling and NMDA receptor expression in the amygdala in response to MS. Together, these findings support a potential role for 5-HT-dependent signalling in the amygdala in regulating the long-term effects of early life stress on anxiety-like behaviour and behavioural disinhibition.

Objective: Evidence suggests that childhood separation anxiety disorder may be associated with a heightened risk for the development of other disorders in adulthood. The authors conducted a meta-analysis to examine the relationship between childhood separation anxiety disorder and future psychopathology., Method: PubMed, PsycINFO, and Embase were searched for studies published through December 2011. Case-control, prospective, and retrospective cohort studies comparing children with and without separation anxiety disorder with regard to future panic disorder, major depressive disorder, any anxiety disorder, and substance use disorders were included in the analysis. Effects were summarized as pooled odds ratios in a random-effects model., Results: Twenty-five studies met all inclusion criteria (14,855 participants). A meta-analysis of 20 studies indicated that children with separation anxiety disorder were more likely to develop panic disorder later on (odds ratio=3.45; 95% CI=2.37-5.03). Five studies suggested that a childhood diagnosis of separation anxiety disorder increases the risk of future anxiety (odds ratio=2.19; 95% CI=1.40-3.42). After adjusting for publication bias, the results of 14 studies indicated that childhood separation anxiety disorder does not increase the risk of future depression (odds ratio=1.06; 95% CI=0.78-1.45). Five studies indicated that childhood separation anxiety disorder does not increase the risk of substance use disorders (odds ratio=1.27; 95% CI=0.80-2.03). Of the subgroup analyses performed, differences in comparison groups and sample type significantly affected odds ratio sizes., Conclusions: A childhood diagnosis of separation anxiety disorder significantly increases the risk of panic disorder and any anxiety disorder. These results support a developmental psychopathology conceptualization of anxiety disorders.

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.

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.

There is a need to explain the high level of comorbidity between separation anxiety disorder (SAD) in adulthood and panic disorder with agoraphobia (Pd-Ag). One possibility is that inadequate specification of symptom domains and/or diagnostic questions accounts for some of the comorbidity. The present anxiety clinic study examined responses of adult patients (n = 646) with SAD and/or Pd-Ag on eight symptom domains based on a previous factor analysis of a commonly used separation anxiety measure, the ASA-27, as well as on the Anxiety Sensitivity Index. We also examined questionnaire items that did not load on the factor structure. All separation anxiety domains distinguished strongly between SAD and Pd-Ag. Comparisons across three groups (SAD alone, Pd-Ag alone and comorbid SAD/Pd-Ag) revealed that two symptom domains (anxiety about embarking on trips, and sleep disturbances) showed some overlap between Pd-Ag and SAD. Two of the items of the ASA-27 that did not load with other items in the factor analysis also showed overlap with Pd-Ag, with both referring to anxieties about leaving home. Patients with SAD (with or without Pd-Ag) returned higher scores on anxiety sensitivity than those with Pd-Ag alone. The findings support the distinctiveness of the construct of SAD and the capacity of the ASA-27 to discriminate between that disorder and Pd-Ag. SAD appears to be a more severe form of anxiety than Pd-Ag. There may be a need to refine items to include the reasons for avoiding leaving home, reluctance to sleep alone and to embark on trips, to ensure accurate discrimination between Pd-Ag and SAD in adulthood., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Maternal separation (MS) induces depressive-like behavior and long-term changes in cognition in rats. Escitalopram is an antidepressant drug shown to reverse the depressive-like features caused by this stress model. However, it is not known if it can ameliorate the affected cognition. We now characterized the effect of escitalopram on hippocampal-dependent memory in rats submitted to the MS protocol. Male Wistar rats were assigned either to control (CTR) or maternal separated (MS) group. MS were separated from their dams between 2-14 postnatal days (PND) for 180min daily. Escitalopram was given in food pellets (0.34g/kg/day first 2 weeks and 0.41g/kg/day the subsequent period, average dose 25mg/kg) from PND 43 onwards, during 1 month. Depressive behavior was assessed in the forced swimming test (FST), and memory performance in the Morris water maze (MWM). Escitalopram significantly improved the FST's latency to despair in the MS group (n=6), but did not change the immobility time. All groups showed a significant learning effect in the MWM over time, but no differences have been found upon treatment (n=6). However, escitalopram treatment significantly increased the time spent on the platform quadrant in the probe trial in the MS group. We report here that chronic treatment with escitalopram is able to improve hippocampal dependent memory in a chronic stress model, while not changing the learning ability. Moreover, this is accompanied by an amelioration of the depressive like behavior. These results support the use of escitalopram to tackle underlying cognitive deficits caused by stress in early-life., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Since the mid-90s several studies have proven the existence of an Adult form of the Separation Anxiety Disorder (ASAD) not yet nosologically recognized by the international psychiatric classification systems (DSM and ICD). An increasing amount of evidence showed that the separation anxiety disorder may arise at any age, not always in continuation with the correspondent childhood disorder. So, a revision of the diagnostic criteria for this disorder is brought into question, as the onset is currently limited before 18 years of age. Different tools have been developed for the assessment of ASAD: 1) the Adult Separation Anxiety Structured Interview (ASA-SI), a semi-structured interview with items derived and adapted from the DSM-IV-TR childhood disorder; 2) the Adult Separation Anxiety-27 (ASA-27), a self-administered rating scale containing the same items of ASA-SI; 3) the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS), a structured interview including two specific forms for childhood and adulthood. However, according to available evidence, the separation anxiety may be a dimension with cross-nosographical presentation in nearly all the commonest mood and anxiety disorders; moreover, it is connected to greater personal dysfunction and lower responsiveness to treatment. Furthermore, a deeper comprehension of the psychobiological nature of separation anxiety should lead to newer and more effective therapeutic intervention. Literature is reviewed awaiting the publication of DSM-V.

Visceral hypersensitivity is an important characteristic feature of functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). This study evaluated the effect of Schisandra chinensis on visceral hyperalgesia induced by neonatal maternal separation (NMS) in an IBS rat model. The visceromotor responses to colorectal balloon distension (CRD) were measured by abdominal withdrawal reflex (AWR) and electromyographic (EMG) activities. NMS control rats (receiving vehicle) underwent aggravated visceral pain in response to CRD as compared to normal rats, evidenced by the reduced pain threshold, enhanced AWR scores and EMG responses. Treatment with a 70% ethanol extract of S. chinensis (0.3g/kg and 1.5g/kg/day) for 7 days resulted in an increase in the pain threshold (NMS control: 19.1±1.0mmHg vs low-dose: 24.8±1.3mmHg and high-dose: 25.2±1.8mmHg, p<0.01), and abolished the elevated AWR and EMG responses to CRD in NMS rats (AUC values of EMG response curve were: 1952±202 in NMS control group vs 1074±90 in low-dose group and 1145±92 in high-dose group, p<0.001), indicating that S. chinensis could reverse the visceral hypersensitivity induced by early-life stress event. The result of ELSA measurement shows that the elevated serotonin (5-HT) level in the distal colon of NMS rats returned to normal level after treatment with S. chinensis. Moreover, the increase in pain threshold in rats treated with S. chinensis was associated with a decline of the mRNA level of 5-HT(3) receptor in the distal colon. All available results demonstrate that S. chinensis can reverse visceral hypersensitivity induced by neonatal-maternal separation, and the effect may be mediated through colonic 5-HT pathway in the rat., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Background: Efficacy of treatments for panic disorder is well established, but not all patients respond. Adult separation anxiety has been found to predict poorer response to CBT, but its effect on response to medication has not been previously explored., Study Aim: The aim of this study is to investigate if panic-agoraphobic spectrum factors, including 'separation anxiety' factor predict treatment outcome in patients with panic disorder., Study Sample: Participants who met criteria for PD (n=57) completed baseline assessment and 12 months follow-up. Patients were administered the Panic Agoraphobic Spectrum Self-Report (PAS-SR, Lifetime and Last-Month Versions), and the Panic Disorder Severity Scale (PDSS). We examined patients who met the following criteria at baseline: 1) PDSS total score>7; 2) no current Axis I comorbidity with major depression; 3) no lifetime or current bipolar disorder. All patients were treated with evidence-based psychopharmacological treatment for panic disorder during the 12-month observation period., Results: Twenty eight patients (48.1%) achieved remission during the follow-up period. In a logistic regression model, controlling for baseline severity, gender and age, only the last-month PAS-SR 'separation anxiety' factor was associated with a lower likelihood of remission., Conclusions: Signs and symptoms of separation anxiety in adulthood, as assessed with the PAS-SR Last Month version, are predictors of poor treatment outcome in patients with PD. We submit that the assessment of panic-agoraphobic spectrum features, including adult separation anxiety, should become routine of clinical assessment of patients with PD. It is likely that a better psychopathological characterization of patients may inform treatment selection, and result in better treatment outcome., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (10(9) microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05). Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05), whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05) compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01) and α-linolenic acid in adipose tissue (p<0.001), whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05), and α-linolenic acid in adipose tissue (p<0.001). B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats significantly modified the palmitoleic acid, arachidonic acid and docosahexaenoic acid contents in tissues. The effect was not observed in non-separated animals.

Background: In man, many different events implying childhood separation from caregivers/unstable parental environment are associated with heightened risk for panic disorder in adulthood. Twin data show that the occurrence of such events in childhood contributes to explaining the covariation between separation anxiety disorder, panic, and the related psychobiological trait of CO(2) hypersensitivity. We hypothesized that early interference with infant-mother interaction could moderate the interspecific trait of response to CO(2) through genetic control of sensitivity to the environment., Methodology: Having spent the first 24 hours after birth with their biological mother, outbred NMRI mice were cross-fostered to adoptive mothers for the following 4 post-natal days. They were successively compared to normally-reared individuals for: number of ultrasonic vocalizations during isolation, respiratory physiology responses to normal air (20%O(2)), CO(2)-enriched air (6% CO(2)), hypoxic air (10%O(2)), and avoidance of CO(2)-enriched environments., Results: Cross-fostered pups showed significantly more ultrasonic vocalizations, more pronounced hyperventilatory responses (larger tidal volume and minute volume increments) to CO(2)-enriched air and heightened aversion towards CO(2)-enriched environments, than normally-reared individuals. Enhanced tidal volume increment response to 6%CO(2) was present at 16-20, and 75-90 postnatal days, implying the trait's stability. Quantitative genetic analyses of unrelated individuals, sibs and half-sibs, showed that the genetic variance for tidal volume increment during 6%CO(2) breathing was significantly higher (Bartlett χ = 8.3, p = 0.004) among the cross-fostered than the normally-reared individuals, yielding heritability of 0.37 and 0.21 respectively. These results support a stress-diathesis model whereby the genetic influences underlying the response to 6%CO(2) increase their contribution in the presence of an environmental adversity. Maternal grooming/licking behaviour, and corticosterone basal levels were similar among cross-fostered and normally-reared individuals., Conclusions: A mechanism of gene-by-environment interplay connects this form of early perturbation of infant-mother interaction, heightened CO(2) sensitivity and anxiety. Some non-inferential physiological measurements can enhance animal models of human neurodevelopmental anxiety disorders.

Research Questions: Separation anxiety disorder (SAD) is one of the most common mental disorders in childhood, and one of the earliest emerging. Little is known about the association between SAD and the hypothalamic-pituitary-adrenocortical (HPA) axis activity. Therefore, the present study aimed at investigating this association in children suffering from separation anxiety compared to healthy controls., Methods: A total of 31 children with diagnosed SAD (mean age: 8.45; 17 females, 14 males) and 25 healthy controls (HC; mean age: 9.74; 12 females, 13 males) took part in the study. All participants underwent psycho-physiological testing for HPA axis challenge. Testing consisted of a separation and a social exposure paradigm. Saliva samples to assess HPA axis-related cortisol secretion were gathered in parallel., Results: Compared to healthy controls, children with SAD showed greatly increased HPA axis activity, as reflected by an increased cortisol secretion throughout the entire period of investigation. The rise of cortisol was already observed in anticipation of, but not following the separation paradigm. No gender-related differences of cortisol secretion were observed., Conclusions: Separation anxiety disorder (SAD) in children is reflected in greatly increased HPA axis activity. Compared to healthy controls, children with SAD showed increased cortisol values from the beginning of, and throughout, the entire investigation. This pattern of results suggests that both the anticipation of a separation and a persistent hyperactivity of the HPA axis system leads to an increased cortisol secretion., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

A recent study has suggested a link between early separation anxiety and personality disorder. It is possible that this relationship is mediated or confounded by the presence of adult separation anxiety disorder (ASAD). In a clinic study of 397 anxiety patients, we found that ASAD patients with heightened early separation anxiety had higher rates of any Cluster C personality disorder compared to ASAD patients without elevated early separation anxiety, and higher rates of any Cluster B or C personality disorder compared to anxiety patients with low early separation anxiety and no ASAD. Although cross-sectional in design, the study supports a direct link between early separation anxiety and some adult personality disorders, irrespective of the type of adult anxiety disorder present, including ASAD.

Candidates for emigration are susceptible to a psychotic breakdown accompanied by feelings of guilt arising from abandoning their community of origin. The elimination of this guilt involves, essentially, a denial of identity with a touch of megalomania which makes treatment difficult.

Aim: To investigate the pharmacological effect of JCM-16021, a Chinese herbal formula, and its underlying mechanisms., Methods: JCM-16021 is composed of seven herbal plant materials. All raw materials of the formula were examined according to the quality control criteria listed in the Chinese Pharmacopeia (2005). In a neonatal maternal separation (NMS) model, male Sprague-Dawley rats were submitted to daily maternal separation from postnatal day 2 to day 14, or no specific handling (NH). Starting from postnatal day 60, rats were administered JCM-16021 (2, 4, 8 g/kg per day) orally twice a day for 28 d. Pain threshold pressure and electromyographic activities of external oblique muscles in response to colorectal distention recorded with a Power Lab System (AD Instruments International), were tested as pain indices. Changes in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the colon of rats were analyzed; the enterochromaffin cell numbers and serotonin transporter in the colon of rats were also evaluated with an immunohistochemistry method., Results: NMS treatment significantly reduced pain threshold pressure (37.4 +/- 1.4 mmHg), as compared to that of NH rats (57.7 +/- 1.9 mmHg, P < 0.05). After JCM-16021 treatment, the pain threshold pressure significantly increased when compared to that before treatment (34.2 +/- 0.9 mmHg vs 52.8 +/- 2.3 mmHg in the high dose group, 40.2 +/- 1.6 mmHg vs 46.5 +/- 1.3 mmHg in the middle dose group, and 39.3 +/- 0.7 mmHg vs 46.5 +/- 1.6 mmHg in the low dose group, P < 0.05). Also JCM-16021 significantly and dose-dependently decreased electromyographic activity to the graded colorectal distension (CRD), (the mean DeltaAUC values were: 0.17 +/- 0.03, 0.53 +/- 0.15, 1.06 +/- 0.18, 1.22 +/- 0.24 in the high dose group; 0.23 +/- 0.04, 0.68 +/- 0.17, 1.27 +/- 0.26, 1.8 +/- 0.3 in the middle dose group; and 0.29 +/- 0.06, 0.8 +/- 0.16, 1.53 +/- 0.24, 2.1 +/- 0.21 in the low dose group for the pressures 20, 40, 60, 80 mmHg), as compared to the NMS vehicle group. The mean DeltaAUC values were: 0.57 +/- 0.12, 1.33 +/- 0.18, 2.57 +/- 0.37, 3.08 +/- 0.37 for the pressures 20, 40, 60, 80 mmHg (P < 0.05). JCM-16021 treatment significantly reduced the 5-HT concentrations (from high, middle and low dosage groups: 60.25 +/- 5.98 ng/100 mg, 60.32 +/- 4.22 ng/100 mg, 73.31 +/- 7.65 ng/100 mg), as compared to the NMS vehicle groups (93.11 +/- 9.85 ng/100 mg, P < 0.05); and increased the 5-HIAA concentrations (after treatment, from high, middle and low dosage groups: 54.24 +/- 3.27 ng/100 mg, 50.34 +/- 1.26 ng/100 mg, 51.37 +/- 2.13 ng/100 mg) when compared to that in the NMS vehicle group (51.75 +/- 1.98 ng/100 mg, P < 0.05); but did not change the enterochromaffin cell numbers in the colon of rats. In addition, NMS rats had higher SERT expression (n = 10) than NH rats (n = 8, P < 0.05). JCM-16021 treatment significantly decreased SERT expression when compared to the NMS group (P < 0.01-0.001)., Conclusion: JCM-16021 can attenuate visceral hypersensitivity, and this analgesic effect may be mediated through the serotonin signaling pathway in the colon of rats.

Background: Recent studies indicate that adult separation anxiety disorder is a discrete diagnostic entity and worthy of attention. Previously, we found a significant association between platelet expression of the 18-kDa translocator protein (TSPO) and adult separation anxiety in patients with panic disorder or major depression. The aim of this study was to explore whether adult separation anxiety might be a factor differentiating TSPO expression in a sample of patients with bipolar disorder., Methods: The equilibrium binding parameters of the specific TSPO ligand [(3)H]PK 11195 were estimated on the platelet membranes of 24 adult outpatients with a DSM-IV diagnosis of bipolar disorder (with or without separation anxiety disorder) and 14 healthy controls. Patients were assessed by SCID-I, HAM-D, YMRS, the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS-A) and the Adult Separation Anxiety Self-Report Checklist (ASA-27)., Results: A significant reduction in mean platelet TSPO density was found in bipolar patients with respect to controls. However, the lower density was only evident in the subgroup of bipolar patients who also fulfilled DSM-IV criteria for adult separation anxiety disorder. Individual TSPO density values correlated significantly and negatively with both SCI-SAS-A and ASA-27 total scores., Conclusions: TSPO expression may be a useful biological marker of adult separation anxiety co-occurring with other anxiety and mood disorders, including bipolar disorder., (Copyright 2010 S. Karger AG, Basel.)

Extended maternal separations before age 5 were evaluated as a predictor of long-term risk for offspring borderline personality disorder (BPD) symptoms in longitudinal data from a large random community sample. Early separations from mother predicted elevations in BPD symptoms assessed repeatedly from early adolescence to middle adulthood. Early separations also predicted a slower than normal rate of decline in symptoms with age. Other theoretically grounded risks were examined and shown to predict elevated BPD symptoms over the developmental trajectory. Long-term effects of early separations were largely independent of childhood temperament, child abuse, maternal problems, and parenting risks. These data provide the first prospectively collected data on the developmental course of BPD symptoms and suggest a series of environmental and other influences on these very disabling problems.

The aim of this study was to investigate possible interactions between the gene coding for activating protein-2 beta (AP-2 beta) and psychosocial factors to predict depressive symptoms in adolescents. Two-hundred 16- and 19-year-old adolescents from the county of Västmanland, Sweden, were asked to complete a questionnaire, interviewed about psychosocial risk factors, and genotyped with regard to the transcription factor AP-2 beta intron 2 polymorphism. AP-2 beta genotype interacted significantly both with type of housing and parental separation to predict depressive symptoms. Individuals who were homozygous for the short AP-2 beta allele displayed higher depression scores when psychosocial adversity was taken into account. Amongst carriers of one or two copies of the long allele, there was no difference in depressive symptoms despite differences in psychosocial environments.

Objectives: The aim of this study is to survey parental report of screening signs of auditory processing problem in attention deficit hyperactivity disorder (ADHD) children and its association with gender and co-morbidity with oppositional defiant disorder (ODD) and separation anxiety (SAD)., Methods: 104 children and adolescents referrals to the child and adolescent psychiatry clinic were interviewed. The auditory processing problem checklist asked parents to indicate their child's reaction to sounds. It screens signs of two aspects of auditory processing problem including hypersensitivity to sounds (HES) (or auditory defensiveness) and hyposensitivity to sound (HOS) (under-registers)., Results: The mean age of the children was 8.5 (SD=1.8). Children with ODD had significantly higher HES, HOS and the whole checklist mean scores. Subtypes of ADHD were not associated with the auditory processing problems., Conclusions: ADHD children with ODD are likely to be at a significant risk for manifesting both of the auditory processing problem including defensiveness and auditory hyposensitivity to sounds. Auditory processing problems do not differentiate different subtypes of ADHD.

The aim of this work was to determine the effect of chronic treatment with 5 mg/kg of tianeptine in male adult Wistar rats separated from the mother as neonates and submitted to variable chronic stress, plasma catecholamines, and anxiety. The plus maze test was performed in order to calculate the anxiety index and catecholamine levels were determined by high-pressure liquid chromatography. Both stress and maternal separation elevated catecholamine levels without affecting anxiety. In the maternally separated stress group, tianeptine decreased epinephrine. Anxiety was reduced in the maternally separated unstressed tianeptine group. Also, all groups showed a tendency to lower anxiety index.

A 4-year-old female Persian cat was referred with the history of separation from the owner. There was no clinical sign and everything had been reported as normal during the veterinary checkup just before separation and traveling. The history and clinical signs were fit to separation anxiety when the cat referred to us. Ten days after the diagnosis and starting of the treatment for separation anxiety, the cat was referred again with the clinical signs of chronic renal failure. Further assessments showed an inherited polycystic kidney disease. Spontaneous manifestation of polycystic kidney disease after separation anxiety indicate that this phenomenon may cause the chronic process of polycystic kidney disease to promote.

Objectives: While a group of children with ADHD may have normal behavioral responses to sensory stimuli, another group may be hyperreactive. The aim of this survey was studying association of tactile sensory responsivity with co-morbidity of oppositional defiant disorder (ODD) symptoms, subtypes of ADHD, and gender in children with ADHD., Methods: The subjects were 81 children with ADHD from a child psychiatry clinic. The diagnoses were made according to DSM-IV diagnostic criteria. Tactile dysfunction Checklist was used to assess the three types of tactile sensory dysfunction including Hypersensitivity, hyposensitivity, and poor tactile perception and discrimination (PTPD)., Results: Their mean age was 8.4 (SD = 1.9) years. None of the gender, number of symptoms of ODD co-morbidity, and ADHD subtypes was as a predictor of scores of Hyposensitivity and PTPD subscales. Tactile defensiveness was not different between genders and different subtypes of ADHD., Conclusions: Number of ODD symptoms in children with ADHD is a predictor in association with hypersensitivity score of tactile sensory function. Girls are no more than the boys impaired in Hypersensitivity aspect. Different subtypes of ADHD are not distinct disorders regarding to tactile sensory function.

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.