Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease

The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario.     

Altitudinal variation in behavioural thermoregulation: local adaptation vs. plasticity in California grasshoppers

We investigated the adaptive significance of behavioural thermoregulation in univoltine populations of the grasshopper Melanoplus sanguinipes along an altitudinal gradient in California using laboratory tests of animals raised under different temperatures. Trials consisted of continuous body temperature measurements with semi-implanted microprobes in a test arena, and observation and simultaneous recording of behavioural responses. These responses included mobility, basking and orientation of the body axes (aspect angle) towards a radiation source. Mobility and basking are determined by the altitudinal origin of the parental generation and not by the temperature treatments. With increasing altitude, individuals tend increasingly to raise body temperatures via mobility and increased basking. In contrast, body orientation towards the radiation source is influenced by the temperature treatments but not by the altitude of origin. Individuals experiencing higher temperatures during rearing show a lower tendency to lateral flanking. We conclude that body orientation responses are not adapted locally. In contrast other components of the behavioural syndrome that increase body temperature, such as mobility and basking, are adaptive in response to local selection pressure. The thermoregulatory syndrome of these grasshoppers is an important contribution to life-history adaptations that appropriately match season lengths.     

Mood and anxiety disorders in women with PCOS

Women with polycystic ovary syndrome have gynecologic, reproductive and metabolic co-morbidities that span their entire lifespan. More recently a higher risk of mood and anxiety disorders has been reported in women with PCOS. Women with PCOS have higher depression scores and a higher risk of depression independent of BMI. Although clinical features of hyperandrogenism affect health related quality of life, the association between hirsutism, acne, body image and depression is currently unclear. Similarly there is limited data on the association between variables such as biochemical hyperandrogenism or infertility and depression. Women with PCOS are also at risk for symptoms of generalized anxiety disorder. There is insufficient data examining the risk of other anxiety disorders such as social phobia, obsessive compulsive disorders and panic disorder. In a number of patients some of these disorders coexist increasing the health burden. These data underscore the need to screen all women with PCOS for mood and anxiety disorders and adequately treat women who are diagnosed with these conditions.     

Developmental and behavioural phenotype in Noonan syndrome?

Developmental and behavioural phenotype in Noonan syndrome? Noonan syndrome is characteristic by facial dysmorphology, congenital heart defects, short stature, developmental retardation and severe early feeding disorders in many cases. Data from a postal survey on physical development, feeding difficulties, developmental problems and behavioural aspects in 26 children are reported. The findings suggest developmental and behavioural difficulties in 46 per cent, but do not support the notion of a behavioural phenotype specific to Noonan syndrome. Having to cope with early surgery, feeding, developmental and behavioural problems establishes a need for psychological counseling for families receiving a diagnosis of Noonan syndrome.     

Altered behavioural adaptation in mice with neural corticotrophin-releasing factor overexpression

Overproduction of corticotrophin-releasing factor (CRF), the major mediator of the stress response, has been linked to anxiety, depression and addiction. CRF excess results in increased arousal, anxiety and altered cognition in rodents. The ability to adapt to a potentially threatening stimulus is crucial for survival, and impaired adaptation may underlie stress-related psychiatric disorders. Therefore, we examined the effects of chronic transgenic neural CRF overproduction on behavioural adaptation to repeated exposure to a non-home cage environment. We report that CRF transgenic mice show impaired adaptation in locomotor response to the novel open field. In contrast to wild-type (WT) mice, anxiety-related behaviour of CRF transgenic mice does not change during repeated exposure to the same environment over the period of 7 days or at retest 1 week later. We found that locomotor response to novelty correlates significantly with total locomotor activity and activity in the centre at the last day of testing and at retest in WT but not in CRF transgenic mice. Mice were divided into low responders and high responders on the basis of their initial locomotor response to novelty. We found that differences in habituation and re-exposure response are related to individual differences in locomotor response to novelty. In summary, these results show that CRF transgenic mice are fundamentally different from WT in their ability to adapt to an environmental stressor. This may be related to individual differences in stress reactivity. These findings have implications for our understanding of the role of CRF overproduction in behavioural maladaptation and stress-related psychiatric disorders.     

Early life environment determines the development of adult phobic‐like fear responses in BALB/cAnN mice

Environmental factors may unleash genetically determined susceptibility to psychopathology. Great effort has been spent in identifying both the genetic basis and environmental sources of exaggerated fear in animal models of anxiety disorders. Here, we show that the origin of inbred mice, probably via subtle differences in breeding and rearing conditions, may have large consequences specifically on acquisition and retention of fear memories, while leaving anxiety‐related behaviours unaffected. These effects could be seen in BALB/cAnN (BALB), but not in C57BL/6N (C57BL/6) mice, thus suggesting their dependency on the genetic background. Increased susceptibility for developing exaggerated fear responses was accompanied by decreased long‐term depression and increased surface trafficking of the AMPA receptor GluR1 subunit at the level of the basolateral amygdala complex. Together, these data raise a novel caveat in the debate about the origins of variation in behavioural studies with experimental animals. Considering that there are currently no animal models which explicitly consider conceptual analogy to the specific gene–environment interactions observed in the aetiology of phobias, our study might suggest a novel approach and direction for further preclinical studies focusing on such aspects of phobic‐like fears.     

Memory and anxiety disorders.

Experimental psychopathologists have identified varying patterns in memory bias in people with depressive and anxiety disorders. Individuals suffering from depression tend to exhibit explicit memory deficits for positively-valanced material, and sometimes exhibit biases for retrieving negative self-relevant information as well. Most studies, however, provide scant evidence for implicit memory biases in depression. In contrast to depression, anxiety disorders are rarely associated with enhanced explicit memory for threat-related information (with the exception of panic disorder). Evidence for implicit memory biases for threat in these syndromes is mixed. After providing an overview of findings on memory abnormalities in depressive and anxiety disorders, data from several new studies bearing on posttraumatic stress disorder (PTSD) in Vietnam combat veterans and in women with histories of childhood sexual abuse are presented. Involving directed forgetting, implicit memory and autobiographical cueing paradigms, these experiments point to a pattern of abnormalities linked to PTSD rather than to trauma per se.     

Effects Of A Post-Weaning Cafeteria Diet In Young Rats: Metabolic Syndrome,Reduced Activity And Low Anxiety-Like Behaviour

Among adolescents, overweight, obesity and metabolic syndrome are rapidly increasing in recent years as a consequence of unhealthy palatable diets. Animal models of diet-induced obesity have been developed, but little is known about the behavioural patterns produced by the consumption of such diets. The aim of the present study was to determine the behavioural and biochemical effects of a cafeteria diet fed to juvenile male and female rats, as well as to evaluate the possible recovery from these effects by administering standard feeding during the last week of the study. Two groups of male and female rats were fed with either a standard chow diet (ST) or a cafeteria (CAF) diet from weaning and for 8 weeks. A third group of males (CAF withdrawal) was fed with the CAF diet for 7 weeks and the ST in the 8th week. Both males and females developed metabolic syndrome as a consequence of the CAF feeding, showing overweight, higher adiposity and liver weight, increased plasma levels of glucose, insulin and triglycerides, as well as insulin resistance, in comparison with their respective controls. The CAF diet reduced motor activity in all behavioural tests, enhanced exploration, reduced anxiety-like behaviour and increased social interaction; this last effect was more pronounced in females than in males. When compared to animals only fed with a CAF diet, CAF withdrawal increased anxiety in the open field, slightly decreased body weight, and completely recovered the liver weight, insulin sensitivity and the standard levels of glucose, insulin and triglycerides in plasma. In conclusion, a CAF diet fed to young animals for 8 weeks induced obesity and metabolic syndrome, and produced robust behavioural changes in young adult rats, whereas CAF withdrawal in the last week modestly increased anxiety, reversed the metabolic alterations and partially reduced overweight.     

The role of oxidative stress in anxiety disorder: cause or consequence?

Anxiety disorders are the most common mental illness in the USA affecting 18% of the population. The cause(s) of anxiety disorders is/are not completely clear, and research in the neurobiology of anxiety at the molecular level is still rather limited. Although mounting clinical and preclinical evidence now indicates that oxidative stress may be a major component of anxiety pathology, whether oxidative stress is the cause or consequence remains elusive. Studies conducted over the past few years suggest that anxiety disorders may be characterised by lowered antioxidant defences and increased oxidative damage to proteins, lipids, and nucleic acids. In particular, oxidative modifications to proteins have actually been proposed as a potential factor in the onset and progression of several psychiatric disorders, including anxiety and depressive disorders. Oxidised proteins are normally degraded by the proteasome proteolytic complex in the cell cytoplasm, nucleus, and endoplasmic reticulum. The Lon protease performs a similar protective function inside mitochondria. Impairment of the proteasome and/or the Lon protease results in the accumulation of toxic oxidised proteins in the brain, which can cause severe neuronal trauma. Recent evidence points to possible proteolytic dysfunction and accumulation of damaged, oxidised proteins as factors that may determine the appearance and severity of psychotic symptoms in mood disorders. Thus, critical interactions between oxidative stress, proteasome, and the Lon protease may provide keys to the molecular mechanisms involved in emotional regulation, and may also be of great help in designing and screening novel anxiolytics and antidepressants.     

Anxiety disorders in nursing homes: a literature review of prevalence, course and risk indicators

Psychiatric disorders such as dementia and depression are highly prevalent in nursing homes. The prevalence of anxiety disorders is less clear. Prevalence, course and risk-indicators of anxiety disorders among nursing home residents were examined, based on a review of the literature. Medline and PsychINFO searches were conducted for 1966-2002. Twelve studies were considered relevant. These differed substantially with respect to study-population, diagnostic instruments and diagnostic criteria that were used and the specific anxiety disorders investigated. The prevalence of anxiety disorders ranged from 0-20%. Only in one study the course of anxiety disorders was investigated. About 60% of the nursing home residents recovered in one year. The most important risk-indicators for anxiety disorders identified were: female sex, depression, lack of social support, poor physical health and functional and cognitive impairments. Generalization of these results to the Dutch nursing home population is restricted by the substantial heterogeneity of the studies. Further studies are required to provide reliable estimates of prevalence, course and risk-indicators of anxiety disorders among nursing home residents using appropriate diagnostic instruments and adjusted diagnostic criteria. This will enhance detection and improve treatment of anxiety disorders among nursing home residents.     

Comorbid migraine with aura, anxiety, and depression is associated with dopamine D2 receptor (DRD2) NcoI alleles.

BACKGROUND: Unrelated individuals (n = 242) were interviewed directly for the presence of migraine, anxiety disorders, and major depression. MATERIALS AND METHODS: The data described in this study are derived from a clinical genetic relational database that was developed initially for the genetic analysis of migraine. Genotyping of the DRD2 NcoI C to T polymorphism located in exon 6 (His313His) was performed using previously described primers. RESULTS: A significantly increased incidence of migraine with aura (MWA), major depression, generalized anxiety disorder (GAD), panic attacks, and phobia was observed in individuals with the DRD2 NcoI C/C genotype compared with individuals with an DRD2 NcoI T allele. Specifically, 69% (91/131) of DRD2 NcoI C/C individuals in the present study met criteria for at least one of these neuropsychiatric disorders versus only 22% (4/18) of the DRD2 NcoI T/T individuals (Chi-square = 15.29; p < 0.00005). The DRD2 NcoI C allele frequency is significantly higher (Chi-square = 17.13; p < 0.00002) in individuals with MWA, anxiety disorders, and/or major depression (C allele frequency = 0.80) than in individuals who have none of these disorders (C allele frequency = 0.67). CONCLUSIONS: These data indicate that MWA, anxiety disorders, and major depression can be components of a distinct clinical syndrome associated with allelic variations within the DRD2 gene. Clinical recognition of this genetically based syndrome has significant diagnostic and therapeutic implications.     

The Prevalence and Correlates of Lifetime Psychiatric Disorders and Trauma Exposures in Urban and Rural Settings: Results from the National Comorbidity Survey Replication (NCS-R)

Introduction

Distinctions between rural and urban environments produce different frequencies of traumatic exposures and psychiatric disorders. We examine the prevalence of psychiatric disorders and frequency of trauma exposures by position on the rural-urban continuum.

Methods

The National Comorbidity Survey Replication (NCS-R) was used to evaluate psychiatric disorders among a nationally-representative sample of the U.S. population. Rurality was designated using the Department of Agriculture''s 2003 rural-urban continuum codes (RUCC), which differentiate counties into levels of rurality by population density and adjacency to metropolitan areas. Lifetime psychiatric disorders included post-traumatic stress disorder (PTSD), anxiety disorders, major depressive disorder, mood disorders, impulse-control disorders, and substance abuse. Trauma exposures were classified as war-related, accident-related, disaster-related, interpersonal or other. Weighted logistic regression models examined the odds of psychiatric disorders and trauma exposures by position on the rural-urban continuum, adjusted for relevant covariates.

Results

75% of participants were metropolitan, 12.2% were suburban, and 12.8% were from rural counties. The most common disorder reported was any anxiety disorder (38.5%). Drug abuse was more common among metropolitan (8.7%, p = 0.018), compared to nonmetropolitan (5.1% suburban, 6.1% rural) participants. A one-category increase in rurality was associated with decreased odds for war-related trauma (aOR = 0.86, 95%CI 0.78–0.95). Rurality was not associated with risk for any other lifetime psychiatric disorders or trauma exposure.

Discussion/Conclusions

Contrary to the expectation of some rural primary care providers, the frequencies of most psychiatric disorders and trauma exposures are similar across the rural-urban continuum, reinforcing calls to improve mental healthcare access in resource-poor rural communities.     

Structural brain imaging in frontotemporal dementia

Frontotemporal dementia (FTD) is the second commonest young-onset neurodegenerative dementia. The canonical clinical syndromes are a behavioural variant (bvFTD) and two language variants (progressive nonfluent aphasia, PNFA, and semantic dementia, SD) although there is overlap with motor neurone disease and the atypical parkinsonian disorders corticobasal syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). Characteristic patterns of atrophy or hypometabolism are described in each of the variants but in reality imaging studies are rather heterogeneous. This review attempts to address four key questions in the neuroimaging of FTD: 1) what are the early imaging features of the different FTD syndromes (and how do these change as the disease progresses); 2) what do studies of presymptomatic genetic cases of FTD tell us about the very early stages of the disease; 3) can neuroimaging help to differentiate the different FTD syndromes; and 4) can neuroimaging help to differentiate FTD from other neurodegenerative diseases? This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Corticotropin-releasing hormone in depression and post-traumatic stress disorder

Corticotropin-releasing hormone (CRH) has been implicated in the regulation of a wide range of behaviors including arousal, motor function, feeding, and reproduction. Because depressed patients are often hypercortisolemic and intracerebroventricular administration of CRH to experimental animals produces a syndrome reminiscent of depression, dysregulation of this compound has been suggested to be involved in the pathogenesis of depressive and anxiety disorders. Studies of cerebrospinal fluid CRH levels and clinical neuroendocrine tests in patients with anxiety and affective disorders have supported this hypothesis. This review discusses these neuroendocrine findings in melancholic and atypical depression as well as post-traumatic stress disorder (PTSD). Overall, the data suggest that melancholic depression is characterized by hyperactive central CRH systems with overactivity of the pituitary-adrenal (HPA) axis. On the other hand, atypical depression is characterized by hypoactive central CRH systems and accompanying underactivity of the hypothalamic-pituitary-adrenal axis. Furthermore, the neuroendocrinology of PTSD appears to be unique, in that patients have hyperactive central CRH systems with underactivity of the pituitary-adrenal axis.     

Depression's multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways

There is now evidence that depression, as characterized by melancholic symptoms, anxiety, and fatigue and somatic (F&S) symptoms, is the clinical expression of peripheral cell-mediated activation, inflammation and induction of oxidative and nitrosative stress (IO&NS) pathways and of central microglial activation, decreased neurogenesis and increased apoptosis. This review gives an explanation for the multiple "co-morbidities" between depression and a large variety of a) brain disorders related to neurodegeneration, e.g. Alzheimer's, Parkinson's and Huntington's disease, multiple sclerosis and stroke; b) medical disorders, such as cardiovascular disorder, chronic fatigue syndrome, chronic obstructive pulmonary disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, inflammatory bowel disease, irritable bowel syndrome, leaky gut, diabetes type 1 and 2, obesity and the metabolic syndrome, and HIV infection; and c) conditions, such as hemodialysis, interferon-α-based immunotherapy, the postnatal period and psychosocial stressors. The common denominator of all those disorders/conditions is the presence of microglial activation and/or activation of peripheral IO&NS pathways. There is evidence that shared peripheral and / or central IO&NS pathways underpin the pathophysiology of depression and the previously mentioned disorders and that activation of these IO&NS pathways contributes to shared risk. The IO&NS pathways function as a smoke sensor that detect threats in the peripheral and central parts of the body and signal these threats as melancholic, anxiety, and fatigue and somatic (F&S) symptoms. The presence of concomitant depression is strongly associated with a lower quality of life and increased morbidity and mortality in medical disorders. This may be explained since depression contributes to increased (neuro)inflammatory burden and may therefore drive the inflammatory and degenerative progression. It is concluded that the activation of peripheral and / or central IO&NS pathways may explain the co-occurrence of depression with the above disorders. This shows that depression belongs to the spectrum of inflammatory and degenerative disorders.     

The Disenchanted Self: Anthropological Notes on Existential Distress and Ontological Insecurity Among ex-Mormons in Utah

This paper describes a pervasive form of psychological distress occurring among people undergoing a sudden and acute collapse of faith in the teachings of the Church of Jesus Christ of Latter-day Saints (aka LDS, or Mormon Church). Drawing on 18 months of fieldwork in Utah, I trace the cultural–historical etiology of this unique form of psycho-existential trauma, focusing on ex-Mormons’ narratives of ‘world collapse’—in which the all-encompassing symbolic-existential framework of reality once provided by religion disintegrated once they lost faith in the Mormon Church. Although marked by symptoms resembling depression, anxiety, dissociation and paranoia, this condition is however unlike mental health disorders described in psychiatric diagnostic manuals, and has thus been largely overlooked within the mental health professions. I thereby discuss the extent to which the distress of religious disenchantment constitutes a unique form of ‘cultural syndrome’ (Hinton and Lewis-Fernandez in Cult Med Psychiatry 34(2):209–218, 2010), reflective of complex historical, cultural, and religious transformations occurring within contemporary Utah Mormonism.

     

Risk Perception and Risk-Taking Behaviour during Adolescence: The Influence of Personality and Gender

This study investigated the influence of personality characteristics and gender on adolescents’ perception of risk and their risk-taking behaviour. Male and female participants (157 females: 116 males, aged 13–20) completed self-report measures on risk perception, risk-taking and personality. Male participants perceived behaviours as less risky, reportedly took more risks, were less sensitive to negative outcomes and less socially anxious than female participants. Path analysis identified a model in which age, behavioural inhibition and impulsiveness directly influenced risk perception, while age, social anxiety, impulsiveness, sensitivity to reward, behavioural inhibition and risk perception itself were directly or indirectly associated with risk-taking behaviour. Age and behavioural inhibition had direct relationships with social anxiety, and reward sensitivity was associated with impulsiveness. The model was representative for the whole sample and male and female groups separately. The observed relationship between age and social anxiety and the influence this may have on risk-taking behaviour could be key for reducing adolescent risk-taking behaviour. Even though adolescents may understand the riskiness of their behaviour and estimate their vulnerability to risk at a similar level to adults, factors such as anxiety regarding social situations, sensitivity to reward and impulsiveness may exert their influence and make these individuals prone to taking risks. If these associations are proven causal, these factors are, and will continue to be, important targets in prevention and intervention efforts.     

The role of oxytocin in relationships between dogs and humans and potential applications for the treatment of separation anxiety in dogs

The hormone oxytocin plays an important role in attachment formation and bonding between humans and domestic dogs. Recent research has led to increased interest in potential applications for intranasal oxytocin to aid with the treatment of psychological disorders in humans. While a few studies have explored the effects of intranasally administered oxytocin on social cognition and social bonding in dogs, alternative applications have not yet been explored for the treatment of behavioural problems in this species. One potentially important application for intranasal oxytocin in dogs could be the treatment of separation anxiety, a common attachment disorder in dogs. Here we provide an overview of what is known about the role of oxytocin in the human–dog bond and canine separation anxiety, and discuss considerations for future research looking to integrate oxytocin into behavioural treatment based on recent findings from both the human and dog literature.     

Childhood physical abuse in outpatients with psychosomatic symptoms

Background

In Japan and Asia, few studies have been done of physical and sexual abuse. This study was aimed to determine whether a history of childhood physical abuse is associated with anxiety, depression and self-injurious behavior in outpatients with psychosomatic symptoms.

Methods

We divided 564 consecutive new outpatients at the Department of Psychosomatic Medicine of Kyushu University Hospital into two groups: a physically abused group and a non-abused group. Psychological test scores and the prevalence of self-injurious behavior were compared between the two groups.

Results

A history of childhood physical abuse was reported by patients with depressive disorders(12.7%), anxiety disorders(16.7%), eating disorders (16.3%), pain disorders (10.8%), irritable bowel syndrome (12.5%), and functional dyspepsia(7.5%). In both the patients with depressive disorders and those with anxiety disorders, STAI-I (state anxiety) and STAI-II (trait anxiety) were higher in the abused group than in the non-abused group (p < 0.05).In the patients with depressive disorders, the abused group was younger than the non-abused group (p < 0.05). The prevalence of self-injurious behavior of the patients with depressive disorders, anxiety disorders and pain disorders was higher in the abused groups than in the non-abused groups (p < 0.005).

Conclusion

A history of childhood physical abuse is associated with psychological distress such as anxiety, depression and self-injurious behavior in outpatients with psychosomatic symptoms. It is important for physicians to consider the history of abuse in the primary care of these patients.