Sense of community belonging among immigrants: perspective of immigrant service providers.

OBJECTIVES: This study examined the barriers and facilitators to community belonging for immigrants in Alberta, Canada. STUDY DESIGN: The study used a qualitative descriptive research design. METHODS: A total of 53 immigrant service providers in the province of Alberta participated in interviews and focus groups. The sample was purposively recruited through immigrant service organizations in the province. Interviews lasted approximately 45 min, whereas focus groups lasted approximately 1.5 h. The interviews were audio recorded, transcribed verbatim, and thematically analyzed with the aid of NVivo qualitative software. RESULTS: Participants discuss two forms of community belonging in this study: (a) belonging to an ethnocultural group; and (b) belonging within mainstream Canadian society. Barriers to mainstream community belonging for immigrants include employment barriers, language barriers, and discrimination. Recent immigrants often experience a sense of belonging to their ethnic group within the host country before feeling connected to others in their local geographic community. A major factor contributing to this trend is the lack of ethnocultural diversity in local community organizations in the areas where immigrants live. Immigrant service agencies and religious institutions compensate for this deficiency through creating avenues for social connection within and across ethnocultural groups and to mainstream Canadian society. CONCLUSIONS: Local community organizations should address issues of ethnocultural diversity and discrimination to improve the mental health of immigrants by fostering community belonging. Supporting programs in immigrant service agencies and religious institutions to increase social participation and engagement would, also, help strengthen community belonging and improve immigrant mental health.

Effects of cortisol on hippocampal subfields volumes and memory performance in healthy control subjects and patients with major depressive disorder.

Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis in major depressive disorder (MDD) is among the most consistently replicated biological findings in psychiatry. Magnetic resonance imaging (MRI) studies have consistently demonstrated that hippocampal (HC) volume is decreased in patients with MDD. The improved spatial resolution of high field strength MRI has recently enabled measurements of HC subfield volumes in vivo. The main goal of the present study was to examine the relationship between cortisol concentrations over a day and HC subfield volumes in patients with MDD compared to healthy controls and to investigate whether diurnal cortisol measures are related to memory performance. Fourteen MDD patients with moderate or severe episodes were recruited, together with 14 healthy controls. Imaging was performed using a 4.7T whole-body imaging system. HC subfields and subregions were segmented manually using previously defined protocol. Memory performance was assessed using the Wechsler Memory Scale IV. The salivary cortisol levels were measured over the course of one day. We found that cortisol awakening response to 8h (CAR-8h) was higher in MDD patients compared to controls and that this increase in CAR-8h in MDD patients correlated negatively with left total Cornu Ammonis (CA)1-3 and left HC head volume. In healthy controls mean cortisol levels were negatively associated with right total CA1-3, right HC head, and right total HC volume. In addition, in healthy controls higher CAR-8h was related to worse performance on the immediate content memory. These results provide the first in vivo evidence of the negative associations between cortisol level, CA1-3 HC subfield volume and memory performance in patients with MDD and healthy controls.

Cognitive distortions in an acutely traumatized sample: an investigation of predictive power and neural correlates.

BACKGROUND: Current theories of post-traumatic stress disorder (PTSD) place considerable emphasis on the role cognitive distortions such as self-blame, hopelessness or preoccupation with danger play in the etiology and maintenance of the disorder. Previous studies have shown that cognitive distortions in the early aftermath of traumatic events can predict future PTSD severity but, to date, no studies have investigated the neural correlates of this association. METHOD: We conducted a prospective study with 106 acutely traumatized subjects, assessing symptom severity at three time points within the first 3 months post-trauma. A subsample of 20 subjects additionally underwent a functional 4-T magnetic resonance imaging (MRI) scan at 2 to 4 months post-trauma. RESULTS: Cognitive distortions proved to be a significant predictor of concurrent symptom severity in addition to diagnostic status, but did not predict future symptom severity or diagnostic status over and above the initial symptom severity. Cognitive distortions were correlated with blood oxygen level-dependent (BOLD) signal strength in brain regions previously implicated in visual processing, imagery and autobiographic memory recall. Intrusion characteristics accounted for most of these correlations. CONCLUSIONS: This investigation revealed significant predictive value of cognitive distortions concerning concurrent PTSD severity and also established a significant relationship between cognitive distortions and neural activations during trauma recall in an acutely traumatized sample. These data indicate a direct link between the extent of cognitive distortions and the intrusive nature of trauma memories.

Default mode network connectivity as a predictor of post-traumatic stress disorder symptom severity in acutely traumatized subjects.

OBJECTIVE: The goal of this study was to investigate the relationship between default mode network connectivity and the severity of post-traumatic stress disorder (PTSD) symptoms in a sample of eleven acutely traumatized subjects. METHOD: Participants underwent a 5.5 min resting functional magnetic resonance imaging scan. Brain areas whose activity positively correlated with that of the posterior cingulate/precuneus (PCC) were assessed. To assess the relationship between severity of PTSD symptoms and PCC connectivity, the contrast image representing areas positively correlated with the PCC was correlated with the subjects' Clinician Administered PTSD Scale scores. RESULTS: Results suggest that resting state connectivity of the PCC with the perigenual anterior cingulate and the right amygdala is associated with current PTSD symptoms and that correlation with the right amygdala predicts future PTSD symptoms. CONCLUSION: These results may contribute to the development of prognostic tools to distinguish between those who will and those who will not develop PTSD.

The role of beta-endorphin in the pathophysiology of major depression.

A role for beta-endorphin (beta-END) in the pathophysiology of major depressive disorder (MDD) is suggested by both animal research and studies examining clinical populations. The major etiological theories of depression include brain regions and neural systems that interact with opioid systems and beta-END. Recent preclinical data have demonstrated multiple roles for beta-END in the regulation of complex homeostatic and behavioural processes that are affected during a depressive episode. Additionally, beta-END inputs to regulatory pathways involving feeding behaviours, motivation, and specific types of motor activity have important implications in defining the biological foundations for specific depressive symptoms. Early research linking beta-END to MDD did so in the context of the hypothalamic-pituitary-adrenal (HPA) axis activity, where it was suggested that HPA axis dysregulation may account for depressive symptoms in some individuals. The primary aims of this paper are to use both preclinical and clinical research (a) to critically review data that explores potential roles for beta-END in the pathophysiology of MDD and (b) to highlight gaps in the literature that limit further development of etiological theories of depression and testable hypotheses. In addition to examining methodological and theoretical challenges of past clinical studies, we summarize studies that have investigated basal beta-END levels in MDD and that have used challenge tests to examine beta-END responses to a variety of experimental paradigms. A brief description of the synthesis, location in the CNS and behavioural pharmacology of this neuropeptide is also provided to frame this discussion. Given the lack of clinical improvement observed with currently available antidepressants in a significant proportion of depressed individuals, it is imperative that novel mechanisms be investigated for antidepressant potential. We conclude that the renewed interest in elucidating the role of beta-END in the pathophysiology of MDD must be paralleled by consensus building within the research community around the heterogeneity inherent in mood disorders, standardization of experimental protocols, improved discrimination of POMC products in analytical techniques and consistent attention paid to important confounds like age and gender.

The effects of estradiol on central serotonergic systems and its relationship to mood in women.

Lifetime prevalence rates of depression are higher in women than men. Because this gender disparity appears after the onset of puberty and declines after menopause, gonadal hormones may play a role in women's increased vulnerability to dysphoric states. Estrogens have powerful effects beyond their role in reproduction. Fluctuations in estrogen occur naturally throughout the reproductive years and can be associated with disruptions in mood. Treatment for depression with exogenous estrogen has produced equivocal results. To shed light on the complex interactions among estrogens, serotonin, and mood, we briefly examine (a) central serotonin systems and their relationship to mood and mood disorders, (b) nonreproductive effects of estrogens on those systems, (c) potential points of intersection between serotonin systems and estrogens, and (d) research into the use of exogenous estrogen in depression in women. In conclusion, we reiterate the call for carefully controlled research into the etiology and treatment of depression in women.

Posttraumatic stress disorder Part III: health effects of interpersonal violence among women.

TOPIC: The aim of this three-part series is to examine the sufficiency of the posttraumatic stress (PTSD) diagnostic construct to capture the full spectrum of human responses to psychological trauma. Part I (Lasiuk & Hegadoren, 2006a) reviewed the conceptual history of PTSD from the nineteenth century to its inclusion in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1980), while Part II (Lasiuk & Hegadoren, 2006b) described subsequent refinements to the original PTSD diagnostic criteria and highlighted subsequent controversies. PURPOSE: This paper focuses on interpersonal violence (sexual, physical, and emotional abuse/assault) and its sequelae in women. We argue in support of Judith Herman's (1992) conceptualization of the human trauma response as a spectrum, anchored at one end by an acute stress reaction that resolves on its own without treatment, and on the other by "complex" PTSD, with "classic" or "simple" PTSD somewhere between the two. SOURCES OF INFORMATION: he existing theoretical, clinical and research literatures related to humans responses to trauma. CONCLUSION: The paper concludes with a call for the need to increase a gendered perspective in all aspects of trauma research and clinical service delivery.

Posttraumatic stress disorder part II: development of the construct within the North American psychiatric taxonomy.

TOPIC: The impairment associated with posttraumatic stress disorder (PTSD) carries with it staggering costs to the individual, to the family, and to society as a whole. Although there is strong evidence that gender plays a significant role in responses to stress and trauma, gender specificity is still not well incorporated into clinical or research work in the area of PTSD. PURPOSE: This is the second of three articles examining the sufficiency of the current PTSD construct to articulate the full spectrum of human responses to trauma. This article chronicles ongoing refinements to the original PTSD criteria and the subsequent controversies. SOURCE OF INFORMATION: Existing bodies of theoretical and research literature related to the effects of trauma. CONCLUSION: In a third article we will review evidence supporting the existence of a more complex posttraumatic stress reaction associated with interpersonal trauma (physical/sexual abuse/assault).

Posttraumatic stress disorder part I: historical development of the concept.

TOPIC: Posttraumatic Stress Disorder (PTSD) is a significant health problem, characterized by high rates of chronicity and comorbidity. PURPOSE: This is the first of three articles examining the sufficiency of the current PTSD construct to articulate the spectrum of human responses to trauma, in particular as it relates to women and interpersonal trauma. This paper reviews the conceptual history of PTSD from the nineteenth century up to its inclusion in the DSM-III (American Psychiatric Association, 1980). SOURCES OF INFORMATION: Existing bodies of theoretical and research literature related to the effects of trauma. CONCLUSION: Although there is strong evidence that gender plays a role in responses to stress and trauma, gender specificity is not well-incorporated into clinical services or research in the area of PTSD.

Noradrenergic mechanisms in the pathophysiology of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a serious psychiatric illness that may develop in individuals after exposure to a traumatic event. Recent data suggest that trauma and/or long-term stressors can cause alterations in the functioning of neuroanatomical structures and neural networks throughout the central nervous system. Specifically, dysregulation in central and perhaps, peripheral noradrenergic neural networks has been implicated as the cause of specific symptom clusters in the pathophysiology of PTSD. In this review, both clinical and preclinical data are presented to highlight types of noradrenergic dysfunction observed in individuals with PTSD. Additionally, the role of noradrenaline dysregulation in the acquisition/initiation, and maintenance of hyperarousal and reexperiencing symptom clusters in PTSD will be addressed.

3,4-Methylenedioxy analogues of amphetamine: defining the risks to humans.

The 3,4-methylenedioxy analogues of amphetamine [MDMA ("Ecstasy", "Adam"), MDA ("Love") and MDE ("Eve")] are recreational drugs that produce feelings of euphoria and energy and a desire to socialize, which go far to explain their current popularity as "rave drugs". In addition to these positive effects, the drugs are relatively inexpensive to purchase and have the reputation of being safe compared to other recreational drugs. Yet there is mounting evidence that these drugs do not deserve this reputation of being safe. This review examines the relevant human and animal literature to delineate the possible risks MDMA, MDA and MDE engender with oral consumption in humans. Following a summary of the behavioral and cognitive effects of MDMA, MDA and MDE, risks will be discussed in terms of toxicity, psychopathology, neurotoxicity, abuse potential and the potential for drug-drug interactions associated with acute and chronic use.

Major depression in individuals with a history of childhood physical or sexual abuse: relationship to neurovegetative features, mania, and gender.

OBJECTIVE: Numerous studies have linked childhood trauma with depressive symptoms over the life span. However, it is not known whether particular neurovegetative symptom clusters or affective disorders are more closely linked with early abuse than are others. In a large community sample from Ontario, the authors examined whether a history of physical or sexual abuse in childhood was associated with particular neurovegetative symptom clusters of depression, with mania, or with both. METHOD: The World Health Organization Composite International Diagnostic Interview was used to assess 8,116 individuals aged 15-64 years. Each subject was asked about early physical and sexual abuse experiences on a structured supplement to the interview. Six hundred fifty-three cases of major depression were identified. Rates of physical and sexual abuse in depressive subgroups defined by typical and reversed neurovegetative symptom clusters (i.e., decreased appetite, weight loss, and insomnia versus increased appetite, weight gain, and hypersomnia, respectively) and by the presence or absence of lifetime mania were compared by gender. RESULTS: A history of physical or sexual abuse in childhood was associated with major depression with reversed neurovegetative features, whether or not manic subjects were included in the analysis. A strong relationship between mania and childhood physical abuse was found. Across analyses there was a significant main effect of female gender on risk of early sexual abuse; however, none of the group-by-gender interactions predicted early abuse. CONCLUSIONS: These results suggest an association between early traumatic experiences and particular symptom clusters of depression, mania, or both in adults.

Analysis of the enantiomers of 3,4-methylenedioxy-N-ethylamphetamine (MDE, "Eve") and its metabolite 3,4-methylenedioxyamphetamine (MDA) in rat brain.

The methylenedioxy analogues of amphetamine are used recreationally despite concerns raised regarding potential neurotoxicity of the parent compounds and a number of metabolites. Much has been written regarding 3,4-methylenedioxymethamphetamine (MDMA; 3,4-methylenedioxy-N-ethylamphetamine (MDE; "Eve"), despite recent reports indicating the abuse of this drug and its potentially serious side effects. An assay procedure was developed for the simultaneous quantitation of both enantiomers of MDE and its metabolite MDA; the method involves derivatization with an optically pure reagent and analysis on a gas chromatograph equipped with a capillary column and a nitrogen-phosphorus detector. Brain levels of the enantiomers of MDE and MDA were examined in the rat at different time periods after acute i.p. injections of racemic MDE and the results were compared with levels of MDMA and MDA obtained after i.p. injection of MDMA in a previous study from our laboratories. The levels of the enantiomers of MDE and MDA achieved at 1, 4, and 8 hr were lower than in the case of MDMA. Stereoselective differences in brain levels of enantiomers of the parent drug and metabolite were much less marked with MDE than with MDMA, but where these small differences did exist in the case of MDE, the (R)-(-) vs (S)-(+) relationship was opposite to that reported for MDMA.

Comparative behavioural and neurochemical studies with a psychomotor stimulant, an hallucinogen and 3,4-methylenedioxy analogues of amphetamine.

Spontaneous behaviours were assessed in freely moving rats after treatment with equimolar doses of drugs that share a basic amphetamine structure. The drugs used included a psychomotor stimulant [(+)-amphetamine (AMPH)], an hallucinogen [para-methoxyamphetamine (PMA)] and the entactogens 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxy-N-ethylamphetamine (MDE). A detailed analysis of the frequency and duration of 30 different behaviours and the temporal organization of the behaviours was conducted in addition to measuring motor activity with an automated device. Levels of the biogenic amines and their acid metabolites in discrete brain regions and brain drug levels were also obtained. The automated motor activity measures discriminated among entactogens, the stimulant and the hallucinogen, but failed to distinguish between the hallucinogen and vehicle. Principal components analysis and cluster analysis of the frequencies and durations of the behaviours did not improve the classification of the drugs over the automated motor activity measures. Only the cluster analysis of the transitions between individual behaviours succeeded in differentiating the drug classes from each other and from vehicle treatment. All the behavioural measures classified one entactogen (MDE) as an hallucinogen. Cortical 5-hydroxytryptamine (5-HT) measures grouped MDE with the other entactogens but did not distinguish AMPH from vehicle. However, striatal dopamine measures differentiated AMPH from vehicle treatment. Variations in the durations of behavioural effects across drugs were associated with large differences in drug levels 3 h after injection. Although the neurochemical data provided a classification system that most closely parallels human subjective effects of these drugs, both the neurochemical and the behavioural measures supported the existence of an entactogen class distinct from a psychomotor stimulant and an hallucinogen.

4-Ethoxyamphetamine: effects on intracranial self-stimulation and in vitro uptake and release of 3H-dopamine and 3H-serotonin in the brains of rats.

Experiments were conducted to compare the effects of 4-ethoxyamphetamine, a novel "designer" amphetamine, with (+)-amphetamine and an earlier "designer" amphetamine, 4-methoxyamphetamine, on rats. (+)-Amphetamine significantly decreased frequency threshold measures in an intracranial self-stimulation (ICSS) procedure using medial forebrain bundle electrodes, while 4-methoxyamphetamine and 4-ethoxyamphetamine increased these ICSS frequency thresholds. 4-Methoxyamphetamine and 4-ethoxyamphetamine had more potent effects on inhibition of uptake and stimulation of spontaneous release of 5-hydroxytryptamine (serotonin) than of dopamine. It is concluded that the neuropsychopharmacological profile of 4-ethoxyamphetamine is unlike that of (+)-amphetamine, but similar to that of 4-methoxyamphetamine, a potent hallucinogen in humans.

Interactions of iprindole with fenfluramine metabolism in rat brain and liver.

An assay procedure utilizing electron-capture gas chromatography was developed for simultaneous analysis of fenfluramine and norfenfluramine. This method was applied to brain and liver samples from rats which had been injected with fenfluramine with or without pretreatment with iprindole. The tissues from rats treated with fenfluramine showed extensive formation of norfenfluramine, consistent with findings reported previously in the literature. Pretreatment with iprindole led to an increase in brain and liver levels of fenfluramine, and, unexpectedly, to a marked decrease in levels of norfenfluramine in these tissues. These findings suggest that iprindole blocks N-deethylation and that it may be a useful tool with which to study the effects of fenfluramine in the absence of norfenfluramine. The results also emphasize the importance of considering drug-drug interactions in future research on fenfluramine.