Mental health and academic outcomes over the first year at university in international compared to domestic Canadian students.

OBJECTIVE: To compare risk factors and associated mental health and academic outcomes between international and domestic students. PARTICIPANTS: Canadian university undergraduate students. METHODS: Electronic surveys were completed at university entry and the end of first year. Surveys assessed demographics, risk factors, symptoms of mental disorders, and access to support. Academic outcomes were obtained from university databases. RESULTS: International students had comparable or lower rates of clinically significant anxiety, depression, and insomnia. Domestic female students reported the highest screening rates for common mental disorders. However, international students were more likely to report having attempted suicide. International students felt less connected to the university community and had lower academic performance. Psychosocial risk factor profiles and proportions accessing mental health services were similar. CONCLUSIONS: The scope of mental health need appears more similar than different between international and domestic students; however, international students may benefit from targeted academic and social support initiatives.

Predictors of mental health and academic outcomes in first-year university students: Identifying prevention and early-intervention targets.

BACKGROUND: Although there is growing interest in mental health problems in university students there is limited understanding of the scope of need and determinants to inform intervention efforts. AIMS: To longitudinally examine the extent and persistence of mental health symptoms and the importance of psychosocial and lifestyle factors for student mental health and academic outcomes. METHOD: Undergraduates at a Canadian university were invited to complete electronic surveys at entry and completion of their first year. The baseline survey measured important distal and proximal risk factors and the follow-up assessed mental health and well-being. Surveys were linked to academic grades. Multivariable models of risk factors and mental health and academic outcomes were fit and adjusted for confounders. RESULTS: In 1530 students surveyed at entry to university 28% and 33% screened positive for clinically significant depressive and anxiety symptoms respectively, which increased to 36% and 39% at the completion of first year. Over the academic year, 14% of students reported suicidal thoughts and 1.6% suicide attempts. Moreover, there was persistence and overlap in these mental health outcomes. Modifiable psychosocial and lifestyle factors at entry were associated with positive screens for mental health outcomes at completion of first year, while anxiety and depressive symptoms were associated with lower grades and university well-being. CONCLUSIONS: Clinically significant mental health symptoms are common and persistent among first-year university students and have a negative impact on academic performance and well-being. A comprehensive mental health strategy that includes a whole university approach to prevention and targeted early-intervention measures and associated research is justified.

Stressful Life Events Prior to Depression Onset and the Cortisol Response to Stress in Youth with First Onset Versus Recurrent Depression.

The strongest proximal predictors of depression onset in adolescence are stressful life events (SLEs). Changes in the hypothalamic-pituitary-adrenal (HPA) axis response to stress are theorized to mediate the etiological effect of SLEs on depression onset. The goal of the current study was to examine differences in the cortisol response to a laboratory-induced stressor between youth with versus without at least one SLE in the etiologically-central 3-month period prior to depression onset. One hundred adolescents (24 first-onset depression, 18 recurrent depression, and 58 non-depressed controls) had five salivary cortisol samples collected over the course of the Trier Social Stress Test (TSST). SLEs were assessed using a rigorous contextual interview and rating system. Among those with an SLE, youth on their first onset of depression had a flatter cortisol reactivity slope relative to non-depressed adolescents, and youth on a recurrent episode of depression had a steeper recovery slope relative to first-onsets and non-depressed adolescents. In contrast, no between-group differences were found among those with no SLE prior to onset. These results suggest that differences in the HPA axis response pattern may represent a neurobiological mechanism that distinguishes depressed and non-depressed groups but only for adolescents whose depression is precipitated by SLEs. Further, this neurobiological mechanism may play a different role in the very first episode of depression than it does in recurrent episodes.

Is depression a chronic mental illness?

Over the past few decades, theory and research on depression have increasingly focused on the recurrent and chronic nature of the disorder. These recurrent and chronic forms of depression are extremely important to study, as they may account for the bulk of the burden associated with the disorder. Paradoxically, however, research focusing on depression as a recurrent condition has generally failed to reveal any useful early indicators of risk for recurrence. We suggest that this present impasse is due to the lack of recognition that depression can also be an acute, time-limited condition. We argue that individuals with acute, single lifetime episodes of depression have been systematically eclipsed from the research agenda, thereby effectively preventing the discovery of factors that may predict who, after experiencing a first lifetime episode of depression, goes on to have a recurrent or chronic clinical course. Greater awareness of the high prevalence of people with a single lifetime episode of depression, and the development of research designs that identify these individuals and allow comparisons with those who have recurrent forms of the disorder, could yield substantial gains in understanding the lifetime pathology of this devastating mental illness.

Lone atrial septal aneurysm and stroke--a case report and review of the literature.

The aetiology of stroke in young patients is usually difficult to establish. Despite extensive investigations, the cause of stroke remains unknown in a large percentage of these patients. We report a case of stroke in a young patient in whom the only associated aetiological factor was a lone atrial septal aneurysm. We discuss the investigational tools in the diagnosis of atrial septal aneurysms and study the aetiopathogenesis of strokes and the risk of recurrent strokes associated with their presence. We also review the evidence for the presently available therapies for prevention of further strokes in such patients.

Utility of an ultrafast magnetic resonance imaging protocol in recent and semi-recent strokes.

OBJECTIVE: To evaluate the technical feasibility of an integrated ultrafast head magnetic resonance (MR) protocol using a sensitivity encoding (SENSE) technique for depicting parenchymal ischaemia and vascular compromise in patients with suspected recent stroke. METHODS: 23 patients were evaluated with the ultrafast MR protocol using T2, T1, fluid attenuated inversion recovery (FLAIR), 3D time of flight magnetic resonance angiography (MRA), and diffusion weighted imaging (DWI) sequences. These were compared with routine conventional MR sequences. RESULTS: One patient could not tolerate conventional imaging, although imaging using the three minute head SENSE protocol was diagnostic. Both conventional and ultrafast protocols were of similar diagnostic yield in the remaining patients. There were no significant differences in clinical diagnostic quality for the T1, T2, FLAIR, and DWI sequences. One MRA examination was of better quality when SENSE was used, owing to reduced motion artefacts and shorter imaging time. CONCLUSIONS: It is possible to undertake a comprehensive MR examination in stroke patients in approximately three to five minutes. Ultrafast imaging may become a useful triage tool before thrombolytic therapy. It may be of particular benefit in patients unable to tolerate longer sequences. Further work is necessary to confirm these findings in hyperacute stroke.

MR venography in idiopathic intracranial hypertension: unappreciated and misunderstood.

BACKGROUND: Venous sinus disease must be excluded before diagnosing idiopathic intracranial hypertension but is found only rarely in typical cases. Magnetic resonance venography (MRV) is the technique of choice for investigating this, and provides images that are diagnostic and easy to interpret. However, recent work using more invasive techniques has documented pressure gradients and stenoses in the lateral venous sinuses in many cases of idiopathic intracranial hypertension. OBJECTIVE: To examine the reason for this discrepancy and to establish whether there are characteristic appearances on MRV in idiopathic intracranial hypertension that are routinely overlooked in clinical practice. METHODS: MRVs from 20 patients with idiopathic intracranial hypertension were reviewed, unblinded, by two neuroradiologists, and their appearances rated for focal narrowings and signal gaps. A control group of 40 asymptomatic volunteers, matched for age and sex with the patient group, was recruited prospectively for MRV, and their scans rated in the same way. RESULTS: The lateral sinuses presented a range of appearances with quite different distributions in the two groups (p<0.001). Bilateral lateral sinus flow gaps were seen in 13 of 20 patients with idiopathic intracranial hypertension and in none of 40 controls. CONCLUSIONS: A historical failure to use normal healthy controls to establish the boundaries between imaging artefact, normal anatomical variant, and disease means that the pathological significance of the different appearances of the lateral sinuses on MRV has not so far been appreciated.

Rapidly reversible dementia in cerebral amyloid inflammatory vasculopathy.

This report discusses a biopsy proven case of cerebral amyloid angiopathy, with additional prominent vascular inflammatory features, characterized by a rapidly progressive dementia and leukoencephalopathy, where the clinical and radiological abnormalities resolved rapidly with minimal therapeutic intervention. We propose the term cerebral amyloid inflammatory vasculopathy (CAIV) to describe this condition.

Cytokine regulation of MCP-1 expression in brain and retinal microvascular endothelial cells.

Chemokines have a pivotal role in the selective mediation and amplification of inflammation. The CNS vascular endothelial cells, which form part of the blood-brain barrier (BBB) and blood-retinal barrier (BRB), are ideally situated to present chemokines to circulating lymphocytes leading to their recruitment. Monocyte-chemoattractant protein-1 (MCP-1), also known as CCL2, a potent chemoattractant of T cells and monocytes, has been implicated in inflammatory and angio-proliferative brain and retinal disease. In this study, MCP-1 expression by CNS endothelial cells was investigated in vitro. Rat brain (GP8/3.9) and retinal (JG2/1) vascular endothelial cell lines expressed MCP-1 constitutively in vitro as assessed by immunocytochemistry and enzyme linked immunosorbant assay (ELISA). Upregulation of secreted MCP-1 was observed following activation with the pro-inflammatory cytokines TNF-alpha, IL-1 beta and IFN-gamma, and was reduced following dexamethasone treatment. Functional chemotactic activity of brain and retinal endothelial cell supernatants was demonstrated in an in vitro chemotaxis assay, which was inhibited by anti-MCP-1 antibodies. These findings suggest that endothelial cell-derived MCP-1 plays a key role in leukocyte recruitment across the blood-brain and blood-retinal barriers in vivo.

Clinical risk factors for the generation of life events in major depression.

This study examines the relationship of anxiety disorder and dysthymia comorbidity to the generation of life events prior to major depression episode onset in a cross-sectional community sample of 76 women. Those with comorbid anxiety and dysthymia experienced higher rates of events that were at least partly dependent on their own behavior but did not differ from those without these clinical risk factors on independent life events outside of their control. This relationship remained significant even after controlling for overall severity of depression and demographic covariates. The implications of these results for understanding the increased rates of major depression onset and recurrence among those with comorbid anxiety and dysthymia are discussed as avenues of future research.

Life stress and the symptoms of major depression.

Life stress has been found to be associated with onset of depression and with greater severity of depressive symptoms. It is unclear, though, if life stress is related to particular classes or specific symptoms in depression. The association between severe life events and depressive symptoms was tested in 59 individuals diagnosed by Research Diagnostic Criteria with endogenous primary nonpsychotic major depression. As predicted, life stress was associated principally with cognitive-affective symptoms, not somatic symptoms. There also was a consistent association across different assessment methods between severe events and suicidal ideation. Finally, associations held specifically for severe events occurring before onset, not for severe events occurring after onset. Symptom variation in major depression is related specifically to severe stressors before onset and includes primarily cognitive-affective types of symptoms. There is an especially pronounced association of prior severe stress with suicidal ideation. The implications of stress-symptom associations are addressed for enlarging understanding of symptom heterogeneity and subtype distinctions in major depression.

Ototoxicity after high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin followed by stem cell transplantation in patients with breast cancer.

Our purpose was to determine the risk of ototoxicity in breast cancer patients receiving a myeloablative regimen consisting of cyclophosphamide 6000 mg/m2, thiotepa 500 mg/m2 and carboplatin 800 mg/m2 (CTCb) followed by stem cell transplantation. Fourteen consecutive patients with breast cancer were treated with high dose chemotherapy consisting of the CTCb regimen followed by stem cell transplantation. A pretransplant complete hearing study was obtained which consisted of hearing case history, audiometry and tympanometry. In addition, DPOAE (Distortion Product Otoaccoustic Emissions) was done to evaluate measurable changes in the cochlear (outer hair cell) functioning. Pre-transplant, all patients had no clinical evidence of hearing impairment and hearing studies were normal. Eleven patients had hearing studies and a telephone interview posttransplant. One patient was lost to follow-up and two patients died. One of the 11 patients tested had an abnormal post-transplant hearing study but none of them had clinically detectable hearing impairment. In our prospective study of breast cancer patients treated with the CTCb regimen, we did not observe clinically detectable hearing impairment in any of the patients tested.

Dexamethasone regulation of matrix metalloproteinase expression in CNS vascular endothelium.

Matrix metalloproteinases (MMPs) have been implicated in the early breakdown of the blood-brain barrier in neuroinflammatory disease. Although expression of these enzymes by resident glial cells and recruited immune cells has been described, altered expression of MMPs by the CNS vascular endothelial cells may also contribute to barrier disruption. In the present study, the in vitro expression of MMP-2 and -9 as well as tissue inhibitor of metalloproteinase (TIMP)-2 by rat CNS microvascular endothelial cells has been determined and compared with that by endothelial cell lines derived from rat aorta and high endothelial venules. Primary cultures of rat brain microvascular endothelial cells as well as the rat brain (GP8/3.9) and rat retinal endothelial (JG2/1) cell lines constitutively expressed MMP-2, -9 and TIMP-2. In vitro activation of CNS endothelium with the pro-inflammatory cytokines, tumour necrosis factor-alpha and interleukin-1beta, resulted in selective upregulation of MMP-9 activity, whereas no significant changes were seen in MMP-2 or TIMP-2 levels at 24 h. The addition of dexamethasone partially inhibited the cytokine-induced upregulation of MMP-9. Treatment of GP8/3.9 brain endothelial cells with active MMP-9 caused subtle but distinct alterations in the expression of the junctional protein, ZO-1. Quantitative differences found between CNS and non-CNS endothelial cells in the expression of both MMP-2 and -9, and in the expression of TIMP-2 demonstrate that CNS vascular endothelium is functionally distinct from non-CNS endothelium. These results suggest that cytokine-induced upregulation of MMP-9 expression by the CNS vascular endothelium may play a role in the pathogenesis of blood-brain and blood-retinal barrier breakdown in vivo.

The generation of life events in recurrent and non-recurrent depression.

BACKGROUND: The stress generation hypothesis proposed by Hammen (1991) holds that depressed individuals generate stressful conditions for themselves, which lead to recurrence. The original test of this hypothesis compared dependent life events in women with recurrent depression to medical and normal controls. Two further research questions emerged from this work: (a) do individuals with a history of many depressive episodes generate more dependent life events than depressives with fewer episodes?; and (b) what is the aetiological relevance of any stress that may be generated? METHODS: The present research tested differences in dependent and independent events between depressed individuals who had experienced: (a) no previous major depressive episodes; (b) one previous episode; and (c) two or more previous episodes. We predicted that, based on the stress generation hypothesis, recurrent depressives would show more dependent events than people without a depression history, and that these generated stressors would be of aetiological importance for precipitating recurrence (i.e. severe events in the 3 months preceding recurrence). RESULTS: Recurrent depressives experienced significantly more total dependent events than first-onset depressives in the 12 months, but not the 3 months, preceding their episode. CONCLUSIONS: Although the findings supported the general premise of stress generation, the aetiological relevance of the generated stress for recurrence requires further study.

Development of a web based electronic patient record extending accessibility to clinical information and integrating ancillary applications.

Web-technology offers a powerful mechanism for providing access to clinic information. Applications need no longer to be tied to a specific client operating system. The Johns Hopkins Hospital has designed a web based electronic patient record system which seamlessly incorporates multiple web sites. This paper will discuss the motivations for building the system, the architecture, and the challenges faced in designing the architecture.

Seasonal and non-seasonal depression and the five-factor model of personality.

The purpose of this study was to compare the personality characteristics of patients with non-psychotic, major depression, seasonal subtype (SAD) to patients with non-psychotic, major depression, without seasonality (non-SAD). The patients were consecutive referrals to a university-affiliated mood disorders outpatient clinic. The personality characteristics were assessed using the five-factor model of personality (FFM) as measured by the revised NEO Personality Inventory (NEO PI-R). Patients were assessed during the acute depressive episode. Controlling for severity of depression, differences were found on only one of the five dimensions, with the SAD patients (n = 43) scoring significantly higher on the Openness dimension than non-SAD patients (n = 57). Based on these results we infer SAD patients may represent a psychologically distinct subgroup of depressed patients-more imaginative, more emotionally sensitive and likely to entertain unconventional ideas than non-SAD patients. This personality constellation may explain why individuals with SAD are more sensitive to and may amplify the mild dysphoria typically associated with winter months.