Cognitive performance in suicidal depressed elderly: preliminary report.

OBJECTIVE: Deficits in executive functions may play an important role in late-life suicide; however the association is understudied. This study examined cognitive function in general and executive functioning specifically in depressed elderly with and without suicidal ideation and attempts. DESIGN: Case-control study. Setting: University-affiliated psychiatric hospital. PARTICIPANTS: We compared 32 suicidal depressed participants aged 60 and older with 32 non-suicidal depressed participants equated for age, education, and gender. MEASUREMENTS: We assessed global cognitive function and executive function with the Dementia Rating Scale (DRS) and the Executive Interview (EXIT25), respectively. RESULTS: Suicidal and non-suicidal depressed groups were comparable in terms of severity of depression and burden of physical illness. Suicidal participants performed worse on the EXIT25, and on the DRS total scale, as well as on Memory and Attention subscales. The differences were not explained by the presence of dementia, substance use, medication exposure, or brain injury from suicide attempts. CONCLUSIONS: Poor performance on tests of executive function, attention, and memory is associated with suicidal behavior in late-life depression.     

Reinforcement and reversal learning in first-episode psychosis

Background: Abnormalities in reinforcement learning and reversal learning have been reported in psychosis, possibly secondary to subcortical dopamine abnormalities. Methods: We studied simple discrimination (SD) learning and reversal learning in a sample of 119 first-episode psychosis patients from the Cambridge early psychosis service (CAMEO) and 107 control participants. We used data on reinforcement learning and reversal learning extracted from the Cambridge Neuropsychological Test Automated Battery Intradimensional-Extradimensional shift task, which measures cognitive flexibility but also involves simple reinforcement learning (SD learning) and reversal learning stages. We also gathered diagnostic information to examine whether there were any differences between patients ultimately diagnosed with schizophrenia-spectrum disorders and those diagnosed with affective psychosis. Results: Psychosis patients demonstrated deficits in simple reinforcement learning (SD learning) and in reversal learning, with no differences between affective psychosis and schizophrenia-spectrum psychosis. There was a significant modest correlation between reversal errors and negative symptoms (Spearman rho = 0.3, P = .02). Conclusions: There are reinforcement learning abnormalities in first-episode psychosis, which correlate with negative symptoms, suggesting a possible role for orbitofrontal cortex and ventral striatal pathology in the pathogenesis of motivational deficits in psychosis.     

Blockade of cytosolic phospholipase A2 alpha prevents experimental autoimmune encephalomyelitis and diminishes development of Th1 and Th17 responses

Cytosolic phospholipase A2 alpha (cPLA2 alpha) is the rate-limiting enzyme for release of arachidonic acid, which is converted primarily to prostaglandins via the cyclooxygenase (COX) 1/2 pathways, and leukotrienes via the 5-lipoxygenase (LO) pathway. We utilized inhibitors of cPLA2 alpha, COX-1/2 and 5-LO to determine the potential roles of these enzymes in development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Blocking cPLA2 alpha prevented EAE development and greatly reduced antigen-induced production of Th1-type cytokines and IL-17. Blocking COX-1/2 delayed onset and reduced severity of EAE, and reduced production of Th1-type cytokines, but not IL-17. Blocking 5-LO delayed onset and reduced cumulative severity of EAE, but did not reduce production of Th1-type cytokines or IL-17. Finally, blockade of cPLA2 alpha from the onset of clinical EAE reduced duration of EAE relapses. Therefore, cPLA2 alpha represents a potential therapeutic target for treatment of MS.     

Mechanical reperfusion is associated with post-ischemic hemorrhage in rat brain

A major complication of recanalization therapy after an acute arterial occlusion in brain is hemorrhagic transformation (HT). Although it is known that prolonged ischemia is important in the development of HT, the role of reperfusion in ischemia–reperfusion induced HT is less well studied. To address the effect of reperfusion on HT, we assessed the incidence and severity of hemorrhage in rats after 5 h of middle cerebral artery occlusion (MCAO) followed by 19-hour reperfusion compared to rats with permanent occlusion (PMCAO) at the same 24-hour time point. The incidence and amount of hemorrhage, neurological function, and mortality rates were measured. MCAO (5 h) with 19-hour reperfusion was associated with a significantly higher incidence of cortical hemorrhage compared to PMCAO (81.8% vs 18.2%, p < 0.05). Hemorrhage scores were higher in the 5-hour MCAO/reperfusion group compared to PMCAO rats (17.6 ± 11.5 vs 2.4 ± 5.3 in cortex, 20.4 ± 4.6 vs 9.7 ± 4.5 in striatum, p < 0.01). Neurological function was worse in the ischemia–reperfusion group compared to PMCAO (p < 0.05) and mortality rates were insignificantly higher in the 5-hour MCAO/reperfusion group vs PMCAO group (54.5% vs18.1%; p < 0.08). The results suggest that reperfusion after prolonged ischemia is associated with increased hemorrhagic transformation and neurological deterioration as compared to permanent ischemia. Whether pharmacological treatments prior to reperfusion attenuate post-ischemic HT requires further study.     

The prevalence and correlates of hallucinations in Australian adolescents: Results from a national survey

There is an emerging interest in children and adolescents who have hallucinations and other psychotic-like experiences to enable identification of those potentially at risk for schizophrenia in adulthood. This study examines the prevalence, demographic and clinical correlates of hallucinations in the adolescent subgroup of the Australian National Survey of Mental Health and Well-Being. Participants were a nationally representative sample of 1261 adolescents aged 13–17 years. Adolescents completed self-report questionnaires with two questions relating to hallucinations and questions pertaining to depressive symptoms and cannabis use. Parents completed the Child Behavior Checklist (CBCL) and the Diagnostic Interview Schedule for Children (DISC-IV).Hallucinations were reported by 8.4% of adolescents. Those living in blended or sole parent families were more likely to report hallucinations than those living with both biological parents (OR 3.27; 95% CI 1.93, 5.54; OR 2.60; 95% CI 1.63, 4.13 respectively). Hallucinations were more prevalent in adolescents who scored in the highest decile of the CBCL or had elevated depression symptoms (OR 3.30; 95% CI 2.10, 5.20; OR 5.02; 95% CI 3.38, 7.45 respectively). Hallucinations were associated with depressive disorder (OR 2.70; 95% CI 1.16, 6.28) and were more prevalent in those adolescents who had smoked cannabis more than twice in the month prior to the survey (OR 3.27; 95% CI 1.76, 6.08). Hallucinations occur relatively frequently in adolescents and are associated with a range of demographic and clinical correlates. Further research may assist in understanding the variable trajectory of children and adolescents who hallucinate.     

The mental health of young people in Australia: key findings from the child and adolescent component of the national survey of mental health and well-being

OBJECTIVE: To identify the prevalence of three mental disorders (Depressive Disorder, Conduct Disorder and Attention-Deficit/Hyperactivity Disorder), the prevalence of mental health problems, the health-related quality of life of those with problems, and patterns of service utilisation of those with and without mental health problems, among 4-17-year-olds in Australia. To identify rates of health-risk behaviours among adolescents with mental health problems. METHOD: The mental disorders were assessed using the parent-version of the Diagnostic Interview Schedule for Children Version IV. Parents completed the Child Behaviour Checklist to identify mental health problems and standard questionnaires to assess health-related quality of life and service use. The Youth Risk Behaviour Questionnaire completed by adolescents was employed to identify health-risk behaviours. RESULTS: Fourteen percent of children and adolescents were identified as having mental health problems. Many of those with mental health problems had problems in other areas of their lives and were at increased risk for suicidal behaviour. Only 25% of those with mental health problems had attended a professional service during the six months prior to the survey. CONCLUSION: Child and adolescent mental health problems are an important public health problem in Australia. The appropriate balance between funding provided for clinical interventions focusing on individual children and families and funding for interventions that focus on populations, requires careful study. The latter are an essential component of any strategy to reduce mental health problems as the high prevalence of problems makes it unlikely that individual care will ever be available for all those needing help. Clinical and population health interventions must take into account the comorbid problems experienced by children with mental disorders.     

A community stroke study: Factors influencing stroke awareness and hospital arrival time

Background: One reason patients do not receive thrombolytic therapy for the treatment of stroke is late arrival to the emergency department (ED). One factor could be due to lack of awareness of stroke symptoms. We tested our hypothesis at 2 hospitals in central Illinois. Objective: To determine hospital arrival times and the level of stroke awareness in an urban/rural setting. Methods: Data were collected from transient ischemic attack (TIA)/stroke patients over a 6-month period. Patients were asked if they knew they were having a stroke, time from symptom onset to hospital arrival, and how they arrived at the hospital. Patient medical records were reviewed to determine risk factor data and classify stroke subtype using the Trial of ORG-10172 in Acute Stroke Treatment (TOAST) criteria. Results: Data were obtained from 185 patients. Only 33% of patients arrived at the hospital within 2 hours of symptom onset. Predictors for early arrival were identified as perceived awareness of having a stroke (odds ratio [OR] = 2.13, 95% confidence interval [CI], 1.01-4.46), calling 911 (OR = 3.40, 95% CI, 1.70-6.82), and TIA (OR = 3.57, 95% CI, 1.50-8.61). Twenty-six percent of the patients were aware they were having a stroke. Diagnosis of a TIA was identified as a predictor of stroke awareness (OR = 2.46, 95% CI, 1.01-5.96). Patients who did not have any stroke risk factors were more aware of having a stroke compared with patients who had documented risk factors (OR = 3.33, 95% CI, 1.09-10.0). Conclusions: Results from this study indicate a lack of public knowledge regarding stroke symptoms in this urban/rural community.     

Functional connectivity along the anterior–posterior axis of hippocampal subfields in the ageing human brain

While age‐related volumetric changes in human hippocampal subfields have been reported, little is known about patterns of subfield functional connectivity (FC) in the context of healthy ageing. Here we investigated age‐related changes in patterns of FC down the anterior–posterior axis of each subfield. Using high resolution structural MRI we delineated the dentate gyrus (DG), CA fields (including separating DG from CA3), the subiculum, pre/parasubiculum, and the uncus in healthy young and older adults. We then used high resolution resting state functional MRI to measure FC in each group and to directly compare them. We first examined the FC of each subfield in its entirety, in terms of FC with other subfields and with neighboring cortical regions, namely, entorhinal, perirhinal, posterior parahippocampal, and retrosplenial cortices. Next, we analyzed subfield to subfield FC within different portions along the hippocampal anterior–posterior axis, and FC of each subfield portion with the neighboring cortical regions of interest. In general, the FC of the older adults was similar to that observed in the younger adults. We found that, as in the young group, the older group displayed intrinsic FC between the subfields that aligned with the tri‐synaptic circuit but also extended beyond it, and that FC between the subfields and neighboring cortical areas differed markedly along the anterior–posterior axis of each subfield. We observed only one significant difference between the young and older groups. Compared to the young group, the older participants had significantly reduced FC between the anterior CA1‐subiculum transition region and the transentorhinal cortex, two brain regions known to be disproportionately affected during the early stages of age‐related tau accumulation. Overall, these results contribute to ongoing efforts to characterize human hippocampal subfield connectivity, with implications for understanding hippocampal function and its modulation in the ageing brain.     

Mean diffusivity and fractional anisotropy as indicators of disease and genetic liability to schizophrenia

The goals of this study were to first determine whether the fractional anisotropy (FA) and mean diffusivity (MD) of major white matter pathways associate with schizophrenia, and secondly to characterize the extent to which differences in these metrics might reflect a genetic predisposition to schizophrenia. Differences in FA and MD were identified using a comprehensive atlas-based tract mapping approach using diffusion tensor imaging and high-resolution structural data from 35 patients, 28 unaffected first-degree relatives of patients, 29 community controls, and 14 first-degree relatives of controls. Schizophrenia patients had significantly higher MD in the following tracts compared to controls: the right anterior thalamic radiations, the forceps minor, the bilateral inferior fronto-occipital fasciculus (IFO), the temporal component of the left superior longitudinal fasciculus (tSLF), and the bilateral uncinate. FA showed schizophrenia effects and a linear relationship to genetic liability (represented by schizophrenia patients, first-degree relatives, and controls) for the bilateral IFO, the left inferior longitudinal fasciculus (ILF), and the left tSLF. Diffusion tensor imaging studies have previously identified white matter abnormalities in all three of these tracts in schizophrenia; however, this study is the first to identify a significant genetic liability. Thus, FA of these three tracts may serve as biomarkers for studies seeking to identify how genes influence brain structure predisposing to schizophrenia. However, differences in FA and MD in frontal and temporal white matter pathways may be additionally driven by state variables that involve processes associated with the disease.