Sociocultural factors associated with attitudes toward suicide in Australia.

To investigate the role of cultural and economic factors on suicide attitudes and stigma toward suicide, we recruited 230 Australian adults for an online survey, assessing demographic characteristics (including ethnicity and socioeconomic status, SES), suicide attitudes, stigma toward people who die by suicide, and public knowledge of suicide prevention (suicide literacy). Regression analyses indicated that participants affiliated with non-Anglo cultures or with higher SES had higher suicide stigma and lower suicide literacy than Anglo participants and those in lower SES areas. Increased stigma in minority cultural groups may impact help-seeking behaviors that protect against suicide.

Suicide: What the General Public and the Individual Should Know.

BACKGROUND: The predominant, current western view is that all suicide is the result of mental disorder. This view is much too narrow and does not admit extensive information regarding the social, economic, and forensic factors (among many others) which may contribute to completed suicide. A consequence of this narrow view is that prevention strategies mainly focus on the detection and treatment of mental disorder. A preferred approach is to place greater emphasis on public health approaches to suicide prevention. OBJECTIVE: To develop and suggest a body of information which may be useful in a public health approach to suicide. CONCLUSION: It is suggested that the following be available to the general public: i) suicide is a fact of life which should be minimised, ii) suicide has many different triggers, iii) most people who take their lives are able to make decisions, and iv) increased public discussion and understanding of suicide is desirable. Five pieces of information that may be useful to those contemplating suicide include: i) don't murder the part of you that wants to live, ii) suicide actions may leave you alive but disabled, iii) suicide hurts other people, iv) suicidal impulses do pass if you hold on, and v) suicide is a waste.

Suicidal thinking and behaviour as of 600 BCE (Aesop's fables).

OBJECTIVE: Psychiatry has ignored history, anthropology, sociology and literature in the search for enlightenment regarding suicide. Our objective was to determine what, if anything, Aesop's fables had to teach us about suicide in around 600 BCE. Aesop's account is around two centuries older than the oldest text (Herodotus: The histories) previously examined by our group. METHOD: We examined two translations of Aesop's fables, seeking accounts fitting the following categories: (1) suicidal thinking, (2) suicidal behaviour without fatal consequences, and (3) suicidal behaviour with fatal consequences. RESULTS: One account fitting each of these categories was identified. The triggers were: (i) self-doubt and criticism, (ii) unpleasant predicament (constant fear), and (iii) inescapable physical pain. CONCLUSION: Evidence indicates that around 600 BCE, suicide was practised as a means of coping with self-doubt and criticism, unpleasant predicaments and inescapable physical pain. Recent scientific evidence confirms these observations.

Widespread decreases in cortical muscarinic receptors in a subset of people with schizophrenia.

These studies were undertaken to investigate the selectivity of cortical muscarinic receptor radioligand binding in muscarinic M(1) and M(4) receptor knockout mice and to determine whether a marked decrease in [(3)H]pirenzepine binding in Brodmann's area (BA) 9 from a subset of people with schizophrenia was predictive of decreased muscarinic receptors in other central nervous system (CNS) regions. Our data show that, under the conditions used, [(3)H]pirenzepine binding was highly selective for the muscarinic M(1) receptor whereas both [(3)H]AF-DX 386 and [(3)H]4DAMP had less discriminatory power. In addition, the data suggest that a marked decrease in [(3)H]pirenzepine binding in BA 9 from a subset of people with schizophrenia is predictive of decreases in muscarinic receptors in other CNS regions. However, there were some region-specific decreases in muscarinic receptors in tissue from people with schizophrenia who were outside this subset. These data add to a growing body of evidence suggesting there are widespread decreases in muscarinic receptors in the CNS of some subjects with schizophrenia, as demonstrated by neuroimaging. Our data have implications for understanding the potential clinical utility of drugs directed at the orthosteric and allosteric sites of muscarinic receptors to treat schizophrenia.

Mu opioid receptor availability in people with psychiatric disorders who died by suicide: a case control study.

BACKGROUND: Mu opioid receptors have previously been shown to be altered in people with affective disorders who died as a result of suicide. We wished to determine whether these changes were more widespread and independent of psychiatric diagnoses. METHODS: Mu receptor levels were determined using [3 H]DAMGO binding in BA24 from 51 control subjects; 38 people with schizophrenia (12 suicides); 20 people with major depressive disorder (15 suicides); 13 people with bipolar disorder (5 suicides) and 9 people who had no history of psychiatric disorders but who died as a result of suicide. Mu receptor levels were further determined in BA9 and caudate-putamen from 38 people with schizophrenia and 20 control subjects using [3 H]DAMGO binding and, in all three regions, using Western blots. Data was analysed using one-way ANOVAs with Bonferroni's Multiple Comparison Test or, where data either didn't approximate to a binomial distribution or the sample size was too small to determine distribution, a Kruskal-Wallis test with Dunn's Multiple Comparison Test. RESULTS: [3 H]DAMGO binding density was lower in people who had died as a result of suicide (p<0.01). People with schizophrenia who had died as a result of suicide had lower binding than control subjects (p<0.001), whilst people with bipolar disorder (non- suicide) had higher levels of binding (p<0.05). [3 H]DAMGO binding densities, but not mu protein levels, were significantly decreased in BA9 from people with schizophrenia who died as a result of suicide (p<0.01). CONCLUSIONS: Overall these data suggest that mu opioid receptor availability is decreased in the brains of people with schizophrenia who died as a result of suicide, which would be consistent with increased levels of endogenous ligands occupying these receptors.

Increased cortical expression of the zinc transporter SLC39A12 suggests a breakdown in zinc cellular homeostasis as part of the pathophysiology of schizophrenia.

Our expression microarray studies showed messenger RNA (mRNA) for solute carrier family 39 (zinc transporter), member 12 (SLC39A12) was higher in dorsolateral prefrontal cortex from subjects with schizophrenia (Sz) in comparison with controls. To better understand the significance of these data we ascertained whether SLC39A12 mRNA was altered in a number of cortical regions (Brodmann's area (BA) 8, 9, 44) from subjects with Sz, in BA 9 from subjects with mood disorders and in rats treated with antipsychotic drugs. In addition, we determined whether inducing the expression of SLC39A12 resulted in an increased cellular zinc uptake. SLC39A12 variant 1 and 2 mRNA was measured using quantitative PCR. Zinc uptake was measured in CHO cells transfected with human SLC39A12 variant 1 and 2. In Sz, compared with controls, SLC39A12 variant 1 and 2 mRNA was higher in all cortical regions studied. The were no differences in levels of mRNA for either variant of SLC39A12 in BA 9 from subjects with mood disorders and levels of mRNA for Slc39a12 was not different in the cortex of rats treated with antipsychotic drugs. Finally, expressing both variants in CHO-K1 cells was associated with an increase in radioactive zinc uptake. As increased levels of murine Slc39a12 mRNA has been shown to correlate with increasing cellular zinc uptake, our data would be consistent with the possibility of a dysregulated zinc homeostasis in the cortex of subjects with schizophrenia due to altered expression of SLC39A12.

Biomarker investigations related to pathophysiological pathways in schizophrenia and psychosis.

Post-mortem brain investigations of schizophrenia have generated swathes of data in the last few decades implicating candidate genes and protein. However, the relation of these findings to peripheral biomarker indicators and symptomatology remain to be elucidated. While biomarkers for disease do not have to be involved with underlying pathophysiology and may be largely indicative of diagnosis or prognosis, the ideal may be a biomarker that is involved in underlying disease processes and which is therefore more likely to change with progression of the illness as well as potentially being more responsive to treatment. One of the main difficulties in conducting biomarker investigations for major psychiatric disorders is the relative inconsistency in clinical diagnoses between disorders such as bipolar and schizophrenia. This has led some researchers to investigate biomarkers associated with core symptoms of these disorders, such as psychosis. The aim of this review is to evaluate the contribution of post-mortem brain investigations to elucidating the pathophysiology pathways involved in schizophrenia and psychosis, with an emphasis on major neurotransmitter systems that have been implicated. This data will then be compared to functional neuroimaging findings as well as findings from blood based gene expression investigations in schizophrenia in order to highlight the relative overlap in pathological processes between these different modalities used to elucidate pathogenesis of schizophrenia. In addition we will cover some recent and exciting findings demonstrating microRNA (miRNA) dysregulation in both the blood and the brain in patients with schizophrenia. These changes are pertinent to the topic due to their known role in post-transcriptional modification of gene expression with the potential to contribute or underlie gene expression changes observed in schizophrenia. Finally, we will discuss how post-mortem studies may aid future biomarker investigations.

Recent advances in postmortem pathology and neurochemistry in schizophrenia.

PURPOSE OF REVIEW: This is a review examining recent data from the study of the postmortem central nervous system (CNS) of patients with schizophrenia. RECENT FINDINGS: Studies on the human CNS transcriptome suggest changes in pro-inflammatory pathways and myelination in schizophrenia, whereas changes in the proteome suggest that pathways involved in energy and metabolism may be particularly stressed. There appear to be complex changes in the expression of proposed candidate genes for schizophrenia such as NRG1, DISC1, RGS4 and DTNB1, and there are continued reports of alterations in central gamma-aminobutyric acidergic, dopaminergic, glutamatergic and cholinergic pathways in patients with the disorder. Data on epigenetic mechanisms and transcriptome regulation suggest that at least some changes in gene expression may be due to changes in levels of gene promoter methylation or microRNAs in the CNS of patients with schizophrenia. SUMMARY: Postmortem CNS studies have begun to unravel changes in the epigenetic regulation of gene expression that may be central to how gene-environment interactions contribute to the onset of schizophrenia. In addition, a recent study indicates that it is possible to use biomarkers to segregate the syndrome of schizophrenia into more biologically homogeneous populations, which should decrease the biological complexity observed within that group within the schizophrenia syndrome.