Are BPI and BPII suicide attempters distinct neuropsychologically?

It is not clear if bipolar disorder I (BPI) and bipolar disorder II (BPII) represent the same disorder on a continuum of severity or two distinct syndromes. Neuropsychological functioning is a means of understanding similarities and differences between diagnostic groups. OBJECTIVE: To compare the neuropsychological functioning of depressed suicide attempters with BPI or BPII and healthy controls. METHODS: Fifty-one individuals with bipolar disorder (BPI n=32, BPII n=19) and a history of suicide attempt were compared with 58 healthy controls with respect to neuropsychological functioning in the following domains: motor functioning, psychomotor performance, attention, memory, working memory, impulsiveness and language fluency. RESULTS: Participants with BPI and BPII performed significantly more poorly than healthy controls on tests of Digit Symbol Test of psychomotor functioning, the N Back Test of working memory and the Go-No-Go Test of impulsiveness. Participants with BPI were significantly worse than controls but not those with BPII on the Test of Verbal Fluency. Participants with BPII performed significantly worse than either controls or those with BPI on the Simple Reaction Time Motor Test and the Stroop Test of attention. CONCLUSION: While participants with both BPI and BPII performed more poorly than healthy controls, individuals with BPII also performed more poorly than those with BPI on some tests suggesting that they may have a unique syndrome. The findings have implications for assessment and treatment in bipolar disorder.     

Do neurocognitive abilities distinguish suicide attempters from suicide ideators? A systematic review of an emerging research area

Recent findings suggest that neurocognitive deficits may hasten progression from suicidal thoughts to behavior. To test this proposition, we examined whether neurocognitive deficits distinguish individuals who have attempted suicide (attempters) from those who have considered suicide but never attempted (ideators). A comprehensive literature search yielded 14 studies comparing attempters to ideators on a range of neurocognitive abilities. In general, attempters and ideators scored comparably across neurocognitive abilities (median Hedges' g = ?.18). An exception was a moderate difference for inhibition and decision making (median Hedges' g = ?.50 and g = ?.49, respectively). Results suggest that some neurocognitive abilities might help explain the transition from suicidal thoughts to suicide attempts. However, findings are regarded as suggestive, given the small number of studies, few cross‐study examinations of neurocognitive domains, and variability in sample characteristics. Recommendations for future research are included.     

Is occupation relevant in suicide?

BACKGROUND: The seasonality of suicide rates and methods of suicide may be related to changes in weather and conditions of employment. Particularly the amount of occupational outdoor exposure could show differences in the distribution of suicides by season and the selection of suicide method, in addition to age at the time of death. METHODS: The data consisted of all death certificates (n=1359) of completed suicides in the province of Oulu, Finland, during the years 1988-1999. For male subjects included in this study, four occupational groups were identified according to decreasing occupational outdoor exposure. The mean ages, the distribution of suicide methods and the seasonal variation in suicides for each occupational group were analyzed. RESULTS: Farmers were significantly older at the time of suicide than construction or indoor workers, and farmers employed significantly more violent methods than the other occupational groups. In the spring, farmers had a significant peak in the rate of suicides. In the winter, forest workers had a significant trough in the rate of suicides. In the summer, indoor workers had a significant peak in the rate of suicides. LIMITATIONS: The analyses were restricted to males due to the low number of females in the study population. CONCLUSIONS: The novel finding in this study was that the seasonality of violent suicides was most strongly seen as a spring peak and a winter trough among outdoor workers. The recognition of typical risk factors of different occupations, such as outdoor exposure, and occupational-related susceptibility towards certain suicide methods could benefit in the prevention of suicides.     

History and geography of suicide: could genetic risk factors account for the variation in suicide rates?

The current state of knowledge of genetic predisposition towards the suicidal behavior allows for a question whether genetic risk factors account for the variation in suicide rates through time and space. Accordingly, the presented paper will attempt to tackle the genetics behind suicidal behavior from the perspective of the populational genetics. First, the variability of suicide rates across Europe is discussed. This is followed by a brief discussion of the J curve (on a map of Europe, the countries with a higher suicide rate form a so-called J curve, which starts in Finland and extends down to Slovenia), which maps on to the second principal component identified for European gene distribution, representing the ancestral adaptation to cold climates and the Uralic language dispersion. Furthermore, we will discuss whether the group of people living within the J-curve could share genes, which may not tolerate excessive amounts alcohol, the combination of which is more likely to end in suicidal behavior. Further along we list possible ways in which suicidal behaviour could have been selected for genetically in populations and identify those specific populations in which it may have appeared. Finally, we point at other locations in the world where a similar interplay of genes and environment has probably occurred, Greenland being the best example of the malignant interaction of alcohol consumption and the trait-like characteristics, which might constitute the vulnerability to suicidal behaviour.     

Does type of first contact in depressive and bipolar disorders predict subsequent hospitalisation and risk of suicide?

BACKGROUND: Only a few studies have investigated how the type of first contact is associated with the risk of subsequent hospitalisation and the risk of committing suicide for patients with depressive or bipolar disorders. METHOD: All outpatients (patients in psychiatric ambulatories and community psychiatry centres) and in-patients (patients admitted during daytime or overnight to a psychiatric hospital) with a diagnosis of depressive or bipolar disorder at first contact ever in a period from 1995 to 1999 in Denmark were identified from the Danish Psychiatric Central Research Register (DPCRR). The risk of subsequent hospitalisation and the risk of suicide were compared according to type of first contact. RESULTS: The risk of subsequent hospitalisation was significantly increased for patients who were admitted to inpatient facilities during first contact compared to patients with outpatient treatment as their first contact. Patients with depressive disorder who were admitted also had increased risk of committing suicide eventually. LIMITATIONS: The diagnoses are clinician based. CONCLUSIONS: Patients referred to inpatient treatment have a poorer long-term prognosis than patients treated as outpatients.     

How well does the CSF inform upon pathology in the brain in Creutzfeldt-Jakob and Alzheimer's diseases?

Analysis of lumbar cerebrospinal fluid (CSF) plays a major role in the investigation of central nervous system disease, but how well do the changes in the CSF reflect pathology within the brain and spinal cord parenchyma? Both Creutzfeldt-Jakob (CJD) and Alzheimer's disease (AD) are characterized by the deposition of insoluble beta-pleated sheet peptides [prion protein (PrP) and beta-amyloid (Abeta), respectively] in the extracellular spaces of grey matter in the brain, but there is discordance in both diseases between the peptide levels in the brain and in the CSF. Experimental studies using tracers have shown that interstitial fluid (ISF) drains through very narrow intercellular spaces within grey matter into bulk flow perivascular channels that surround penetrating arteries. ISF then flows to the surface of the brain and joins CSF to drain to cervical lymph nodes. Such drainage of ISF and CSF to regional lymph nodes in the rat plays a significant role in B-cell and T-cell immune reactions within the brain. In man, the pia mater separates the periarterial ISF drainage pathways from the CSF in the subarachnoid space. The almost complete lack of insoluble protease-resistant PrP entering the CSF from the brain in patients with CJD, reported by Wong et al. in this issue of the Journal of Pathology, illustrates the limitations of ISF drainage pathways for the elimination of insoluble peptides from brain tissue. Insoluble Abeta accumulates in the extracellular spaces as plaques in AD and in periarterial ISF drainage pathways as cerebral amyloid angiopathy. Soluble Abeta appears to become entrapped by the insoluble Abeta in the ISF drainage pathways; thus, as the level of soluble Abeta in the brain rises in AD, the level in the CSF falls. Thus, the changes in the CSF do not accurately reflect the accumulation of the abnormal peptides in the brain parenchyma in either CJD or AD. In both diseases, facilitation of ISF drainage and elimination of PrP and Abeta peptides from the extracellular spaces of the brain may lead to practical therapeutic strategies for these devastating disorders.     

What predicts suicide attempts in women with eating disorders?

BACKGROUND: Suicide is a common cause of death in anorexia nervosa and suicide attempts occur often in both anorexia nervosa and bulimia nervosa. No studies have examined predictors of suicide attempts in a longitudinal study of eating disorders with frequent follow-up intervals. The objective of this study was to determine predictors of serious suicide attempts in women with eating disorders. METHOD: In a prospective longitudinal study, women diagnosed with either DSM-IV anorexia nervosa (n = 136) or bulimia nervosa (n = 110) were interviewed and assessed for suicide attempts and suicidal intent every 6-12 months over 8.6 years. RESULTS: Fifteen percent of subjects reported at least one prospective suicide attempt over the course of the study. Significantly more anorexic (22.1%) than bulimic subjects (10.9%) made a suicide attempt. Multivariate analyses indicated that the unique predictors of suicide attempts for anorexia nervosa included the severity of both depressive symptoms and drug use over the course of the study. For bulimia nervosa, a history of drug use disorder at intake and the use of laxatives during the study significantly predicted suicide attempts. CONCLUSIONS: Women with anorexia nervosa or bulimia nervosa are at considerable risk to attempt suicide. Clinicians should be aware of this risk, particularly in anorexic patients with substantial co-morbidity.     

Are cytokines and chemokines suitable biomarkers for Takayasu arteritis?

There is a growing need for disease related biomarkers in Takayasu arteritis (TA).The assessment of pro-inflammatory cytokines and chemokines in TA may provide a better understanding of its pathophysiology, and circulating levels of these mediators may act as biomarkers of disease activity. Serum level of interleukin 6 (IL-6) is a potential biomarker for TA, which is mostly associated with TA status and disease activity. Associations between TA and serum/plasma levels of other cytokines are less clear. mRNA expression of IL-4 and tumor necrosis factor α (TNFα) are constitutively increased in peripheral blood mononuclear cells (PBMC) from TA patients and the expression of both cytokines increases even more after PBMC stimulation in vitro, while the expression of IL-10 mRNA decreases. In addition, circulating T cells from TA patients produce increased levels of both Th1- and Th17-related cytokines upon in vitro stimulation. In the aorta from TA patients, an increased expression of interferon γ (IFNγ), IL-6, IL-12 and IL-17 has been described. Regarding circulating chemokines in TA, serum/plasma levels of IL-8 (CXCL8), CCL2 and CCL5 were shown to be elevated in TA patients compared with healthy controls as well as in TA patients with active disease compared with those in remission. Serum IL-6 seems to be the best biomarker for disease state and disease activity in TA and increased Th1 and Th17 responses are predominant in the pathophysiology of TA.     

Are biomarkers a useful aid in smoking cessation? A review and analysis of the literature

Healthcare providers' ability to motivate people to try to quit smoking or to remain abstinent is limited. Even with our best treatments, most smokers relapse within 1 year. Therefore it is important that we constantly strive to develop and test new, effective smoking interventions. Providing feedback on one's biomarkers (e.g., biological indices of smoking-related harm, harm exposure, or genetic susceptibility to disease) have been suggested as potentially useful for increasing smokers' motivation or ability to quit smoking. In fact, variations of this strategy are commonly incorporated into behavioral smoking-cessation interventions, but little empirical evidence has specifically addressed whether this approach is effective. In this article, the author reviews the theoretical rationale and empirical evidence regarding this practice. Although the preliminary evidence is promising, more research is needed to determine the efficacy of using biomarkers and the limits of the strategy's effectiveness. Future investigations should address these issues.     

Suicides and serious suicide attempts: two populations or one?

BACKGROUND: Few studies have examined the extent to which populations of suicides and attempted suicides are similar, or different. This paper compares suicides and serious suicide attempts in terms of known risk factors for suicidal behaviour. METHODS: Using case-control methodology, risk factors for suicidal behaviour were examined in 202 individuals who died by suicide, 275 individuals who made medically serious suicide attempts and 984 randomly selected control subjects. Based on data from significant others, measures used spanned sociodemographic factors, childhood experiences, psychiatric morbidity and psychiatric history, exposure to recent stressful life events and social interaction. RESULTS: Multiple logistic regression identified the following risk factors that were common to suicide and serious suicide attempts: current mood disorder; previous suicide attempts; prior outpatient psychiatric treatment; admission to psychiatric hospital within the previous year; low income; a lack of formal educational qualifications; exposure to recent stressful interpersonal, legal and work-related life events. Suicides and suicide attempts were distinguished in the following ways: suicides were more likely to be male (OR = 1.9, 95% CI 1.1, 3.2); older (OR = 1.03, 95% CI 1.02, 1.04); and to have a current diagnosis of non-affective psychosis (OR = 8.5, 95% CI 2.0, 35.9). Suicide attempts were more likely than suicides to have a current diagnosis of anxiety disorder (OR = 3.5, 95% CI 1.6, 7.8) and to be socially isolated (OR = 2.0, 95% CI 1.2, 3.5). These findings were confirmed by discriminant function analysis, which identified two functions that described the three subject groups: the first function discriminated the two suicide groups from control subjects on a dimension corresponding to risk factors for suicide; the second function discriminated suicide from suicide attempt subjects on a series of factors including gender, non-affective psychosis and anxiety disorder. CONCLUSIONS: Suicides and medically serious suicide attempts are two overlapping populations that share common psychiatric diagnostic and history features, but are distinguished by gender and patterning of psychiatric disorder.     

Do SSRIs cause suicide in children? The evidence is underwhelming

After regulatory agencies in the United Kingdom and United States recommended severe restrictions on antidepressant use in children, many lessons were learned, although one was not that these drugs cause suicide. We learned that pharmaceutical companies selectively released data that reflected positively on their products and that combining suppressed and published data suggested that most of these medications had questionable efficacy. We also learned that the studies lacked uniformity both in which age groups constituted children and which behavior was considered suicidal. Several recent, large nonindustry studies indicated that rates of suicide and suicidal behavior were actually reduced in children who used antidepressants, despite piteous anecdotal tales in the popular press purporting that selective serotonin reuptake inhibitors (SSRIs) caused children to kill themselves. Patients in pharmaceutical trials probably do not represent typical patients in routine clinical practice. Emerging implications are that suicidal behavior-if it does occur-is most likely soon after starting antidepressant use and that prescribers must be both vigilant in educating patients and families about warning signs and available to manage worrisome behavior.     

Recombinant WNTs differentially activate β-catenin-dependent and -independent signalling in mouse microglia-like cells

Aim: The objective of this study was to compare the efficacy of different recombinant, commercially available Wingless/Int‐1 (WNTs) with regard to WNT/β‐catenin signalling, dishevelled (DVL) and G protein activation and the induction of cell proliferation in a microglia‐like cell line called N13. Methods: For detection of activated signalling molecules, cell lysates are analysed by immunoblotting. Furthermore, we used a [γ³⁵S] GTP binding assay to monitor the exchange of GDP for GTP in heterotrimeric G proteins in N13 membrane preparations. Cell proliferation was assessed by the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay measuring mitochondrial function, which is proportional to the amount of viable cells. Results: Of the WNTs tested (WNT‐3A, ‐4, ‐5A, ‐5B, ‐7A,‐9B), only WNT‐3A activated WNT/β‐catenin signalling in N13 cells. All WNTs induced the formation of P hosphorylated and S hifted DVL (PS‐DVL) and the activation of heterotrimeric G proteins with variable efficacies. WNT‐5A and WNT‐9B, which had the highest efficacy in the G protein assay, also induced N13 cell proliferation. Conclusion: WNTs show significant differences in their efficacy to activate β‐catenin‐dependent and ‐independent signalling. The WNTs tested are present during maturation of the central nervous system and/or in the adult brain and are thus potential regulators of microglia‐mediated neuroinflammation.     

Urinary procollagen III aminoterminal propeptide and β-catenin – New diagnostic biomarkers in solitary functioning kidney?

Purpose: We aimed at evaluating urinary levels of procollagen III aminoterminal propeptide (PIIINP) and β-catenin and the relationship between these markers and clinical and laboratory variables in children with a solitary functioning kidney (SFK).Patients and methods: The study group consisted of 98 (M/F: 62/36) children with an SFK with a median age of 8 years. An age-matched control group contained 54 healthy peers. Urinary levels of procollagen III aminoterminal propeptide and β-catenin were measured using a commercially available immunoassay kit.Results: The urinary values of PIIINP (UPIIINP) were significantly increased in patients with SFK versus controls (p < 0.01). Our analysis revealed no significant differences in urinary β-catenin levels between the SFK patients and control subjects (p > 0.05). Only urinary PIIINP levels were correlated to renal function tests, such as serum creatinine, urea, uric acid, and estimated glomerular filtration rate (p<0.05).Conclusions: An increased urinary level of PIIINP may indicate early kidney impairment in children with SFK. Urinary β-catenin does not seem to play any important role as a marker of renal function in children with SFK. Further long-term studies are required in order to evaluate the clinical usefulness of these markers and their predictive value of chronic kidney disease (CKD) progression.     

Is there a relationship between Wolfram syndrome carrier status and suicide?

Wolfram syndrome (WFS) is a rare, autosomal recessive neurodegenerative disorder. An increased risk of psychiatric disorders and suicide has been reported for heterozygote carriers. In this study we investigated whether mutations in the WFS gene are associated with suicide in the general population. The gene for WFS (WFS1) has recently been mapped to chromosome 4p16.1, and its genomic structure has been characterized. We screened the entire WFS1 ORF in a panel of 100 completed suicides, 60 blood donors not known to have psychiatric illness, and 100 donors with a negative history of depression or suicidal behavior. We did not find evidence of an increased incidence of WFS carriers in the suicide panel and concluded that WFS1 carrier status is not a significant contributor to suicide in the general population. Screening of this highly polymorphic gene resulted in the detection of 33 variants, 13 of which cause amino acid changes. Seven of these changes have not been previously reported and six were unique to our suicide panel.     

Is there a relationship between Wolfram syndrome carrier status and suicide?

Wolfram syndrome (WFS) is a rare, autosomal recessive neurodegenerative disorder. An increased risk of psychiatric disorders and suicide has been reported for heterozygote carriers. In this study we investigated whether mutations in the WFS gene are associated with suicide in the general population. The gene for WFS (WFS1) has recently been mapped to chromosome 4p16.1, and its genomic structure has been characterized. We screened the entire WFS1 ORF in a panel of 100 completed suicides, 60 blood donors not known to have psychiatric illness, and 100 donors with a negative history of depression or suicidal behavior. We did not find evidence of an increased incidence of WFS carriers in the suicide panel and concluded that WFS1 carrier status is not a significant contributor to suicide in the general population. Screening of this highly polymorphic gene resulted in the detection of 33 variants, 13 of which cause amino acid changes. Seven of these changes have not been previously reported and six were unique to our suicide panel. © 2002 Wiley‐Liss, Inc.     

Fas and Fas ligand: strong co-expression in human hepatocytes surrounding hepatocellular carcinoma; can cancer induce suicide in peritumoural cells?

Fas (Apo-1, CD95), a member of the nerve growth factor/tumour necrosis factor receptor superfamily, mediates apoptosis in response to agonistic antibodies or Fas ligand (Fas-L) binding. Fas has been shown to be present on hepatocyte membranes in normal liver and in chronic hepatitis C. At the present time, very limited data are available on the expression of Fas-L. This paper describes a study of 20 cases of active chronic hepatitis of different aetiologies, 20 hepatocellular carcinomas (HCCs) and the adjacent non-tumoural liver parenchyma, and five normal livers. The immunohistochemical expression of Fas and Fas-L was determined using specific monoclonal antibodies. In normal liver, Fas was faintly expressed on membranes of hepatocytes and bile duct cells, while Fas-L was negative. In active chronic hepatitis, Fas expression in hepatocytes was enhanced, resulting in a diffuse honeycomb pattern. Fas-L showed cytoplasmic positivity in hepatocytes in areas of interface hepatitis. Strong expression of Fas as well as Fas-L in the hepatocytes immediately adjacent to HCC was a constant finding. Within the HCCs, Fas-L expression was variable, but present only in a minority of cells. Fas varied from a diffuse honeycomb pattern to focal positivity in occasional cells. There was no correlation between Fas and Fas-L expression in the tumours. In conclusion, hepatocytes can co-express Fas and Fas-L in areas of interface hepatitis and adjacent to HCC, suggesting that they have the ability to induce apoptosis in an autocrine or paracrine way. Within the tumour, the Fas-Fas-L apoptosis pathway seems to be little involved.     

Genetic variants in PSEN2 and correlation to CSF β-amyloid42 levels in AD

Beta-amyloid 42 (Aβ42) concentrations in cerebrospinal fluid (CSF) are significantly decreased in Alzheimer's disease (AD). The aim of this study was to correlate genetic variability in presenilin 2 (PSEN2) in relation to Aβ42 concentrations and to confirm association of apolipoprotein E (APOE) alleles E4/E4 genotype with lower CSF Aβ42. Haplotype analysis of PSEN2 and APOE genotyping were performed in 175 Alzheimer's disease patients, as defined by clinical diagnosis and Aβ42 levels. One distinct haploblock in PSEN2 was detected and the frequent haplotypes were analyzed using 4 tagging single nucleotide polymorphisms (SNPs). We found an association between haplotype 2 and higher CSF Aβ42 concentrations (p = 0.021) and lower Aβ42 concentrations in haplotype 5 carriers (p < 0.001). APOE E4/E4 carriers had lower Aβ42 levels (p = 0.009). Additive regression analysis showed an association of Aβ42 level with APOE genotype (p = 0.024), haplotype 4 (p = 0.064), and haplotype 5 (p = 0.04), whereas gender, age at onset and Mini Mental State Examination (MMSE) remained insignificant. Using CSF Aβ42 as a biomarker we replicated genetic influences in APOE and observed a significant influence of a new haplotype in PSEN2. A better understanding of genetic influences on biomarkers like CSF Aβ42 might help to stratify patients and develop specific treatment strategies.