Role In Mental Disorders Research Articles

Suicidal drowning deaths in northern Sweden 1992–2009 – The role of mental disorder and intoxication

Suicides by drowning have received limited attention by researchers. A recent finding that almost one-third of all drowning deaths in Sweden were classified as suicide instigated this study. We identified 129 cases of suicide by drowning in Northern Sweden and analyzed the circumstances and the psychiatric history prior to the suicide. Information was obtained from autopsy, police and medical records, as well as from the National Inpatient Register. One-third of the suicide victims had previously attempted suicide and half of the victims had been hospitalized due to mental health problems. One-third of these had left the hospital less than one week before the suicide. Alcohol and psychoactive drugs were present in 16% and 62% of the cases, respectively.A history of mental disorder and previous suicide attempt (s), especially by drowning, is an ominous combination necessitating efficient clinical identification, treatment and follow-up if a complete suicide is to be prevented.

Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis.

Despite the potential importance of understanding excess mortality among people with mental disorders, no comprehensive meta-analyses have been conducted quantifying mortality across mental disorders. To conduct a systematic review and meta-analysis of mortality among people with mental disorders and examine differences in mortality risks by type of death, diagnosis, and study characteristics. We searched EMBASE, MEDLINE, PsychINFO, and Web of Science from inception through May 7, 2014, including references of eligible articles. Our search strategy included terms for mental disorders (eg, mental disorders, serious mental illness, and severe mental illness), specific diagnoses (eg, schizophrenia, depression, anxiety, and bipolar disorder), and mortality. We also used Google Scholar to identify articles that cited eligible articles. English-language cohort studies that reported a mortality estimate of mental disorders compared with a general population or controls from the same study setting without mental illness were included. Two reviewers independently reviewed the titles, abstracts, and articles. Of 2481 studies identified, 203 articles met the eligibility criteria and represented 29 countries in 6 continents. One reviewer conducted a full abstraction of all data, and 2 reviewers verified accuracy. Mortality estimates (eg, standardized mortality ratios, relative risks, hazard ratios, odds ratios, and years of potential life lost) comparing people with mental disorders and the general population or people without mental disorders. We used random-effects meta-analysis models to pool mortality ratios for all, natural, and unnatural causes of death. We also examined years of potential life lost and estimated the population attributable risk of mortality due to mental disorders. For all-cause mortality, the pooled relative risk of mortality among those with mental disorders (from 148 studies) was 2.22 (95% CI, 2.12-2.33). Of these, 135 studies revealed that mortality was significantly higher among people with mental disorders than among the comparison population. A total of 67.3% of deaths among people with mental disorders were due to natural causes, 17.5% to unnatural causes, and the remainder to other or unknown causes. The median years of potential life lost was 10 years (n = 24 studies). We estimate that 14.3% of deaths worldwide, or approximately 8 million deaths each year, are attributable to mental disorders. These estimates suggest that mental disorders rank among the most substantial causes of death worldwide. Efforts to quantify and address the global burden of illness need to better consider the role of mental disorders in preventable mortality.

Quality of life in a community sample of young cocaine and/or heroin users: the role of mental disorders.

Drug addiction and psychiatric disorders are frequently concomitant; however, few studies have investigated the impact of psychiatric disorders other than substance use disorder (SUD) on health-related quality of life (HRQoL) in drug users not in treatment. We studied the association of psychiatric disorders other than SUD with HRQoL in a street-recruited sample of cocaine and/or heroin users. It is a cross-sectional study involving 287 young users of cocaine and/or heroin in Barcelona, Spain. HRQoL was assessed with the Nottingham health profile (NHP). Patterns of drug use and mental disorders were assessed using the Spanish version of the psychiatric research interview for substance and mental disorders IV, and degree of dependence through the severity of dependence scale (SDS). The association of mental disorders with HRQoL was assessed through a Tobit regression analysis. The overall NHP score was 23.9 (SD=20.5, range 0-91.7). Sixty-one percent of the sample had two or more SUDs; 22% had at least one non-SUD Axis I disorder (anxiety, mood, psychotic, or eating disorder); and 27.2% had a borderline personality disorder (BPD) and/or antisocial personality disorder. Variables negatively associated with the global NHP score were psychosis [transformed beta coefficient: 15.23; 95% confidence interval [CI] 4.48-25.97], BPD (9.55; 95% CI 2.95-16.15), severity of dependence (8.12; 95% CI 3.37-12.87), having two or more SUDs (for two or three SUDs: 6.83; 95% CI 2.08-11.59) (>3 SUDs: 7.70; 95% CI 1.72-13.68) and the intravenous use of some substance (10.20; 95% CI 6.00-14.40). HRQoL among street-recruited illegal substance users was impaired, particularly among those with psychiatric comorbidity, psychosis, and BPD being especially relevant.

DNA methylation patterns of protein coding genes and long noncoding RNAs in female schizophrenic patients

Schizophrenia (SCZ) is a complex mental disorder contributed by both genetic and epigenetic factors. Long noncoding RNAs (lncRNAs) was recently found playing an important regulatory role in mental disorders. However, little was known about the DNA methylation of lncRNAs, although numerous SCZ studies have been performed on genetic polymorphisms or epigenetic marks in protein coding genes. We presented a comprehensive genome wide DNA methylation study of both protein coding genes and lncRNAs in female patients with paranoid and undifferentiated SCZ. Using the methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq), 8,163 and 764 peaks were identified in paranoid and undifferentiated SCZ, respectively (p < 1 × 10−5). Gene ontology analysis showed that the hypermethylated regions were enriched in the genes related to neuron system and brain for both paranoid and undifferentiated SCZ (p < 0.05). Among these peaks, 121 peaks were located in gene promoter regions that might affect gene expression and influence the SCZ related pathways. Interestingly, DNA methylation of 136 and 23 known lncRNAs in Refseq database were identified in paranoid and undifferentiated SCZ, respectively. In addition, ∼20% of intergenic peaks annotated based on Refseq genes were overlapped with lncRNAs in UCSC and gencode databases. In order to show the results well for most biological researchers, we created an online database to display and visualize the information of DNA methyation peaks in both types of SCZ (http://www.bioinfo.org/scz/scz.htm). Our results showed that the aberrant DNA methylation of lncRNAs might be another important epigenetic factor for SCZ.

Predictors of burnout: results from a prospective community study.

The possible link between work strain and subsequent mental disorders has attracted public attention in many European countries. Burnout has become a favored concept within this context. Most burnout research has concentrated on various professional groups and less so on ordinary community samples. We analyzed the data collected from a 30-year community sample during seven measuring occasions, beginning in 1978. In the last assessment (2008), we included for the first time the Maslach Burnout Inventory (MBI). Making the diagnosis of a lifetime mental disorder a predictor for burnout required us to compile the cumulative prevalence rate over all seven occasions. We also evaluated various psycho-social predictors of burnout over the life cycle of our sample. Concurrent associations of the MBI with subscales from the SCL-90-R were also investigated. The relationship of burnout with several SCL-90-R subscales demonstrated that, in all dimensions, burnout is associated with significant psychopathology. Persons with a lifetime mood disorder, and especially those with a combination of mood and anxiety disorders, had a higher risk for subsequent burnout. Various partnership problems were another predictor for burnout. In conclusion, the role of mental disorder as an occupational illness remains controversial. Various forms of such disorders as well as some psycho-social predictors can predispose to burnout. By contrast, work-related predictors appear to be less important.

Inflammatory biomarker profiles of mental disorders and their relation to clinical, social and lifestyle factors.

In the last few decades, mental health research has increasingly provided evidence supporting the role of inflammation in pathogenesis, course and treatment of mental disorders. With such a steep incline of research, resulting in a wealth of emerged findings, it has become difficult to follow developments within the field. The present review sets out to present the recent developments and to give an overview of the inflammatory profiles of depression, psychosis and bipolar disorder, as well as variations within these disorders. Moreover, mediating factors such as social environment and childhood experience are discussed, both in terms of their potential in elucidating the complex interface between the inflammation and other closely related biological systems, as well as the possibly confounding impact of various lifestyle factors. Whilst many issues in this fascinating area of research remain to be fully understood and elaborated, all current evidence suggests that inflammation plays a key role in mental disorders and may open up novel avenues for clinical treatment.

Is there a role for “climatotherapy” in the sustainable development of mental health?

Climate, diet, lifestyle, and environmental settings have all been shown to modulate mood, play a role in mental disorders, and even pose a mental health risk. Can climatotherapy, in its adaptive approach aiming to restore balance among the economic, social, and ecological realms of human societies, situate itself as a therapeutic avenue for the promotion of sustainable mental health?

The Neurochemical Mobile with Non-Linear Interaction Matrix: An Exploratory Computational Model

Several years ago, the "neurochemical mobile" was introduced as a visual tool for explaining the different balances between neurotransmitters in the brain and their role in mental disorders. Here we complement this concept with a non-linear computational systems model representing the direct and indirect interactions between neurotransmitters, as they have been described in the "neurochemical interaction matrix." The model is constructed within the framework of biochemical systems theory, which facilitates the mapping of numerically ill-characterized systems into a mathematical and computational construct that permits a variety of analyses. Simulations show how short- and long-term perturbations in any of the neurotransmitters migrate through the entire system, thereby affecting the balances within the mobile. In cases of short-term alterations, transients are of particular interest, whereas long-term changes shed light on persistently altered, allostatic states, which in mental diseases and sleep disorders could be due to a combination of unfavorable factors, resulting from a specific genetic predisposition, epigenetic effects, disease, or the repeated use of drugs, such as opioids and amphetamines.

War and first onset of suicidality: the role of mental disorders

Suicide rates increase following periods of war; however, the mechanism through which this occurs is not known. The aim of this paper is to shed some light on the associations of war exposure, mental disorders, and subsequent suicidal behavior. A national sample of Lebanese adults was administered the Composite International Diagnostic Interview to collect data on lifetime prevalence and age of onset of suicide ideation, plan, and attempt, and mental disorders, in addition to information about exposure to stressors associated with the 1975-1989 Lebanon war. The onset of suicide ideation, plan, and attempt was associated with female gender, younger age, post-war period, major depression, impulse-control disorders, and social phobia. The effect of post-war period on each type of suicide outcome was largely explained by the post-war onset of mental disorders. Finally, the conjunction of having a prior impulse-control disorder and either being a civilian in a terror region or witnessing war-related stressors was associated with especially high risk of suicide attempt. The association of war with increased risk of suicidality appears to be partially explained by the emergence of mental disorders in the context of war. Exposure to war may exacerbate disinhibition among those who have prior impulse-control disorders, thus magnifying the association of mental disorders with suicidality.

Effects of a Selective Cannabinoid CB2 Agonist and Antagonist on Intravenous Nicotine Self Administration and Reinstatement of Nicotine Seeking

Over the last decade there have been significant advances in the discovery and understanding of the cannabinoid system along with the development of pharmacologic tools that modulate its function. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications on our understanding of the neurobiological mechanisms underlying nicotine dependence. Two types of cannabinoid receptors (CB1 and CB2) have been identified. CB1 receptors are expressed in the brain and modulate drug taking and drug seeking for various drugs of abuse, including nicotine. CB2 receptors have been recently identified in the brain and have been proposed to play a functional role in mental disorders and drug addiction. Our objective was to explore the role of CB2 receptors on intravenous nicotine self administration under two schedules of reinforcement (fixed and progressive ratio) and on nicotine seeking induced by nicotine priming or by nicotine associated cues. For this, we evaluated the effects of various doses of the selective CB2 antagonist AM630 (1.25 to 5 mg/kg) and CB2 agonist AM1241 (1 to 10 mg/kg) on these behavioral responses in rats. Different groups of male Long Evans rats were trained to lever press for nicotine at a unit dose of 30 µg/kg/infusion. Subsequently, animals were randomized using a Latin-square design and injected with either AM1241 or AM630 using a counterbalanced within subject design. Administration of the CB2 ligands did not affect either nicotine-taking nicotine-seeking behavior. Our results do not support the involvement of CB2 receptors in nicotine-taking or nicotine-seeking behavior.

The role of mental disorders in the risk and speed of transition to alcohol use disorders among community youth

Among adolescents and young adults with DSM-IV alcohol use disorders (AUDs), there are inter-individual differences in the speed of transition from initial alcohol use (AU) to AUD. AUDs are highly co-morbid with other mental disorders. The factors associated with rapid transition from first AU to AUD remain unknown and the role of mental disorders in rapid transitions is unclear. Given this background we examined (1) whether prior anxiety, mood, externalizing and non-alcohol substance use disorders are related to the risk and speed of transition from first AU to DSM-IV alcohol abuse (AA) and alcohol dependence (AD) and (2) whether early age of onset of prior mental disorders (PMDs) is a promoter of rapid transition. A total of 3021 community subjects (97.7% lifetime AU) aged 14-24 years at baseline were followed up prospectively for up to 10 years. AU and mental disorders were assessed with the DSM-IV/M-CIDI. Among subjects with lifetime AU, several PMDs, such as specific phobia, bipolar disorder and nicotine dependence, were associated with an increased risk of AUD independent of externalizing disorders. Associations of PMDs with the speed of transition to AUDs were mostly weak and inconsistent. Only social phobia and externalizing disorders were associated with faster transitions to AD even after adjustment for other PMDs. Earlier age of onset of PMD was not associated with rapid transition. Mental disorders are associated with the risk of AUD. With the possible exception of social phobia and externalizing disorders, they do not promote rapid transition, even if they occur particularly early. Future research needs to identify factors relevant to rapid transition to AUD.

Predictors of Preventable Nursing Home Hospitalizations: The Role of Mental Disorders and Dementia

Nursing home (NH) hospitalizations place an enormous economic burden on an already overtaxed American healthcare system. Hospitalizations for "ambulatory care-sensitive" (ACS) conditions are considered preventable, as these are physical health conditions that can potentially be treated safely in a NH. The authors examined risk factors, including mental disorders and dementia, for hospitalization of Medicaid-enrolled NH residents with ACS conditions during fiscal year 2003-2006. The authors merged Medicaid claims and enrollment data and Online Survey Certification and Reporting information for 72,251 Medicaid-enrolled NH residents in 647 NHs in Florida. The authors identified at least one ACS hospitalization in 8,382 residents for a total of 10,091 hospital admissions (18.5% of all hospitalizations). The authors used Cox proportional hazard regression to assess time to the first ACS hospitalization. In a fully adjusted model, younger age, non-white race, dementia, and serious mental disorder were associated with greater risk of ACS hospitalization. In addition, residents with a diagnosed mental disorder and no dementia incurred relatively high expenditures for ACS hospitalizations. Among facility characteristics, participants from for-profit facilities, facilities that were not a member of a chain, had more Medicaid recipients, and fewer than 120 beds had greater risk of ACS hospitalizations. Attention to the identified predictors of hospitalization for ACS conditions, which are potentially preventable, could reduce the risk and cost of these hospitalizations among Medicaid-enrolled NH residents. The need to reduce unnecessary hospitalization will become only more urgent as the population ages and healthcare expenses continue to escalate.

Structural properties of the extracellular domain of the synaptic adhesion protein α‐neurexin

The neurexin (NRXN) family constitutes a class of membrane proteins ubiquitously expressed at pre‐synaptic glutamatergic and GABAergic terminals. NRXNs help maintain synaptic function and integrity through trans‐synaptic associations with neuroligins. Studies indicate that genomic aberrations play a role in mental disorders, including autism. NRXNs are expressed by 3 genes, each with 2 promoters corresponding to the α‐ or β‐NRXNs. α‐NRXNs differ from β‐NRXNs in their extracellular domain, which contains an additional 5 independently folding LNS domains and 3 EGF domains. Each LNS domain is structurally homologous to the extracellular domain of β‐NRXN. Neuroligins, α‐dystroglycan, neurexophilin, and the spider toxin α‐latrotoxin, are binding partners of 2 of the 6 LNS domains of α‐NRXN. Structural and functional roles of the remaining domains are unknown. By negative‐stain single particle EM we obtained a low resolution (~20 Å) structure of the extracellular domain of α‐ NRXN, providing a description of the conformation and insights into regions of flexibility. These insights enabled us to pursue higher resolution studies. From these data we present a model of the extracellular domain of α‐ NRXN that shows the structural arrangement of the domains, as well as the accessibility of known sites of protein interaction.R37‐GM18360 and PO1‐ES10337

Role of Mental Disorders in Nosocomial Infections after Hip Fracture Treatment

The association between mental disorders (MDs) and iatrogenic complications after hip fracture surgery has been poorly studied. Among iatrogenic complications, nosocomial infections (NIs) are a major factor in hip fracture surgery. The aim of this paper was to determine whether patients with a MD and a hip fracture develop more NIs after hip surgery than patients with no MD. We studied 912 patients who underwent surgery for a hip fracture (223 patients with a MD who underwent surgery for a hip fracture and 689 control patients without a MD who also underwent surgery for a hip fracture) and followed them after surgery. Univariable and multivariable analyses were performed using simple and multiple logistic regression analysis (confidence interval, crude and adjusted odds ratios, and P value). We found that MDs, gender, and comorbidities were not associated with a higher risk of developing a NI after surgery for a hip fracture. Only age increases the risk of a NI.

Fabricating a New Stabilized Lipid-Based Platform for Handling and Presenting GPCRs

G protein-coupled receptors (GPCRs) are members of large family of signaling molecules. They have a key function in neuronal biology and play a critical rule in transmitting extracellular signals in eukaryotic cells. GPCRs include receptors for many neurotransmitters like serotonin. The serotonin receptor 5HT1A has an important role in mental disorders like anxiety, and is the target of some anti anxiety drugs. Here we constructed a novel biomimetic lipid membrane-based platform to be used for screening molecules that interact with GPCRs. Since fragility and short life time limit the applicability of liposomes that are normally used to present membrane proteins, we have developed a platform based on nanoscale liposomes with enhanced longevity and stability. We developed two approaches to make stable liposomes: liposomes containing a UV-initiated poly(ethylene glycol) (PEG) hydrogel and conjugated hydrogel liposomes made from lipids covalently anchored to the hydrogel network. Stability of nanoscale liposomes was confirmed by addition of high concentration of sodium dodecyl sulfate (SDS) to the liposome suspension. The liposome/detergent micelle mixture was passed over a size exclusion chromatography (SEC) column, separating intact liposomes from micelles. Using dynamic light scattering (DLS), we could confirm the existence of intact 160 nm liposomes. This result was in good agreement with the SEC result for polymerized liposomes without detergent. Since our goal is making GPCR-bearing liposomes, serotonin receptor 5HT1A was incorporated into liposomes using a detergent-mediated method. GPCR incorporation was confirmed by binding labeled HTR1A antibody to liposomes containing biotinylated lipids and subsequently separating them from bulk with streptavidin-coated magnetic beads. We are currently undertaking further studies on antibody-liposome binding by fluorescence anisotropy to validate our approach.

The role of mental disorder in attacks on European politicians 1990–2004

The only systematic studies of attacks on public figures come from the USA. These studies de-emphasize the role of mental illness and suggest threats are of no predictive value. This study re-examines these questions through a study of attacks on European politicians. All non-terrorist attacks on elected politicians in Western Europe between 1990 and 2004 were analysed. Twenty-four attacks were identified, including five involving fatalities, and eight serious injuries. Ten attackers were psychotic, four drunk, nine politically motivated and one unclassifiable. Eleven attackers evidenced warning behaviours. The mentally disordered, most of whom gave warnings, were responsible for most of the fatal and seriously injurious attacks. A greater awareness of the link between delusional fixations on public figures and subsequent attacks could aid prevention. Equally importantly, recognition would encourage earlier intervention in people who, irrespective of whether they eventually attack, have delusional preoccupations which ruin their lives.

Increased Levels of Glutamate in Brains from Patients with Mood Disorders

Glutamate has been thought to have a role in mental disorders. Because the postmortem interval (PMI) has such a pronounced effect on glutamate and other amino acids, it is important that a study be conducted to examine the effects of PMI on these amino acids in postmortem brains and that the analysis of intergroup differences be adjusted accordingly. We determined the levels of amino acids in postmortem brains from patients with major mental disorders by normalizing the effects of the postmortem interval with equations derived from control studies using rodent and primate postmortem brains. First, we examined the influence of postmortem intervals on the levels of the amino acids by using rodent brains and derived equations for normalizing the raw data of the amino acids from human brains according to their postmortem intervals. Second, we measured the levels of the amino acids in postmortem human brains, normalized their raw data with the equations, and analyzed the normalized data. Increased levels of glutamate were observed in the frontal cortex from patients with bipolar disorder and major depression. In addition, positive correlations were observed between several pairs of amino acids, including D-serine and glutamate. This study suggests that glutamate plays a role in the pathophysiology of bipolar disorder and major depression.

Smoking and Suicidal Behaviors in the National Comorbidity Survey: Replication

Controversy exists about the role of mental disorders in the consistently documented association between smoking and suicidal behavior. This controversy is addressed here with data from the nationally representative National Comorbidity Survey-Replication (NCS-R). Assessments were made of 12-month smoking, suicidal behaviors (ideation, plans, attempts), and DSM-IV disorders (anxiety, mood, impulse-control, and substance use disorders). Statistically significant odds ratios (2.9-3.1) were found between 12-month smoking and 12-month suicidal behaviors. However, the associations of smoking with the outcomes became insignificant with controls for DSM-IV mental disorders. Although clear adjudication among contending hypotheses about causal mechanisms cannot be made from the cross-sectional NCS-R data, the results make it clear that future research on smoking and suicidal behaviors should focus more centrally than previous research on mental disorders either as common causes, markers, or mediators.

Role of G q protein in behavioral effects of the hallucinogenic drug 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane

Extensive evidence suggests that 5-HT2 receptors may play a role in mental disorders including schizophrenia. In addition, several studies indicate that G q-coupled 5-HT 2A receptors are likely targets for the initiation of events leading to the hallucinogenic behavior elicited by lysergic acid diethylamide (LSD), (±)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and related drugs. However, 5-HT 2A receptors couple to other G proteins in addition to G q protein. To evaluate the role of the G q signaling pathway in DOI-induced behaviors, we utilized two behavioral models of 5-HT 2A receptor activation: induction of head-twitches by DOI, a common response to hallucinogenic drugs in rodents, and DOI elicited anxiolytic-like effects in the elevated plus maze. Experimental subjects were genetically modified mice [Gα q(−/−)] in which the G q alpha gene was eliminated. Gα q(−/−) mice exhibited a decrease in DOI-induced head-twitches, when compared to wild-type littermates. In addition, the DOI-induced increase in anxiolytic-like behavior was abolished in Gα q(−/−) mice. These results, combined with our finding that DOI-induced FOS expression in the medial prefrontal cortex was also eliminated in Gα q(−/−) mice, suggests a key role for G q protein in hallucinogenic drug effects.

Differential effects of classical neuroleptics and a newer generation antipsychotics on the MK-801 induced behavioural primitivization in mouse

Cognitive dysfunction plays an important role in mental disorders like schizophrenia and may involve inadequate glutamatergic signalling in different regions of the brain, mediated by e.g. glutamatergic N-methyl- d-aspartate (NMDA) receptors. In rodents, NMDA receptor antagonists often increase motor activity; in addition they induce a more primitive and undifferentiated behavioural pattern, which we believe may correspond to some of the cognitive defects seen in schizophrenia. In the present study, the movement pattern of mice treated with the uncompetitive NMDA receptor antagonist MK-801 in conjunction with six antipsychotic agents, some with reported clinical effects on cognition, was characterised and quantified. The classical neuroleptic drugs chlorpromazine and trifluoperazine, the atypical antipsychotic agents ziprasidone and olanzapine, the γ-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-receptor potentiator CX516 and the serotonin (5-HT)2A-antagonist M100907 were tested. In accordance with previous observations, MK-801 was found to induce a primitive and monotonous behavioural pattern dominated by forward locomotion; spatial movements, the number of switches between the states moving and stationary, and rearing frequency were reduced. All test substances counteracted MK-801-induced hyperactivity, but differed in their ability to improve behavioural quality. Chlorpromazine and trifluoperazine were unable to restore behavioural diversity while ziprasidone, olanzapine, CX516 and M100907 restored it to varying degrees. A striking similarity in movement pattern was seen between the hypoglutamatergic mice treated with the AMPA-receptor agonist CX516, and those receiving the 5HT2A-antagonist M100907.