Suicide risk and mental health in the general population of French Polynesia.

OBJECTIVE: There are no reports on the burden of suicidal ideation and suicide attempts in the general population of French Polynesia (FP). We aimed to improve suicide prevention and mental health care by assessing the prevalence of suicide risk and major mental health disorders and care among adults in FP. METHODS: We conducted the Mental Health in General Population Survey in FP during 2015 to 2017. Participants were selected using the quota method to obtain a representative sample of the general population. Suicide risk and psychiatric diagnoses were assessed using the Mini International Neuropsychiatric Interview. RESULTS: We included 968 people aged 18 years or older. The prevalence of current suicidal ideation (13.1%) and current (2.6%) and lifetime suicide attempts (18.6%), as well as mental health disorders (42.8%), was high in FP. A notable proportion of participants with these conditions did not seek medical assistance. CONCLUSION: A high prevalence of suicide risk and mental health disorders was found in the general population of FP. Suicide prevention and mental health plans are needed in FP that include better access to primary care for the diagnosis and treatment of mental health disorders. Further research is needed to clarify cultural risk and protective factors.

Cortical Cyclin A controls spindle orientation during asymmetric cell divisions in Drosophila.

The coordination between cell proliferation and cell polarity is crucial to orient the asymmetric cell divisions to generate cell diversity in epithelia. In many instances, the Frizzled/Dishevelled planar cell polarity pathway is involved in mitotic spindle orientation, but how this is spatially and temporally coordinated with cell cycle progression has remained elusive. Using Drosophila sensory organ precursor cells as a model system, we show that Cyclin A, the main Cyclin driving the transition to M-phase of the cell cycle, is recruited to the apical-posterior cortex in prophase by the Frizzled/Dishevelled complex. This cortically localized Cyclin A then regulates the orientation of the division by recruiting Mud, a homologue of NuMA, the well-known spindle-associated protein. The observed non-canonical subcellular localization of Cyclin A reveals this mitotic factor as a direct link between cell proliferation, cell polarity and spindle orientation.

A neural progenitor mitotic wave is required for asynchronous axon outgrowth and morphology.

Spatiotemporal mechanisms generating neural diversity are fundamental for understanding neural processes. Here, we investigated how neural diversity arises from neurons coming from identical progenitors. In the dorsal thorax of Drosophila, rows of mechanosensory organs originate from the division of sensory organ progenitor (SOPs). We show that in each row of the notum, an anteromedial located central SOP divides first, then neighbouring SOPs divide, and so on. This centrifugal wave of mitoses depends on cell-cell inhibitory interactions mediated by SOP cytoplasmic protrusions and Scabrous, a secreted protein interacting with the Delta/Notch complex. Furthermore, when this mitotic wave was reduced, axonal growth was more synchronous, axonal terminals had a complex branching pattern and fly behaviour was impaired. We show that the temporal order of progenitor divisions influences the birth order of sensory neurons, axon branching and impact on grooming behaviour. These data support the idea that developmental timing controls axon wiring neural diversity.

A positive association between a polymorphism in the HTR2B gene and cocaine-crack in a French Afro-Caribbean population.

OBJECTIVES: Cocaine dependence has a strong heritability component. The aim of this study was to investigate the putative association between the serotonin 2B receptor gene (HTR2B), crack use disorders and impulsivity. METHODS: A French Afro-Caribbean male population of patients with crack use disorders (n = 80) was compared to healthy Afro-Caribbean male controls (n = 60). Comorbid ADHD and impulsivity were assessed. Five single nucleotide polymorphisms (SNPs) in the HTR2B gene were selected: rs643700, rs6736017, rs1549339, rs17586428 and rs3806545. These SNPs were chosen to include most of the linkage disequilibrium blocks in the HTR2B gene. The French translation of the Barratt Impulsivity Scale BIS-11 was used to evaluate impulsivity. Comorbid ADHD was diagnosed using the Wender Utah Rating Scale-25 item for Attention Deficit-Hyperactivity Disorder. RESULTS: We have observed a positive association between the rs6736017 polymorphism and crack use disorders in a French Afro-Caribbean male population. CONCLUSIONS: In our population, the risk effect of HTR2B rs6736017 appeared to be specific to individuals with crack use disorders rather than being driven by impulsivity or ADHD alone.

Proline oxidation fuels mitochondrial respiration during dark-induced leaf senescence in Arabidopsis thaliana.

Leaf senescence is a form of developmentally programmed cell death that allows the remobilization of nutrients and cellular materials from leaves to sink tissues and organs. Among the catabolic reactions that occur upon senescence, little is known about the role of proline catabolism. In this study, the involvement in dark-induced senescence of proline dehydrogenases (ProDHs), which catalyse the first and rate-limiting step of proline oxidation in mitochondria, was investigated using prodh single- and double-mutants with the help of biochemical, proteomic, and metabolomic approaches. The presence of ProDH2 in mitochondria was confirmed by mass spectrometry and immunogold labelling in dark-induced leaves of Arabidopsis. The prodh1 prodh2 mutant exhibited enhanced levels of most tricarboxylic acid cycle intermediates and free amino acids, demonstrating a role of ProDH in mitochondrial metabolism. We also found evidence of the involvement and the importance of ProDH in respiration, with proline as an alternative substrate, and in remobilization of proline during senescence to generate glutamate and energy that can then be exported to sink tissues and organs.

Shaping of Drosophila Neural Cell Lineages Through Coordination of Cell Proliferation and Cell Fate by the BTB-ZF Transcription Factor Tramtrack-69.

Cell diversity in multicellular organisms relies on coordination between cell proliferation and the acquisition of cell identity. The equilibrium between these two processes is essential to assure the correct number of determined cells at a given time at a given place. Using genetic approaches and correlative microscopy, we show that Tramtrack-69 (Ttk69, a Broad-complex, Tramtrack and Bric-à-brac - Zinc Finger (BTB-ZF) transcription factor ortholog of the human promyelocytic leukemia zinc finger factor) plays an essential role in controlling this balance. In the Drosophila bristle cell lineage, which produces the external sensory organs composed by a neuron and accessory cells, we show that ttk69 loss-of-function leads to supplementary neural-type cells at the expense of accessory cells. Our data indicate that Ttk69 (1) promotes cell cycle exit of newborn terminal cells by downregulating CycE, the principal cyclin involved in S-phase entry, and (2) regulates cell-fate acquisition and terminal differentiation, by downregulating the expression of hamlet and upregulating that of Suppressor of Hairless, two transcription factors involved in neural-fate acquisition and accessory cell differentiation, respectively. Thus, Ttk69 plays a central role in shaping neural cell lineages by integrating molecular mechanisms that regulate progenitor cell cycle exit and cell-fate commitment.

Mental Health Impact of Hosting Disaster Refugees: Analyses from a Random Sample Survey Among Haitians Living in Miami.

OBJECTIVES: Studies on the mental health of families hosting disaster refugees are lacking. This study compares participants in households that hosted 2010 Haitian earthquake disaster refugees with their nonhost counterparts. METHODS: A random sample survey was conducted from October 2011 through December 2012 in Miami-Dade County, Florida. Haitian participants were assessed regarding their 2010 earthquake exposure and impact on family and friends and whether they hosted earthquake refugees. Using standardized scores and thresholds, they were evaluated for symptoms of three common mental disorders (CMDs): posttraumatic stress disorder, generalized anxiety disorder, and major depressive disorder (MDD). RESULTS: Participants who hosted refugees (n = 51) had significantly higher percentages of scores beyond thresholds for MDD than those who did not host refugees (n = 365) and for at least one CMD, after adjusting for participants' earthquake exposures and effects on family and friends. CONCLUSIONS: Hosting refugees from a natural disaster appears to elevate the risk for MDD and possibly other CMDs, independent of risks posed by exposure to the disaster itself. Families hosting refugees deserve special attention.

N-acetylcysteine Facilitates Self-Imposed Abstinence After Escalation of Cocaine Intake.

BACKGROUND: N-acetylcysteine (NAC) has been suggested to prevent relapse to cocaine seeking. However, the psychological processes underlying its potential therapeutic benefit remain largely unknown. METHODS: We investigated the hallmark features of addiction that were influenced by chronic NAC treatment in rats given extended access to cocaine: escalation, motivation, self-imposed abstinence in the face of punishment, or propensity to relapse. For this, Sprague Dawley rats were given access either to 1 hour (short access) or 6 hours (long access [LgA]) self-administration (SA) sessions until LgA rats displayed a robust escalation. Rats then received daily saline or NAC (60 mg/kg, intraperitoneal) treatment and were tested under a progressive ratio and several consecutive sessions in which lever presses were punished by mild electric foot shocks. RESULTS: NAC increased the sensitivity to punishment in LgA rats only, thereby promoting abstinence. Following the cessation of punishment, NAC-treated LgA rats failed to recover fully their prepunishment cocaine intake levels and resumed cocaine SA at a lower rate than short access and vehicle-treated LgA rats. However, NAC altered neither the escalation of SA nor the motivation for cocaine. At the neurobiological level, NAC reversed cocaine-induced decreases in the glutamate type 1 transporter observed in both the nucleus accumbens and the dorsolateral striatum. NAC also increased the expression of Zif268 in the nucleus accumbens and dorsolateral striatum of LgA rats. CONCLUSIONS: Our results indicate that NAC contributes to the restoration of control over cocaine SA following adverse consequences, an effect associated with plasticity mechanisms in both the ventral and dorsolateral striatum.

Early cannabis use is associated with severity of Cocaine-Induced Psychosis among cocaine smokers in Martinique, French West Indies.

OBJECTIVES: Cocaine intoxication can induce transient psychotic symptoms. The principal aim of this study was to determine sociodemographic and clinical characteristics associated with cocaine-induced psychosis (CIP) and to identify clinical factors predicting CIP in crack cocaine smokers in Martinique. The second aim was to identify clinical factors associated with severity of CIP, assessed with the Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis (SAPS-CIP). METHODS: Fifty-three cocaine-dependent smokers (45 men and 8 women) seeking treatment for cocaine dependence were included. Patients were assessed using the Cocaine Experience Questionnaire (CEQ), an instrument for the identification of cocaine-induced paranoia, and a French version of the SAPS-CIP, for the severity of CIP. RESULTS: Thirty-five (66%) patients reported cocaine-induced paranoia on the CEQ (CIP(+) patients). The mean SAPS-CIP total score was 6.1 ± 3.7, with a significant difference between CIP(+) and CIP(-) patients (P < 0.0001). Age at first cannabis use was associated with occurrence of CIP on the CEQ, and adolescent-onset cannabis use was associated with severity of hallucinations score on the SAPS-CIP. CONCLUSIONS: Cocaine-induced psychosis is frequent in crack cocaine smokers in Martinique, and early cannabis use is associated with the occurrence and the severity of psychotic symptoms during cocaine intoxication in this population. Patients developing psychotic symptoms during cocaine use began smoking cannabis earlier during adolescence than patients without CIP. These results confirm those of previous studies, highlighting the need to better assess early cannabis use in cocaine users, because early cannabis use is associated with severity of CIP.

Psychosis in a cocaine-dependent patient with ADHD during treatment with methylphenidate.

OBJECTIVE: The objective was to report a case of experienced psychosis during the treatment with methylphenidate (MPH) in a cocaine-dependent adult treated for attention-deficit/hyperactivity disorder (ADHD) with comorbid cocaine dependence. CONCLUSION: ADHD is a frequent comorbidity in substance use disorder (SUD) patients. MPH may be effective in treating ADHD symptoms in SUD patients, thus preventing possible adverse outcomes. Cocaine-induced psychosis may be a risk factor for development of psychosis in the presence of a concurrent treatment with MPH.

[Addiction to cocaine and other stimulants]. / Addiction à la cocaïne et aux psychostimulants.

Due to many available forms (powder, pasta base, freebase and crack…) and because of multiple routes of administration (intranasal, intravenous, or smoked), cocaine has become in 30 years one of the most consumed illegal drugs worldwide, after cannabis. While the frequency of consumption decreases in North America, it continues to rise in Europe, and in some countries in South America, including Brazil, despite a growing knowledge of its specific effects, physical complications and psychiatric consequences. Elsewhere (notably in Asia and Indian Ocean), amphetamine and other stimulants (including methamphetamine), whose properties and patterns of use are very similar to those of cocaine, tend to replace it. Another amphetamine derivative, MDMA or ecstasy, is also consumed by many young people of less than 25 years, in Europe and North America, in a festive setting, with specific consequences and special procedures of care. Although there is currently no consensus for a specific medication, the most appropriate therapeutic approach seems to involve a psychosocial treatment associated with an anticraving medication, which will reduce compulsive desire to consume, in order to facilitate the psychotherapeutic and social care. However, pharmacological research remains very active, and many options are explored (GABAergic or dopaminergic agonists, amphetamine derivatives with long half-life, vaccine…), whether to treat addiction to cocaine or to methamphetamine.

Attention deficit hyperactivity disorder is associated with a more severe pattern of cocaine consumption in cocaine users from French West Indies.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a frequent comorbidity in patients with substance use disorder. The aim of this cross-sectional study was to evaluate the consequences of ADHD comorbidity in cocaine users seeking treatment in Martinique. METHODS: During 15 months, all patients seeking treatment for cocaine dependence in a specialized center were assessed using the ADHD DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision) criteria and the French version of the Wender Utah Rating Scale. RESULTS: Forty-six (44 men and 2 women) cocaine abusers were included. Among them, 10 (21.7%) patients met DSM-IV-TR full criteria for adult ADHD. Patients with ADHD spend significantly more money (3 fold) on cocaine per week than those without ADHD, which means that they use a higher dose. All patients with ADHD used cocaine in a pipe, which allowed a greater absorption compared to smoking cocaine in a joint or snorting cocaine powder; in contrast, only 53% of the subjects without ADHD used cocaine in a pipe. CONCLUSIONS: Our study shows that cocaine users seeking treatment in Martinique with reported ADHD have a more severe pattern of cocaine consumption and the prevalence of ADHD's comorbidity in cocaine users is proximately equal to values previously found in the literature.

The relationship between insight and uncertainty in obsessive-compulsive disorder.

BACKGROUND: The aim of this study was to investigate the relationship between the levels of insight and checking-related uncertainty in patients with obsessive-compulsive disorder (OCD). SAMPLING AND METHODS: Twenty OCD patients with checking compulsions and without current comorbidity were recruited. We used an experimental paradigm that gave subjects the opportunity to check during a decision-making task, thereby allowing for the calculation of a response time index (RTI) as the 'uncertainty cost' during decision-making. The level of insight was assessed with the Brown Assessment of Beliefs Scale (BABS). RESULTS: Regression analyses indicated a significant positive correlation between RTI and BABS scores (r = 0.49). CONCLUSIONS: The level of insight is related to cognitive characteristics underlying OCD symptoms, in particular, checking-related uncertainty in checking OCD patients. STUDY LIMITATIONS: The absence of a comparison group and the low number of included patients are the main limitations of the present study.

[Cocaine and alcohol: a risky association]. / Cocaïne et alcool : des liaisons dangereuses.

Key points. Cocaine, the second most frequently consumed illicit substance after cannabis in both United States and Europe, remains the psychostimulant of choice for many, often mixed with other psychoactive substances. It is most frequently associated with alcohol, and a diagnosis of alcohol dependence may be made in 50%-90% of cocaine-dependent subjects. When treating cocaine addicts, it is important to characterize not only the modalities of cocaine use but also the modes of consumption of other substances, notably alcohol. Alcohol is often consumed to reduce the anxiety and discomfort resulting from cocaine withdrawal. Alcohol may also trigger an irresistible craving for cocaine, which can result in frequent relapses even after several months of cocaine abstinence. Brief intervention and motivational interview techniques can help to reduce alcohol use and prevent cocaine relapses in this context. In the absence of severe cocaine withdrawal symptoms, the guidelines for treating alcohol withdrawal syndrome may be applied for cocaine and alcohol codependence. Lower doses of benzodiazepine are needed for treating this alcohol-cocaine withdrawal syndrome. Cognitive behavioral therapies, alone or in combination with psychotropic medication, are accepted therapeutic approaches for alcohol-cocaine dependence. It is also accepted that over the long term the combination of psychotherapeutic treatments is usually more effective than any single approach. In the absence of a therapeutic consensus, four drugs (disulfiram, baclofen, topiramate and naltrexone) are most often recommended to promote and maintain abstinence; nevertheless, their efficacy has not been proven and their use remains experimental and off-label: they have not been approved by health authorities as treatment for addictions.

Auto-assembly of E. coli DsrA small noncoding RNA: Molecular characteristics and functional consequences.

RNA molecules are important factors involved in different cellular processes and have a multitude of roles in the cell. These roles include serving as a temporary copy of genes used for protein synthesis or functions in translational machinery. Interestingly, RNA is so far the only biological molecule that serves both as a catalyst (like proteins) and as information storage (like DNA). However, in contrast to proteins well known to be able to self-associate in order to maintain the architecture of the cell, such RNA polymers are not prevalent in cells and are usually not favored by the flexibility of this molecule. In this work, we present evidence that such a polymer of a natural RNA, the DsrA RNA, exists in the bacterial cell. DsrA is a small noncoding RNA (87 nucleotides) of Escherichia coli that acts by base-pairing to mRNA in order to control the translation and the turnover of some mRNA, including rpoS mRNA, which encodes the sigma(s) RNA polymerase subunit involved in bacterial stress response. A putative model is proposed for the structure of this RNA polymer. Although the function of this polymerization is not known completely, we propose that the formation of such a structure could be involved in the regulation of DsrA ncRNA concentration in vivo or in a quality control mechanism used by the cell to eliminate misfolded RNAs.

IS1 transposition is enhanced by translation errors and by bacterial growth at extreme glucose levels.

Transposition of insertion sequences (IS) is an enzyme-mediated process that only occurs in a minority of cells within a bacterial culture. Transposition is thus a rare event, but transposition frequency may vary depending on experimental conditions. For instance in a rich broth, IS elements are known to transpose during stationary phase but not during exponential growth. Using a reporter system which involves the activation of the cryptic bgl operon in Escherichia coli, we show that the frequency of IS1 transposition is a function of glucose concentration in the growth medium, it is increased by streptomycin amounts that are below minimum inhibitory concentration (sub-MIC) and is inhibited in an rpsL150 strain with high translation accuracy. Since starved cells are known to enhance ribosome frameshifting, our data suggests that growth conditions applied in this study could affect IS1 transposition by increasing translation infidelity.

Triple helix formation with Drosophila satellite repeats. Unexpected stabilization by copper ions.

The Drosophila melanogaster (AAGAGAG)(n) satellite repeat represents up to 1.5% of the entire fly genome and may adopt non-B DNA structures such as pyrimidine triple helices. UV melting and electrophoretic mobility shift assay experiments were used to monitor the stability of intermolecular triple helices as a function of size, pH, and backbone or base modification. Three to four repeats of the heptanucleotide motif were sufficient to allow the formation of a stable complex, especially when modified TFOs were used. Unexpectedly, low concentrations (40-100 microM) of Cu(2+) were found to favor strongly pyrimidine triplex formation under near-physiological conditions. In contrast, a much higher magnesium concentration was required to stabilize these triplexes significantly, suggesting that copper may be an essential stabilizing factor for pyrimidine triplexes.