Anxious and depressive symptoms and health-related quality of life in a cohort of people who recently attempted suicide: A network analysis.

BACKGROUND: Suicide is an international health concern with immeasurable impact from the perspective of human and social suffering. Prior suicide attempts, anxious and depressive symptoms, and relatively lower health-related quality of life (HRQoL) are among the most replicated risk factors for suicide. Our goal was to visualize the distribution of these features and their interconnections with use of a network analysis approach in individuals who recently attempted suicide. METHODS: Individuals with a recent suicide attempt were recruited from nine University Hospitals across Spain as part of the SURVIVE cohort study. Anxious and depressive symptoms, and perceived HRQoL were included in the network analysis. Network structures were estimated with the EBICglasso model. Centrality measures and bridge symptoms connecting communities were explored. Subnetworks comparing younger and older individuals, and women and men were analyzed. RESULTS: A total of 1106 individuals with a recent suicide attempt were included. Depressed mood was the symptom with the greatest influence in the overall network, followed by anxiety symptoms such as feeling nervous, worrying, restless, and having difficulties to relax. Perceived general health was associated with increased suicidal ideation in the whole sample. Older people showed a specific connection between perceived general health and depressed mood. LIMITATIONS: The cross-sectional design does not allow determination of established causality. CONCLUSIONS: Depressed mood was the core network's symptom and, therefore, an important target in the management and prevention of suicide. HRQoL had more influence on the network of older populations, in which it should be a primary focus.

Psychiatric profiles in suicidal attempters: Relationships with suicide behaviour features.

BACKGROUND: Suicide constitutes a major health concern worldwide, being a significant contributor of death, globally. The diagnosis of a mental disorder has been extensively linked to the varying forms of suicidal ideation and behaviour. The aim of our study was to identify the varying diagnostic profiles in a sample of suicide attempters. METHODS: A sample of 683 adults (71.3% females, 40.10±15.74 years) admitted at a hospital emergency department due to a suicide attempt was recruited. Latent class analysis was used to identify diagnostic profiles and logistic regression to study the relationship between comorbidity profile membership and sociodemographic and clinical variables. RESULTS: Two comorbidity profiles were identified (Class I: low comorbidity class, 71.3% of attempters; Class II: high comorbidity class, 28.7% of attempters). Class I members were featured by the diagnosis of depression and general anxiety disorder, and low comorbidity; by contrast, the high comorbidity profile was characterized by a higher probability of presenting two or more coexisting psychiatric disorders. Class II included more females, younger, with more depressive symptoms and with higher impulsivity levels. Moreover, Class II members showed more severe suicidal ideation, higher number of suicide behaviours and a greater number of previous suicide attempts (p<.01, for all the outcomes), compared to Class I members. CONCLUSIONS: Psychiatric profiles may be considered for treatment provision and personalized psychiatric treatment in suicidal attempters as well as tackle suicide risk.

Inflammatory profiles in women with eating disorder: Linking inflammatory biomarkers to clinical phenotypes.

INTRODUCTION: Eating disorders (ED) represent a group of very complex and serious diagnoses characterized by emotional dysregulation and impulsivity. New approaches are necessary to achieve effective diagnosis and treatments. Shifting biomarker research away from the constraints of diagnostic categories may effectively contribute to a dimensional differentiation across disorders according to neurobiology (e.g., inflammatory biomarkers). Thus, the aim of our study was to identify inflammatory profiles in patients with ED. METHODS: A sample of 100 women with an ED (23.4 ± 8.55 years) and 59 healthy controls (HC) (20.22 ± 4.18 years) was used. K-means cluster analysis was followed to identify inflammatory clusters considering seven blood biomarkers (iNOS, TNFα, COX2, p38, ERK, TBARS and PPARγ). Moreover, a wide assessment of clinical features was conducted. RESULTS: Two distinct clusters were identified. Cluster 1 patients were characterized by higher inflammatory levels of TNF-α, COX2, p38, and ERK, and had more restrictive anorexia diagnosis than cluster 2. Cluster 2 participants showed higher inflammatory levels of iNOS and were older than cluster 1 and controls and had lower BMI than HC. In addition, they had higher levels of bulimic symptoms than those from the cluster 1 and HC, and higher impulsivity than HC. All ED patients (regardless of cluster) showed higher ED symptoms and more trauma than HC. CONCLUSIONS: Our study revealed that inflammatory dysfunction may be linked with clinical endophenotypes in ED, one more restrictive (cluster 1) with an inflammation/oxidative endophenotype more cytokine and MAPK/ERK mediated, and the other more impulsive, with more bulimic symptoms (cluster 2) with NO free radical high output source iNOS. Trauma seems to be a vulnerability factor for both endophenotypes.

Neurocognitive profile associated with borderline personality disorder: building specific indices of executive function.

The objective of this work is the creation of specific indices of the different executive functions (EF).

Perfil neurocognitivo asociado al trastorno límite de personalidad: creación de índices específicos de función ejecutiva / Neurocognitive profile associated with borderline personality disorder: building specific indices of executive function

Introducción. El objetivo de este trabajo es la creación de índices específicos de las distintas funciones ejecutivas (FE), que permitan comprender de forma más completa y no mediante pruebas aisladas el rendimiento ejecutivo asociado al trastorno límite de la personalidad (TLP). Metodología. 118 pacientes con TLP y 81 controles fueron evaluados con una batería neuropsicológica. Se crearon tres índices de atención, memoria y FE. Las pruebas que forman el índice ejecutivo se agruparon en cuatro índices ejecutivos diferentes: flexibilidad cognitiva, planificación, memoria de trabajo e inhibición de respuesta. Las puntuaciones para cada dominio se obtuvieron a través de las puntuaciones estandarizadas de las pruebas que los componían. Resultados. Los resultados mostraron diferencias significativas en los índices de memoria, atención y FE, así como en los diferentes índices ejecutivos de flexibilidad cognitiva, planificación, memoria de trabajo e inhibición de respuesta, entre los pacientes con TLP y los controles. Conclusiones. Este estudio ha permitido la creación de cuatro índices ejecutivos, siendo el primero hasta la fecha en hacerlo. Estos resultados establecen un perfil neurocognitivo del TLP caracterizado por un deterioro ejecutivo específico de la flexibilidad cognitiva, la planificación, la memoria de trabajo y la inhibición de la respuesta. Estos hallazgos avalan que los pacientes con TLP podrían beneficiarse de la aplicación de programas neuropsicológicos, especialmente enfocados en mejorar determinadas FE, y sientan las bases para la investigación de la relación entre estos déficits ejecutivos específicos y ciertas características clínicas del TLP, como diferentes tipos de comportamiento impulsivo y diferentes errores de mentalización. (AU)

Introduction. The objective of this work is the creation of specific indices of the different executive functions (EF), which allow a more complete understanding of the executive performance associated with borderline personality disorder (BPD) and not through isolated tests. Methodology. 118 patients with BPD and 81 controls were evaluated with a neuropsychological battery. Three indices of attention, memory and FE were created. The tests that make up the executive domain were grouped into four different executive indices: cognitive flexibility, planning, working memory, and response inhibition. The batteries for each domain were compared through the standardized batteries of the tests that comprised them. Results. The results showed differences in the memory, attention, and EF indices, as well as in the different executive indices of cognitive flexibility, planning, working memory, and response inhibition, between BPD patients and controls. Conclusions. This study has allowed the creation of four executive indexes, being the first to do so. These results established a neurocognitive profile of BPD characterized by executive-specific impairment of cognitive flexibility, planning, working memory, and response inhibition. These findings support that patients with BPD will benefit from the application of neuropsychological programs, especially focused on improving a certain EF, and lay the foundations for the investigation of the relationship between these specific executive deficits and certain clinical characteristics of BPD, such as different types of Impulsive behavior and different mentalization errors. (AU)

Clinical predictors and psychosocial risk factors of suicide attempt severity.

BACKGROUND: Suicide attempts are an important predictor of completed suicide and may differ in terms of severity of medical consequences or medical lethality. There is little evidence on serious suicide attempt (SSA) and very few studies have compared SSA with non-SSA. OBJECTIVE: The aim of this multisite, coordinated, cohort study was to analyze the role of clinical variables and the sociodemographic and psychological risk factors of SSA. METHOD: In this multisite, coordinated, cohort study, 684 participants (222 for the mild suicide attempt group, 371 for the moderate suicide attempt group and 91 for the SSA group) were included in the study. Ordinal regression models were performed to analyze the predictor variables of SSA. RESULTS: Early physical abuse (OR=1.231) and impulsivity (OR=1.036) were predictors of SSA, while depressive symptoms were associated with a lower risk of SSA. CONCLUSION: Environmental and psychological factors as physical abuse and impulsivity are related with severe suicide severity. These findings will help to develop strategies to prevent suicide and may be considered for the treatment and management of suicide.

Risk factors for suicidal behaviour in late-life depression: A systematic review.

BACKGROUND: Suicide is a leading cause of preventable death worldwide, with its peak of maximum incidence in later life. Depression often puts an individual at higher risk for suicidal behaviour. In turn, depression deserves particular interest in old age due to its high prevalence and dramatic impact on health and wellbeing. AIM: To gather integrated evidence on the potential risk factors for suicide behaviour development in depressive older adults, and to examine the effects of depression treatment to tackle suicide behaviour in this population. METHODS: A systematic review of empirical studies, published from 2000 onwards, was conducted. Suicidal behaviour was addressed considering its varying forms (i.e., wish to die, ideation, attempt, and completed suicide). RESULTS: Thirty-five papers were selected for review, comprising both clinical and epidemiological studies. Most of studies focused on suicidal ideation (60%). The studies consistently pointed out that the risk was related to depressive episode severity, psychiatric comorbidity (anxiety or substance use disorders), poorer health status, and loss of functionality. Reduced social support and loneliness were also associated with suicide behaviour in depressive older adults. Finally, the intervention studies showed that suicidal behaviour was a robust predictor of depression treatment response. Reductions in suicidal ideation were moderated by reductions in risk factors for suicide symptoms. CONCLUSION: To sum up, common and age-specific risk factors seem to be involved in suicide development in depressive older adults. A major effort should be made to tackle this serious public health concern so as to promote older people to age healthily and well.

The first instrument for complex PTSD assessment: psychometric properties of the ICD-11 Trauma Questionnaire

Objective: The ICD-11 Trauma Questionnaire (ITQ) was developed as a joint effort by researchers from several countries to evaluate post-traumatic stress (PTSD) and complex-PTSD (C-PTSD) symptoms. This study is part of a multi-center international collaborative research project that aims to provide psychometric support for this initial instrument in different languages, considering the specific contexts related to complex traumatization. This study verified the psychometric characteristics of the Portuguese version of the ITQ, evaluating symptoms beyond those described the existing literature. Methods: We examined the results of a convenience sample totaling 268 Portuguese and Angolan participants. Two instruments were applied: the ITQ, which evaluates symptoms resulting from a traumatic life event, and the Life Events Checklist (LEC), which evaluates stressful life events. The general characteristics of the scales are described, and reliability analysis and validity studies were performed. Results: Cronbach's alpha varied between 0.84 and 0.88, and the exploratory factorial analysis results were consistent with the concept of C-PTSD, with five components explaining 61.58% of scale variance. Conclusion: The results suggest good psychometric characteristics for the Portuguese version of the ITQ, and thus it can be included in protocols intended evaluating complex traumatic symptoms.

Perfil cardiovascular de atletas do sexo feminino do Estado de São Paulo / Cardiovascular profile of female athletes from the State of São Paulo

INTRODUÇÃO: A avaliação pré-participação (APP) em atletas é de fundamental importância para prevenção de doenças cardiovasculares e morte súbita (MS), visto que essa população submete-se a cargas excessivas de treinamento, com possíveis desfechos graves. Nos últimos anos, houve um aumento da participação de mulheres em atividades competitivas, no entanto existe uma carência de informações sobre parâmetros clínicos e cardiográficos nessa população. OBJETIVO: Descrição do perfil cardiovascular em atletas do sexo feminino do estado de São Paulo. MÉTODOS: Foram avaliadas 105 atletas entre 11 a 45 anos, residentes no estado de São Paulo no ano de 2019. Essa avaliação foi composta por anamnese, exame físico, eletrocardiograma (ECG), teste do exercício (TE) e exames adicionais quando pertinentes, a saber: Ecocardiograma Transtorácico e Angiotomografia de Coronárias. RESULTADOS: As atletas estudadas praticavam principalmente futebol (58,5%), seguido por basquete (18%) e corrida (12,4%). Quanto à anamnese, 6,6% apresentavam dor torácica atípica; 1,9% dispneia e 0,95% palpitação; nenhuma delas apresentava comorbidades cardiovasculares e apenas três relatavam histórico familiar de MS. No que diz respeito ao ECG, os achados mais prevalentes foram bradicardia sinusal (46,6%) e repolarização ventricular precoce (40%), ambos compatíveis com adaptações do coração do atleta. No TE todas tiveram comportamento hemodinâmico normal e boa/excelente capacidade funcional; com incidência de 3,8% ectopias ventriculares; 4,8% ectopias supraventriculares e ausência de arritmias complexas. Apenas uma paciente apresentou resposta isquêmica por critérios eletrocardiográficos, assintomática durante exame, sendo progredido investigação com Angiotomografia de Coronárias que excluiu doença arterial coronariana. Dentre as atletas submetidas a Ecocardiograma apenas duas apresentaram alterações não compatíveis com coração de atleta, sendo uma com forame oval patente e outra com sinais de doença valvar reumática, porém ambas sem repercussão hemodinâmica e ao TE apresentaram excelente capacidade funcional. CONCLUSÃO: As atletas estudadas tiveram adequada avaliação cardiológica, estando todas aptas à prática esportiva competitiva. Seguimento e ampliação do estudo são necessários para que se possa estabelecer um perfil cardiovascular de atletas do sexo feminino no Brasil.

The first instrument for complex PTSD assessment: psychometric properties of the ICD-11 Trauma Questionnaire.

OBJECTIVE: The ICD-11 Trauma Questionnaire (ITQ) was developed as a joint effort by researchers from several countries to evaluate post-traumatic stress (PTSD) and complex-PTSD (C-PTSD) symptoms. This study is part of a multi-center international collaborative research project that aims to provide psychometric support for this initial instrument in different languages, considering the specific contexts related to complex traumatization. This study verified the psychometric characteristics of the Portuguese version of the ITQ, evaluating symptoms beyond those described the existing literature. METHODS: We examined the results of a convenience sample totaling 268 Portuguese and Angolan participants. Two instruments were applied: the ITQ, which evaluates symptoms resulting from a traumatic life event, and the Life Events Checklist (LEC), which evaluates stressful life events. The general characteristics of the scales are described, and reliability analysis and validity studies were performed. RESULTS: Cronbach's alpha varied between 0.84 and 0.88, and the exploratory factorial analysis results were consistent with the concept of C-PTSD, with five components explaining 61.58% of scale variance. CONCLUSION: The results suggest good psychometric characteristics for the Portuguese version of the ITQ, and thus it can be included in protocols intended evaluating complex traumatic symptoms.

Correction: Sensory Neuron-Derived Eph Regulates Glomerular Arbors and Modulatory Function of a Central Serotonergic Neuron.

[This corrects the article DOI: 10.1371/journal.pgen.1003452.].

Synapsin function in GABA-ergic interneurons is required for short-term olfactory habituation.

In Drosophila, short-term (STH) and long-term habituation (LTH) of olfactory avoidance behavior are believed to arise from the selective potentiation of GABAergic synapses between multiglomerular local circuit interneurons (LNs) and projection neurons in the antennal lobe. However, the underlying mechanisms remain poorly understood. Here, we show that synapsin (syn) function is necessary for STH and that syn(97)-null mutant defects in STH can be rescued by syn(+) cDNA expression solely in the LN1 subset of GABAergic local interneurons. As synapsin is a synaptic vesicle-clustering phosphoprotein, these observations identify a presynaptic mechanism for STH as well as the inhibitory interneurons in which this mechanism is deployed. Serine residues 6 and/or 533, potential kinase target sites of synapsin, are necessary for synapsin function suggesting that synapsin phosphorylation is essential for STH. Consistently, biochemical analyses using a phospho-synapsin-specific antiserum show that synapsin is a target of Ca(2+) calmodulin-dependent kinase II (CaMKII) phosphorylation in vivo. Additional behavioral and genetic observations demonstrate that CaMKII function is necessary in LNs for STH. Together, these data support a model in which CaMKII-mediated synapsin phosphorylation in LNs induces synaptic vesicle mobilization and thereby presynaptic facilitation of GABA release that underlies olfactory STH. Finally, the striking observation that LTH occurs normally in syn(97) mutants indicates that signaling pathways for STH and LTH diverge upstream of synapsin function in GABAergic interneurons.

Identification and structural characterization of interneurons of the Drosophila brain by monoclonal antibodies of the würzburg hybridoma library.

Several novel synaptic proteins have been identified by monoclonal antibodies (mAbs) of the Würzburg hybridoma library generated against homogenized Drosophila brains, e.g. cysteine string protein, synapse-associated protein of 47 kDa, and Bruchpilot. However, at present no routine technique exists to identify the antigens of mAbs of our library that label only a small number of cells in the brain. Yet these antibodies can be used to reproducibly label and thereby identify these cells by immunohistochemical staining. Here we describe the staining patterns in the Drosophila brain for ten mAbs of the Würzburg hybridoma library. Besides revealing the neuroanatomical structure and distribution of ten different sets of cells we compare the staining patterns with those of antibodies against known antigens and GFP expression patterns driven by selected Gal4 lines employing regulatory sequences of neuronal genes. We present examples where our antibodies apparently stain the same cells in different Gal4 lines suggesting that the corresponding regulatory sequences can be exploited by the split-Gal4 technique for transgene expression exclusively in these cells. The detection of Gal4 expression in cells labeled by mAbs may also help in the identification of the antigens recognized by the antibodies which then in addition to their value for neuroanatomy will represent important tools for the characterization of the antigens. Implications and future strategies for the identification of the antigens are discussed.

The zinc finger transcription factor Jing is required for dendrite/axonal targeting in Drosophila antennal lobe development.

An important role in olfactory system development is played by transcription factors which act in sensory neurons or in their interneuron targets as cell autonomous regulators of downstream effectors such as cell surface molecules and signalling systems that control neuronal identity and process guidance. Some of these transcriptional regulators have been characterized in detail in the development of the neural elements that innervate the antennal lobe in the olfactory system of Drosophila. Here we identify the zinc finger transcription factor Jing as a cell autonomously acting transcriptional regulator that is required both for dendrite targeting of projection neurons and local interneurons as well as for axonal targeting of olfactory sensory neurons in Drosophila olfactory system development. Immunocytochemical analysis shows that Jing is widely expressed in the neural cells during postembryonic development. MARCM-based clonal analysis of projection neuron and local interneuron lineages reveals a requirement for Jing in dendrite targeting; Jing loss-of-function results in loss of innervation in specific glomeruli, ectopic innervation of inappropriate glomeruli, aberrant profuse dendrite arborisation throughout the antennal lobe, as well as mistargeting to other parts of the CNS. ey-FLP-based MARCM analysis of olfactory sensory neurons reveals an additional requirement for Jing in axonal targeting; mutational inactivation of Jing causes specific mistargeting of some olfactory sensory neuron axons to the DA1 glomerulus, reduction of targeting to other glomeruli, as well as aberrant stalling of axons in the antennal lobe. Taken together, these findings indicate that Jing acts as a key transcriptional control element in wiring of the circuitry in the developing olfactory sensory system in Drosophila.

Sensory neuron-derived eph regulates glomerular arbors and modulatory function of a central serotonergic neuron.

Olfactory sensory neurons connect to the antennal lobe of the fly to create the primary units for processing odor cues, the glomeruli. Unique amongst antennal-lobe neurons is an identified wide-field serotonergic neuron, the contralaterally-projecting, serotonin-immunoreactive deutocerebral neuron (CSDn). The CSDn spreads its termini all over the contralateral antennal lobe, suggesting a diffuse neuromodulatory role. A closer examination, however, reveals a restricted pattern of the CSDn arborization in some glomeruli. We show that sensory neuron-derived Eph interacts with Ephrin in the CSDn, to regulate these arborizations. Behavioural analysis of animals with altered Eph-ephrin signaling and with consequent arborization defects suggests that neuromodulation requires local glomerular-specific patterning of the CSDn termini. Our results show the importance of developmental regulation of terminal arborization of even the diffuse modulatory neurons to allow them to route sensory-inputs according to the behavioural contexts.

Gustatory habituation in Drosophila relies on rutabaga (adenylate cyclase)-dependent plasticity of GABAergic inhibitory neurons.

In some situations, animals seem to ignore stimuli which in other contexts elicit a robust response. This attenuation in behavior, which enables animals to ignore a familiar, unreinforced stimulus, is called habituation. Despite the ubiquity of this phenomenon, it is generally poorly understood in terms of the underlying neural circuitry. Hungry fruit flies show a proboscis extension reflex (PER) when sensory receptors are stimulated by sugars. The PER is usually followed by feeding. However, if feeding is disallowed following sugar stimulation, PER is no longer robust, and the animal is considered to be habituated to this stimulus. Our results suggest that PER habituation requires an adenylate cyclase-dependent enhancement of inhibitory output of GABAergic neurons in the subesophageal ganglion (SOG), which mediates PER. GABA synthesis in and release from glutamic acid decarboxylase (GAD1) expressing neurons is necessary, and GABA(A) receptors on cholinergic neurons are required for PER habituation. The proposed inhibitory potentiation requires glutamate/NMDA-receptor signaling, possibly playing a role in stimulus selectivity. We explain why these data provide significant and independent support for a general model in which inhibitory potentiation underlies habituation in multiple neural systems and species.

Mutants in Drosophila TRPC channels reduce olfactory sensitivity to carbon dioxide.

BACKGROUND: Members of the canonical Transient Receptor Potential (TRPC) class of cationic channels function downstream of Gαq and PLCß in Drosophila photoreceptors for transducing visual stimuli. Gαq has recently been implicated in olfactory sensing of carbon dioxide (CO(2)) and other odorants. Here we investigated the role of PLCß and TRPC channels for sensing CO(2) in Drosophila. METHODOLOGY/PRINCIPAL FINDINGS: Through behavioral assays it was demonstrated that Drosophila mutants for plc21c, trp and trpl have a reduced sensitivity for CO(2). Immuno-histochemical staining for TRP, TRPL and TRPγ indicates that all three channels are expressed in Drosophila antennae including the sensory neurons that express CO(2) receptors. Electrophysiological recordings obtained from the antennae of protein null alleles of TRP (trp(343)) and TRPL (trpl(302)), showed that the sensory response to multiple concentrations of CO(2) was reduced. However, trpl(302); trp(343) double mutants still have a residual response to CO(2). Down-regulation of TRPC channels specifically in CO(2) sensing olfactory neurons reduced the response to CO(2) and this reduction was obtained even upon down-regulation of the TRPCs in adult olfactory sensory neurons. Thus the reduced response to CO(2) obtained from the antennae of TRPC RNAi strains is not due to a developmental defect. CONCLUSION: These observations show that reduction in TRPC channel function significantly reduces the sensitivity of the olfactory response to CO(2) concentrations of 5% or less in adult Drosophila. It is possible that the CO(2) receptors Gr63a and Gr21a activate the TRPC channels through Gαq and PLC21C.

Plasticity of recurrent inhibition in the Drosophila antennal lobe.

Recurrent inhibition, wherein excitatory principal neurons stimulate inhibitory interneurons that feedback on the same principal cells, occurs ubiquitously in the brain. However, the regulation and function of recurrent inhibition are poorly understood in terms of the contributing interneuron subtypes as well as their effect on neural and cognitive outputs. In the Drosophila olfactory system, odorants activate olfactory sensory neurons (OSNs), which stimulate projection neurons (PNs) in the antennal lobe. Both OSNs and PNs activate local inhibitory neurons (LNs) that provide either feedforward or recurrent/feedback inhibition in the lobe. During olfactory habituation, prior exposure to an odorant selectively decreases the animal's subsequent response to the odorant. We show here that habituation occurs in response to feedback from PNs. Output from PNs is necessary for olfactory habituation and, in the absence of odorant, direct PN activation is sufficient to induce the odorant-selective behavioral attenuation characteristic of olfactory habituation. PN-induced habituation occludes further odor-induced habituation and similarly requires GABA(A)Rs and NMDARs in PNs, as well as VGLUT and cAMP signaling in the multiglomerular inhibitory local interneurons (LN1) type of LN. Thus, PN output is monitored by an LN subtype whose resultant plasticity underlies behavioral habituation. We propose that recurrent inhibitory motifs common in neural circuits may similarly underlie habituation to other complex stimuli.