Homelessness and health-related outcomes: an umbrella review of observational studies and randomized controlled trials.

BACKGROUND: Homelessness has been associated with multiple detrimental health outcomes across observational studies. However, relatively few randomized controlled trials (RCTs) have been conducted on people who experience homelessness (PEH). Thus, this umbrella review ranked the credibility of evidence derived from systematic reviews (SRs) and meta-analyses (MAs) of observational studies investigating the associations between homelessness and any health outcome as well as RCTs targeting health needs in this population. METHODS: Several databases were systematically searched from inception through April 28, 2021. Any SR and/or MA reporting quantitative data and providing a control group were eligible for inclusion. The credibility of the evidence derived from observational studies was appraised by considering the significance level of the association and the largest study, the degree of heterogeneity, the presence of small-study effects as well as excess significance bias. The credibility of evidence was then ranked in five classes. For SRs and/or MAs of RCTs, we considered the level of significance and whether the prediction interval crossed the null. The AMSTAR-2 and AMSTAR-plus instruments were adopted to further assess the methodological quality of SRs and/or MAs. The Newcastle-Ottawa Scale (NOS) was employed to further appraise the methodological quality of prospective cohort studies only; a sensitivity analysis limited to higher quality studies was conducted. RESULTS: Out of 1549 references, 8 MAs and 2 SRs were included. Among those considering observational studies, 23 unique associations were appraised. Twelve of them were statistically significant at the p≤0.005 level. Included cases had worst health-related outcomes than controls, but only two associations reached a priori-defined criteria for convincing (class I) evidence namely hospitalization due to any cause among PEH diagnosed with HIV infection, and the occurrence of falls within the past year among PEH. According to the AMSTAR-2 instrument, the methodological quality of all included SRs and/or MAs was "critically low." Interventional studies were scant. CONCLUSION: While homelessness has been repeatedly associated with detrimental health outcomes, only two associations met the criteria for convincing evidence. Furthermore, few RCTs were appraised by SRs and/or MAs. Our umbrella review also highlights the need to standardize definitions of homelessness to be incorporated by forthcoming studies to improve the external validity of the findings in this vulnerable population.

[Evidence-based psychotherapeutic methods of prevention and intervention in suicidal behaviour]. / A szuicid prevenció és intervenció bizonyítékokon alapuló pszichoterápiás lehetoségei.

There are several approached to suicide prevention based on various psychotherapeutic interventions, which are effective, especially when these are matched to the given psychiatric patient population, environment and context. In this paper the possibilities of psychotherapeutic methods of suicide prevention and intervention are described along with their indications. The following interventions are discussed: Cognitive Behavioral Therapy for Suicide Prevention (CBT-SP), Cognitive Therapy for Suicide Prevention (CT-SP), Brief Cognitive-Behavioral Therapy for Suicide Prevention (BCBT), Problem Solving Therapy (PST), Problem Adaptation Therapy (PATH), Dialectial Behavior Therapy (DBT), SchemaFocused Therapy (SFT), Mindfulness-Based Cognitive Therapy (MBCT), Mindfulness-Based Stress Reduction (MBSR), Acceptance and Commitment Therapy (ACT), Mentalization-Based Treatment (MBT), Interpersonal Psychotherapy (IPT), Transference-Focused Psychotherapy (TFP), Collaborative Assessment and Management of Suicidality (CAMS), Teachable Moment Brief Intervention (TMBI), Motivational Interviewing (MI), Attempted Suicide Short Intervention Program (ASSIP) and other Interned-Based Interventions (IBI). The effectiveness of the above methods may vary, however, they focus on the psychological processes playing a role in the emergence of suicidal behaviours including cognitive processes, as well as difficulties of problem solving and emotion regulation. As the efficacy of these interventions are supported by clinical trials, their use is recommended in case of this vulnerable patient population. The importance of using such methods in the clinical work with suicidal patients should be prioritized in our effort to provide a complex treatment for suicidal behaviour based on the most optimal and appropriate intervention considering the given patient.

The opioid system and the social brain: implications for depression and suicide.

In the past decade, considerable attention has been drawn to social interactions and behaviors as sources of pleasurable (social reward) and painful (social pain) emotional states. While the role of the opioid system in the regulation of reward and pain processes has long been recognized, it has more recently been investigated and characterized in the specific context of social experiences across several mammalian species. Accordingly, the present narrative review provides a comprehensive summary of studies detailing how the opioid system controls social reward and social pain. From a translational and pathophysiological perspective, we further discuss how opioid-dependent regulation of social behaviors may contribute to depressive illness and suicidal behaviors, and ultimately provide innovative therapeutic opportunities.

Candidate Biomarkers of Suicide Crisis Syndrome: What to Test Next? A Concept Paper.

BACKGROUND: There has been increasing interest in both suicide-specific diagnoses within the psychiatric nomenclature and related biomarkers. Because the Suicide Crisis Syndrome-an emotional crescendo of several interrelated symptoms-seems to be promising for the identification of individuals at risk of suicide, the aim of the present paper is to review the putative biological underpinnings of the Suicide Crisis Syndrome symptoms (entrapment, affective disturbance, loss of cognitive control, hyperarousal, social withdrawal). METHODS: A PubMed literature search was performed to identify studies reporting a link between each of the 5 Suicide Crisis Syndrome symptoms and biomarkers previously reported to be associated with suicidal outcomes. RESULTS: Disturbances in the hypothalamic-pituitary-adrenal axis, with dysregulated corticotropin-releasing hormone and cortisol levels, may be linked to a sense of entrapment. Affective disturbance is likely mediated by alterations in dopaminergic circuits involved in reward and antireward systems as well as endogenous opioids. Loss of cognitive control is linked to altered neurocognitive function in the areas of executive function, attention, and decision-making. Hyperarousal is linked to autonomic dysregulation, which may be characterized by a reduction in both heart rate variability and electrodermal activity. Social withdrawal has been associated with oxytocin availability. There is also evidence that inflammatory processes may contribute to individual Suicide Crisis Syndrome symptoms. CONCLUSION: The Suicide Crisis Syndrome is a complex syndrome that is likely the consequence of distinct changes in interconnected neural, neuroendocrine, and autonomic systems. Available clinical and research data allow for development of empirically testable hypotheses and experimental paradigms to scrutinize the biological substrates of the Suicide Crisis Syndrome.

Personality Disorders in Time of Pandemic.

PURPOSE OF REVIEW: We report evidence on the negative psychological effects of pandemics in people with personality disorders (PDs) and on the role of personality pathology in compliance with mitigation-related behaviors. Considering the paucity of studies, after a description of the main features of PDs, on the basis of the current literature on pandemic and quarantine mental health impact, we trace some clinical hypotheses. RECENT FINDINGS: Paranoid traits and detachment (cluster A) might lead to worse psychological outcomes. Cluster B patients may show more intense stress-related reactions and react strongly to social distancing, especially considering borderline personality disorder. Cluster C patients might be particularly prone to anxiety and stress due to fear of contagion and may be less flexible in adaptation to new routines. Evidence on compliance with mitigation measures is mixed, with lower compliance in cluster B patients and higher in cluster C ones. We suggest that PD patients might be particularly affected by pandemics. Furthermore, they might react differently, according to their main diagnosis. Similarly, compliance with mitigation measures may differ according to specific PDs. Our results should be considered as a starting point to reflect on therapeutic strategies to be adopted in the post-COVID-19 situation.

The Psychological Impact of Epidemic and Pandemic Outbreaks on Healthcare Workers: Rapid Review of the Evidence.

PURPOSE OF REVIEW: We aim to provide quantitative evidence on the psychological impact of epidemic/pandemic outbreaks (i.e., SARS, MERS, COVID-19, ebola, and influenza A) on healthcare workers (HCWs). RECENT FINDINGS: Forty-four studies are included in this review. Between 11 and 73.4% of HCWs, mainly including physicians, nurses, and auxiliary staff, reported post-traumatic stress symptoms during outbreaks, with symptoms lasting after 1-3 years in 10-40%. Depressive symptoms are reported in 27.5-50.7%, insomnia symptoms in 34-36.1%, and severe anxiety symptoms in 45%. General psychiatric symptoms during outbreaks have a range comprised between 17.3 and 75.3%; high levels of stress related to working are reported in 18.1 to 80.1%. Several individual and work-related features can be considered risk or protective factors, such as personality characteristics, the level of exposure to affected patients, and organizational support. Empirical evidence underlines the need to address the detrimental effects of epidemic/pandemic outbreaks on HCWs' mental health. Recommendations should include the assessment and promotion of coping strategies and resilience, special attention to frontline HCWs, provision of adequate protective supplies, and organization of online support services.

The suicide crisis syndrome: A network analysis.

Recent studies introduced the suicide crisis syndrome (SCS), a condition associated with imminent suicidal behavior and characterized by (a) a pervasive feeling of entrapment in which the escape from an unbearable life situation is perceived as both urgent and impossible (Criterion A) and (b) affective disturbance, loss of cognitive control, hyperarousal, and social withdrawal (Criterion B). The goal of the present study was to use some of the analytic tools provided by network analyses to further the understanding of the psychological, emotional, cognitive, behavioral, and physiological processes involved in the SCS by testing (a) whether the different symptoms of the proposed syndrome are related to each other, (b) whether symptoms form meaningful clusters, and (c) whether certain symptoms are more central than others. The study included 500 outpatient and 223 inpatient participants. A network analysis of the participants' scores on the various symptoms of the SCS was conducted. The network analysis suggested that most SCS symptoms are linked by strong connections and that entrapment and ruminative flooding are highly correlated with the other SCS symptoms. Three clusters of symptoms were identified, suggesting the existence of several interdependent psychological processes potentially involved in SCS phenomenology. Our findings support both the suggested symptoms of the SCS and the central role of entrapment in the proposed criteria for the syndrome. Emotional pain appears to be closely linked to entrapment and may belong in Criterion A. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Suicide Crisis Syndrome: A review of supporting evidence for a new suicide-specific diagnosis.

Suicide is a major public health problem, and suicide rates are still on the rise. Current strategies for identifying individuals at risk for suicide, such as the use of a patient's self-reported suicidal ideation or evidence of past suicide attempts, have not been sufficient in reducing suicide rates. Recently, research groups have been focused on determining the acute mental state preceding a suicide attempt. The development of an acute suicidal diagnosis, the Suicide Crisis Syndrome (SCS), is aimed at capturing this state to better treat individuals. The SCS has five main evidence-based components-entrapment, affective disturbance, loss of cognitive control, hyperarousal, and social withdrawal. The SCS may provide clinicians with the ability to identify individuals who are experiencing an acute pre-suicidal mental state, regardless of their self-reported suicidal ideation. Future research leading to the incorporation of this diagnosis into clinical practice could improve the quality of care and reduce the personal, societal, and legal burden of suicide.

Rational Suicide in Late Life: A Systematic Review of the Literature.

Background and Objectives: The complex concept of rational suicide, defined as a well-thought-out decision to die by an individual who is mentally competent, is even more controversial in the case of older adults. Materials and Methods: With the aim of better understanding the concept of rational suicide in older adults, we performed a systematic review of the literature, searching PubMed and Scopus databases and eventually including 23 published studies. Results: The main related topics emerging from the papers were: depression, self-determination, mental competence; physicians' and population's perspectives; approach to rational suicide; ageism; slippery slope. Conclusions: Despite contrasting positions and inconsistencies of the studies, the need to carefully investigate and address the expression of suicidal thoughts in older adults, as well as behaviours suggesting "silent" suicidal attitudes, clearly emerges, even in those situations where there is no diagnosable mental disorder. While premature conclusions about the "rationality" of patients' decision to die should be avoided, the possibility of rational suicide cannot be precluded.

Acceptance and Commitment Therapy for the Management of Suicidal Patients: A Randomized Controlled Trial.

BACKGROUND: The management of suicidal crisis remains a major issue for clinicians, driving the development of new strategies to improve suicide prevention. METHODS: We conducted a randomized controlled trial comparing a 7-week acceptance and commitment therapy (ACT) versus relaxation group, as adjunct to treatment as usual for adult outpatients suffering from a current suicidal behavior disorder. The primary outcome was the rate of change in the Columbia Suicide Severity Rating Scale suicidal ideation subscore (adding severity and intensity subscores). Secondary outcomes were the rates of change for depressive symptomatology, psychological pain, anxiety, hopelessness, anger, quality of life, and therapeutic processes. Assessments were performed in the 2 weeks preceding the beginning of the treatment (pretreatment assessment), and within 1 week (posttherapy assessment) and 3 months (follow-up assessment) after therapy completion. RESULTS: Forty adults were included and randomized. The rate of change in ACT for suicidal ideation at the posttherapy assessment was higher than in the relaxation group (ß [SE] = -1.88 [0.34] vs. -0.79 [0.37], respectively; p = 0.03). ACT effectiveness remained stable at the 3-month follow-up. We found a similar pattern of change for depressive symptomatology and anxiety, psychological pain, hopelessness, anger, and quality of life. Therapeutic processes improved more in the ACT group than in the relaxation group. Treatment adherence was high in the ACT group, all participants reported satisfaction with the program. CONCLUSIONS: Through its effectiveness in reducing suicidal ideation and improving the clinical dimensions associated with suicidal risk in patients suffering from a suicidal behavior disorder, ACT could be developed as an adjunctive strategy in programs for suicide prevention.

Refining Suicide Prevention: a Narrative Review on Advances in Psychotherapeutic Tools.

PURPOSE OF REVIEW: Since psychotherapies for suicide prevention are receiving increasing attention, our purpose was to evaluate the related literature [meta-analyses and reviews on their effect on suicidal outcomes (A), perspective reviews concerning specific socio-demographic and clinical features (B), original studies with particular interest (C)] published over the last 3 years. RECENT FINDINGS: (A) Across different diagnoses, particularly, efficacious psychotherapies were cognitive behavioral therapy-based ones and interventions directly addressing suicidal thoughts and behaviors during the treatment. When the focus was restricted to specific diagnoses, results were different: for example, in borderline patients, dialectical behavior therapy and psychodynamic psychotherapies were the only efficacious interventions. (B) Family therapies for adolescents and treatments for elderly depressed patients with disability/cognitive impairment should be further developed. (C) General long-term effects seem to be present, but specific interventions and treatment duration should be considered. Results indicated the presence of a number of promising interventions.

Psychological Pain, Depression, and Suicide: Recent Evidences and Future Directions.

PURPOSE OF REVIEW: The definition of psychological pain is complex. It is a lasting unpleasant and unsustainable feeling characterized by a perception of inability or deficiency of the self, as well as frustrated psychological needs and social disconnection. The aim of our review was to summarize the most recent and updated findings supporting the role of psychological pain in the pathophysiology of depression and suicidal behavior. We also explored the relationship between psychological and physical pain in depression and suicide. RECENT FINDINGS: Psychological pain is a prominent dimension of depressive disorder and has been associated with higher risk of suicidal ideation and suicidal behavior. Sensitivity to psychological and physical pain is increased in depression. Conversely, higher tolerance to physical pain is associated with suicidal behavior. A better understanding of the pathophysiology of pain processing in depression and suicide offers new therapeutic options for the treatment of depression through the use of analgesic drugs.

The Impact of BDNF Polymorphisms on Suicidality in Treatment-Resistant Major Depressive Disorder: A European Multicenter Study.

Background: Numerous studies have reported associations between the brain-derived neurotrophic factor (BDNF) gene and psychiatric disorders, including suicidal behavior, although with conflicting results. Methods: A total of 250 major depressive disorder patients were collected in the context of a European multicenter resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using the Mini International Neuropsychiatric Interview and Hamilton Rating Scale for Depression, and treatment response using the HAM-D. Genotyping was performed for the functional Val66Met polymorphism (rs6265) and 7 additional tagging single nucleotide polymorphisms within the BDNF gene. Results: Neither BDNF single markers nor haplotypes were found to be associated with suicide risk and lifetime history of suicide attempts. Gender-specific analyses revealed nonsignificant single marker (rs908867) and haplotypic association with suicide risk in males after multiple testing correction. Analyzing treatment response phenotypes, the functional Val66Met polymorphism as well as rs10501087 showed significant genotypic and haplotypic association with suicide risk in remitters (n=34, 13.6%). Conclusions: Considering the sample size, the present findings need to be replicated in larger samples to confirm or refute a role of BDNF in the investigated suicidal behavior phenotypes.

Neuroplasticity and second messenger pathways in antidepressant efficacy: pharmacogenetic results from a prospective trial investigating treatment resistance.

Genes belonging to neuroplasticity, monoamine, circadian rhythm, and transcription factor pathways were investigated as modulators of antidepressant efficacy. The present study aimed (1) to replicate previous findings in an independent sample with treatment-resistant depression (TRD), and (2) to perform a pathway analysis to investigate the possible molecular mechanisms involved. 220 patients with major depressive disorder who were non-responders to a previous antidepressant were treated with venlafaxine for 4-6 weeks and in case of non-response with escitalopram for 4-6 weeks. Symptoms were assessed using the Montgomery Asberg Depression Rating Scale. The phenotypes were response and remission to venlafaxine, non-response (TRDA) and non-remission (TRDB) to neither venlafaxine nor escitalopram. 50 tag SNPs in 14 genes belonging to the pathways of interest were tested for association with phenotypes. Molecular pathways (KEGG database) that included one or more of the genes associated with the phenotypes were investigated also in the STAR*D sample. The associations between ZNF804A rs7603001 and response, CREB1 rs2254137 and remission were replicated, as well as CHL1 rs2133402 and lower risk of TRD. Other CHL1 SNPs were potential predictors of TRD (rs1516340, rs2272522, rs1516338, rs2133402). The MAPK1 rs6928 SNP was consistently associated with all the phenotypes. The protein processing in endoplasmic reticulum pathway (hsa04141) was the best pathway that may explain the mechanisms of MAPK1 involvement in antidepressant response. Signals in genes previously associated with antidepressant efficacy were confirmed for CREB1, ZNF804A and CHL1. These genes play pivotal roles in synaptic plasticity, neural activity and connectivity.

Genetics of psychotropic medication induced side effects in two independent samples of bipolar patients.

The treatment of bipolar disorder (BD) usually requires combination therapies, with the critical issue of the emergence of adverse drug reactions (ADRs) and the possibility of low treatment adherence. Genetic polymorphisms are hypothesized to modulate the pharmacodynamics of psychotropic drugs, representing potential biological markers of ADRs. This study investigated genes involved in the regulation of neuroplasticity (BDNF, ST8SIA2), second messenger cascades (GSK3B, MAPK1, and CREB1), circadian rhythms (RORA), transcription (SP4, ZNF804A), and monoaminergic system (HTR2A and COMT) in the risk of neurological, psychic, autonomic, and other ADRs. Two independent samples of BD patients naturalistically treated were included (COPE-BD n = 147; STEP-BD n = 659). In the COPE-BD 34 SNPs were genotyped, while in the STEP-BD polymorphisms in the selected genes were extracted from the genome-wide dataset. Each ADRs group was categorized as absent-mild or moderate-severe and logistic regression with appropriate covariates was applied to identify possible risk genotypes/alleles. 58.5 and 93.5 % of patients were treated with mood stabilizers, 44.2 and 50.7 % were treated with antipsychotics, and 69.4 and 46.1 % were treated with antidepressants in the COPE-BD and STEP-BD, respectively. Our findings suggested that ST8SIA2 may be associated with psychic ADRs, as shown in the COPE-BD (rs4777989 p = 0.0017) and STEP-BD (rs56027313, rs13379489 and rs10852173). A cluster of RORA SNPs around rs2083074 showed an effect on psychic ADRs in the STEP-BD. Trends supporting the association between HTR2A and autonomic ADRs were found in both samples. Confirmations are needed particularly for ST8SIA2 and RORA since the few available data regarding their role in relation to psychotropic ADRs.

Association study of CREB1 polymorphisms and suicidality in MDD: results from a European multicenter study on treatment resistant depression.

PURPOSE: Mood disorders are present in more than 90% of suicides, and a genetic vulnerability to suicidality is well established. Numerous lines of evidence relate the transcription factor Cyclic adenosine monophosphate Response Element Binding protein (CREB1) to suicide, and to the aetiology of major depressive disorder (MDD). Our aim was to test for association between CREB1 single nucleotide polymorphisms (SNPs) and both suicide risk (SR) and a personal history of suicide attempt (SA) in MDD patients. MATERIALS AND METHODS: A sample of 250 MDD patients collected in the context of a European multicenter resistant depression study and treated with antidepressants over a period of at least 4 weeks were genotyped for five CREB1 SNPs (rs2709376, rs2253206, rs7569963, rs7594560, and rs4675690). To assess suicidality, the Mini International Neuropsychiatric Interview (MINI) and the Hamilton Rating Scale for Depression (HAM-D) were applied. RESULTS: Neither single-marker nor haplotypic association were found between SR and/or a personal history of SA with any of the investigated SNPs after multiple testing correction. For females, an association between rs2709376 and a personal history of SA was found (p = 0.016), however not resisting multiple testing correction. CONCLUSIONS: Although we found significant CREB1 single marker association with a personal history of SA in female MDD patients, this finding could not be confirmed in haplotypic analyses after multiple testing correction. Larger well-defined cohorts are required to confirm or refute a possible association of CREB1 and SA in female MDD patients.

Mixed, melancholic, and anxious features in depression: a cross-sectional study of sociodemographic and clinical correlates.

BACKGROUND: Major depression (MD) is currently viewed as a heterogeneous condition, characterized by different psychopathological dimensions. METHODS: Our sample was composed of 1,289 nonpsychotic bipolar/unipolar depressed patients. Participants were divided into mixed (MXD), melancholic (MEL), and anxious (ANX) depressed, according to a hierarchical functional model. Sociodemographic and clinical variables were compared across depressive subtypes by χ2 test and analysis of variance. The Young Mania Rating Scale (YMRS) and 2 subscales (melancholic [MEL-S] and psychic-somatic anxiety [PSOM-ANX]) from the Hamilton Depression Rating Scale also served as continuous outcome measures. RESULTS: MXD patients more frequently had bipolar I disorder (BD I), younger age of onset, and a higher familial load for mood disorders. MEL and ANX patients were more frequently diagnosed with major depressive disorder and reported a higher suicide risk. YMRS scores in depression was associated with BD I diagnosis (P < .0001) and manic polarity of the last episode (P < .0001), while a depressive polarity of the last episode (P < .0001) was associated with higher MEL-S score. No specific predictor was associated with PSOM-ANX score. CONCLUSIONS: Overall, our findings suggest that mixed depressive features are associated with significant hallmarks of bipolarity, and melancholic features may be influenced by previous depressive polarity. The symptom domain of anxiety appears to have no specific predictor.

Influence of differentially expressed genes from suicide post-mortem study on personality traits as endophenotypes on healthy subjects and suicide attempters.

Although a genetic contribution to the complex aetiology of suicidal behaviour has been suggested since many years, the attempt to identify specific genes related to suicide has led to contrasting results. In a post-mortem study on suicide, we previously detected several differentially expressed genes which, however, have not been subsequently associated with suicidal behaviour, or only nominally. Therefore, personality traits may represent good intermediate endophenotypes. Our primary aim was to investigate the potential modulation of several single-nucleotide polymorphisms (SNPs) of the same previously investigated genes (S100A13, EFEMP1, PCDHB5, PDGFRB, CDCA7L, SCN2B, PTPRR, MLC1 and ZFP36) on personality traits, as measured with the Temperament and Character Inventory (TCI), in a German sample composed of 287 healthy subjects (males: 123, 42.9 %; mean age: 45.2 ± 14.9 years) and in 111 psychiatric patients who attempted suicide (males: 43, 38.6 %; mean age: 39.2 ± 13.6 years). Multivariate analysis of covariance was used to test possible influence of single SNPs on TCI scores. Genotypic, allelic and haplotypic analyses have been performed. Controlling for sex, age and educational level, genotypic analyses showed a modulation of EFEMP1 rs960993 and rs2903838 polymorphisms on both harm avoidance and self-directedness in healthy subjects. Interestingly, we could replicate these associations in haploblocks within controls (p < 0.0001) and in the independent sample of suicide attempters for harm avoidance (p < 0.00001), a phenotype highly associated with suicidal behaviour. This study suggests that EFEMP1 SNPs, never investigated in association with suicidal behaviour and related personality, could be involved in its modulation in healthy subjects as well as in suicide attempters.