•Social isolation is strongly associated with suicidal outcomes.•The subjective feeling of loneliness has a major impact, even transculturally.•Objective and subjective social isolation should be ...added in suicide risk assessment.
Social isolation is one of the main risk factors associated with suicidal outcomes. The aim of this narrative review was to provide an overview on the link between social isolation and suicidal thoughts and behaviors.
We used the PubMed database to identify relevant articles published until April 13, 2018. We focused on: (a) systematic reviews, meta-analyses, and narrative reviews; (b) original observational studies with large samples (N ≥ 500); and (c) qualitative studies. We included all relevant suicidal outcomes: suicidal ideation (SI), suicidal planning, non-suicidal self-injury, deliberate self-harm, suicide attempt (SA), and suicide.
The main social constructs associated with suicidal outcomes were marital status (being single, separated, divorced, or widowed) and living alone, social isolation, loneliness, alienation, and belongingness. We included 40 original observational studies, the majority of them performed on adolescents and/or young adults (k = 23, 57.5%). Both the objective condition (e.g., living alone) and the subjective feeling of being alone (i.e., loneliness) were strongly associated with suicidal outcomes, in particular with SA and SI. However, loneliness, which was investigated in most studies (k = 24, 60%), had a major impact on both SI and SA. These associations were transculturally consistent.
Confounding factors can limit the weight of the results obtained in observational studies.
Data from the observational studies suggest that both objective social isolation and the subjective feeling of loneliness should be incorporated in the risk assessment of suicide. Interventional studies targeting social isolation for suicide prevention are needed.
The new field of 'precision psychiatry' Fernandes, Brisa S; Williams, Leanne M; Steiner, Johann ...
BMC medicine,
04/2017, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Precision medicine is a new and important topic in psychiatry. Psychiatry has not yet benefited from the advanced diagnostic and therapeutic technologies that form an integral part of other clinical ...specialties. Thus, the vision of precision medicine as applied to psychiatry - 'precision psychiatry' - promises to be even more transformative than in other fields of medicine, which have already lessened the translational gap.
Herein, we describe 'precision psychiatry' and how its several implications promise to transform the psychiatric landscape. We pay particular attention to biomarkers and to how the development of new technologies now makes their discovery possible and timely. The adoption of the term 'precision psychiatry' will help propel the field, since the current term 'precision medicine', as applied to psychiatry, is impractical and does not appropriately distinguish the field. Naming the field 'precision psychiatry' will help establish a stronger, unique identity to what promises to be the most important area in psychiatry in years to come.
In summary, we provide a wide-angle lens overview of what this new field is, suggest how to propel the field forward, and provide a vision of the near future, with 'precision psychiatry' representing a paradigm shift that promises to change the landscape of how psychiatry is currently conceived.
Poor diet can be detrimental to mental health. However, the overall evidence for the effects of dietary interventions on mood and mental well-being has yet to be assessed. We conducted a systematic ...review and meta-analysis examining effects of dietary interventions on symptoms of depression and anxiety.
Major electronic databases were searched through March 2018 for all randomized controlled trials of dietary interventions reporting changes in symptoms of depression and/or anxiety in clinical and nonclinical populations. Random-effects meta-analyses were conducted to determine effect sizes (Hedges' g with 95% confidence intervals CI) for dietary interventions compared with control conditions. Potential sources of heterogeneity were explored using subgroups and meta-regression analyses.
Sixteen eligible randomized controlled trials (published in English) with outcome data for 45,826 participants were included; the majority of which examined samples with nonclinical depression (n = 15 studies). Nonetheless, dietary interventions significantly reduced depressive symptoms (g = 0.275, 95% CI = 0.10 to 0.45, p = .002). Similar effects were observed among high-quality trials (g = 0.321, 95% CI = 0.12 to 0.53, p = .002) and when compared with both inactive (g = 0.308, 95% CI = 0.02 to 0.60, p = .038) and active controls (g = 0.174, 95% CI = 0.01 to 0.34, p = .035). No effect of dietary interventions was observed for anxiety (k = 11, n = 2270, g = 0.100, 95% CI = -0.04 to 0.24, p = .148). Studies with female samples observed significantly greater benefits from dietary interventions, for symptoms of both depression and anxiety.
Dietary interventions hold promise as a novel intervention for reducing symptoms of depression across the population. Future research is required to determine the specific components of dietary interventions that improve mental health, explore underlying mechanisms, and establish effective schemes for delivering these interventions in clinical and public health settings.
PROSPERO Online Protocol: CRD42018091256.
Increasing evidence suggests that inflammation is involved in Alzheimer's disease (AD) pathology. This study quantitatively summarised the data on peripheral inflammatory markers in patients with AD ...compared with healthy controls (HC).
Original reports containing measurements of peripheral inflammatory markers in AD patients and HC were included for meta-analysis. Standardised mean differences were calculated using a random effects model. Meta-regression and exploration of heterogeneity was performed using publication year, age, gender, Mini-Mental State Examination (MMSE) scores, plasma versus serum measurements and immunoassay type.
A total of 175 studies were combined to review 51 analytes in 13 344 AD and 12 912 HC patients. Elevated peripheral interleukin (IL)-1β, IL-2, IL-6, IL-18, interferon-γ, homocysteine, high-sensitivity C reactive protein, C-X-C motif chemokine-10, epidermal growth factor, vascular cell adhesion molecule-1, tumour necrosis factor (TNF)-α converting enzyme, soluble TNF receptors 1 and 2, α1-antichymotrypsin and decreased IL-1 receptor antagonist and leptin were found in patients with AD compared with HC. IL-6 levels were inversely correlated with mean MMSE scores.
These findings suggest that AD is accompanied by a peripheral inflammatory response and that IL-6 may be a useful biological marker to correlate with the severity of cognitive impairment. Further studies are needed to determine the clinical utility of these markers.
Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large ...numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients - psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific
(
) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the "behavioral toxicity" conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed first. However, alongside with safety, efficacy should also be considered on a patient-tailored basis.
Abstract Treatment-resistant depression affects up to 20% of individuals suffering from major depressive disorder (MDD). The medications currently available to treat depression, including serotonin ...re-uptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs), fail to produce adequate remission of depressive symptoms for a large number of patients. The monoamine hypothesis upon which these medications are predicated should be expanded and revised as research elucidates alternative mechanisms of depression and effective methods to treat the underlying pathologic consequences. Research into the role of tryptophan degradation and the kynurenine pathway in the setting of inflammation has brought new insight into potential etiologies of MDD. Further investigation into the connection between inflammatory mediators, tryptophan degradation, and MDD can provide many targets for novel antidepressant therapies. Thus, this review will highlight the role of the kynurenine pathway in the pathophysiology of depression, as well as a novel therapeutic target to classic and new modulators to treat depression based on findings from preclinical and clinical studies.
Depression is a prevalent and disabling mental disorder that frequently co-occurs with a wide range of chronic conditions. Evidence has suggested that depression could be associated with excess ...all-cause mortality across different settings and populations, although the causality of these associations remains unclear.
We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, PsycINFO, and Embase electronic databases were searched through January 20, 2018. Systematic reviews and meta-analyses that investigated associations of depression and all-cause and cause-specific mortality were selected for the review. The evidence was graded as convincing, highly suggestive, suggestive, or weak based on quantitative criteria that included an assessment of heterogeneity, 95% prediction intervals, small-study effects, and excess significance bias.
A total of 26 references providing 2 systematic reviews and data for 17 meta-analytic estimates met inclusion criteria (19 of them on all-cause mortality); data from 246 unique studies (N = 3,825,380) were synthesized. All 17 associations had P < 0.05 per random effects summary effects, but none of them met criteria for convincing evidence. Associations of depression and all-cause mortality in patients after acute myocardial infarction, in individuals with heart failure, in cancer patients as well as in samples from mixed settings met criteria for highly suggestive evidence. However, none of the associations remained supported by highly suggestive evidence in sensitivity analyses that considered studies employing structured diagnostic interviews. In addition, associations of depression and all-cause mortality in cancer and post-acute myocardial infarction samples were supported only by suggestive evidence when studies that tried to adjust for potential confounders were considered.
Even though associations between depression and mortality have nominally significant results in all assessed settings and populations, the evidence becomes weaker when focusing on studies that used structured interviews and those that tried to adjust for potential confounders. A causal effect of depression on all-cause and cause-specific mortality remains unproven, and thus interventions targeting depression are not expected to result in lower mortality rates at least based on current evidence from observational studies.
Alzheimer's disease (AD), the most common form of dementia, is a progressive disorder manifested by gradual memory loss and subsequent impairment in mental and behavioral functions. Though the ...primary risk factor for AD is advancing age, other factors such as diabetes mellitus, hyperlipidemia, obesity, vascular factors and depression play a role in its pathogenesis. The human gastrointestinal tract has a diverse commensal microbial population, which has bidirectional interactions with the human host that are symbiotic in health, and in addition to nutrition, digestion, plays major roles in inflammation and immunity. The most prevalent hypothesis for AD is the amyloid hypothesis, which states that changes in the proteolytic processing of the amyloid precursor protein leads to the accumulation of the amyloid beta (Aβ) peptide. Aβ then triggers an immune response that drives neuroinflammation and neurodegeneration in AD. The specific role of gut microbiota in modulating neuro-immune functions well beyond the gastrointestinal tract may constitute an important influence on the process of neurodegeneration. We first review the main mechanisms involved in AD physiopathology. Then, we review the alterations in gut microbiota and gut-brain axis that might be relevant to mediate or otherwise affect AD pathogenesis, especially those associated with aging. We finally summarize possible mechanisms that could mediate the involvement of gut-brain axis in AD physiopathology, and propose an integrative model.
Newer generation antidepressant drugs (ADs) are widely used as the first line of treatment for major depressive disorders and are considered to be safer than tricyclic agents. In this critical ...review, we evaluated the literature on adverse events, tolerability and safety of selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, bupropion, mirtazapine, trazodone, agomelatine, vilazodone, levomilnacipran and vortioxetine. Several side effects are transient and may disappear after a few weeks following treatment initiation, but potentially serious adverse events may persist or ensue later. They encompass gastrointestinal symptoms (nausea, diarrhea, gastric bleeding, dyspepsia), hepatotoxicity, weight gain and metabolic abnormalities, cardiovascular disturbances (heart rate, QT interval prolongation, hypertension, orthostatic hypotension), genitourinary symptoms (urinary retention, incontinence), sexual dysfunction, hyponatremia, osteoporosis and risk of fractures, bleeding, central nervous system disturbances (lowering of seizure threshold, extrapyramidal side effects, cognitive disturbances), sweating, sleep disturbances, affective disturbances (apathy, switches, paradoxical effects), ophthalmic manifestations (glaucoma, cataract) and hyperprolactinemia. At times, such adverse events may persist after drug discontinuation, yielding iatrogenic comorbidity. Other areas of concern involve suicidality, safety in overdose, discontinuation syndromes, risks during pregnancy and breast feeding, as well as risk of malignancies. Thus, the rational selection of ADs should consider the potential benefits and risks, likelihood of responsiveness to the treatment option and vulnerability to adverse events. The findings of this review should alert the physician to carefully review the appropriateness of AD prescription on an individual basis and to consider alternative treatments if available.
Many, if not all, chronic medical, neurodegenerative and neuroprogressive illnesses are characterised by chronic immune activation, oxidative and nitrosative stress (O&NS) and systemic inflammation. ...These factors, notably elevated pro-inflammatory cytokines, activate indoleamine 2,3-dioxygenase (IDO) leading to an upregulated tryptophan catabolite (TRYCAT) pathway of tryptophan degradation in the periphery and in the brain. In such conditions the TRYCAT pathway becomes the predominant system for tryptophan degradation in all body compartments. In this paper we review the pathways whereby TRYCATs may play a role in neuro-inflammatory and neuroprogressive disease. Thus chronic activation of the TRYCAT pathway leads to the production of a range of neuroactive, neuroprotective and neurotoxic TRYCATs. Some TRYCATs such as quinolinic acid act as potent neurotoxins which inhibit ATP production by mitochondria, provoke increases in O&NS, disrupt neuron glial communication and blood brain barrier integrity, induce apoptosis of glial cells, directly damage neurons and function as a N-methyl D-aspartate (NMDA) receptor agonist. Other TRYCATs such as kynurenic acid function as antagonists of NMDA, α- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors and act to regulate levels of glutamate and dopamine. The neuroprotective functions of this TRYCAT are likely exercised via engagement with alpha7 nicotinic acetylcholine and aryl hydrocarbon receptors but the neuroprotective effects stemming from elevated kynurenic acid levels come at the price of severely compromised neurocognitive function and emotional processing. Other TRYCATS also possess neurotoxic or neuroprotective properties via pro-oxidant and antioxidant effects. Here we discuss the involvement of the abovementioned TRYCAT pathways in schizophrenia, Alzheimer's disease and chronic fatigue syndrome.