The new field of 'precision psychiatry' Fernandes, Brisa S; Williams, Leanne M; Steiner, Johann ...
BMC medicine,
04/2017, Letnik:
15, Številka:
1
Journal Article
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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.
•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.
Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not ...fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.
Here, we review a novel concept namely the compensatory immune-regulatory reflex system (CIRS) as applied to the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). There is ...evidence that a substantial subset of individuals with MDD and BD exhibit an activation of the immune-inflammatory response system (IRS), as indicated by an increased production of macrophagic M1 and T helper (Th)-1 pro-inflammatory cytokines, interleukin (IL)-6 trans-signaling, positive acute phase proteins (APPs), and complement factors. These immune aberrations appear to be evident during the course of major affective episodes of either depressive or (hypo) manic polarity. Here, we review (a) the current state of the art of CIRS functions in both mood disorders and (b) the possible role of CIRS-related biomarkers for the understanding of affective disorders within the framework of precision psychiatry that could also provide novel drug targets for both MDD and BD. CIRS-related abnormalities in mood disorders include elevated Th-2 and T regulatory (Treg) activities with increased IL-4 and IL-10 production, classical IL-6 signaling, increased levels of sIL-1R antagonist (sIL-1RA), soluble IL-2 (sIL-2R) and tumor necrosis factor–α- receptors, and positive APPs, including haptoglobin, hemopexin, α1-acid glycoprotein, α1-antitrypsin, and ceruloplasmin. It is concluded that CIRS is involved in MDD and BD by regulating the primary immune-inflammatory response, thereby contributing to spontaneous and antidepressant-promoted recovery from the acute phase of illness. Signs of activated IRS and CIRS pathways are observed in the remitted phases of both disorders indicating that there is no return to the original homeostasis after an acute episode, while later episodes of mood disorders are characterized by sensitized IRS and CIRS responses. New z-unit weighted composite biomarker scores are proposed, which reflect different aspects of IRS versus CIRS activation and may be used to estimate different IRS/CIRS activity ratios in mood and other neuroimmune disorders.
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.
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.
Hierarchical Multi-Label Classification is a classification task where the classes to be predicted are hierarchically organized. Each instance can be assigned to classes belonging to more than one ...path in the hierarchy. This scenario is typically found in protein function prediction, considering that each protein may perform many functions, which can be further specialized into sub-functions. We present a new hierarchical multi-label classification method based on multiple neural networks for the task of protein function prediction. A set of neural networks are incrementally training, each being responsible for the prediction of the classes belonging to a given level.
The method proposed here is an extension of our previous work. Here we use the neural network output of a level to complement the feature vectors used as input to train the neural network in the next level. We experimentally compare this novel method with several other reduction strategies, showing that it obtains the best predictive performance. Empirical results also show that the proposed method achieves better or comparable predictive performance when compared with state-of-the-art methods for hierarchical multi-label classification in the context of protein function prediction.
The experiments showed that using the output in one level as input to the next level contributed to better classification results. We believe the method was able to learn the relationships between the protein functions during training, and this information was useful for classification. We also identified in which functional classes our method performed better.
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.
The authors examined the prospective relationship between physical activity and incident depression and explored potential moderators.
Prospective cohort studies evaluating incident depression were ...searched from database inception through Oct. 18, 2017, on PubMed, PsycINFO, Embase, and SPORTDiscus. Demographic and clinical data, data on physical activity and depression assessments, and odds ratios, relative risks, and hazard ratios with 95% confidence intervals were extracted. Random-effects meta-analyses were conducted, and the potential sources of heterogeneity were explored. Methodological quality was assessed using the Newcastle-Ottawa Scale.
A total of 49 unique prospective studies (N=266,939; median proportion of males across studies, 47%) were followed up for 1,837,794 person-years. Compared with people with low levels of physical activity, those with high levels had lower odds of developing depression (adjusted odds ratio=0.83, 95% CI=0.79, 0.88; I
=0.00). Furthermore, physical activity had a protective effect against the emergence of depression in youths (adjusted odds ratio=0.90, 95% CI=0.83, 0.98), in adults (adjusted odds ratio=0.78, 95% CI=0.70, 0.87), and in elderly persons (adjusted odds ratio=0.79, 95% CI=0.72, 0.86). Protective effects against depression were found across geographical regions, with adjusted odds ratios ranging from 0.65 to 0.84 in Asia, Europe, North America, and Oceania, and against increased incidence of positive screen for depressive symptoms (adjusted odds ratio=0.84, 95% CI=0.79, 0.89) or major depression diagnosis (adjusted odds ratio=0.86, 95% CI=0.75, 0.98). No moderators were identified. Results were consistent for unadjusted odds ratios and for adjusted and unadjusted relative risks/hazard ratios. Overall study quality was moderate to high (Newcastle-Ottawa Scale score, 6.3). Although significant publication bias was found, adjusting for this did not change the magnitude of the associations.
Available evidence supports the notion that physical activity can confer protection against the emergence of depression regardless of age and geographical region.
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.
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