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.
Increased insulin resistance is recognized in psychiatric disorders, such as schizophrenia and bipolar disorder, but its occurrence in depression is less clear. Our aims were to verify if insulin ...resistance is altered in depression, to test the metabolic subgroup hypothesis of depression and if there are changes with antidepressants. Inclusion criteria were studies including adult subjects with depression and either a control group or follow-up after treatment with antidepressants, and assessing fasting insulin or glucose levels or the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index. Seventy studies with 240,704 participants were included. Both insulin levels and the HOMA-IR index were increased in acute depression. Neither insulin nor the HOMA-IR index were altered during remission. Insulin was increased in atypical, but not typical depression. There was higher variation in insulin in individuals with depression than in controls. Insulin resistance did not change with antidepressant treatment. Insulin resistance is increased in depression during acute episodes. Heterogeneity was high in most of the analyses. Laboratory assessment of insulin resistance might have clinical utility in people with depression for diagnosis of the metabolic subtype and treatment selection, following precision psychiatry standards.
•Is there an association between insulin resistance and depression?•Is there a metabolic subtype of depression?•Insulin resistance was increased in acute depression but not remitted depression.•Variation in insulin levels was larger in the individuals with depression.•Insulin resistance is a state biomarker in acute depression.
Highlights • Depression and frailty are two common and pervasive conditions in older age. • We conducted the first meta-analysis exploring the relationship between these constructs. • In ...cross-sectional studies, participants with frailty had fourfold increased odds of depression. • People with depression were at approximately fourfold increased odds of having frailty. • Pooled data from longitudinal studies confirmed the heighted risk of comorbidity.
The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is ...an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges' g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.
Highlights • Depression is highly prevalent among individuals with cancer. • Co-morbid depression may lead to a worse prognosis among cancer patients. • Evidence instantiates the role of inflammation ...and oxidative and nitrosative stress in the pathophysiology both of cancer and depression. • Psychosocial stressors in cancer promote inflammation, a dysregulation of the hypothalamic-pituitary-adrenal axis and reduced immunosurveilence. • Behavioral strategies may target biological mechanisms relevant to tumor progression and depressive clinical manifestations.
Early Intervention in Bipolar Disorder Vieta, Eduard; Salagre, Estela; Grande, Iria ...
The American journal of psychiatry,
05/2018, Letnik:
175, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Bipolar disorder is a recurrent disorder that affects more than 1% of the world population and usually has its onset during youth. Its chronic course is associated with high rates of morbidity and ...mortality, making bipolar disorder one of the main causes of disability among young and working-age people. The implementation of early intervention strategies may help to change the outcome of the illness and avert potentially irreversible harm to patients with bipolar disorder, as early phases may be more responsive to treatment and may need less aggressive therapies. Early intervention in bipolar disorder is gaining momentum. Current evidence emerging from longitudinal studies indicates that parental early-onset bipolar disorder is the most consistent risk factor for bipolar disorder. Longitudinal studies also indicate that a full-blown manic episode is often preceded by a variety of prodromal symptoms, particularly subsyndromal manic symptoms, therefore supporting the existence of an at-risk state in bipolar disorder that could be targeted through early intervention. There are also identifiable risk factors that influence the course of bipolar disorder, some of them potentially modifiable. Valid biomarkers or diagnosis tools to help clinicians identify individuals at high risk of conversion to bipolar disorder are still lacking, although there are some promising early results. Pending more solid evidence on the best treatment strategy in early phases of bipolar disorder, physicians should carefully weigh the risks and benefits of each intervention. Further studies will provide the evidence needed to finish shaping the concept of early intervention. AJP AT 175 Remembering Our Past As We Envision Our Future April 1925: Interpretations of Manic-Depressive Phases Earl Bond and G.E. Partridge reviewed a number of patients with manic-depressive illness in search of a unifying endo-psychic conflict. They concluded that understanding either phase of illness was "elusive" and "tantalizing beyond reach." (Am J Psychiatry 1925: 81: 643-662 ).
Abstract Background In epidemiological studies, statins appear to benefit mood, and there are now some randomized controlled trials examining the efficacy of statins. However, the role of statins in ...depression remains uncertain. Thus the aim of this paper was to assess the effect of statins on depressive symptoms by performing a meta-analysis of all double-blind, randomized, placebo controlled clinical trials (RCT) conducted in subjects with depression. Methods A systematic search was executed using PubMed and ClinicalTrials.gov in November 30th , 2015 for all double-blind, RCT of statins versus placebo in persons with depressive symptoms. Sixty-seven potential articles were identified through search of electronic databases, of those three met inclusion criteria and were included in the meta-analysis. The outcome measure was change in Hamilton Depression Rating Scale (HDRS) scores associated with statin use. A meta-analysis was conducted and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. GRADE was used to assess study quality. Results The three articles included provided data on 165 participants with moderate to severe depression. Of these, 82 were randomized to statins as an adjuvant therapy to antidepressant treatment (i.e., citalopram or fluoxetine) and 83 to the placebo arm. All studies were double-blind RCTs, with a follow-up of 6 to 12 weeks. The statin agents evaluated were lovastatin, atorvastatin, and simvastatin. When compared to placebo, statins, as add-on to treatment as usual, largely improved depressive symptoms as assessed by the HDRS (SMD = −0.73, 95% IC −1.04 to −0.42, p<0.001, 3 between-group comparisons, n = 165). No serious adverse effects were reported. Conclusions Our results suggest that adjunctive treatment with statins could be useful for the treatment of depressive symptoms. Additional double-blind, randomised, placebo-controlled trials are necessary to settle the matter.
Background:
The blood–brain barrier acts as a highly regulated interface; its dysfunction may exacerbate, and perhaps initiate, neurological and neuropsychiatric disorders.
Methods:
In this narrative ...review, focussing on redox, inflammatory and mitochondrial pathways and their effects on the blood–brain barrier, a model is proposed detailing mechanisms which might explain how increases in blood–brain barrier permeability occur and can be maintained with increasing inflammatory and oxidative and nitrosative stress being the initial drivers.
Results:
Peripheral inflammation, which is causatively implicated in the pathogenesis of major psychiatric disorders, is associated with elevated peripheral pro-inflammatory cytokines, which in turn cause increased blood–brain barrier permeability. Reactive oxygen species, such as superoxide radicals and hydrogen peroxide, and reactive nitrogen species, such as nitric oxide and peroxynitrite, play essential roles in normal brain capillary endothelial cell functioning; however, chronically elevated oxidative and nitrosative stress can lead to mitochondrial dysfunction and damage to the blood–brain barrier. Activated microglia, redox control of which is mediated by nitric oxide synthases and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, secrete neurotoxic molecules such as reactive oxygen species, nitric oxide, prostaglandin, cyclooxygenase-2, quinolinic acid, several chemokines (including monocyte chemoattractant protein-1 MCP-1, C-X-C motif chemokine ligand 1 CXCL-1 and macrophage inflammatory protein 1α MIP-1α) and the pro-inflammatory cytokines interleukin-6, tumour necrosis factor-α and interleukin-1β, which can exert a detrimental effect on blood–brain barrier integrity and function. Similarly, reactive astrocytes produce neurotoxic molecules such as prostaglandin E2 and pro-inflammatory cytokines, which can cause a ‘leaky brain’.
Conclusion:
Chronic inflammatory and oxidative and nitrosative stress is associated with the development of a ‘leaky gut’. The following evidence-based approaches, which address the leaky gut and blood–brain barrier dysfunction, are suggested as potential therapeutic interventions for neurological and neuropsychiatric disorders: melatonin, statins, probiotics containing Bifidobacteria and Lactobacilli, N-acetylcysteine, and prebiotics containing fructo-oligosaccharides and galacto-oligosaccharides.
PDF
