We investigated whether a Mediterranean-style diet (MedDiet) supplemented with fish oil can improve mental health in adults suffering depression. Adults with self-reported depression were randomized to receive fortnightly food hampers and MedDiet cooking workshops for 3 months and fish oil supplements for 6 months, or attend social groups fortnightly for 3 months. Assessments at baseline, 3 and 6 months included mental health, quality of life (QoL) and dietary questionnaires, and blood samples for erythrocyte fatty acid analysis. n = 152 eligible adults aged 18-65 were recruited (n = 95 completed 3-month and n = 85 completed 6-month assessments). At 3 months, the MedDiet group had a higher MedDiet score (t = 3.95, P < 0.01), consumed more vegetables (t = 3.95, P < 0.01), fruit (t = 2.10, P = 0.04), nuts (t = 2.29, P = 0.02), legumes (t = 2.41, P = 0.02) wholegrains (t = 2.63, P = 0.01), and vegetable diversity (t = 3.27, P < 0.01); less unhealthy snacks (t = -2.10, P = 0.04) and red meat/chicken (t = -2.13, P = 0.04). The MedDiet group had greater reduction in depression (t = -2.24, P = 0.03) and improved mental health QoL scores (t = 2.10, P = 0.04) at 3 months. Improved diet and mental health were sustained at 6 months. Reduced depression was correlated with an increased MedDiet score (r = -0.298, P = 0.01), nuts (r = -0.264, P = 0.01), and vegetable diversity (r = -0.303, P = 0.01). Other mental health improvements had similar correlations, most notably for increased vegetable diversity and legumes. There were some correlations between increased omega-3, decreased omega-6 and improved mental health. This is one of the first randomized controlled trials to show that healthy dietary changes are achievable and, supplemented with fish oil, can improve mental health in people with depression.

Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12–88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen’s d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen’s d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.

Meta-analyses of genome-wide association studies (meta-GWASs) and candidate gene studies have identified genetic variants associated with cardiovascular diseases, metabolic diseases and mood disorders. Although previous efforts were successful for individual disease conditions (single disease), limited information exists on shared genetic risk between these disorders. This article presents a detailed review and analysis of cardiometabolic diseases risk (CMD-R) genes that are also associated with mood disorders. First, we reviewed meta-GWASs published until January 2016, for the diseases ‘type 2 diabetes, coronary artery disease, hypertension’ and/or for the risk factors ‘blood pressure, obesity, plasma lipid levels, insulin and glucose related traits’. We then searched the literature for published associations of these CMD-R genes with mood disorders. We considered studies that reported a significant association of at least one of the CMD-R genes and ‘depression’ or ‘depressive disorder’ or ‘depressive symptoms’ or ‘bipolar disorder’ or ‘lithium treatment response in bipolar disorder’, or ‘serotonin reuptake inhibitors treatment response in major depression’. Our review revealed 24 potential pleiotropic genes that are likely to be shared between mood disorders and CMD-Rs. These genes includeMTHFR,CACNA1D,CACNB2,GNAS,ADRB1,NCAN,REST,FTO,POMC,BDNF,CREB,ITIH4,LEP,GSK3B,SLC18A1,TLR4,PPP1R1B,APOE,CRY2,HTR1A,ADRA2A,TCF7L2,MTNR1BandIGF1. A pathway analysis of these genes revealed significant pathways:corticotrophin-releasing hormone signaling,AMPK signaling,cAMP-mediated or G-protein coupled receptor signaling,axonal guidance signaling,serotonin or dopamine receptors signaling, dopamine-DARPP32 feedback in cAMP signaling,circadian rhythm signalingandleptin signaling. Our review provides insights into the shared biological mechanisms of mood disorders and cardiometabolic diseases.

Recent literature has pointed to the existence of inflammasome-mediated inflammatory pathways in central nervous system disorders and associated changes in behavior. Neuroinflammation, which is an innate immune response in the central nervous system against harmful and irritable stimuli such as pathogens and metabolic toxic waste, as well as to chronic mild stress, is mediated by protein complexes known as inflammasomes. Inflammasomes activate pro-inflammatory caspases 1 and 5, which then cleave the precursor forms of pro-inflammatory cytokines IL-1β, IL-18 and IL-33 into their active forms. These pro-inflammatory cytokines have been shown to promote a variety of innate immune processes associated with infection, inflammation and autoimmunity, and thereby play an instrumental role in the instigation of neuroinflammation during old age and subsequent occurrence of neurodegenerative diseases, cognitive impairment and dementia. In particular, NLRP inflammasomes may also have a role in the etiologies of depression, Alzheimer’s disease and in metabolic disorders, such as Type II diabetes, obesity and cardiovascular diseases that have been shown to be co-morbid with psychiatric illnesses. It has been reported that while these inflammasomes may be activated through TNF-α dependent pathways, other cytokines, like IFN-γ, may assist in inhibiting their activation and thus delay disease progression. Furthermore some other cytokines, including IL-6, may not have a direct role in inflammasome-mediated diseases. An array of recent research suggests that NLRP inflammasomes targeted therapies could be used for alleviating neuroinflammation and for treatment of associated psychiatric illnesses, although this still remains a challenge and necessitates further extensive research. This review examines the complex inflammatory signaling pathways involved in the activation of NLRP inflammasomes and the role they play in promoting neuroinflammation and subsequent behavioral changes.

Background: Social cognition – the ability to identify, perceive and interpret socially-relevant information – is an important skill that plays a significant role in successful interpersonal functioning. Social cognitive performance is recognised to be impaired in several psychiatric conditions, but the relationship with major depressive disorder is less well understood. The aim of this review is to characterise the current understanding of (i) the different domains of social cognition and a possible relationship with major depressive disorder, (ii) the clinical presentation of social cognition in acute and remitted depressive states, and (iii) the effect of severity of depression on social cognitive performance. Methods: Electronic databases were searched to identify clinical studies investigating social cognition in a major depressive disorder population, yielding 31 studies for this review. Results: Patients with major depressive disorder appear to interpret social cognitive stimuli differently to healthy controls: depressed individuals may interpret emotion through a mood-congruent bias and have difficulty with cognitive theory of mind tasks requiring interpretation of complex mental states. Social cognitive performance appears to be inversely associated with severity of depression, whilst the bias toward negative emotions persists even in remission. Some deficits may normalise following effective pharmacotherapy. Conclusions: The difficulties with social interaction observed in major depressive disorder may, at least in part, be due to an altered ability to correctly interpret emotional stimuli and mental states. These features seem to persist even in the remitted state, although some may respond to intervention. Further research is required in this area to better understand the functional impact of these findings and the way in which targeted therapy could aid depressed individuals with social interactions.