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In this collection we present 12 of Translational Psychiatry's highest impact articles from 2021, selected by Editor-in-Chief Julio Licinio. These remarkable papers cover the full spectrum of translational psychiatry, including topics such as the COVID-19 pandemic, post-traumatic stress disorder (PTSD), depression and suicidality, schizophrenia, autism, and Alzheimer’s disease.
Given the drastic effects of SARS-CoV-2 on the brain, mental health, and translational psychiatry, it is not surprising that three of our highlighted papers are about various aspects of the COVID-19 pandemic, which has so drastically affected us all. While most of us naturally focus on the negative outcomes of COVID-19, Veer et al (21 Jan 2021) had a different approach and studied the psycho-social factors associated with mental resilience during the Coronavirus lockdown. They showed that in comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors.
Using a large dataset analyzed from the English Longitudinal Study of Ageing (ELSA), Hamilton, Cadar, and Steptoe (09 Dec 2021) demonstrated that systemic inflammation measured 1–3 years pre-pandemic was associated with greater depressed mood during the early months of the pandemic. This finding is consistent with the hypothesis that higher levels of inflammation increase the vulnerability of older people to impaired mental health in the presence of the widespread stress of the COVID-19 pandemic.
Psychiatric symptoms and behavioral adjustment during the COVID-19 pandemic were studied by Hou et al (17 Mar 2021), as they searched for evidence from two population-representative samples of 6,029 Hong Kong residents during a period of low infection and limited intervention (survey 1: n = 4021) and high incidence and intensive measures (survey 2: n = 2008). Prevalence of anxiety for survey 1 and survey 2 were 14.9% and 14% and depression were 19.6% and 15.3%, respectively. Increased odds of anxiety and depression were associated with disrupted routines and lower socioeconomic status in both surveys, whereas depression was inversely related to the novel preventive routine of avoiding going to crowded places in survey 1. A heavier burden of psychiatric conditions was evidenced amongst people experiencing disrupted daily routines across different phases of the pandemic and without novel preventive routines in the early phase.
The work of Pearce et al (10 Dec 2021) does not directly address COVID-19, but it is relevant to loneliness, which only increased during the pandemic. The authors report that “loneliness is a relatively common problem in young people (14–24 years) and predicts the onset of depression and anxiety.” They conducted a Critical Interpretative Synthesis, a systematic review method that iteratively synthesizes qualitative and quantitative evidence and is explicitly focused on building theory through a critical approach to the evidence that questions underlying assumptions. Through synthesizing 27 studies (total participants n = 105,649; range 1–102,072 in different studies) and grey literature, and iteratively consulting with stakeholders, a conceptual framework was developed. The most convincing evidence of effectiveness was found in support of intrapersonal strategies: two randomized controlled studies quality-rated as ‘good’ found decreases in loneliness associated with different forms of therapy (Cognitive Behavioral Therapy or peer network counselling). They conclude that “strategies to address loneliness and prevent or alleviate anxiety and depression need to be co-designed and personalized. Promising elements to incorporate into these strategies are social support, including from peers with similar experiences, and psychological therapy.”
North et al from Cyndi Shannon Weickert’s group (15 Dec 2021) provide conceptually novel data that a schizophrenia subgroup with elevated inflammation displays reduced microglia, increased peripheral immune cell and altered neurogenesis marker gene expression in the subependymal zone.
Chatterjee and colleagues from Ralph Martins’ group (11 Jan 2021) provide evidence that plasma glial fibrillary acidic protein (GFAP) is elevated in cognitively normal older adults at risk of Alzheimer’s disease. Their observations suggest that astrocytic damage or activation begins from the pre-symptomatic stage of AD and is associated with brain Aβ load. Observations from their study highlight the potential of plasma GFAP to contribute to a diagnostic blood biomarker panel (along with plasma Aβ1–42/Aβ1–40 ratios) for cognitively normal older adults at risk of AD.
Another article that did not directly COVID-19, but which may be relevant to those with pandemic-related chronic inflammation, by Han et al from Russell Dale’s team (21 Jan 2021), showed through a systematic review that maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders (NDDs). Specifically, they showed that maternal states associated with autism spectrum disorder (ASD) include obesity, gestational diabetes mellitus, pre-eclampsia, pollution, stress, depression, autoimmune diseases, and infection. Maternal states associated with attention deficit hyperactivity disorder (ADHD) include obesity, pre-eclampsia, smoking, low socioeconomic status (SES), stress, autoimmune disease, and asthma. Maternal states associated with Tourette syndrome (TS) include low SES, depression, and autoimmune diseases. They conclude that “diverse maternal inflammatory states in pregnancy are associated with common offspring NDDs. Given the increased prevalence of NDDs, there is urgent need to explore relative and cumulative maternal risk factors and disease mechanisms. Defining preventable risk factors in high-risk pregnancies could mitigate the expression and severity of NDDs.”
Mild behavioral impairment and its relation to tau pathology in preclinical Alzheimer’s disease (AD) were examined by Johansson et al (26 Jan 2021). They found that that in preclinical AD, mild behavioral impairment (MBI) is associated with tau independently from memory deficits. This denotes MBI as an important early clinical manifestation related to tau pathology in AD.
Zhou et al (04 Feb 2021) conducted in China a large study of first-episode drug-naïve major depressive disorder (MDD) patients comorbid with anxiety to examine the association of clinical correlates, metabolic parameters, and thyroid hormones with suicide attempts. In their population, the prevalence of suicide attempts in MDD patients with comorbid anxiety symptoms was 24.28%, which was 9.51 times higher than that in MDD patients without anxiety symptoms (3.25%). Compared to non-attempters, MDD patients with anxiety symptoms who attempted suicide scored higher on HAMD and HAMA, and had higher systolic blood pressure, higher levels of thyroid stimulating hormone (TSH), and thyroid peroxidases antibody (TPOAb), which were also correlated with suicide attempts in MDD patients with comorbid anxiety symptoms. They also found that the combination of HAMA score, HAMD score, and TSH could differentiate suicide attempters from non-suicide attempters.
In a study of adolescent rats fed a sugar-sweetened beverage (SSB) during the adolescent stage of development, Noble et al (31 Mar 2021) identified a role for gut microbiota “dysbiosis” in mediating the detrimental effects of early life unhealthy dietary factors on hippocampal-dependent memory function.
Chen et al (05 Jan 2021) conducted a systematic review and meta-analysis of 87 studies of oxidative stress marker aberrations in children with autism spectrum disorder (ASD) (n = 9109). Their results strengthened the clinical evidence of increased oxidative stress in ASD. Additionally, they suggested that glutathione metabolism biomarkers have the potential to inform the early diagnosis of ASD.
The last paper in this selection, by Zheng et al (16 Dec 2021), tested the hypothesis that trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and function.