Struggling Can Also Show on the Inside: Current Knowledge of the Impact of Childhood Maltreatment on Biomarkers in Mood Disorders.

The link between childhood maltreatment and mood disorders is complex and involves multiple bio-psycho-social factors that affect multiple molecular pathways. The present narrative review aims to clarify the current understanding of the impact of childhood maltreatment on biomarkers in patients with mood disorders and their first-degree relatives. Neurotransmitters, such as serotonin, dopamine, norepinephrine, and hormones (eg the stress hormone cortisol), play a crucial role in regulating mood and emotion. Childhood maltreatment can alter and affect the levels and functioning of these neurotransmitters in the brain; further, childhood maltreatment can lead to structural and connectivity changes in the brain, hence contributing to the development of mood disorders and moderating illness presentation and modifying response to treatments. Childhood maltreatment information, therefore, appears mandatory in treatment planning and is a critical factor in therapeutic algorithms. Further research is needed to fully understand these pathways and develop new treatment modalities for individuals with mood disorders who have experienced childhood maltreatment and effective preventive interventions for individuals at risk of developing mood disorders.

Socio-economic status, functioning and cognition in young versus adult patients newly diagnosed with bipolar disorder and their unaffected relatives; results from a cross-sectional study.

BACKGROUND: Bipolar disorders (BD) figures on top of the World Health Organization classification of disabling disorders. It is unclear if there are socioeconomic, functioning, and cognition differences in young patients newly diagnosed with BD and whether these are different for young and adult patients newly diagnosed with BD. Understanding these differences is important for tailored treatment and support. METHODS: Participant groups included 401 patients newly diagnosed with BD, 145 of their unaffected first-degree relatives (UR) and 209 healthy control individuals (HC). First, we compared socio-economic status, functioning and cognition between young patients newly diagnosed with BD (150), UR (61) and HC (92) (15-25 years) and adult patients newly diagnosed with BD (251), UR (84) and HC (117) (>25 years), respectively. Second, within patients, we compared functioning and cognition between young and adult patients newly diagnosed with BD. RESULTS: In both participant groups, patients newly diagnosed with BD, and to a lesser degree UR, had lower socio-economic status and impaired functioning and cognition compared with HC. Further, young patients newly diagnosed with BD were less functionally impaired, than adults newly diagnosed with BD, whereas cognition did not differ between groups. LIMITATIONS: Applied tools for assessments of functioning and cognition are not validated below age 18. CONCLUSIONS: Overall, lower socio-economic status and impaired functioning and cognition were found both in young and adult patients newly diagnosed with BD and their UR compared with young and adult HC, respectively. Young patients were less functionally impaired than adults, but cognition was similarly impaired.

Socio-economic status and functioning in patients newly diagnosed with bipolar disorder and their unaffected siblings - Results from a cross-sectional clinical study.

BACKGROUND: Few studies have reported socio-economic status and functioning in patients newly diagnosed with bipolar disorder (BD) and their unaffected siblings (US). METHODS: Socio-economic status and functioning were compared in a cross-sectional clinical study including 382 patients newly diagnosed with BD, 129 of their US, and 200 healthy control individuals (HC). RESULTS: Socio-economic status was lower in patients newly diagnosed with BD compared with HC within educational achievement, employment status, workability and relationship status (p < 0.001, OR between 0.02 and 0.53). Regarding US and HC, US had lower educational achievement (p < 0.001, OR = 0.27 [0.16; 0.46]), as the only affected socio-economic outcome. Functioning was substantially impaired according to the Functional Assessment Short Test (FAST) (p < 0.001, Cohen's d = 2.12) and Work and Social Adjustment Scale (WSAS) (p < 0.001, Cohen's d = 2.76) in patients newly diagnosed with BD compared with HC. US expressed the same pattern with impaired overall functioning. Within patients, the impaired functioning was associated with a longer illness duration. LIMITATIONS: Patients had an illness duration of 10.5 [IQR: 6.1; 16.2] years, even though they were included shortly after a diagnosis of BD (0.3 [IQR: 0.1; 0.7] years), highlighting the obstacles of research in illness onset of BD. CONCLUSIONS: Patients newly diagnosed with BD, and to a lesser degree their US, exhibit lower socio-economic status and impaired overall functioning. These findings emphasise the importance of early diagnosis, treatment and focus on functional recovery and stress that intervention strategies and further research in high-risk individuals are needed.

Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative.

BACKGROUND: Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. STRUCTURE: The H2020-funded Response to Lithium Network (R-LiNK; http://www.r-link.eu.com/ ) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants' response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. CONCLUSIONS: The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.