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.

Assessment of functional ability in affective disorders.

This review investigates that up to 50% of patients with affective disorders present with impaired overall functioning, also in remitted phases. Nevertheless, functioning is often overlooked in clinical settings and not incorporated as an essential outcome in research. It is recommended clinically and in research to use the International Classification of Functioning (ICF), e.g. the semi-structured interview Functioning Assessment Short Test (FAST) to ensure a common language and coordination cross-sectionally, interdisciplinarily and across mental and physical diseases.

Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions.

Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population.

Socio-economic functioning in patients with bipolar disorder and their unaffected siblings - results from a nation-wide population-based longitudinal study.

BACKGROUND: Few studies have reported real-life data on socio-economic functioning in patients with bipolar disorder and their unaffected first-degree relatives. METHODS: We used Danish nation-wide population-based longitudinal register linkage to investigate socio-economic functioning in 19 955 patients with bipolar disorder, their 13 923 siblings and 20 sex, age and calendar-matched control individuals from the general population. Follow-up was from 1995 to 2017. RESULTS: Patients with a diagnosis of bipolar disorder had lower odds of having achieved the highest educational level [OR 0.75 (95% confidence interval (CI) 0.73-0.77)], being employed [OR 0.16 (95% CI 0.159-0.168)], having achieved the 80% highest quartile of income [OR 0.33 (95% CI 0.32-0.35)], cohabitating [OR 0.44 (95% CI 0.43-0.46)] and being married [OR 0.54 (95% CI 0.52-0.55)] at first contact to hospital psychiatry as inpatient or outpatient compared with control individuals from the general population. Similarly, siblings to patients with bipolar disorder had a lower functioning within all five socio-economic areas than control individuals. Furthermore, patients and partly siblings showed substantially decreased ability to enhance their socio-economic functioning during the 23 years follow-up compared to controls. CONCLUSIONS: Socio-economic functioning is substantially decreased in patients with bipolar disorder and their siblings and does not improve during long-term follow-up after the initial hospital contact, highlighting a severe and overlooked treatment gap.

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.

Assessment of subjective and objective cognitive function in bipolar disorder: Correlations, predictors and the relation to psychosocial function.

Cognitive dysfunction is prevalent in bipolar disorder (BD). However, the evidence regarding the association between subjective cognitive complaints, objective cognitive performance and psychosocial function is sparse and inconsistent. Seventy seven patients with bipolar disorder who presented cognitive complaints underwent assessment of objective and subjective cognitive function and psychosocial functioning as part of their participation in two clinical trials. We investigated the association between global and domain-specific objective and subjective cognitive function and between global cognitive function and psychosocial function. We also identified clinical variables that predicted objective and subjective cognitive function and psychosocial functioning. There was a correlation between global subjective and objective measures of cognitive dysfunction but not within the individual cognitive domains. However, the correlation was weak, suggesting that cognitive complaints are not an assay of cognition per se. Self-rated psychosocial difficulties were associated with subjective (but not objective) cognitive impairment and both subjective cognitive and psychosocial difficulties were predicted by depressive symptoms. Our findings indicate that adequate assessment of cognition in the clinical treatment of BD and in drug trials targeting cognition requires implementation of not only subjective measures but also of objective neuropsychological tests.

Clinical utility of Standardised Assessment of Personality - Abbreviated Scale (SAPAS) among patients with first episode depression.

BACKGROUND: Personality disorder frequently co-occurs with depression and seems to be associated with a poorer outcome of treatment and increased risk for recurrences. However, the diagnosing of personality disorder can be lengthy and requires some training. Therefore, a brief screening interview for comorbid personality disorder among patients suffering from depression would be of clinical use. METHOD: The present study aimed to assess the utility of the Standardised Assessment of Personality - Abbreviated Scale (SAPAS) as a screen for personality disorder in a population of patients recently diagnosed with first episode depression. A total number of 394 patients with an ICD-10 diagnosis of a single depressive episode were sampled consecutively via the Danish Psychiatric Central Research Register during a 2years inclusion period and assessed by the screening interview and, subsequently, by the Structured Clinical Interview for DSM-IV Personality Disorders. RESULTS: We found, that a cut-off of 3 on the screen correctly identified the presence of comorbid personality disorder in 73.1% of the patients. The sensitivity and specificity were 0.80 and 0.70, respectively. LIMITATIONS: The findings cannot be generalized to patients outside hospital settings. CONCLUSION: The study provides evidence for the clinical utility of SAPAS as a screening interview for comorbid personality disorder in a population of patients with a primary diagnosis of depression.