Circadian markers as a predictor of response in the treatment of depression-A systematic review.

Despite many available treatment options for depression, response rates remain suboptimal. To improve outcome, circadian markers may be suitable as markers of treatment response. This systematic review provides an overview of circadian markers that have been studied as predictors of response in treatment of depression. A search was performed (EMBASE, PUBMED, PSYCHINFO) for research studies or articles, randomized controlled trials and case report/series with no time boundaries on March 2, 2024 (PROSPERO: CRD42021252333). Other criteria were; an antidepressant treatment as intervention, treatment response measured by depression symptom severity and/or occurrence of a clinical diagnosis of depression and assessment of a circadian marker at baseline. 44 articles, encompassing 8,772 participants were included in the analysis. Although additional research is needed with less variation in types of markers and treatments to provide definitive recommendations, circadian markers, especially diurnal mood variation and chronotype, show potential to implement as response markers in the clinic.

Chronotype changes with age; seven-year follow-up from the Netherlands study of depression and anxiety cohort.

BACKGROUND: Chronotype reflects an individual's optimal daily timing of sleep, activity, and cognitive performance. Previous, cross-sectional, studies have suggested an age effect on chronotype with later chronotypes in adolescents and earlier chronotypes in children and elderly. Additionally, later chronotypes have been associated with more depressive symptoms. Few studies have been able to study longitudinal associations between chronotype and age, while adjusting for depressive symptoms. METHODS: Chronotype was assessed twice with the Munich Chronotype Questionnaire 7 years apart in the Netherlands Study of Depression and Anxiety (T1: N = 1842, mean age (SD): 42.63 years (12.66)) and T2: N = 1829, mean age (SD) 50.67 (13.11)). The longitudinal association between change in age and change in chronotype was tested using a generalized estimated equation analysis adjusted for covariates (including level of depressive symptoms). Using age-bins of 5 years (age at T2), change in chronotype between T1 and T2 was analyzed with Linear Mixed Models. RESULTS: We found a change towards an earlier chronotype with higher age (B (95% CI): -0.011 (-0.014-0.008), p < 0.001). For the age-bins, the difference in chronotype was significant for the 25-29 years age-bin. LIMITATIONS: The sample did not include individuals younger than 19 years or older than 68 years. CONCLUSIONS: In the whole sample chronotype changed towards becoming more morning-type over a period of 7 years, but this change was only significant for those aged 25-29 years. The study was performed in a large naturalistic cohort study with a wide age-range, including patients with a diagnosis of depressive and anxiety disorder and healthy controls.

Increased prevalence of metabolic syndrome in patients with bipolar disorder compared to a selected control group-a Northern Netherlands LifeLines population cohort study.

OBJECTIVES: Metabolic syndrome (MetS) is highly prevalent among patients with bipolar disorder (BD). The aims of this cross-sectional study were to determine the prevalence of MetS in Dutch BD subjects and compare it with a control group, to examine the association of demographic and clinical characteristics with MetS in BD, and to determine the extent to which metabolic dysregulation is treated in those patients. METHODS: 493 Dutch adult patients (≥ 18 years) with BD receiving psychotropic drugs and 493 matched control subjects were compared using data from the biobank Lifelines. We determined MetS according to the National Cholesterol Education Program Adult Treatment Panel III-Adapted (NCEP ATP III-A) criteria. The difference in the prevalence of MetS and the associations with characteristics were analyzed with logistic regression. RESULTS: BD subjects (30.6%) showed a significantly higher prevalence of MetS compared to the control group (14.2%) (p < .001, OR:2.67, 95% CI:1.94-3.66). Univariate analysis showed that smoking, body mass index (BMI) and antidepressant drug use were associated with MetS. Multivariate analysis showed that smoking (OR:2.01) was independently associated with MetS in BD. For hypertension, hyperglycemia and lipid disorder pharmacological treatment was provided to respectively 69.5%, 24% and 18.4% of the BD subjects in our sample. LIMITATIONS: Duration of illness of BD subjects was unknown. CONCLUSIONS: This study demonstrated a higher prevalence of MetS in Dutch BD subjects compared to persons without BD. In addition, a remarkable undertreatment of some of the components of MetS was found.

Towards precision medicine: What are the stratification hypotheses to identify homogeneous inflammatory subgroups.

Diverse lines of research testify a link, presumably causal, between immune dysregulation and the development, course and clinical outcome of psychiatric disorders. However, there is a large heterogeneity among the patients' individual immune profile and this heterogeneity prevents the development of precise diagnostic tools and the identification of therapeutic targets. The aim of this review was to delineate possible subgroups of patients on the basis of clinical dimensions, investigating whether they could lead to particular immune signatures and tailored treatments. We discuss six clinical entry points; genetic liability to immune dysregulation, childhood maltreatment, metabolic syndrome, cognitive dysfunction, negative symptoms and treatment resistance. We describe the associated immune signature and outline the effects of anti-inflammatory drugs so far. Finally, we discuss advantages of this approach, challenges and future research directions.

[Electroconvulsive therapy in a 12-year-old boy with a severe depression]. / Elektroconvulsietherapie bij een 12-jarige jongen met een ernstige depressie.

Electroconvulsive therapy (ect) is an uncommon treatment in children and adolescents. This could partially be explained by the fact that a large proportion of the (child and adolescent) psychiatrists have little knowledge on ect in youths. We describe a case of a 12-year-old boy with a severe depression refractory to pharmacotherapy and psychotherapy, in which ect treatment was successful, including six years follow-up. Additionally, this report represents the state of the art concerning the efficacy and safety of ect in youths.

Combined sleep deprivation and light therapy: Clinical treatment outcomes in patients with complex unipolar and bipolar depression.

BACKGROUND: The combination of sleep deprivation and light therapy, called combined chronotherapy, may yield positive short- and long-term results, even in patients with treatment resistant depression (TRD). The implementation of combined chronotherapy in daily clinical practice is rare. This study describes the implementation and the effectiveness in a clinical setting. METHODS: Twenty six depressed patients with unipolar or bipolar depression received combined chronotherapy consisting of three nights of sleep deprivation with alternating recovery nights, light therapy, and continuation of antidepressant medication. Inventory of Depressive Symptoms C (IDS-C) scores were determined before chronotherapy and at week 1, 2, and 4. Paired t-tests were used to compare the IDS-C scores over time. RESULTS: The mean pre-treatment IDS-C score was 39.3 ±â€¯9.6, the mean score in week 2 was 28.4 ±â€¯10.2, and 28.6 ±â€¯14.0 in week 4. A subsample of patients with psychiatric co-morbidities showed a reduction in depression severity from a mean score of 42.9 ±â€¯11.0 to a mean score of 34.9 ±â€¯13.0 after 4 weeks. The overall response rate was 34.6%, the remission rate 19.2%. LIMITATIONS: This open label case series has a relative small sample size and no control group CONCLUSION: In a clinical setting patients with major depressive disorder or bipolar disorder benefited significantly from combined chronotherapy. This chronotherapeutic intervention appears to have a rapid effect that lasts for at least several weeks, even in patients with psychiatric comorbidity or TRD. Indicating that chronotherapy can be a valuable treatment addition for depressed patients.

[rTMS for treatment resistant depression - proposal for a treatment protocol]. / Repetitieve transcraniële magnetische stimulatie bij therapieresistente depressie; voorstel voor een behandelprotocol.

BACKGROUND: At present, the use of repetitive transcranial magnetic stimulation (rtms) for treatment-resistant depression is sufficiently substantiated to be applied in clinical practice. In the Netherlands, it will be reimbursed when offered in combination with cognitive behavior therapy.
AIM: Proposal for a clinical treatment protocol for rtms in The Netherlands.
METHOD: A study of the literature and a critical appraisal of available international guidelines for rtms.
RESULTS: rtms is a safe treatment for patients suffering from a moderate to severe depressive disorder that is relatively treatment-resistant. The duration of the effect is still unknown. It is advised to stimulate the left dorsolateral prefrontal cortex using an intensity of 120% of the resting motor threshold, with a frequency of 10 Hz and using 3000 pulses per session during a total of 20-30 sessions.
CONCLUSION: The proposed treatment protocol is favored based on the available evidence when rtms is used as a treatment aimed to acutely decrease the severity of depressive symptoms. It is further proposed to systematically collect technical and outcome data on treatment with rtms to further improve treatment with rtms in clinical practice.

[The dysregulated brain - Consequences of spatial and temporal brain complexity for bipolar disorder pathophysiology and diagnosis]. / Het ontregelde brein; consequenties van ruimtelijke en temporele complexiteit van het brein voor pathofysiologie en diagnostiek van de bipolaire stoornis.

BACKGROUND: Despite the existence of several pathophysiological theories about bipolar disorder, it has so far been difficult to find diagnostic biomarkers and to develop new pharmacologic treatments based on the more novel theories. AIM: To reflect on the causes and consequences of problems that beset pathophysiological research into psychiatric disorders in general and bipolar disorder in particular. METHOD: In this essay we address the problems facing professionals engaged in research into bipolar disorder and we interpret these problem in the light of brain complexity. RESULTS: The complexity of the brain can be divided into two types: spatial complexity, which reflects the various physiological levels of the central nervous system (genetic, molecular, cellular, neuronal circuits and phenomenological levels), and temporal complexity, i.e. neurodevelopment. We discuss the consequences of these two types of complexity and make suggestions relating to clinical practice and pathophysiological psychiatric research. CONCLUSION: To achieve further progress in the field of brain research, we need to acquire a deeper understanding of the spatial and temporal complexity of the brain and consider the possible consequences of such knowledge for the pathophysiology and treatment of psychiatric illnesses such as bipolar disorder.

Inflammatory monocyte gene expression: trait or state marker in bipolar disorder?

BACKGROUND: This study aimed to examine whether inflammatory gene expression was a trait or a state marker in patients with bipolar disorder (BD). METHODS: 69 healthy controls (HC), 82 euthymic BD patients and 8 BD patients with a mood episode (7 depressed, 1 manic) were included from the MOODINFLAME study. Six of the eight patients who had a mood episode were also investigated when they were euthymic (6 of the 82 euthymic patients). Of these participants the expression of 35 inflammatory genes was determined in monocytes using quantitative-polymerase chain reaction, of which a total gene expression score was calculated as well as a gene expression score per sub-cluster. RESULTS: There were no significant differences in inflammatory monocyte gene expression between healthy controls and euthymic patients. Patients experiencing a mood episode, however, had a significantly higher total gene expression score (10.63 ± 2.58) compared to healthy controls (p = .004) and euthymic patients (p = .009), as well as when compared to their own scores when they were euthymic (p = .02). This applied in particular for the sub-cluster 1 gene expression score, but not for the sub-cluster 2 gene expression score. CONCLUSIONS: Our study indicates that in BD inflammatory monocyte, gene expression is especially elevated while in a mood episode compared to being euthymic.

The association between immune activation and manic symptoms in patients with a depressive disorder.

Although recent studies have shown that immunological processes play an important role in the pathophysiology of mood disorders, immune activation may only be present in specific subgroups of patients. Our study aimed to examine whether immune activation was associated with (a) the presence of manic symptoms and (b) the onset of manic symptoms during 2 years of follow-up in depressed patients. Patients with a depressive disorder at baseline (N=957) and healthy controls (N=430) were selected from the Netherlands Study of Depression and Anxiety. Assessments included lifetime manic symptoms at baseline and two-year follow up, as well as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) at baseline. Within depressed patients, immune activation was not related to the presence or absence of lifetime manic symptoms at baseline. However, CRP levels were strongly elevated in depressed men who developed manic symptoms compared with those who did not develop manic symptoms over 2 years (P<0.001, Cohen's d=0.89). IL-6 and TNF-α were also higher in depressed men with an onset of manic symptoms, but this association was not significant. However, we found that the onset of manic symptoms was particularly high in men with multiple elevated levels of inflammatory markers. Depressed men who developed manic symptoms during follow-up had increased immunological activity (especially CRP) compared with depressed men who did not develop manic symptoms. Further research should explore whether a treatment approach focusing on inflammatory processes may be more effective in this specific subgroup of depressed patients.