Individual and common patterns in the order of symptom improvement during outpatient treatment for major depression

BACKGROUND: Research so far provided few clues on the order in which depressive symptoms typically remit during treatment. This study examined which depressive symptoms improve first, and whether symptoms changed before, simultaneous with, or after the core symptoms of depression (i.e., sad mood, loss of pleasure, and loss of interest). METHODS: Participants were 176 patients with Major Depressive Disorder (MDD) receiving outpatient treatment (a combination of pharmacotherapy and psychological interventions) for depression. Participants filled out the Inventory of Depressive Symptomatology - Self Report (IDS-SR) for 16 to 20 consecutive weeks. For each symptom, the timing of onset of a persistent improvement was determined for each single-subject separately. RESULTS: Which symptoms improved first differed markedly across patients. The core depression symptoms improved 1.5 to 2 times more often before (48% - 60%) than after (19% -28%) depressive cognitions ('view of myself' and 'view of the future'), anxiety symptoms ('feeling irritable' and 'feeling anxious / tense') and vegetative symptoms ('loss of energy', 'slowed down', and 'physical energy'). Only improvements in suicidal thoughts were more likely to occur before (46% - 48%) than after (29%) improvements in the depression core symptoms. LIMITATIONS: Not all 'core depression-non-core symptom' combinations could be tested because some symptoms did not improve in a sufficient number of patients. CONCLUSIONS: Which improvements mark the start of symptom remission differed between patients. Improvements in the core depression symptoms 'sad mood', 'loss of interest', and 'loss of pleasure' were more likely to occur before than after improvements in non-core symptoms

On the transience of stability of subthreshold psychopathology

Symptoms of psychopathology lie on a continuum ranging from mental health to psychiatric disorders. Although much research has focused on progression along this continuum, for most individuals, subthreshold symptoms do not escalate into full-blown disorders. This study investigated how the stability of psychopathological symptoms (attractor strength) varies across severity levels (homebase). Data were retrieved from the TRAILS TRANS-ID study, where 122 at-risk young adults (mean age 23.6 years old, 57% males) monitored their mental states daily for a period of six months (± 183 observations per participant). We estimated each individual’s homebase and attractor strength using generalized additive mixed models. Regression analyses showed no association between homebases and attractor strengths (linear model: B = 0.02, p = 0.47, R(2) < 0.01; polynomial model: B < 0.01, p = 0.61, R(2) < 0.01). Sensitivity analyses where we (1) weighed estimates according to their uncertainty and (2) removed individuals with a DSM-5 diagnosis from the analyses did not change this finding. This suggests that stability is similar across severity levels, implying that subthreshold psychopathology may resemble a stable state rather than a transient intermediate between mental health and psychiatric disorder. Our study thus provides additional support for a dimensional view on psychopathology, which implies that symptoms differ in degree rather than kind

Critical slowing down in momentary affect as early warning signal of impending transitions in depression

Based on dynamical systems theory, the current study aimed to investigate if recurrence of depression is systematically preceded by within-person early warning signals (EWS) in positive and negative affect. Ecological momentary assessments were collected 5 times a day for a period of 4 months (averaging 524 assessments per individual) in 37 formerly depressed individuals discontinuing antidepressant medication. EWS (increases in window autocorrelation and variance) preceded recurrence of depression in 32.9% of the participants across robustness checks. Compared to participants that remained in remission, participants with a recurrence showed (1) significantly more positive trends in the variance, but not in autocorrelation, and (2) the average number of significant EWS was over three times larger across tested affect variables. Although the results provide the first systematic evidence that EWS occur more often before the recurrence of depression, the low sensitivity of EWS poses a substantial challenge for clinical applications

Evidence that bipolar disorder is the poor outcome fraction of a common developmental phenotype: an 8-year cohort study in young people

Background Reported rates of bipolar syndromes are highly variable between studies because of age differences, differences in diagnostic criteria, or restriction of sampling to clinical contacts. Method In 1395 adolescents aged 14-17 years, DSM-IV (hypo)manic episodes (manic and hypomanic episodes combined), use of mental health care, and five ordinal subcategories representing the underlying continuous score of (hypo)manic symptoms (‘mania symptom scale') were measured at baseline and approximately 1.5, 4 and 10 years later using the Munich-Composite International Diagnostic Interview (DIA-X/M-CIDI). Results Incidence rates (IRs) of both (hypo)manic episodes and (hypo)manic symptoms (at least one DSM-IV core symptom) were far higher (714/105 person-years and 1720/105 person-years respectively) than traditional estimates. In addition, the risk of developing (hypo)manic episodes was very low after the age of 21 years [hazard ratio (HR) 0.031, 95% confidence interval (CI) 0.0050-0.19], independent of childhood disorders such as attention deficit hyperactivity disorder (ADHD). Most individuals with hypomanic and manic episodes were never in care (87% and 62% respectively) and not presenting co-morbid depressive episodes (69% and 60% respectively). The probability of mental health care increased linearly with the number of symptoms on the mania symptom scale. The incidence of the bipolar categories, in particular at the level of clinical morbidity, was strongly associated with previous childhood disorders and male sex. Conclusions This study showed, for the first time, that experiencing (hypo)manic symptoms is a common adolescent phenomenon that infrequently predicts mental health care use. The findings suggest that the onset of bipolar disorder can be elucidated by studying the pathway from non-pathological behavioural expression to dysfunction and need for car

Detecting impending symptom transitions using early warning signals in individuals receiving treatment for depression

Background: The path to depressive symptom improvement during therapy is often complex, as many individuals experience periods of instability and discontinuous symptom change. If the process of remission follows complex dynamic systems principles, early warning signals (EWS) may precede such depressive symptom transitions. Aims: We aimed to test whether EWS, in the form of rises in lag-1 autocorrelation and variance, occur in momentary affect time series preceding transitions towards lower levels of depressive symptoms during therapy. We also investigated the presence of EWS in patients without symptom transitions. Methods: In a sample of 41 depressed individuals who were starting psychological treatment, positive affect and negative affect (high and low arousal) were measured five times a day using ecological momentary assessments (EMA) for four months (521 observations per individual on average; yielding 25,197 observations in total), and depressive symptoms were assessed weekly over six months. We used a moving window method and time-varying autoregressive generalized additive modeling (TV-AR GAM) to determine whether EWS occurred in these momentary affect measures, within-persons. Results: For the moving-window autocorrelation, 89% of individuals with transitions showed at least one EWS in one of the variables (versus 62.5% in the no-transition group), and the proportion of EWS in the separate variables was consistently higher (~44% across affect measures) than for individuals without transitions (~27%). Rising variance was found for few individuals, both preceding transitions (~11%) and for individuals without a transition (~12%). Conclusions: The process of symptom remission showed critical slowing down in at least part of our sample. Our findings indicate that EWS are not generic across all affect measures and may have limited value as a personalized prediction method

The Associations of Affection and Rejection During Adolescence with Interpersonal Functioning in Young Adulthood:A Macro- and Micro-Level Investigation Using the TRAILS TRANS-ID Study

Affection and rejection in close relationships during adolescence are thought to impact adult interpersonal functioning, but few studies focused on how the quality of adolescents' relationships with different people (e.g. parents, peers, and teachers) impacts the daily, micro-level social experiences as well as general, macro-level interpersonal functioning in young adulthood. The present study investigated the associations between: (i) parental, teacher and peer affection and rejection during adolescence and macro-level (over several months) interpersonal functioning as well as different patterns (i.e. mean, variability and inertia) of micro-level (daily social experiences) during young adulthood; (ii) macro-level interpersonal functioning and the patterns of micro-level social experiences during young adulthood. The sample consisted of N = 122 (43% female) youth. At 11.2 +/- 0.4 and 16.0 +/- 0.6 years old, self- and other-reported parental, peer and teacher affection and rejection were assessed. At 23.7 +/- 0.6 years old, participants reported daily social experiences and interpersonal functioning across six months. The results suggested that: (i) higher teacher-reported peer rejection was associated with lower macro-level interpersonal functioning, higher means and higher variability in negative social experiences during adulthood; (ii) higher macro-level interpersonal functioning during young adulthood was associated with higher means and lower inertia in positive and lower variability in negative daily social experiences. These findings indicate that the affection and rejection during adolescence impact interpersonal functioning at macro- and micro-level during adulthood. The present study also shows distinct associations between macro-level interpersonal functioning and dynamics in daily social experiences

Amorphous carbon nanoparticles: a versatile label for rapid diagnostic (immuno)assays

Carbon nanoparticles (CNPs) labeled with reporter molecules can serve as signaling labels in rapid diagnostic assays as an alternative to gold, colored latex, silica, quantum dots, or up-converting phosphor nanoparticles. Detailed here is the preparation of biomolecule-labeled CNPs and examples of their use as a versatile label. CNPs can be loaded with a range of biomolecules, such as DNA, antibodies, and proteins (e.g., neutravidin or a fusion protein of neutravidin with an enzyme), and the resulting conjugates can be used to detect analytes of high or low molecular mass

Anticipating Transitions in Mental Health in At-Risk Youths:A 6-Month Daily Diary Study Into Early-Warning Signals

If psychopathology behaves like a complex dynamic system, sudden onset or worsening of symptoms may be preceded by early-warning signals (EWSs). EWSs could thus reflect personalized warning signals for impending psychopathology. We empirically investigated this hypothesis in at-risk youths (N = 122, mean age = 23.6 ± 0.7 years, 57% males) from the clinical cohort of Tracking Adolescents’ Individual Lives Survey (TRAILS-CC), who provided daily emotion assessments for 6 months. We analyzed whether EWSs (rising autocorrelations and standard deviations in emotions) preceded transitions toward psychopathology. Across indicators and a range of analytical options, EWSs had low sensitivity (M = 26%, SD = 11%) and moderate specificity (M = 75%, SD = 14%). Thus, in the present sample, the proposed generic nature and clinical utility of EWSs could not be substantiated. Given this finding, we call for a more nuanced view on the application of complex-dynamic-systems principles to psychopathology and lay out key questions to be addressed in the future

Pulmonary diffusing capacity disturbances are related to nailfold capillary changes in patients with Raynaud's phenomenon with and without an underlying connective tissue disease

PURPOSE: The aim of this study was to evaluate whether pulmonary microvascular damage is part of a more generalized involvement of the microvasculature in the spectrum of scleroderma (Scl)-like syndromes. PATIENTS AND METHODS: We studied four groups of patients, all with Raynaud's phenomenon (RP), distinguished by the extent and nature of their underlying connective tissue disease. Twenty-two patients had primary RP (pRP), another 22 patients had RP and an undifferentiated connective tissue disease (uCTD), 15 patients had Scl, and eight patients had the CREST syndrome (CREST). Pulmonary vascular damage in these groups was assessed by measuring the pulmonary diffusing capacity (T1,CO) and its components: the diffusing capacity of the alveolocapillary membrane (Dm) and the pulmonary capillary blood volume (Vc). Results were compared with morphologic abnormalities of the nailfold capillaries, as determined by nailfold capillary microscopy, and related to the presence of antinuclear antibodies. RESULTS: Vc was below normal in 38% and 43% of patients with pRP and uCTD, respectively (versus 52% in patients with Scl or CREST combined). In contrast, Dm was below normal in only 5% and 26% of patients with pRP and uCTD, respectively (versus 61% in patients with Scl or CREST combined). In patients with Scl and CREST, Dm was significantly decreased as compared with the former groups (p less than 0.01). Dm was also the pulmonary function parameter that correlated most strongly with both nailfold capillary abnormalities and the presence of antinuclear antibodies, whereas Vc did not. CONCLUSION: Early pulmonary involvement in Scl syndromes is functionally characterized by a lowered Dm, correlating with morphologic changes of the nailfold capillaries. Decreased Vc is probably a reflection of RP of the pulmonary vasculature