Atypical antipsychotic (AAP) drugs are the gold-standard treatment for psychotic patients but are nowadays also widely prescribed among people with other mental disorders. Notwithstanding the benefits of AAP in terms of symptom improvement, there are severe adverse effects including the metabolic syndrome. A novel hypothesis is that part of these undesirable effects of antipsychotics could be mediated by their deleterious effects on the microbiome. This may result in dysbiosis, the disruption of bacterial species of the gut microbiota. Recently, dysbiosis has been linked to poor quality of life, depression and anxiety through the gut-brain axis. Mounting evidence proposes that prebiotic consumption may be helpful in the recovery of dysbiosis, although this effect is unclear among long-term antipsychotic users.

The main objective of this study is to assess the potential beneficial effects of the prebiotic Galacto-oligosaccharides (GOS) in combination with 2′-fucosyllactose (2’-FL) on the gut microbiota, by showing a relative increase in Bifidobacteria in fecal samples following intervention. The secondary objective is to assess the effects of GOS on mental wellbeing, sleep, and metabolic parameters. We hypothesize that GOS+2’FL supplementation will improve gut health, mental wellbeing, sleep, and metabolic parameters. Data will be collected 4 weeks prior to the start of the intervention during an observation only phase [t0], at baseline [t1], and after 2 [t2] and 6 [t3] weeks of GOS+2’FL intake. A follow-up will take place at week 10, 4 weeks after the intervention [t4]. Other outcomes that are assessed include the FiberScreen tool, the form of human faeces (Bristol Stool Chart), side effects and the defined daily dosis (DDD) of antipsychotic medication.

The study is a single-arm pilot study (non-randomized and non-blinded). We aim to include 30 psychiatric patients on long-term atypical antipsychotic use, irrespective of their specific psychiatric disorder, with a BMI > 25 kg/m2. Following a run-in period of 4 weeks (no intervention but all other aspects of the study), the participants will consume GOSplus (7.0 g BiotisTMGOS + 0.7 g 2’-FL) daily during the first consumption moment of the day (preferably in the morning) for 42 days. The GOSplus powder has a slightly sweet flavour. The primary endpoint is the change in Bifidobacteria in fecal samples from week 0 to week 6.

The study started recruiting participants in October 2023.

Conclusions are expected by the end of 2024.

None Declared

Depression is a highly recurrent disorder, with more than 50% of those affected experiencing a subsequent episode. Although there is relatively little stability in symptoms across episodes, some evidence indicates that suicidal ideation may be an exception. However, these findings warrant replication, especially over longer periods and across multiple episodes.

To assess the relative stability of suicidal ideation in comparison with other non-core depressive symptoms across episodes.

We examined 490 individuals with current major depressive disorder (MDD) at baseline and at least one subsequent episode during 9-year follow-up within the Netherlands Study of Depression and Anxiety (NESDA). The Inventory of Depressive Symptomatology (IDS) was used to assess DSM-5 non-core MDD symptoms (fatigue, appetite/weight change, sleep disturbance, psychomotor disturbance, concentration difficulties, worthlessness/guilt, suicidal ideation) at baseline and 2-, 4-, 6- and 9-year follow-up. We examined consistency in symptom presentation (i.e. whether the symptom met the diagnostic threshold, based on a binary categorisation of the IDS) using kappa (κ) and percentage agreement, and stability in symptom severity using Spearman correlation, based on the continuous IDS scores.

Out of all non-core depressive symptoms, insomnia appeared the most stable across episodes (r = 0.55–0.69, κ = 0.31–0.47) and weight decrease the least stable (r = 0.03–0.33, κ = 0.06–0.19). For suicidal ideation, correlations across episodes ranged from r = 0.36 to r = 0.55 and consistency ranged from κ = 0.28 to κ = 0.49.

Suicidal ideation is moderately stable in recurrent depression over 9 years. Contrary to prior reports, however, it does not exhibit substantially more stability than most other non-core symptoms of depression.

Manic and depressive mood states in bipolar disorder (BD) may emerge from the non-linear relations between constantly changing mood symptoms exhibited as a complex dynamic system. Dynamic Time Warp (DTW) is an algorithm that may capture symptom interactions from panel data with sparse observations over time.

The current study is the first to analyze a time series of depression and manic symptoms using DTW analyses in patients with BD. We studied interactions and relative changes in symptom severity within and between participants.

The Young Mania Rating Scale and Quick Inventory of Depressive Symptomatology were repeatedly assessed in 141 patients with BD, with on average 5.5 assessments per patient every 3 to 6 months. DTW calculated the distance between each of the 27*27 pairs of standardized symptom scores. The changing profile of standardized symptom scores of BD patients was analyzed in individual patients, yielding symptom dimensions in aggregated group-level analyses. Using an asymmetric time-window, symptom changes that preceded other symptom changes (i.e., Granger causality) yielded a directed network.

The mean age of the patients was 40.1 (SD 13.5) years old, and 60% were female. Idiographic symptom networks were highly variable between patients. Yet, nomothetic analyses showed five symptom dimensions: core (hypo)mania (6 items), dysphoric mania (5 items), lethargy (7 items), somatic/suicidality (6 items), and sleep (3 items). Symptoms of the ‘Lethargy’ dimension showed the highest out-strength, and its changes preceded those of ‘somatic/suicidality’, while changes in ‘core (hypo)mania’ preceded those of ‘dysphoric mania’.

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DTW may help to capture meaningful BD symptom interactions from panel data with sparse observations. It may increase insight into the temporal dynamics of symptoms, as those with high out-strength (rather than high in-strength) could be promising targets for intervention.

None Declared

First generation immigrants in many European countries have insufficient mastery of the host language to complete self-report questionnaires. To address this problem, we translated and validated Turkish, Moroccan Arabic and Moroccan Berber versions of the Dutch 48-item Symptom Questionnaire (SQ-48), which is a validated and clinical useful measure of psychopathology.

Therefore, this study describes the translation and cross cultural validation of the Turkish, Moroccan Arabic, and Moroccan Berber versions of the 48-item Symptom Questionnaire.

Four samples were used: 1) psychiatric outpatients with Turkish or Moroccan background (n=150); 2) non-psychiatric subjects with Turkish or Moroccan background (n=103); 3) native Dutch psychiatric outpatients (n=189); 4) native Dutch non-psychiatric subjects (n=463). Data were analysed by confirmatory factor analysis and receiver operating characteristic curves.

The 253 psychiatric non-native patients and controls were on average 38,3 years old (SD 12,4), and 61% were women. Internal consistency of SQ-48 subscales across groups was adequate to high, the seven-factor structure of SQ-48 fitted the data adequately in the total sample and in each separate group, and AUC values showed acceptable to excellent discrimination. However, the mean severity scores for all SQ-48 subscales were significantly higher in the immigrant groups than those of the Dutch native group. We found full configural, metric and partial scalar invariance.

Psychopathology measured by SQ-48 can largely be interpreted in the same way for persons from different immigrant backgrounds. However, cut-off values for Dutch natives should be ascertained using larger samples as these are likely higher than in Dutch psychiatric patients.

None Declared

Childhood trauma (CT) is associated with severe sequelae, including personality disorders and stress-related mental health disorders that can perpetuate long into adulthood.

We aimed to investigate (1) whether childhood trauma is associated with anger in adulthood, and, if so, (2) to explore which types of childhood trauma predominate in the prediction of anger, and (3) to explore whether the association is independent of psychopathology in a cohort that included participants without lifetime psychiatric disorders, with current or remitted depressive and anxiety disorders, or comorbid depressive and anxiety disorders.

In the Netherlands Study of Depression and Anxiety (NESDA), childhood trauma was assessed with a semi-structured Childhood Trauma Interview (CTI) at baseline, and analyzed in relation to anger as measured at 4-year follow-up with the Spielberger Trait Anger Subscale (STAS), the Anger Attacks Questionnaire, and cluster B personality traits (i.e., borderline, antisocial) of the Personality Disorder Questionnaire 4 (PDQ-4), using analysis of covariance (ANCOVA) and multivariable logistic regression analyses. Post-hoc analyses comprised cross-sectional regression analyses, using the Childhood Trauma Questionnaire – Short Form (CTQ-SF) obtained at 4-year follow-up.

Participants (n = 2,276) were on average 42.1 years (SD = 13.1), and 66.3% were female. Childhood trauma showed a dose-response association with all anger constructs. Zooming in, all types of childhood trauma except for sexual abuse were associated with higher levels of trait anger, and a higher prevalence of anger attacks and antisocial personality traits in adulthood, independently of depression and anxiety. Additionally, all types of childhood trauma were significantly associated with borderline personality traits. Cross-sectionally, the effect sizes were larger compared to the analyses with the childhood trauma measured four years prior to the anger measures.

Childhood trauma is linked with anger in adulthood, most strongly for trait anger and borderline personality traits. It is of clinical importance to explore childhood traumatic experience and start trauma-focused interventions when appropriate.

None Declared

The Persistent Depression and Self-Management Study is a mixed-methods pragmatic randomized controlled trial that evaluated the “Patient and Partner Education Program for All Chronic Illnesses” (PPEP4All) in patients with persistent depressive disorder (PDD) compared to care as usual (CAU). PPEP4All is a brief, structured self-management program that focuses on functional recovery and involves the partner/caregiver in the program. The latter may improve patient outcomes and reduce caregiver psychosocial burden related to PDD.

In addition to evaluating the cost- and clinical-effectiveness of PPEP4All, we conducted a nested qualitative study to deepen our understanding of how patients with PDD and their caregivers cope with chronic depression. Additionally we identify areas in which they require care and learn how they could benefit from a self-management program like PPEP4All.

In the nested qualitative study, 28 patients (16 from PPEP4All, 12 from CAU) and 9 partners/caregivers agreed to participate. The in-depth semi-structured interviews took place at participant’s home, the main research location, or over telephone. For each interview, we used a topic list, which was initially evaluated in a pilot study of patients with PDD. All interviews were audio recorded, with consent from the participant, and transcribed verbatim. Data were analyzed using Grounded Theory, with a constant comparative analysis method, using Atlas.ti version 9 software.

Qualitative data are currently being analyzed. We expect to identify important themes relevant to the patient’s and caregiver’s personal experience and learn how they use and implement self-management in their lives.

PPEP4All may help patients with PDD and caregivers learn important self-management techniques to effectively cope with chronic depression and its consequences, and thus, it may help them meet their needs for care.

None Declared

Aggression and violent incidents are a major concern in psychiatric inpatient care. Nutritional supplementation was found to reduce aggressive incidents and rule violations in forensic populations and in children with behavioral problems.

To assess whether multivitamin, mineral, and n-3 PUFA supplementation would reduce the number of aggressive incidents among long-stay psychiatric inpatients.

The trial was a pragmatic, multicenter, randomized, double-blind, placebo-controlled study. Data were collected from 25 July 2016 through 29 October 2019 at 8 local sites for mental healthcare in the Netherlands and Belgium. Participants were randomized (1:1) to receive either three supplements containing multivitamins, minerals, and n-3 PUFA or placebo for 6 months. The primary outcome was the number of aggressive incidents using the Staff Observation Aggression Scale – Revised (SOAS-R). Secondary outcomes were the patients’ quality of life, affective symptoms, and adverse events.

In total, 176 participants were randomized (supplements, n = 87; placebo, n = 89). Participants were on average 49.3 years old (SD = 14.5), and 64.2% were male. Most patients had a psychotic disorder (60.8%). The primary outcome of SOAS-R incidents was similar in those assigned to supplements (1.03 incidents per month; 95% confidence interval [CI]: 0.74-1.37) and placebo (0.90; 95% CI: 0.65-1.19), with a rate ratio of 1.08 (95% CI: 0.67-1.74; p = .75). Differential effects were not found in sensitivity analyses on the SOAS-R or on secondary outcomes.

Six months of nutritional supplementation did not reduce aggressive incidents among long-stay psychiatric inpatients.

No significant relationships.

Childhood trauma is associated with an increased risk of anxiety and depressive disorders, but its association with anger, irritability, and related constructs has received less attention.

We aimed to investigate (1) the relationship between childhood trauma and anger constructs in adulthood, and (2) which types of childhood trauma is most predictive.

In the Netherlands Study of Depression and Anxiety (NESDA), childhood trauma at baseline was assessed with a semi-structured interview. Childhood trauma was analyzed in relation to the Spielberger Trait Anger Subscale (STAS), the Anger Attacks Questionnaire, and the cluster B personality traits part of the Personality Disorder Questionnaire 4 (PDQ-4), measured at 4-year follow-up, using analysis of covariance (ANCOVA) and multivariable logistic regression analyses, adjusting for sex, age, level of education, BMI, smoking, alcohol dependency/abuse, disorder status.

Participants were on average 42.1 years (SD = 13.1), and 66.3% (n = 1.508) were female. Childhood trauma showed a dose-response association with all anger constructs. Zooming in, emotional neglect, and psychological, and physical abuse were associated with all anger constructs, independently of depression or anxiety. Additionally, sexual abuse and childhood life events were associated with trait anger and borderline personality traits, and trait anger and antisocial personality traits retrospectively.

Childhood trauma is linked with anger in adulthood. Childhood trauma may cause not only anxiety and depression, but also anger, and tailored interventions (at both childhood trauma and anger itself) might help to improve unsatisfactory relationships and prevent violent behaviors.

No significant relationships.

Aggression and violent incidents are a major concern in psychiatric in-patient care. Nutritional supplementation has been found to reduce aggressive incidents and rule violations in forensic populations and children with behavioural problems.

To assess whether multivitamin, mineral and n-3 polyunsaturated fatty acid supplementation would reduce the number of aggressive incidents among long-stay psychiatric in-patients.

The trial was a pragmatic, multicentre, randomised, double-blind placebo-controlled study. Data were collected from 25 July 2016 to 29 October 2019, at eight local sites for mental healthcare in The Netherlands and Belgium. Participants were randomised (1:1) to receive 6-month treatment with either three supplements containing multivitamins, minerals and n-3 polyunsaturated fatty acid, or placebo. The primary outcome was the number of aggressive incidents, determined by the Staff Observation Aggression Scale – Revised (SOAS-R). Secondary outcomes were patient quality of life, affective symptoms and adverse events.

In total, 176 participants were randomised (supplements, n = 87; placebo, n = 89). Participants were on average 49.3 years old (s.d. 14.5) and 64.2% were male. Most patients had a psychotic disorder (60.8%). The primary outcome of SOAS-R incidents was similar in supplement (1.03 incidents per month, 95% CI 0.74–1.37) and placebo groups (0.90 incidents per month, 95% CI 0.65–1.19), with a rate ratio of 1.08 (95% CI 0.67–1.74, P = 0.75). Differential effects were not found in sensitivity analyses on the SOAS-R or on secondary outcomes.

Six months of nutritional supplementation did not reduce aggressive incidents among long-stay psychiatric in-patients.

The COVID-19 outbreak poses a challenge for health care professionals due to a surge in care demands, overwork, fear of contagion and concerns on the availability of protective equipment, and coping with distress of patients and their families. Although there is emerging evidence on prevalence of stress and its predictors, less is known on the trajectory of stress symptoms and the differences between cohorts of health care professionals.

To sustain and restore health care professionals the Leiden University Medical Center has launched the Digital Stress Buddy, a mobile app, to assess psychological stress, depressive symptoms, anxiety and posttraumatic stress symptoms.

Participants fill in a 14-item questionnaire on stress and resilience resources, followed by a COVID-related questionnaire and finally a set of validated questionnaires on depression and anxiety (DASS-21), posttraumatic stress-symptoms (IES-R), burn-out (CBI) and resilience (RES).

To date, 959 health care workers have completed the stress monitor, of whom 223 (23%) showed relevant stress levels. Within this group, anxiety and posttraumatic symptoms were most prevalent (45%), followed by depressive symptoms (15%). Predictors of stress were being female, coping with distress of patients and their families, teleworking, and overwork.

By identifying vulnerabilities and resilience for psychological distress, we are able to tailor the support interventions for health care workers within our hospital. This is an ongoing study and future follow-up during the second wave of the pandemic will provide more insight on the trajectories of stress-related symptoms.

No significant relationships.

Aggression and violent incidents are a major concern in psychiatric inpatient care, potentially leading to physical and psychological consequences for both patients and staff. Nutritional supplementation was found to reduce aggressive incidents and rule violations in forensic populations and children with behavioural problems.

To assess whether multivitamin, mineral and n-3 PUFA supplementation is effective in reducing the number of aggressive incidents among psychiatric patients who are chronically admitted.

In a pragmatic, multicentre, randomized, double-blind, placebo-controlled study, psychiatric inpatients were randomized to receive either three supplements containing multivitamins, minerals, and n-3 PUFA or placebo. During the intervention period of six months, aggressive incidents were assessed using the Staff Observation Aggression Scale – Revised (SOAS-R). Secondary outcome parameters were the patients’ quality of life and affective symptoms. The trial was registered in the Clinical Trials Register (NCT02498106).

A total of 176 patients were enrolled and randomly assigned to receive supplements (n=87) or placebo (n=89). They were on average 49.3 years old (SD=14.5), and 64.2% were male. Most patients had a psychotic disorder (60.8%). Supplementation versus placebo significantly increased circulating micronutrient levels. The primary outcome of SOAS-R incidents was similar in those assigned to supplements (1.03 incidents per month; 95% confidence interval [CI]: 0.74-1.37) and placebo (0.90; 95%CI: 0.65-1.19), with a rate ratio of 1.08 (95%CI: 0.67-1.74; p=0.75). Differential effects were neither found in sensitivity analyses on the SOAS-R, nor on secondary outcomes.

Six months of nutritional supplementation did not reduce aggressive incidents among chronically admitted psychiatric inpatients.

No significant relationships.

Social withdrawal is an early and common feature of psychiatric disorders. Hypothalamic-pituitary-adrenal (HPA)-axis activation through increased salivary cortisol (sC) and sympathetic activation through increased salivary alpha-amylase (sAA) may play a role.

We aimed to study whether the link between increased sC and sAA on the one hand and depression on the other hand is mediated by social withdrawal.

In this cross-sectional, observational study, sC and sAA measures were measured in seven saliva samples in 843 participants (231 psychiatric patients and 612 healthy controls). Social withdrawal was assessed through the Brief Symptom Inventory (BSI)-, the Short Form 36-, and the Dutch Dimensional Assessment of Personality Pathology social withdrawal subscales, and analyzed using linear regression and mediation analyses. On average, participants were 44.0 years old (SD=12.8; 64.1% female).

Basal and diurnal sAA were unrelated to any social withdrawal scale and depression. Certain sC measures were positively associated with the BSI social withdrawal subscale (i.e., area under the curve with respect to the increase, beta=0.082, p=0.02; evening sC value: beta=0.110, p=0.003; and mean sC value: beta=0.097; p=0.01). We found limited support for statistical mediation by social withdrawal (measured using a composite social withdrawal score) on the relationship between evening sC and depression.

Thus, although we found no support for a role of basal and diurnal sAA in social withdrawal, HPA-axis activation may partly aggravate social withdrawal in depressive disorders.

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that is estimated to be carried by one-third of the world population. While evidence has been found for a relationship between T. gondii infection and schizophrenia, its relationship with other psychiatric disorders like depressive and anxiety disorders shows inconsistent results.

The aim of the present study was to examine whether T. gondii seropositivity is associated with affective disorders, as well as with aggression reactivity and suicidal thoughts.

In the Netherlands Study of Depression and Anxiety (NESDA), T. gondii antibodies were assessed in patients with current depressive (n=133), anxiety (n=188), comorbid depressive and anxiety (n=148), and remitted disorders (n=889), as well as in healthy controls (n=373) based on DSM-IV criteria. Seropositivity was analyzed in relation to disorder status, aggression reactivity and suicidal thoughts using multivariate analyses of covariance and regression analyses.

Participants were on average 51.2 years (SD = 13.2), and 64.4% were female. Seropositivity was found in 673 participants (38.9%). A strong positive association between T. gondii seropositivity and age was observed. No significant associations were found between T. gondii seropositivity and disorder status, aggression reactivity and suicidal thoughts. The adjusted odds ratio (OR) for any remitted disorder versus controls was 1.13 (95% CI: 0.87-1.49), and for any current disorder versus controls was 0.94 (95% CI: 0.69- 1.28).

No evidence was found for a relationship between affective disorders and T. gondii infection

No significant relationships.

In research and clinical practice, familial risk for depression and anxiety is often constructed as a simple Yes/No dichotomous family history (FH) indicator. However, this measure may not fully capture the liability to these conditions. This study investigated whether a continuous familial loading score (FLS), incorporating family- and disorder-specific characteristics (e.g. family size, prevalence of depression/anxiety), (i) is associated with a polygenic risk score (PRS) for major depression and with clinical/psychosocial vulnerabilities and (ii) still captures variation in clinical/psychosocial vulnerabilities after information on FH has been taken into account.

Data came from 1425 participants with lifetime depression and/or anxiety from the Netherlands Study of Depression and Anxiety. The Family Tree Inventory was used to determine FLS/FH indicators for depression and/or anxiety.

Persons with higher FLS had higher PRS for major depression, more severe depression and anxiety symptoms, higher disease burden, younger age of onset, and more neuroticism, rumination, and childhood trauma. Among these variables, FH was not associated with PRS, severity of symptoms, and neuroticism. After regression out the effect of FH from the FLS, the resulting residualized measure of FLS was still associated with severity of symptoms of depression and anxiety, rumination, and childhood trauma.

Familial risk for depression and anxiety deserves clinical attention due to its associated genetic vulnerability and more unfavorable disease profile, and seems to be better captured by a continuous score that incorporates family- and disorder-specific characteristics than by a dichotomous FH measure.

Childhood abuse and neglect often occurs within families and can have a large influence on mental well-being across the lifespan. However, the sibling concordance of emotional abuse and neglect (i.e. together referred to as emotional maltreatment; EM), physical abuse (PA) and sexual abuse (SA) and the long-term impact on the context of siblings' maltreatment experiences are unclear. To examine the influence of EM, PA and SA on adult depressive symptoms within the family framework we differentiate between (a) the family-wide (mean level of all siblings) effects and (b) the individual deviation from the mean family level of maltreatment.

The sample (N = 636) consists of 256 families, including at least one lifetime depressed or anxious individual and their siblings. Multilevel modeling was used to examine the family-wide and relative individual effects of childhood maltreatment (CM).

(a) Siblings showed most similarity in their reports of EM followed by PA. SA was mostly reported by one person within a family. In line with these observations, the mean family levels of EM and PA, but not SA, were associated with more depressive symptoms. In addition, (b) depression levels were more elevated in individuals reporting more EM than the family mean.

Particularly in the case of more visible forms of CM, siblings' experiences of EM and PA are associated with the elevated levels of adult depressive symptoms. Findings implicate that in addition to individual maltreatment experiences, the context of siblings' experiences is another crucial risk factor for an individuals' adult depressive symptomatology.

To report on a first study on the characteristics of people with schizophrenia and a history of homelessness in The Hague, Netherlands.

Parnassia Psychiatric Centre is the sole mental health service provider for The Hague. We screened all 2723 electronic records of schizophrenia spectrum disorders patients at Parnassia in a recent year. We identified 112 patients with a homelessness history in the prior two years. We collected one-year data from the Parnassia Case Register on service use and clinical variables. In standardized interviews, we assessed clinical, substance use and homelessness histories of participants.

The majority, 76% (N: 85) was contacted. Among those contacted, 14% was excluded and 14% refused to participate. We found no significant difference on service use, demographic and clinical characteristics for participants (N:60) and non-participants (N:52). The majority (88%) is male, 45% never married, mean age is 39 and 27% is foreign born. Mean education is 9 years. Prescribed medication history is high (87%), and 44% reports periods of 3 to 12 months and 32% reports periods of more than 12 months of lifetime homelessness. Lifelong substance use histories are high: 64% cocaine, 36% heroine, 25% amphetamine; 63% cannabis, 53% alcohol. Current use is considerable: 32% cocaine, 10% heroine, 15% amphetamine, 52% cannabis, 34% alcohol. The majority (76%) reports an incarceration history. They have a high HIV rate, 2 out of 32 tested (6.3%) were positive.

These individuals need specialized services to address their dual diagnoses, risk of homelessness, and prevent HIV and imprisonment.

There is increasing interest in day-to-day affect fluctuations of patients with depressive and anxiety disorders. Few studies have compared repeated assessments of positive affect (PA) and negative affect (NA) across diagnostic groups, and fluctuation patterns were not uniformly defined. The aim of this study is to compare affect fluctuations in patients with a current episode of depressive or anxiety disorder, in remitted patients and in controls, using affect instability as a core concept but also describing other measures of variability and adjusting for possible confounders.

Ecological momentary assessment (EMA) data were obtained from 365 participants of the Netherlands Study of Depression and Anxiety with current (n = 95), remitted (n = 178) or no (n = 92) DSM-IV defined depression/anxiety disorder. For 2 weeks, five times per day, participants filled-out items on PA and NA. Affect instability was calculated as the root mean square of successive differences (RMSSD). Tests on group differences in RMSSD, within-person variance, and autocorrelation were performed, controlling for mean affect levels.

Current depression/anxiety patients had the highest affect instability in both PA and NA, followed by remitters and then controls. Instability differences between groups remained significant when controlling for mean affect levels, but differences between current and remitted were no longer significant.

Patients with a current disorder have higher instability of NA and PA than remitted patients and controls. Especially with regard to NA, this could be interpreted as patients with a current disorder being more sensitive to internal and external stressors and having suboptimal affect regulation.

Although depression with anxious distress appears to be a clinically relevant subtype of Major Depressive Disorder (MDD), whether it involves specific pathophysiology remains unclear. Inflammation has been implicated, but not comprehensively studied. We examined within a large MDD sample whether anxious distress and related anxiety features are associated with differential basal inflammation and innate cytokine production capacity.

Data are from 1078 MDD patients from the Netherlands study of depression and anxiety. Besides the DSM-5 anxious distress specifier, we studied various dimensional anxiety scales (e.g. Inventory of Depressive Symptomatology anxiety arousal subscale [IDS-AA], Beck Anxiety Inventory [BAI], Mood and Anxiety Symptoms Questionnaire Anxious Arousal scale [MASQ-AA]). Basal inflammatory markers included C-reactive protein, interleukin (IL)-6 and tumor-necrosis factor (TNF)-α. Innate production capacity was assessed by 13 lipopolysaccharide (LPS)-stimulated inflammatory markers. Basal and LPS-stimulated inflammation index scores were created.

Basal inflammation was not associated with anxious distress in MDD patients (anxious distress prevalence 54.3%), except for modest positive associations for IDS-AA and BAI scores. However, anxious distress was associated with higher LPS-stimulated levels (interferon-ɣ, IL-2, IL-6, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, matrix metalloproteinase-2, TNF-α, TNF-β, LPS-stimulated index). Oher anxiety indicators (number of specifier items and anxiety diagnoses, IDS-AA, BAI, MASQ-AA) were also associated with increased innate production capacity.

Within a large MDD sample, the anxious distress specifier was associated with increased innate cytokine production capacity but not with basal inflammation. Results from dimensional anxiety indicators largely confirm these results. These findings provide new insight into the pathophysiology of anxious depression.

Novel research concepts based on therapies aiming to modulate intestinal microbiota are emerging. The evidence is mounting that gut-brain axis plays an important role in the development of mood and depressive disorders [1]. The similarities between blood brain barrier (BBB) and gut vascular barrier (GVB) and their role in chronic diseases have been recently unraveled [2]. Especially convincing data come from animal models, where administration of probiotics and antibiotics in germ and pathogen free mice showed beneficial role in the regulation of behavior, cognition, pain, anxiety and mood.

Based on available data as well as on studies looking at the effect of multispecies probiotics (Ecologic® Barrier containing B.bifidumW23, B.lactisW52, L.acidophilusW37, L.brevisW63, L.caseiW56, L.salivariusW24, L.lactisW19, L.lactisW58) on cognitive reactivity to sad mood in healthy volunteers [3] we designed the human trial aiming to compare microbiome alterations and response to therapy in patients with depression and schizophrenia. Moreover, in vitro and in vivo data support the notion that multispecies probiotics are capable of improving gut barrier function [4] and may alleviate disorders affecting mood and depressive-like behavior. We postulate that therapies modulating the microbiome-gut-brain axis warrant further investigations.

Multispecies probiotics have the potential to influence the gut-brain axis and alleviate mental disorders. Ongoing clinical study in patients with depression and schizophrenia will help to further unravel the role of gut-brain axis in the treatment of patients with psychiatric disturbances.

The authors have not supplied their declaration of competing interest.