Transdiagnostic psychiatry: Symptom profiles and their direct and indirect relationship with well-being.

BACKGROUND: Heterogeneity and comorbidity in psychiatric disorders are common, however, little is known about the impact on well-being and the role of functional limitations. We aimed to identify transdiagnostic psychiatric symptom profiles and to study their association with well-being and the mediating role of functional limitations in a naturalistic psychiatric patient group. METHODS: We used four disorder-specific questionnaires to assess symptom severity within a sample of 448 psychiatric patients with stress-related and/or neurodevelopmental disorders and 101 healthy controls. Using both exploratory and confirmatory factor analyses we identified transdiagnostic symptom profiles, which we entered into a linear regression analysis to assess their association with well-being and the mediating role of functional limitations in this association. RESULTS: We identified eight transdiagnostic symptom profiles, covering mood, self-image, anxiety, agitation, empathy, non-social interest, hyperactivity and cognitive focus. Mood and self-image showed the strongest association with well-being in both patients and controls, while self-image also showed the highest transdiagnostic value. Functional limitations were significantly associated with well-being and fully mediated the relationship between cognitive focus and well-being. LIMITATIONS: The participant sample consisted of a naturalistic group of out-patients. While this strengthens the ecological validity and transdiagnostic perspective of this study, the patients with a single neurodevelopmental disorder were underrepresented. CONCLUSION: Transdiagnostic symptom profiles are valuable in understanding what reduces well-being in psychiatric populations, thereby opening new avenues for functionally meaningful interventions.

Anhedonia as a transdiagnostic symptom across psychological disorders: a network approach.

BACKGROUND: Anhedonia is apparent in different mental disorders and is suggested to be related to dysfunctions in the reward system and/or affect regulation. It may hence be a common underlying feature associated with symptom severity of mental disorders. METHODS: We constructed a cross-sectional graphical Least Absolute Shrinkage and Selection Operator (LASSO) network and a relative importance network to estimate the relationships between anhedonia severity and the severity of symptom clusters of major depressive disorder (MDD), anxiety sensitivity (AS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) in a sample of Dutch adult psychiatric patients (N = 557). RESULTS: Both these networks revealed anhedonia severity and depression symptom severity as central to the network. Results suggest that anhedonia severity may be predictive of the severity of symptom clusters of MDD, AS, ADHD, and ASD. MDD symptom severity may be predictive of AS and ADHD symptom severity. CONCLUSIONS: The results suggest that anhedonia may serve as a common underlying transdiagnostic psychopathology feature, predictive of the severity of symptom clusters of depression, AS, ADHD, and ASD. Thus, anhedonia may be associated with the high comorbidity between these symptom clusters and disorders. If our results will be replicated in future studies, it is recommended for clinicians to be more vigilant about screening for anhedonia and/or depression severity in individuals diagnosed with an anxiety disorder, ADHD and/or ASD.

Negative memory bias as a transdiagnostic cognitive marker for depression symptom severity.

BACKGROUND: Negative memory bias is a strong risk factor for the development and maintenance of depression. Recent evidence also found negative memory bias in other mental disorders. Here, we aim to: 1) assess the presence and strength of negative memory bias in a range of (comorbid) mental disorders, 2) investigate which disorder-specific symptoms are associated with negative memory bias, and 3) test whether negative memory bias might be a transdiagnostic mechanism. METHODS: Negative memory bias was measured in patients with at least one diagnosis of a stress-related disorder (n = 86), a neurodevelopmental disorder (n = 53), or both (n = 68), and 51 controls. Depression, anxiety, attention-deficit/hyperactivity disorder, and autism spectrum disorder symptom severity was assessed using questionnaires. Groups were compared on negative memory bias and the associations between negative memory bias and symptom severity were made using linear regression models. RESULTS: All patient groups showed stronger negative memory bias than the controls. Negative memory bias was individually associated with all symptom severity indices, but when added into a single model, only the association with depressive symptom severity remained. This persisted after controlling for diagnostic group. LIMITATIONS: Due to the cross-sectional sectional study design, we could only look at the associations between negative memory bias and disorder-specific symptoms and not at the direction of the effects. CONCLUSIONS: Negative memory bias is characteristic of a depressotypic processing style and present in different mental disorders. It might play a mechanistic role in the development of (subclinical) co-occurrence between mental disorders.

[Decrease of depression and outcome in treatment of anxiety disorders - an observational study of ROM data]. / Afname van depressie en de uitkomst bij de behandeling van angststoornis ­ een observationele studie van ROM-data.

BACKGROUND: Most mental health hospitals in the Netherlands use disorder specific standards of care. In case of comorbidity, we lack evidence in choosing the treatment of preference when both depressive- and anxiety disorder(s) are present in the same patient.
AIM: To investigate the prevalence of depression and anxiety (including obsessive compulsive disorder and post-traumatic stress disorder) in an outpatient mental health hospital population treated for their anxiety disorder, and to investigate the difference in outcome of (anxiety) treatment between patients with and without a comorbid depressive disorder.
METHOD: A retrospective study using outcome data from 2012 to 2017. In this period, we identified 127 patients for whom outcome data and diagnostic criteria were available. Comorbidity in this group was determined by a clinical interview. During treatment symptoms were monitored using self-reporting scales, among others the Inventory of Depressive Symptomatology (IDS) and the Beck Anxiety Inventory (BAI).
RESULTS: In 46,5% of the patients a comorbid depressive disorder was diagnosed. No significant difference in treatment outcome was observed between the group of patients with and the group of patients without a comorbid depressive disorder. However, the amount of reduction of depressive symptoms measured by the ids was a good predictor of the reduction of anxiety: a faster reduction of depressive symptoms predicts a better outcome of the treatment of anxiety.
CONCLUSION: Comorbid depressive disorders were observed in almost half of the patients treated in specialized (outpatient) clinics for anxiety disorders. A slower reduction of depressive symptoms predicts worse outcome of the treatment of anxiety.

Absence of default mode downregulation in response to a mild psychological stressor marks stress-vulnerability across diverse psychiatric disorders.

Clinically, it is well-established that vulnerability to stress is a common feature across a broad spectrum of psychiatric disorders. However, this link has been mechanistically studied almost exclusively in patients with so-called stress-related disorders such as depression and anxiety. To probe transdiagnostic mechanisms, we set out to study the acute stress response across a broader range of psychiatric disorders taking a large-scale brain network perspective. We investigated the brain's response to a mild, experimentally well-controlled psychological stressor in the form of an aversive movie. We studied 168 patients with stress-related and/or neurodevelopmental disorders (including comorbidity) and 46 control subjects. We focused on three networks that have a central role in the brain's stress response and are affected in a wide range of psychiatric disorders: the salience network (SN), default mode network (DMN) and frontoparietal network (FPN). Our results support an increased vulnerability to stress across all patients, indicated by a higher subjective stress level at baseline and follow-up compared to matched controls. At the brain systems level, the stress response was characterized by a relatively decreased FPN connectivity and an absence of a decrease in the within DMN connectivity across all disorders compared to controls. At the neurocognitive level, these findings may reflect a diminished top-down control and a tendency to more pronounced (negative) self-referential processing. Besides these shared aspects of the maladaptive stress response, we also discuss indications for disorder-specific aspects. Taken together, our results emphasize the importance of investigating the mechanistic underpinnings of psychiatric disorders transdiagnostically as recently done in neurogenetics.

Cognitive reactivity as outcome and working mechanism of mindfulness-based cognitive therapy for recurrently depressed patients in remission.

Major depressive disorder is a prevalent condition with high relapse rates. There is evidence that cognitive reactivity is an important vulnerability factor for the recurrence of depression. Mindfulness-based interventions are designed to reduce relapse rates, with cognitive reactivity as one of the proposed working mechanisms. In a randomised controlled trial we compared the effect of mindfulness-based cognitive therapy (MBCT) with treatment-as-usual (TAU) on cognitive reactivity in recurrently depressed patients (N = 115). Depressive symptoms, cognitive reactivity, and mindfulness skills were assessed pre and post treatment. Patients in the MBCT group reported a significantly greater reduction in cognitive reactivity than those in the TAU group (d = .51). The reduction of cognitive reactivity appeared to mediate the association between MBCT/TAU and decrease of depressive symptoms, using pre and post scores. The current study provides evidence that MBCT reduces cognitive reactivity and preliminary evidence that cognitive reactivity is a working mechanism of MBCT.

Association between genes, stressful childhood events and processing bias in depression vulnerable individuals.

The brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) genes are relevant candidates for depression. Variation in these genes is associated with stress sensitivity and depressotypic cognitive biases. The interaction between genes and stressful events is considered as an important mechanism in the development of depression. This study examined the effects of the BDNF and COMT genes on biased processing and the interaction with childhood stress in vulnerable individuals. A total of 198 remitted depressed individuals performed an n-back task with emotional facial stimuli (happy and sad). Childhood events were measured with a questionnaire. Genotype by childhood events interactions were analyzed for happy and sad expressions for BDNF (Val66Met; rs6265) and COMT (Val158Met; rs4680), individually and combined. BDNF and COMT both interacted significantly (P = 0.006 and P = 0.014, respectively) with childhood trauma on reaction time for happy faces. For both genes, Met-carriers with childhood trauma showed less positive bias for happy faces than those without childhood trauma. Val-carriers did not show a differential bias. Individuals with childhood trauma and 3 or 4 risk alleles (BDNF and COMT combined) showed less positive bias than those without childhood trauma (P = 0.011). The BDNF × COMT × childhood trauma interaction yielded a P = 0.055, but had limited power. A potential weakness is the measurement method of the childhood events, as negative bias might have affected participants' recall. Our findings endorse the association of BDNF and COMT with stress and depression and provide a possible intermediate, i.e. biased processing of positive information. Tailoring treatment to specific risk profiles based on genetic susceptibility and childhood stress could be promising.