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.

The impact of treatment resistance on outcome and course of electroconvulsive therapy in major depressive disorder.

INTRODUCTION: Major depressive disorder (MDD) is a common psychiatric disorder. Despite several treatment options, a subgroup of patients will not respond to the commonly used antidepressant treatments and thus express treatment resistance (TRD). TRD can be quantified with the Dutch Measure for Treatment Resistance in Depression (DM-TRD). Electroconvulsive therapy (ECT) is an effective treatment for MDD, also in TRD. Yet, the position of ECT as "treatment-of-last-resort" may decrease the likelihood of beneficial outcome. Our aim was to investigate the association between treatment resistance and outcome and course of ECT. METHODS: We performed a retrospective, multicenter cohort study with 440 patients of which data was retrieved from patient records as collected in the Dutch ECT Cohort database. Linear and logistic regression models were used to explore the association between level of treatment resistance and outcome of ECT. Median split was used to explore the differences between high and low level of TRD and course of treatment. RESULTS: A higher DM-TRD score was associated with significantly smaller reduction of depression symptoms (R2 = 0.160; ß = -2.968; p < 0.001) and lower chance of response (OR = 0.821 [95 CI: 0.760-0.888]; ß = -0.197; p < 0.001). Low level TRD patients underwent fewer ECT sessions (mean 13 ± 6 SD vs. 16 ± 7 SD; p < 0.001) and fewer switches from right unilateral tot bifrontotemporal electrode placement (29% vs. 40%; p = 0.032). CONCLUSION: Reserving ECT as "treatment-of-last-resort" in the treatment algorithm for MDD seems questionable, because in our study lower level of treatment resistance predicted more beneficial ECT-outcome. Moreover, providing ECT in less treatment resistant patients showed fewer needed ECT-sessions and less switches to BL electrode placement, which may decrease the risk for cognitive side-effects.

[Electroencephalography and connectivity in delirium]. / Eeg en innovatieve behandeling van verminderde hersenconnectiviteit bij delirium.

BACKGROUND: Delirium is associated with neurophysiological changes that can be identified with quantitative EEG analysis techniques (qEEG). AIM: To provide an overview of studies on neurophysiological changes in delirium using various qEEG analysis techniques. METHOD: Literature review. RESULTS: In delirium, there is an increase in delta and theta activity but a decrease in activity in the alpha frequency band. Additionally, there is a decrease in functional connectivity and efficiency of the brain network in the alpha frequency band. CONCLUSION: Delirium is characterized by diffuse slowing of the EEG, reduced functional connectivity, and decreased efficiency of the brain network. Improved functional connectivity could be a new approach to treat delirium.

[Neuropsychiatric recovery after COVID-19 - an observational cohort-study]. / Neuropsychiatrisch herstel na COVID-19; een observationeel cohortonderzoek.

BACKGROUND: Since the end of 2019, COVID-19 and its consequences are present everywhere. Dutch professionals are concerned about the mental consequences, and in particular that during and after hospitalization little attention is paid to psychological problems. AIM: To monitor the short-term course and severity of (neuro)psychiatric symptoms after hospitalization for COVID-19. To make a recommendation regarding whether or not to follow-up these patients psychiatrically to optimize care. METHOD: In an observational cohort-study screening questions and additional questionnaires were used during two follow-up contacts to monitor cognition (MoCA), affective symptoms (HADS and IES) and overall functioning. RESULTS: More than half of the 29 included patients showed (neuro)psychiatric problems at both follow-up moments. Two weeks after discharge, we mainly saw symptoms related to anxiety and depression. Except for complaints related to the traumatic experience of the COVID-19, these seemed to have a favorable natural course. A negative time effect was seen for complaints consistent with post-traumatic stress disorder. Two months after discharge limitations in cognition and overall functioning appeared to be the main complaints after COVID-19. CONCLUSION: (Neuro)psychiatric symptoms after a COVID-19 are common. The natural course for affective complaints is more favorable than for cognitive functions. Specialist follow-up of patients with post-COVID psychological problems is recommended.

Beloop van covid-19-infecties en impact op mentale gezondheid; opzet van een landelijk casusregister.

Course of covid-19 infections and impact on mental health; setting up a national case register.

[Education and training in psychiatry in 2019]. / Onderwijs en opleiding in de psychiatrie anno 2019.

.

[Minimally invasive brain stimulation for unipolar depression]. / Minimaal invasieve hersenstimulatie bij unipolaire depressie.

BACKGROUND: Unipolar depression is one of the most prevalent psychiatric disorders and has a high impact at individual and societal level. Commonly used treatments such as antidepressants and psychotherapy are often not effective. AIM: To determine the efficacy of repetitive transcranial magnetic stimulation (rTMS) and direct current stimulation (tDCS) as minimally invasive forms of treatment for unipolar depression. METHOD: We searched the literature. RESULTS: rTMS is effective in treating unipolar depression and is comparable to existing forms of medication and behavioural therapy. The effects of tDCS are promising, but more research is needed. CONCLUSION: rTMS is a useful addition to the existing arsenal of treatment for unipolar depression.

[Usefulness of repetitive transcranial magnetic stimulation (rTMS) in the treatment of bipolar depression]. / Repetitieve transcraniële magnetische stimulatie (rTMS) als behandeling van bipolaire depressie.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been found to be an effective technique in the treatment of unipolar depression. However, it is not yet clear whether rTMS is also useful in the treatment of bipolar depression. AIM: To evaluate the available evidence that rTMS is effective in the treatment of bipolar depression. METHOD: Review of available literature (RCTs and open-label studies). RESULTS: We looked closely at four RCTs and four open-label studies. In three of the four RCTs the results for patients who had received rTMS were no better than those for patients who had received a placebo. Patients in all four open-label studies showed significant improvement. One individual developed hypomanic symptoms. The studies used many different parameters; some studies included diagnoses, some referred to the type of medication used. CONCLUSION: So far, there is a lack of high quality studies on which we can base our conclusions about the effectiveness of rTMS for the treatment of bipolar depression. The use of rTMS to treat patients with bipolar depression does not seem to increase the risk that a patient will develop (hypo)mania.

Chronic depression is associated with a pronounced decrease in serum brain-derived neurotrophic factor over time.

One of the leading neurobiological hypotheses on depression states that decreased expression of brain-derived neurotrophic factor (BDNF) contributes to depression. This is supported by consistent findings of low serum BDNF levels in depressed patients compared with non-depressed controls. Whereas it has been generally assumed that this is a state characteristic of depression, strong inferences about state or trait effects require a longitudinal study design. To investigate the longitudinal association between serum BDNF and depression, we measured serum BDNF, (current and past) depression status, use of antidepressants, and all potential covariates at baseline and after 2 years in 1751 individuals, consisting of patients with an incident (n=153), remitted (n=420) and persistent depression (n=310) and non-depressed controls (n=868). We analyzed change/differences in serum BDNF across these four groups with analyses of covariance adjusted for covariates and baseline BDNF value, together with the effects of starting and stopping antidepressant treatment. Our analyses revealed a significant difference for the depression course groups (P=0.007). Compared with non-depressed controls, persistently depressed and remitted patients had a steeper decrease of BDNF levels over time (-1.33 (P=0.001) and -0.97 ng ml(-1) (P=0.011), respectively), whereas BDNF reductions in patients with incident depression were similar to those in healthy controls. Initiation or discontinuation of antidepressants was not associated with BDNF change (P=0.72). These findings suggest that BDNF not only contributes to depression, but that depression in turn may also contribute to low BDNF.

Long-term depressive symptoms and anxiety after transient ischaemic attack or ischaemic stroke in young adults.

BACKGROUND AND PURPOSE: Few studies exist on long-term post-stroke depressive symptoms and anxiety in young adults, although these young patients have a particular interest in their long-term prognosis, given their usually long life expectancy and being in the midst of an active social, working and family life. The aims of this study were to investigate the prevalence of depressive symptoms and anxiety and their association with clinical and demographic variables and with functional outcome after stroke in young adults. METHODS AND RESULTS: Long-term prevalence of depressive symptoms and anxiety was calculated in 511 patients with a transient ischaemic attack or ischaemic stroke, aged 18-50 years, using the Hospital Anxiety and Depression scale, compared with 147 controls. Functional outcome was assessed with the modified Rankin Score (mRS) and the Instrumental Activities of Daily Living scale (IADL). 16.8% of patients had depressive symptoms and 23.0% had anxiety, versus 6.1% (P = 0.001) and 12.2% (P < 0.001) in controls. In ischaemic stroke patients, depressive symptoms and anxiety were associated with poor functional outcome (mRS > 2 or IADL < 8). CONCLUSION: Even a decade after stroke at young age, depressive symptoms and anxiety were prevalent and associated with poor functional outcome. Therefore, even in the long term, treating physicians should be aware of the long-term presence of these symptoms as their recognition may be the first step in improving long-term functional independence.

[Anxiety disorders during pregnancy and the post-partum period]. / Angststoornissen tijdens de zwangerschap en post-partumperiode.

BACKGROUND: Although anxiety disorders are more prevalent during the perinatal period, little attention has been given so far to the influence that pregnancy and the post-partum period can have on anxiety disorders. AIM: To review the literature concerning the prevalence, presentation and treatment of anxiety disorders during pregnancy and the post-partum period and to identify the risk factors involved. METHOD: We reviewed the literature in order to find articles concerning the influence of the post-partum period on various types of anxiety disorders. RESULTS: Having selected the most relevant articles, we discuss the findings in relation to specific types of anxiety disorder. CONCLUSION: Women are more vulnerable to anxiety disorders during the perinatal period. Because anxiety disorders can have a significant impact on the mother and her foetus/infant it is important that anxiety disorders are identified and treated at the earliest opportunity.

BDNF Val66Met genotype modulates the effect of childhood adversity on subgenual anterior cingulate cortex volume in healthy subjects.

According to the neurotrophic hypothesis of depression, stress can lead to brain atrophy by modifying brain-derived neurotrophic factor (BDNF) levels. Given that BDNF secretion is affected by a common polymorphism (rs6265, Val66Met), which also is associated with depression, we investigated whether this polymorphism modifies the effect of childhood adversity (CA) on local gray matter (GM) volume in depression-relevant brain regions, using data from two large cohorts of healthy subjects. We included 568 healthy volunteers (aged 18-50 years, 63% female) in our study, for whom complete data were available, with magnetic resonance imaging data at 1.5 Tesla (N=275) or 3 Tesla (N=293). We used a whole brain optimized voxel-based morphometry (VBM) approach assessing genotype-dependent GM differences, with focus on the amygdala, hippocampus and medial prefrontal cortex (PFC; including anterior cingulate cortex (ACC) and orbitomedial PFC). CA was assessed using a validated questionnaire. In both cohorts, we found that BDNF methionine (Met)-allele carriers with a history of CA had significantly less GM in subgenual ACC (P<0.05) compared with Met-allele carriers without CA and Val/Val homozygotes with CA. No differences were found in hippocampus, amygdala and orbitomedial PFC. On the basis of our findings, we conclude that BDNF Met-allele carriers are particularly sensitive to CA. Given the key role of the subgenual ACC in emotion regulation, this finding provides an important mechanistic link between stress and BDNF on one hand and mood impairments on the other hand.

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.

Sex-specifics of ECT outcome.

OBJECTIVE: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. METHODS: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). RESULTS: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. CONCLUSION: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex- specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.

Amygdala to hippocampal volume ratio is associated with negative memory bias in healthy subjects.

BACKGROUND: Negative memory bias is thought to be one of the main cognitive risk and maintenance factors for depression, but its neural substrates are largely unknown. Here, we studied whether memory bias is related to amygdala and hippocampal volume, two structures that are critical for emotional memory processes and that show consistent volume alterations in depression. METHOD: Structural magnetic resonance imaging (MRI) was carried out in 272 healthy participants (62% female, 18-50 years old). All images were acquired on 1.5 T Siemens MRI scanners. Automatic segmentation of amygdala and hippocampus was performed using the FIRST module of FSL. Negative memory bias was assessed by the self-referent encoding/evaluation test. RESULTS: Negative memory bias was associated with larger amygdala (p=0.042) and smaller hippocampal (p=0.029) volumes. In additional analyses, we found that, compared with the associations found with hippocampus and amygdala volume separately, a stronger association was found between negative memory bias and the ratio of amygdala:hippocampus volume (p=0.021). CONCLUSIONS: In non-depressed subjects we found that larger amygdala and smaller hippocampal volumes are associated with negative memory bias. This suggests that an increased amygdala:hippocampus volume ratio plays a role in cognitive vulnerability often seen in individuals with high risk for depression and that these structural brain differences may pre-date the onset of depression.

Multimodal multi-center analysis of electroconvulsive therapy effects in depression: Brainwide gray matter increase without functional changes.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for severe depression and induces gray matter (GM) increases in the brain. Small-scale studies suggest that ECT also leads to changes in brain functioning, but findings are inconsistent. In this study, we investigated the influence of ECT on changes in both brain structure and function and their relation to clinical improvement using multicenter neuroimaging data from the Global ECT-MRI Research Collaboration (GEMRIC). METHODS: We analyzed T1-weighted structural magnetic resonance imaging (MRI) and functional resting-state MRI data of 88 individuals (49 male) with depressive episodes before and within one week after ECT. We performed voxel-based morphometry on the structural data and calculated fractional amplitudes of low-frequency fluctuations, regional homogeneity, degree centrality, functional connectomics, and hippocampus connectivity for the functional data in both unimodal and multimodal analyses. Longitudinal effects in the ECT group were compared to repeated measures of healthy controls (n = 27). RESULTS: Wide-spread increases in GM volume were found in patients following ECT. In contrast, no changes in any of the functional measures were observed, and there were no significant differences in structural or functional changes between ECT responders and non-responders. Multimodal analysis revealed that volume increases in the striatum, supplementary motor area and fusiform gyrus were associated with local changes in brain function. CONCLUSION: These results confirm wide-spread increases in GM volume, but suggest that this is not accompanied by functional changes or associated with clinical response. Instead, focal changes in brain function appear related to individual differences in brain volume increases.

Neural basis of emotion recognition deficits in first-episode major depression.

BACKGROUND: Depressed individuals demonstrate a poorer ability to recognize the emotions of others, which could contribute to difficulties in interpersonal behaviour. This emotion recognition deficit appears related to the depressive state and is particularly pronounced when emotions are labelled semantically. Here, we investigated its neural basis by comparing emotion recognition processing between depressed, recovered and healthy individuals. METHOD: Medication-naive patients with a first major depressive episode, medication-free patients who had recovered from a first episode, and a group of matched healthy individuals participated. They were requested to identify the emotion of angry and fearful face stimuli, either by matching them to other emotional faces on a perceptual basis or by matching them to a semantic label, while their brain activity was measured with functional magnetic resonance imaging. RESULTS: The depressed individuals performed worse than recovered and healthy individuals on the emotion-labelling but not the emotion-matching task. The labelling deficit was related to increased recruitment of the right amygdala, left inferior frontal gyrus and anterior cingulate cortex. CONCLUSIONS: Deficits in semantic labelling of negative emotions are related to increased activation in specific brain regions and these abnormalities are mood state-dependent. These results indicate that accessing semantic knowledge about negative information triggers increased amygdala and left inferior frontal gyrus processing, which subsequently impairs task-relevant behaviour. We propose that this may reflect the activation of negative schemas.

The interaction between cerebrovascular disease and neuroticism in late-life depression: a cross-sectional study.

OBJECTIVE: Vascular disease and neuroticism are both risk factors for late-life depression. In this study we examined the interaction between vascular disease and neuroticism as determinants of clinically relevant depressive symptoms (CRDS) in late-life. METHODS: Multivariate logistic regression in a survey of 1396 population-dwelling people aged ≥70 years. CRDS were defined as scoring ≥16 on the CES-D. Vascular disease was categorised into four levels: none, ≥2 vascular risk factors, cardiac disease or stroke. RESULTS: Neuroticism was strongly associated with CRDS in women (OR: 1.6, 95% CI: 1.4-1.8). In men vascular disease interacted negatively but significantly with neuroticism (cardiac disease by neuroticism: OR: 0.8, 95% CI: 0.6-0.9; stroke by neuroticism: OR: 0.8, 95% CI: 0.6-0.96) when predicting CRDS. CONCLUSIONS: In men vascular disease attenuates the predictive value of neuroticism in CRDS, which might be mediated by apathy caused by cerebrovascular disease.

Neural correlates of pragmatic language comprehension in autism spectrum disorders.

Difficulties with pragmatic aspects of communication are universal across individuals with autism spectrum disorders (ASDs). Here we focused on an aspect of pragmatic language comprehension that is relevant to social interaction in daily life: the integration of speaker characteristics inferred from the voice with the content of a message. Using functional magnetic resonance imaging (fMRI), we examined the neural correlates of the integration of voice-based inferences about the speaker's age, gender or social background, and sentence content in adults with ASD and matched control participants. Relative to the control group, the ASD group showed increased activation in right inferior frontal gyrus (RIFG; Brodmann area 47) for speaker-incongruent sentences compared to speaker-congruent sentences. Given that both groups performed behaviourally at a similar level on a debriefing interview outside the scanner, the increased activation in RIFG for the ASD group was interpreted as being compensatory in nature. It presumably reflects spill-over processing from the language dominant left hemisphere due to higher task demands faced by the participants with ASD when integrating speaker characteristics and the content of a spoken sentence. Furthermore, only the control group showed decreased activation for speaker-incongruent relative to speaker-congruent sentences in right ventral medial prefrontal cortex (vMPFC; Brodmann area 10), including right anterior cingulate cortex (ACC; Brodmann area 24/32). Since vMPFC is involved in self-referential processing related to judgments and inferences about self and others, the absence of such a modulation in vMPFC activation in the ASD group possibly points to atypical default self-referential mental activity in ASD. Our results show that in ASD compensatory mechanisms are necessary in implicit, low-level inferential processes in spoken language understanding. This indicates that pragmatic language problems in ASD are not restricted to high-level inferential processes, but encompass the most basic aspects of pragmatic language processing.

[Non-invasive brain stimulation for the treatment of depression]. / Niet-invasieve hersenstimulatie als behandeling voor depressie.

Depression is one of the most common psychiatric disorders and is a heavy burden, not only for the patient and his or her environment but also in economic and social terms. 35% of depressed patients do not recover after standard treatment with medication or psychotherapy. There is a need for more effective treatment options for depression. In recent decades, new forms of brain stimulation have been developed for the treatment of depression, the most important of which is transcranial magnetic stimulation (TMS). TMS uses magnetic pulses to influence brain activity. Meta-analyses show approximately 30-40% of patients respond to treatment with repetitive TMS. The depression goes into remission in about 20-30% of cases. Research has led to new treatment protocols and variations on the conventional TMS method. More research into the effectiveness of these developments is needed. We recommend using TMS as an add-on treatment more often when the patient has completed two steps of the treatment guideline.