Enhanced Taste Recognition Following Subacute Treatment With The Dopamine D2/D3 Receptor Agonist Pramipexole in Healthy Volunteers.

BACKGROUND: Patients with Parkinson's disease (PD) show impaired performance in taste recognition tests, which suggests a possible dopaminergic influence on gustatory functioning. To experimentally test this hypothesis, we assessed whether pharmacological manipulation of dopaminergic signaling in healthy volunteers can affect performance in a standardized taste recognition test. METHODS: Physically and mentally healthy volunteers (n = 40, age 18-43 years) were randomly allocated to treatment with either pramipexole or placebo using a double-blind, parallel-group design. After 12 to 15 days of treatment (dose titrated up from 0.25 mg/d of pramipexole salt to 1.0 mg/d), taste recognition performance was assessed using a standardized and validated assay (taste strip test). Additionally, visual analogue scale ratings of subjective pleasantness and disgustingness of taste samples were obtained. RESULTS: Compared with the placebo group, participants receiving pramipexole showed significantly higher total recognition accuracy (medianpramipexole = 14.0, medianplacebo = 13.0, U = 264.5, P = .04). This was driven by a higher sensitivity for taste in the pramipexole group. Exploratory analysis of pleasantness and disgustingness ratings of appetitive (sweet) vs aversive (bitter) stimuli suggested that pramipexole treatment was associated with overall blunted hedonic responses, but this effect did not survive the inclusion of nausea (a side effect of treatment) as a covariate in the analysis. CONCLUSIONS: Healthy volunteers who received subacute pramipexole treatment exhibited higher taste recognition performance compared with the placebo group. This finding is consistent with a proposed role of the dopaminergic system in gustatory functioning and could have important theoretical and clinical implications.

Does the relative importance of the OxCAP-MH's capability items differ according to mental ill-health experience?

BACKGROUND: Some capability dimensions may be more important than others in determining someone's well-being, and these preferences might be dependent on ill-health experience. This study aimed to explore the relative preference weights of the 16 items of the German language version of the OxCAP-MH (Oxford Capability questionnaire-Mental Health) capability instrument and their differences across cohorts with alternative levels of mental ill-health experience. METHODS: A Best-Worst-Scaling (BWS) survey was conducted in Austria among 1) psychiatric patients (direct mental ill-health experience), 2) (mental) healthcare experts (indirect mental ill-health experience), and 3) primary care patients with no mental ill-health experience. Relative importance scores for each item of the German OxCAP-MH instrument were calculated using Hierarchical Bayes estimation. Rank analysis and multivariable linear regression analysis with robust standard errors were used to explore the relative importance of the OxCAP-MH items across the three cohorts. RESULTS: The study included 158 participants with complete cases and acceptable fit statistic. The relative importance scores for the full cohort ranged from 0.76 to 15.72. Findings of the BWS experiment indicated that the items Self-determination and Limitation in daily activities were regarded as the most important for all three cohorts. Freedom of expression was rated significantly less important by psychiatric patients than by the other two cohorts, while Having suitable accommodation appeared significantly less important by the expert cohort. There were no further significant differences in the relative preference weights of OxCAP-MH items between the cohorts or according to gender. CONCLUSIONS: Our study indicates significant between-item but limited mental ill-health related heterogeneity in the relative preference weights of the different capability items within the OxCAP-MH. The findings support the future development of preference-based value sets elicited from the general population for comparative economic evaluation purposes.

Cognitive emotional processing across mood disorders.

While impairments in cognitive emotional processing are key to the experience of mood disorders, little is understood of their shared and distinct features across major depressive disorder (MDD) and bipolar disorder (BD). In this review, we discuss the similarities and differences in abnormal emotional processing associated with mood disorders across the cognitive domains of perception, attention, memory, and reward processing, with a particular focus on how these impairments relate to the clinical profile of the disorders. We consider behavioral and neuroimaging evidence, especially that of the growing consensus surrounding mood-congruent biases in cognition, in combination with state- and trait-related characteristics in an attempt to provide a more comprehensive and translational overview of mood disorders. Special consideration is given to the shared phenomenon of mood instability and its role as a potential transdiagnostic marker across the prodrome and maintenance of mood disorders.

Changes over time of the diagnostic and therapeutic characteristics of patients of a psychiatric intensive care unit in Austria.

OBJECTIVE: The aim of this repeated cross-sectional study was to compare patients from a psychiatric intensive care unit (PICU) over ≫30 years regarding their diagnostic and therapeutic characteristics. METHOD: Three samples including 100 consecutive inpatients each from the Viennese PICU were submitted to a chart review: sample no. 1 from the years 1985/86, no. 2 from 1995/96 and no. 3 from 2007/08. RESULTS: Changes in referral modes were associated with a decrease of patients with substance induced disorders and an increase of patients with affective disorders over time. The rate of admissions after accidents and suicides was stable. The use of cranial MRI increased, while intravenous psychopharmacotherapy and parenteral nutrition decreased. Involuntary admission occurred in 43% and in 37% of patients physical restraints were necessary. We saw a shift from tricyclic antidepressants to SSRIs and SNRIs from sample 1 to 3. Likewise, we observed the emergence of atypical antipsychotics and a reduction of use of typical neuroleptics mainly from sample 2 to 3. The percentage of patients receiving benzodiazepines increased over time, while the mean dosage of benzodiazepines decreased. 7% of patients received electroconvulsive therapy. CONCLUSIONS: The changes over time in our samples reflect the medical progress made during the last decades. Future studies should focus on evaluation of efficacy of psychiatric intensive care using standardized measurements.

Do patients with different psychiatric disorders show altered social decision-making? A systematic review of ultimatum game experiments in clinical populations.

BACKGROUND: Impairments in social functioning are a common feature of psychiatric disorders. Game paradigms pose a unique way for studying how people make decisions in interpersonal contexts. In the last decade, researchers have started to use these paradigms to study social decision-making in patients with psychiatric disorders. PURPOSE: The aim of this systematic literature review is to summarise the currently available evidence on the behaviour of patients with psychiatric disorders in the commonly used Ultimatum Game (UG). METHOD: A systematic literature search including MEDLINE, PsycINFO, PSYNDEXplus Tests, PSYNDEXPLUS Literature, EBM Reviews-Cochrane Central Register of Controlled Trials, Embase and PASCAL was performed via the Ovid interface. RESULTS: We found evidence for alterations in UG behaviour for patients with frontotemporal dementia, schizophrenia, affective disorders, alcohol, cocaine, heroin and 3,4-methylenedioxymethamphetamine consumption, alcohol dependence, anxiety disorders, borderline personality disorder, autism, Tourette syndrome and oppositional defiant disorder. CONCLUSION: There is some evidence that different psychiatric disorders might go along with alterations in social decision-making. However, in general, data are currently limited and studies are hard to compare due to differences in methodologies.

Bipolar and related disorders in DSM-5 and ICD-10.

Bipolar disorders are a group of psychiatric disorders with profound negative impact on affected patients. Even if their symptomatology has long been recognized, diagnostic criteria have changed over time and diagnosis often remains difficult. The Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), issued in May 2013, comprises several changes regarding the diagnosis of bipolar disorders compared to the previous edition. Diagnostic categories and criteria for bipolar disorders show some concordance with the internationally also widely used Tenth Edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). However, there are also major differences that are worth highlighting. The aim of the following text is to depict and discuss those.

Pramipexole Enhances Reward Learning by Preserving Value Estimates.

BACKGROUND: Dopamine D2-like agonists show promise as treatments for depression. They are thought to act by enhancing reward learning; however, the mechanisms by which they achieve this are not clear. Reinforcement learning accounts describe 3 distinct candidate mechanisms: increased reward sensitivity, increased inverse decision-temperature, and decreased value decay. As these mechanisms produce equivalent effects on behavior, arbitrating between them requires measurement of how expectations and prediction errors are altered. We characterized the effects of 2 weeks of the D2-like agonist pramipexole on reward learning and used functional magnetic resonance imaging measures of expectation and prediction error to assess which of these 3 mechanistic processes were responsible for the behavioral effects. METHODS: Forty healthy volunteers (50% female) were randomized to 2 weeks of pramipexole (titrated to 1 mg/day) or placebo in a double-blind, between-subject design. Participants completed a probabilistic instrumental learning task before and after the pharmacological intervention, with functional magnetic resonance imaging data collected at the second visit. Asymptotic choice accuracy and a reinforcement learning model were used to assess reward learning. RESULTS: Pramipexole increased choice accuracy in the reward condition with no effect on losses. Participants who received pramipexole had increased blood oxygen level-dependent response in the orbital frontal cortex during the expectation of win trials but decreased blood oxygen level-dependent response to reward prediction errors in the ventromedial prefrontal cortex. This pattern of results indicates that pramipexole enhances choice accuracy by reducing the decay of estimated values during reward learning. CONCLUSIONS: The D2-like receptor agonist pramipexole enhances reward learning by preserving learned values. This is a plausible mechanism for pramipexole's antidepressant effect.

The effects of pramipexole on motivational vigour during a saccade task: a placebo-controlled study in healthy adults.

Motivation allows us to energise actions when we expect reward and is reduced in depression. This effect, termed motivational vigour, has been proposed to rely on central dopamine, with dopaminergic agents showing promise in the treatment of depression. This suggests that dopaminergic agents might act to reduce depression by increasing the effects of reward or by helping energise actions. The aim of the current study was to investigate whether the dopamine agonist pramipexole enhanced motivational vigour during a rewarded saccade task. In addition, we asked whether the effects of pramipexole on vigour differ between reward contingent on performance and guaranteed reward. Healthy adult participants were randomised to receive either pramipexole (n = 19) or placebo (controls n = 18) for 18 days. The vigour of saccades was measured twice, once before the administration of study medication (Time 1) and after taking it for 12-15 days (Time 2). To separate motivation by contingency vs. reward, saccadic vigour was separately measured when (1) rewards were contingent on performance (2) delivered randomly with matched frequency, (3) when reward was guaranteed, (4) when reward was not present at all. Motivation increased response vigour, as expected. Relative to placebo, pramipexole also increased response vigour. However, there was no interaction, meaning that the effects of reward were not modulated by drug, and there was no differential drug effect on contingent vs. guaranteed rewards. The effect of pramipexole on vigour could not be explained by a speed/accuracy trade-off, nor by autonomic arousal as indexed by pupillary dilation. Chronic D2 stimulation increases general vigour, energising movements in healthy adults irrespective of extrinsic reward.

Clinical case report: considerable improvement of severe and difficult-to-treat obsessive-compulsive disorder with comorbid depression under treatment with esketamine and concomitant psychotherapy.

A 28-year-old man was admitted to our psychiatric ward with severe obsessive-compulsive disorder (OCD) and comorbid depression. At intake, obsessive-compulsive symptoms were present most time of the day and were related to an intense fear of causing interpersonal misunderstandings. Various treatment attempts, including cognitive-behavioural therapy (CBT) with exposure and response prevention (ERP), selective serotonin reuptake inhibitors, clomipramine, and add-on antipsychotics were either ineffective and/or were not tolerated, and the patient's condition worsened progressively. Following an in-depth multidisciplinary team discussion and a shared decision-making process, an off-label treatment trial with esketamine and concomitant psychotherapy was started. The patient received 10 esketamine + psychotherapy sessions over a period of about 2 months, followed by two maintenance sessions in about 3-week intervals. After this, he was discharged into regular outpatient care where he continued to receive maintenance esketamine treatment every 4-6 weeks and, independent of this, individual CBT. Following the establishment of esketamine with concurrent psychotherapy, the patient exhibited a remarkable clinical improvement. Obsessive-compulsive symptoms showed a clear and sustained response (Y-BOCS before treatment >35, Y-BOCS at week 8 = 23, Y-BOCS at week 26 = 14). Paralleling this, depressive symptoms also decreased (MADRS before treatment = 47, MADRS at week 9 = 12, MADRS at week 26 = 3). At a naturalistic follow-up at week 66, obsessive-compulsive symptoms were still mild (Y-BOCS = 13), and depression was still in remission (MADRS < 6). This clinical case suggests that (es)ketamine plus concomitant psychotherapy may hold promise as a therapeutic strategy for difficult-to-treat OCD and depression and its full clinical potential should be evaluated in more comprehensive future studies.

How does the COVID-19 pandemic affect the personal lives and care realities of people with a schizophrenia spectrum disorder? A qualitative interview study.

BACKGROUND: The COVID-19 pandemic constitutes one of the greatest recent public crises. This study explored its influence on the lives and care realities of people with a schizophrenia spectrum disorder (SSD). METHODS: Between October 2020 and April 2021, semi-structured in-depth interviews were conducted with 30 volunteers with SSDs receiving inpatient or outpatient treatment in Vienna (Austria). Interviews were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: Three main themes were identified. First, 'Pandemic life is deprived, lonely and surreal - though certain aspects can be perceived as positive'. Second, 'Bio-psycho-social support systems were struck at their core by the pandemic and were left severely compromised'. Last, 'There is a complex interplay between one's prior experience of psychosis and the experience of the COVID-19 pandemic'. The pandemic situation affected interviewees in various ways. For many, it led to a drastic reduction in day-to-day and social activities and contributed to an atmosphere of strangeness and threat. Bio-psycho-social support providers frequently suspended their services and offered alternatives were not always helpful. Participants indicated that whilst having an SSD might render them vulnerable to the pandemic situation, prior experience with psychotic crises can also provide knowledge, skills and self-confidence which enable better coping. Some interviewees also perceived aspects of the pandemic situation as helpful for recovering from psychosis. CONCLUSION: Healthcare providers must acknowledge the perspectives and needs of people with SSDs in present and future public health crises to ensure proper clinical support.

Inhibition of NF-κB-dependent cytokine and inducible nitric oxide synthesis by the macrocyclic ellagitannin oenothein B in TLR-stimulated RAW 264.7 macrophages.

Immunomodulatory effects of oenothein B (1), a macrocyclic ellagitannin from various Onagraceae species, have been described previously. However, the mechanisms underlying the anti-inflammatory activity of 1 have not been fully clarified. The effects of 1 were investigated on inducible nitric oxide synthase, TLR-dependent and TLR-independent signal transduction cascades, and cytokine expression using murine macrophages (RAW 264.7). Compound 1 (10-60 µg/mL) reduced NO production, iNOS mRNA, and iNOS protein levels in a dose-dependent manner, without inhibition of iNOS enzymatic activity. It reduced the binding of the NF-κB p50 subunit to the biotinylated-consensus sequence and decreased nuclear p65 translocation. Gallic acid as a subunit of the macrocyclic ellagitannin 1 showed a far lower inhibitory activity. Nitric oxide production was reduced by 1 after stimulation using TLR2 (Pam2CSK4) and TLR4 (Kdo2) agonists, but this compound did not inhibit inducible nitric oxide synthesis after stimulation using interferon-gamma. IL-1beta, IL-6, and TNF-alpha mRNA synthesis was clearly reduced by the addition of 1. Oenothein B (1) inhibits iNOS after stimulation with LPS, TLR2, and TLR4 agonists via inhibition of TLR/NF-κB-dependent inducible nitric oxide and cytokine synthesis independent from IFN-gamma/JAK/STAT pathways. The full molecular structure of this macrocyclic ellagitannin seems to be required for its immunomodulatory actions.

No antidepressant-like acute effects of bright light on emotional information processing in healthy volunteers.

RATIONALE: Bright light treatment (BLT) is an efficacious antidepressant intervention, but its mechanism of action is not well understood. Antidepressant drugs acutely affect how emotional information is processed, pushing the brain to prioritise positive relative to negative input. Whether BLT could have a similar effect is not known to date. OBJECTIVE: To test whether BLT acutely influences emotional information processing similar to antidepressant drugs, using an established healthy volunteer assay. METHODS: Following a double-blind, parallel-group design, 49 healthy volunteers (18-65 years, 26 females) were randomly allocated to 60-min BLT (≥ 10,000 lux) or sham-placebo treatment early in the morning in autumn/winter. Immediately after treatment, emotional information processing was assessed using the Oxford Emotional Test Battery, a validated set of behavioural tasks tapping into emotional information processing in different cognitive domains. Participants also completed questionnaires before and after treatment to assess changes in subjective state. RESULTS: The BLT group did not show significantly more positively biased emotional information processing compared to the placebo group (p > 0.05 for all measures). After adjustment for pre-treatment scores, there were also no significant post-treatment differences between groups in subjective state (p > 0.05 for all measures). CONCLUSIONS: BLT did not show immediate effects on emotional information processing in an established healthy volunteer assay. Thus, BLT might exert its clinical effects through a different (cognitive) mechanism than other antidepressant interventions. Future studies should corroborate this finding including clinical populations and more intensive treatment regimes, and control for potential chronobiological effects.

An Experimental Medicine Investigation of the Effects of Subacute Pramipexole Treatment on Emotional Information Processing in Healthy Volunteers.

Treatment with the dopamine D2/D3 receptor agonist pramipexole has demonstrated promising clinical effects in patients with depression. However, the mechanisms through which pramipexole might alleviate depressive symptoms are currently not well understood. Conventional antidepressant drugs are thought to work by biasing the processing of emotional information in favour of positive relative to negative appraisal. In this study, we used an established experimental medicine assay to explore whether pramipexole treatment might have a similar effect. Employing a double-blind, parallel-group design, 40 healthy volunteers (aged 18 to 43 years, 50% female) were randomly allocated to 12 to 15 days of treatment with either pramipexole (at a peak daily dose of 1.0 mg pramipexole salt) or placebo. After treatment was established, emotional information processing was assessed on the neural level by measuring amygdala activity in response to positive and negative facial emotional expressions, using functional magnetic resonance imaging (MRI). In addition, behavioural measures of emotional information processing were collected at baseline and on drug, using an established computerized task battery, tapping into different cognitive domains. As predicted, pramipexole-treated participants, compared to those receiving placebo, showed decreased neural activity in response to negative (fearful) vs. positive (happy) facial expressions in bilateral amygdala. Contrary to our predictions, however, pramipexole treatment had no significant antidepressant-like effect on behavioural measures of emotional processing. This study provides the first experimental evidence that subacute pramipexole treatment in healthy volunteers modifies neural responses to emotional information in a manner that resembles the effects of conventional antidepressant drugs.

How representative are neuroimaging samples? Large-scale evidence for trait anxiety differences between fMRI and behaviour-only research participants.

Over the past three decades, functional magnetic resonance imaging (fMRI) has become crucial to study how cognitive processes are implemented in the human brain. However, the question of whether participants recruited into fMRI studies differ from participants recruited into other study contexts has received little to no attention. This is particularly pertinent when effects fail to generalize across study contexts: for example, a behavioural effect discovered in a non-imaging context not replicating in a neuroimaging environment. Here, we tested the hypothesis, motivated by preliminary findings (N = 272), that fMRI participants differ from behaviour-only participants on one fundamental individual difference variable: trait anxiety. Analysing trait anxiety scores and possible confounding variables from healthy volunteers across multiple institutions (N = 3317), we found robust support for lower trait anxiety in fMRI study participants, consistent with a sampling or self-selection bias. The bias was larger in studies that relied on phone screening (compared with full in-person psychiatric screening), recruited at least partly from convenience samples (compared with community samples), and in pharmacology studies. Our findings highlight the need for surveying trait anxiety at recruitment and for appropriate screening procedures or sampling strategies to mitigate this bias.

The neuroscience of depressive disorders: A brief review of the past and some considerations about the future.

Depression is a common and debilitating mental health condition whose underlying aetiology and pathophysiology is still relatively poorly understood. In this article, we first turn to the past and briefly review what neuroscientific investigations have taught us so far about depression. In doing so, we cover neurochemical, neuroendocrine, immunological, functional and structural anatomical, and cognitive levels of description. We then turn our attention to the future and discuss where the field might be moving in the years to come. We argue that future developments may rely on three important lines of enquiry: first, the development of an integrated neuroscientific model of depression and its treatment in which different levels of description can be mechanistically linked, and in which distinct pathophysiological trajectories leading to depressive symptomatology can be identified. Second, the continued search for potentially overlooked pathophysiological factors, especially outside the immediate boundaries of the brain. And third, the improvement in translation of neuroscientific insights to aid and advance clinical practice and research.

Psychotic-like experiences in esoterism: A twilight zone?

BACKGROUND: Over the past decades, research has suggested the existence of a psychosis continuum ranging from psychotic-like experiences (PLEs) in the general population to psychotic symptoms in patients with affective and schizophrenia spectrum disorders. Especially individuals interested in esoterism were more often reported having experienced PLEs. However, there is little information on the extent of PLEs in this subculture. The aim of this study was to assess the extent of PLEs in a non-clinical population with interest in esoterism by means of an anonymized clinically used screening questionnaire. PARTICIPANTS AND METHODS: The 16-item version of the Prodromal Questionnaire (PQ-16), a self-report screening questionnaire assessing the presence of PLEs was administered to individuals with interest in esoterism (IE) and a control group without interest in esoterism (NI). RESULTS: The sample included 402 individuals. 224 subjects (55.7%) reported interest in esoterism and 178 subjects (44.3%) showed no such interest. In an ANCOVA, interest in esoterism was shown to have a significant impact on the PQ-16 score (<0.001). Also, age (p=0.022) and the interaction between age and interest in esoterism had a significant impact on the PQ-16 score (p=0.004). Specifically, younger individuals interested in esoterism showed increased PQ-16 scores, whereas scores decreased with increasing age. In individuals without interest in esoterism, age had no relevant impact on the score. CONCLUSION: Younger individuals interested in esoterism seem to be more prone to reporting psychotic-like experiences compared to individuals without interest in esoterism and compared to their older counterparts.

[Diagnosis of 22q11.2 deletion syndrome in the context of newly developed psychosis]. / Diagnose eines 22q11.2-Mikrodeletionssyndroms im Rahmen einer neu aufgetretenen psychotischen Symptomatik.

22q11.2 deletion syndrome (clinically also known as velocardiofacial or DiGeorge syndrome) is the most common human microdeletion syndrome and can be associated with a multitude of clinical features. In this article we report the case of a 22-year-old patient from Austria who was diagnosed with previously unknown 22q11.2 deletion syndrome in the context of newly developed psychosis. Using this case as an example, we then discuss the implications of 22q11.2 deletion syndrome for clinical psychiatric practice.