Prevention of psychosocial distress consequences in somatic hospital inpatients via a stepped and collaborative care model: protocol of SomPsyNet, a stepped wedge cluster randomised trial.

INTRODUCTION: Approximately 30% of somatic hospital inpatients experience psychosocial distress, contributing to increased (re-)hospitalisation rates, treatment resistance, morbidity, and direct and indirect costs. However, such distress often remains unrecognised and unaddressed. We established 'SomPsyNet', a 'stepped and collaborative care model' (SCCM) for somatic hospital inpatients, aiming at alleviating this issue through early identification of distress and provision of appropriate care, providing problem-focused pathways and strengthening collaborative care. We report the protocol of the 'SomPsyNet' study, aiming to evaluate implementation and impact of the SCCM on distressed patients' health-related quality of life. Secondary objectives include assessing efficacy of the screening procedures, influence of SCCM on other health outcomes and associated costs. METHODS AND ANALYSIS: Our stepped wedge cluster randomised trial conducted at three tertiary hospitals comprises three conditions: treatment as usual (TAU) without screening for distress (phase 0), TAU with screening but without consequences (phase I, main comparator) and TAU with screening and psychosomatic-psychiatric consultations for those distressed (phase II). The time-of-transition between phases I and II was randomised. Sample size target is N=2200-2500 participants, with 6 month follow-up for distressed (anticipated n=640-700) and a subsample of non-distressed (anticipated n=200) patients. Primary outcome is mental health-related quality of life (SF-36 'Mental Health Component Summary score'); secondary outcomes include psychosocial distress, anxiety, depressive and somatic symptoms, symptom burden and distress, resilience, social support and qualitative of life, assessed by internationally accepted instruments, with good psychometric properties. Further, health claims data will be used to assess SCCM's impact on direct and indirect costs. ETHICS AND DISSEMINATION: SomPsyNet adheres to the Helsinki Declaration and is approved by the 'Ethikkommission Nordwest- und Zentralschweiz' (2019-01724). Findings will be published in peer-reviewed journals and communicated to participants, healthcare professionals and the public. TRIAL REGISTRATION NUMBER: Swiss National Clinical Trials Portal; ClinicalTrials.gov (NCT04269005, updated 19.09.2023).

Facilitators and barriers of routine psychosocial distress assessment within a stepped and collaborative care model in a Swiss hospital setting.

BACKGROUND: Stepped and Collaborative Care Models (SCCMs) have shown potential for improving mental health care. Most SCCMs have been used in primary care settings. At the core of such models are initial psychosocial distress assessments commonly in form of patient screening. We aimed to assess the feasibility of such assessments in a general hospital setting in Switzerland. METHODS: We conducted and analyzed eighteen semi-structured interviews with nurses and physicians involved in a recent introduction of a SCCM model in a hospital setting, as part of the SomPsyNet project in Basel-Stadt. Following an implementation research approach, we used the Tailored Implementation for Chronic Diseases (TICD) framework for analysis. The TICD distinguishes seven domains: guideline factors, individual healthcare professional factors, patient factors, professional interactions, incentives and resources, capacity for organizational change, and social, political, and legal factors. Domains were split into themes and subthemes, which were used for line-by-line coding. RESULTS: Nurses and physicians reported factors belonging to all seven TICD domains. An appropriate integration of the psychosocial distress assessment into preexisting hospital processes and information technology systems was the most important facilitator. Subjectivity of the assessment, lack of awareness about the assessment, and time constraints, particularly among physicians, were factors undermining and limiting the implementation of the psychosocial distress assessment. CONCLUSIONS: Awareness raising through regular training of new employees, feedback on performance and patient benefits, and working with champions and opinion leaders can likely support a successful implementation of routine psychosocial distress assessments. Additionally, aligning psychosocial distress assessments with workflows is essential to assure the sustainability of the procedure in a working context with commonly limited time.

Daring to Feel: Emotion-Focused Psychotherapy Increases Amygdala Activation and Connectivity in Euthymic Bipolar Disorder-A Randomized Controlled Trial.

BACKGROUND: In bipolar disorder (BD), the alternation of extreme mood states indicates deficits in emotion processing, accompanied by aberrant neural function of the emotion network. The present study investigated the effects of an emotion-centered psychotherapeutic intervention on amygdala responsivity and connectivity during emotional face processing in BD. METHODS: In a randomized controlled trial within the multicentric BipoLife project, euthymic patients with BD received one of two interventions over 6 months: an unstructured, emotion-focused intervention (FEST), where patients were guided to adequately perceive and label their emotions (n = 28), or a specific, structured, cognitive behavioral intervention (SEKT) (n = 31). Before and after interventions, functional magnetic resonance imaging was conducted while patients completed an emotional face-matching paradigm (final functional magnetic resonance imaging sample of patients completing both measurements: SEKT, n = 17; FEST, n = 17). Healthy control subjects (n = 32) were scanned twice after the same interval without receiving any intervention. Given the focus of FEST on emotion processing, we expected FEST to strengthen amygdala activation and connectivity. RESULTS: Clinically, both interventions stabilized patients' euthymic states in terms of affective symptoms. At the neural level, FEST versus SEKT increased amygdala activation and amygdala-insula connectivity at postintervention relative to preintervention time point. In FEST, the increase in amygdala activation was associated with fewer depressive symptoms (r = 0.72) 6 months after intervention. CONCLUSIONS: Enhanced activation and functional connectivity of the amygdala after FEST versus SEKT may represent a neural marker of improved emotion processing, supporting the FEST intervention as an effective tool in relapse prevention in patients with BD.

Post-COVID-19 condition in the German working population: A cross-sectional study of 200,000 registered stem cell donors.

BACKGROUND: The SARS-CoV-2 pandemic has strained health systems worldwide, and infection numbers continue to rise. While previous data have already shown that many patients suffer from symptoms for months after an acute infection, data on risk factors and long-term outcomes are incomplete, particularly for the working population. OBJECTIVES: We aimed to provide information on the prevalence of post-COVID-19 conditions in a subset of the German working-age population (18-61 years old) and to analyze risk factors. METHODS: We conducted an online survey with a health questionnaire among registered potential stem cell donors with or without a self-reported history of polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection. Logistic regression models were used to examine the risks of severity of acute infection, sex, age, body mass index, diabetes mellitus, and arterial hypertension medication on post-COVID-19 symptoms. RESULTS: A total of 199,377 donors reported evaluable survey questionnaires-12,609 cases had a history of SARS-CoV-2 infection and 186,768 controls had none. Overall, cases reported physical, cognitive, and psychological complaints more frequently compared to controls. Increased rates of complaints persisted throughout 15 months postinfection, for example, 28.4%/19.3% of cases/controls reported fatigue (p <0.0001) and 9.5%/3.6% of cases/controls reported loss of concentration (p <0.0001). No significant differences were observed in the frequency of reported symptoms between 3 and 15 months postinfection. Multivariate analysis revealed a strong influence of the severity of the acute SARS-CoV-2 infection episode and age on the risk for post-COVID-19 conditions. CONCLUSION: We report the prevalence of post-COVID-19 conditions in mainly unvaccinated individuals with SARS-CoV-2 infections between February 2020 and August 2021. The severity of the acute course and age were major risk factors. Vaccinations may reduce the risk of post-COVID-19 conditions by reducing the risk of severe infections.

Boosting the Theory of Mind Network: Specific Psychotherapy Increases Neural Correlates of Affective Theory of Mind in Euthymic Bipolar Disorder.

BACKGROUND: In bipolar disorder, impaired affective theory of mind (aToM) performance and aberrant neural activation in the ToM brain network partly explain social functioning impairments. However, it is not yet known whether psychotherapy of bipolar disorder influences neuroimaging markers of aToM. METHODS: In this study, conducted within the multicentric randomized controlled trial of the BipoLife consortium, patients with euthymic bipolar disorder underwent 2 group interventions over 6 months (mean = 28.45 weeks): 1) a specific, cognitive behavioral intervention (specific psychotherapeutic intervention [SEKT]) (n = 31) targeting impulse regulation, ToM, and social skills and 2) an emotion-focused intervention (FEST) (n = 28). To compare the effect of SEKT and FEST on neural correlates of aToM, patients performed an aToM task during functional magnetic resonance imaging before and after interventions (final functional magnetic resonance imaging sample of pre- and postcompleters, SEKT: n = 16; FEST: n = 17). Healthy control subjects (n = 32) were scanned twice with the same time interval. Because ToM was trained in SEKT, we expected an increased ToM network activation in SEKT relative to FEST postintervention. RESULTS: Both treatments effectively stabilized patients' euthymic state in terms of affective symptoms, life satisfaction, and global functioning. Confirming our expectations, SEKT patients showed increased neural activation within regions of the ToM network, bilateral temporoparietal junction, posterior cingulate cortex, and precuneus, whereas FEST patients did not. CONCLUSIONS: The stabilizing effect of SEKT on clinical outcomes went along with increased neural activation of the ToM network, while FEST possibly exerted its positive effect by other, yet unexplored routes.

Association of Different Restriction Levels With COVID-19-Related Distress and Mental Health in Somatic Inpatients: A Secondary Analysis of Swiss General Hospital Data.

Background: The coronavirus disease 2019 (COVID-19) pandemic and related countermeasures hinder health care access and affect mental wellbeing of non-COVID-19 patients. There is lack of evidence on distress and mental health of patients hospitalized due to other reasons than COVID-19-a vulnerable population group in two ways: First, given their risk for physical diseases, they are at increased risk for severe courses and death related to COVID-19. Second, they may struggle particularly with COVID-19 restrictions due to their dependence on social support. Therefore, we investigated the association of intensity of COVID-19 restrictions with levels of COVID-19-related distress, mental health (depression, anxiety, somatic symptom disorder, and mental quality of life), and perceived social support among Swiss general hospital non-COVID-19 inpatients. Methods: We analyzed distress of 873 hospital inpatients not admitted for COVID-19, recruited from internal medicine, gynecology, rheumatology, rehabilitation, acute geriatrics, and geriatric rehabilitation wards of three hospitals. We assessed distress due to the COVID-19 pandemic, and four indicators of mental health: depressive and anxiety symptom severity, psychological distress associated with somatic symptoms, and the mental component of health-related quality of life; additionally, we assessed social support. The data collection period was divided into modest (June 9 to October 18, 2020) and strong (October 19, 2020, to April 17, 2021) COVID-19 restrictions, based on the Oxford Stringency Index for Switzerland. Results: An additional 13% (95%-Confidence Interval 4-21%) and 9% (1-16%) of hospital inpatients reported distress related to leisure time and loneliness, respectively, during strong COVID-19 restrictions compared to times of modest restrictions. There was no evidence for changes in mental health or social support. Conclusions: Focusing on the vulnerable population of general hospital inpatients not admitted for COVID-19, our results suggest that tightening of COVID-19 restrictions in October 2020 was associated with increased COVID-19-related distress regarding leisure time and loneliness, with no evidence for a related decrease in mental health. If this association was causal, safe measures to increase social interaction (e.g., virtual encounters and outdoor activities) are highly warranted. Trial registration: www.ClinicalTrials.gov, identifier: NCT04269005.

Evolution of psychosocial burden and psychiatric symptoms in patients with psychiatric disorders during the Covid-19 pandemic.

The Covid-19 pandemic highly impacts mental health worldwide. Patients with psychiatric disorders are a vulnerable risk population for worsening of their condition and relapse of symptoms. This study investigates the pandemic-related course of psychosocial burden in patients with pre-existing mental disorders. With the newly developed Goettingen psychosocial Burden and Symptom Inventory (Goe-BSI) psychosocial burden has been traced retrospectively (1) before the pandemic (beginning of 2020), (2) at its beginning under maximum lockdown conditions (March 2020), and (3) for the current state after maximum lockdown conditions (April/May 2020). The Goe-BSI also integrates the Adjustment Disorder New Module (ADNM-20), assesses general psychiatric symptoms, and resilience. A total of 213 patients covering all major psychiatric disorders (ICD-10 F0-F9) were interviewed once in the time range from April, 24th until May 11th, 2020. Across all diagnoses patients exhibited a distinct pattern with an initial rise followed by a decline of psychosocial burden (p < 0.001, partial η2 = 0.09; Bonferroni-corrected pairwise comparisons between all three time-points: p < 0.05 to 0.001). Female gender and high ADNM-20 scores were identified as risk factors for higher levels and an unfavorable course of psychosocial burden over time. Most psychiatric symptoms remained unchanged. Trajectories of psychosocial burden vary in parallel to local lockdown restrictions and seem to reflect an adaptive stress response. For female patients with pre-existing mental disorders and patients with high-stress responses, timely and specific treatment should be scheduled. With the continuation of the pandemic, monitoring of long-term effects is of major importance, especially when long incubation times for the development of mental health issues are considered.

Medium-term and peri-lockdown course of psychosocial burden during the ongoing COVID-19 pandemic: a longitudinal study on patients with pre-existing mental disorders.

While the COVID-19 pandemic continues, patients with pre-existing mental disorders are increasingly recognized as a risk group for adverse outcomes. However, data are conflicting and cover only short time spans so far. Here, we investigate the medium-term and peri-lockdown-related changes of mental health outcomes in such patients in a longitudinal study. A cohort of 159 patients comprising all major mental disorders (ICD-10 F0-F9) were interviewed twice with the Goettingen psychosocial Burden and Symptom Inventory (Goe-BSI) to evaluate psychosocial burden, psychiatric symptoms and resilience at the end of the first (April/May 2020) and the second lockdown in Germany (November/December 2020). For the primary outcome "psychosocial burden" ratings also comprised retrospective pre-pandemic (early 2020) and very early states during the pandemic (March 2020). For all diagnostic groups, psychosocial burden varied significantly over time (p < 0.001) with an increase from the pre-pandemic to the initial phase (p < 0.001), followed by a steady decrease across both lockdowns, normalizing in November/December 2020. Female gender, high adjustment disorder symptom load at baseline and psychiatric comorbidities were risk factors for higher levels and an unfavorable course of psychosocial burden. Most psychiatric symptoms changed minimally, while resilience decreased over time (p = 0.044 and p = 0.037). The longitudinal course of psychosocial burden indicates an initial stress response, followed by a return to pre-pandemic levels even under recurrent lockdown conditions, mimicking symptoms of an adjustment disorder. Strategies for proactive, specific and continuous treatment have to address resilience capacities before their depletion in the pandemic aftermath, especially for patients with additional risk factors.

Individual HLA-A, -B, -C, and -DRB1 Genotypes Are No Major Factors Which Determine COVID-19 Severity.

HLA molecules are key restrictive elements to present intracellular antigens at the crossroads of an effective T-cell response against SARS-CoV-2. To determine the impact of the HLA genotype on the severity of SARS-CoV-2 courses, we investigated data from 6,919 infected individuals. HLA-A, -B, and -DRB1 allotypes grouped into HLA supertypes by functional or predicted structural similarities of the peptide-binding grooves did not predict COVID-19 severity. Further, we did not observe a heterozygote advantage or a benefit from HLA diplotypes with more divergent physicochemical peptide-binding properties. Finally, numbers of in silico predicted viral T-cell epitopes did not correlate with the severity of SARS-CoV-2 infections. These findings suggest that the HLA genotype is no major factor determining COVID-19 severity. Moreover, our data suggest that the spike glycoprotein alone may allow for abundant T-cell epitopes to mount robust T-cell responses not limited by the HLA genotype.

[Electroconvulsive therapy in pregnancy: case report and interdisciplinary treatment suggestions]. / Elektrokonvulsionstherapie in der Schwangerschaft: Fallbericht und interdisziplinäre Behandlungsvorschläge.

BACKGROUND: Psychiatric disorders during pregnancy are common. Electroconvulsive therapy (ECT) can be indicated in severely affective or psychotic disorders with the necessity of a rapid response. Currently available review articles greatly differ in the methodology, leading to divergent conclusions concerning the use of ECT during pregnancy. OBJECTIVE: Description of a new clinical case and interdisciplinary treatment suggestions for the safe application of ECT in pregnancy. METHODS: Clinical case report and selective review of the literature with special consideration of existing systematic reviews. RESULTS AND CONCLUSION: This case report shows the potentially high effectiveness and safe administration of ECT in pregnancy for both mother and fetus. The undesired adverse events associated with ECT described in the literature are largely qualitatively congruent with the risks of severe psychotic disorders in pregnancy per se. For a better risk-benefit analysis, larger case control studies would be desirable. Under the premise of a thorough evaluation of the indications, good interdisciplinary coordination and consideration of the specific practical requirements, ECT is a useful therapeutic option in pregnancy.

Cortical activation abnormalities in bipolar and schizophrenia patients in a combined oddball-incongruence paradigm.

Patients with bipolar disorder and schizophrenia often suffer from severe cognitive impairment even during times of remission. This study investigated the pathomechanisms underlying their deficits in cognitive control. A combined oddball-incongruence fMRI task was applied to examine similarities and differences of neural activation patterns between patients and healthy controls. Bipolar and schizophrenia patients demonstrated hyperactivations in the intraparietal cortex during the oddball condition. Furthermore, bipolar patients revealed diagnosis-specific hyperactivation in the left middle frontal gyrus, precentral gyrus, anteroventral prefrontal cortex and orbitofrontal cortex regions compared to schizophrenia patients and healthy individuals. In comparison to healthy controls the patients showed hypoactivations in the inferior frontal junction and ventral pathway during the cognitively more demanding incongruence. Taken together, bipolar patients seem to recruit frontal and parietal areas during the oddball condition to compensate for potential deficits in their attentional network. During more challenging tasks, i.e., the incongruence condition, their compensatory mechanisms seem to collapse leading to hypoactivations in the same frontal areas as well as the ventral pathway.

[Video presentations for examination questions in psychiatry : A pilot study]. / Videodarstellungen in psychiatrischen Prüfungsfragen : Eine Pilotstudie.

BACKGROUND: The master plan for medical studies 2020 (MM2020) aims at a restructuring of medical education. The examinations should represent the key element of the evaluation and electronically supported examination methods will be expanded. OBJECTIVE: Videos of actors displaying psychopathological phenomena were implemented into examination questions for the first time through the use of an electronically supported examination (e-examination) and therefore in accordance with the aims of MM2020. METHODS: A total of four multiple choice (MC) questions referencing short video representations of different psychopathological phenomena were formulated and shown to medical students within an e­examination. The MC questions were evaluated with respect to scientific quality criteria and the medical students were asked to fill in a questionnaire regarding their evaluation of the content and format of the MC questions after participating in the examination. RESULTS: The MC video questions were presented to the students directly following the regular e­examination of the teaching module in psychiatry. Out of 69 students 60 participated in the study. The MC video questions had a high level of acceptance and positive evaluation by the students. With respect to the scientific quality criteria, the MC questions showed heterogeneous results. CONCLUSION: Due to the versatile applicability and high efficiency, MC questions will continue to play an important role in medical examinations. In accordance with the aims of MM2020, it could be shown that psychiatric knowledge can be examined in a competence-oriented manner and with a practical orientation by means of video presentations in an e­examination. A broader application of video presentations could complement electronically supported examinations in the discipline of psychiatry.

Investigating the Impact of a Genome-Wide Supported Bipolar Risk Variant of MAD1L1 on the Human Reward System.

Recent genome-wide association studies have identified MAD1L1 (mitotic arrest deficient-like 1) as a susceptibility gene for bipolar disorder and schizophrenia. The minor allele of the single-nucleotide polymorphism (SNP) rs11764590 in MAD1L1 was associated with bipolar disorder. Both diseases, bipolar disorder and schizophrenia, are linked to functional alterations in the reward system. We aimed at investigating possible effects of the MAD1L1 rs11764590 risk allele on reward systems functioning in healthy adults. A large homogenous sample of 224 young (aged 18-31 years) participants was genotyped and underwent functional magnetic resonance imaging (fMRI). All participants performed the 'Desire-Reason Dilemma' paradigm investigating the neural correlates that underlie reward processing and active reward dismissal in favor of a long-term goal. We found significant hypoactivations of the ventral tegmental area (VTA), the bilateral striatum and bilateral frontal and parietal cortices in response to conditioned reward stimuli in the risk allele carriers compared with major allele carriers. In the dilemma situation, functional connectivity between prefrontal brain regions and the ventral striatum was significantly diminished in the risk allele carriers. Healthy risk allele carriers showed a significant deficit of their bottom-up response to conditioned reward stimuli in the bilateral VTA and striatum. Furthermore, functional connectivity between the ventral striatum and prefrontal areas exerting top-down control on the mesolimbic reward system was reduced in this group. Similar alterations in reward processing and disturbances of prefrontal control mechanisms on mesolimbic brain circuits have also been reported in bipolar disorder and schizophrenia. Together, these findings suggest the existence of an intermediate phenotype associated with MAD1L1.

Differentiating unipolar and bipolar depression by alterations in large-scale brain networks.

BACKGROUND: Misdiagnosing bipolar depression can lead to very deleterious consequences of mistreatment. Although depressive symptoms may be similarly expressed in unipolar and bipolar disorder, changes in specific brain networks could be very distinct, being therefore informative markers for the differential diagnosis. We aimed to characterize specific alterations in candidate large-scale networks (frontoparietal, cingulo-opercular, and default mode) in symptomatic unipolar and bipolar patients using resting state fMRI, a cognitively low demanding paradigm ideal to investigate patients. METHODS: Networks were selected after independent component analysis, compared across 40 patients acutely depressed (20 unipolar, 20 bipolar), and 20 controls well-matched for age, gender, and education levels, and alterations were correlated to clinical parameters. RESULTS: Despite comparable symptoms, patient groups were robustly differentiated by large-scale network alterations. Differences were driven in bipolar patients by increased functional connectivity in the frontoparietal network, a central executive and externally-oriented network. Conversely, unipolar patients presented increased functional connectivity in the default mode network, an introspective and self-referential network, as much as reduced connectivity of the cingulo-opercular network to default mode regions, a network involved in detecting the need to switch between internally and externally oriented demands. These findings were mostly unaffected by current medication, comorbidity, and structural changes. Moreover, network alterations in unipolar patients were significantly correlated to the number of depressive episodes. CONCLUSION: Unipolar and bipolar groups displaying similar symptomatology could be clearly distinguished by characteristic changes in large-scale networks, encouraging further investigation of network fingerprints for clinical use. Hum Brain Mapp 37:808-818, 2016. © 2015 Wiley Periodicals, Inc.

CREB1 Genotype Modulates Adaptive Reward-Based Decisions in Humans.

Cyclic AMP response element-binding protein (CREB) contributes to adaptation of mesocorticolimbic networks by modulating activity-regulated transcription and plasticity in neurons. Activity or expression changes of CREB in the nucleus accumbens (NAc) and orbital frontal cortex (OFC) interact with behavioral changes during reward-motivated learning. However, these findings from animal models have not been evaluated in humans. We tested whether CREB1 genotypes affect reward-motivated decisions and related brain activation, using BOLD fMRI in 224 young and healthy participants. More specifically, participants needed to adapt their decision to either pursue or resist immediate rewards to optimize the reward outcome. We found significant CREB1 genotype effects on choices to pursue increases of the reward outcome and on BOLD signal in the NAc, OFC, insula cortex, cingulate gyrus, hippocampus, amygdala, and precuneus during these decisions in comparison with those decisions avoiding total reward loss. Our results suggest that CREB1 genotype effects in these regions could contribute to individual differences in reward- and associative memory-based decision-making.

Hyperresponsivity and impaired prefrontal control of the mesolimbic reward system in schizophrenia.

Schizophrenia is characterized by substantial dysfunctions of reward processing, leading to detrimental consequences for decision-making. The neurotransmitter dopamine is responsible for the transmission of reward signals and also known to be involved in the mechanism of psychosis. Using functional magnetic resonance imaging (fMRI), sixteen medicated patients with schizophrenia and sixteen healthy controls performed the 'desire-reason dilemma' (DRD) paradigm. This paradigm allowed us to directly investigate reward-related brain activations depending on the interaction of bottom-up and top-down mechanisms, when a previously conditioned reward stimulus had to be rejected to achieve a superordinate long-term goal. Both patients and controls showed significant activations in the mesolimbic reward system. In patients with schizophrenia, however, we found a significant hyperactivation of the left ventral striatum (vStr) when they were allowed to accept the conditioned reward stimuli, and a reduced top-down regulation of activation in the ventral striatum (vStr) and ventral tegmental area (VTA) while having to reject the immediate reward to pursue the superordinate task-goal. Moreover, while healthy subjects exhibited a negative functional coupling of the vStr with both the anteroventral prefrontal cortex (avPFC) and the ventromedial prefrontal cortex (VMPFC) in the dilemma situation, this functional coupling was significantly impaired in the patient group. These findings provide evidence for an increased ventral striatal activation to reward stimuli and an impaired top-down control of reward signals by prefrontal brain regions in schizophrenia.

Disturbed cortico-amygdalar functional connectivity as pathophysiological correlate of working memory deficits in bipolar affective disorder.

Patients suffering from bipolar affective disorder show deficits in working memory functions. In a previous functional magnetic resonance imaging study, we observed an abnormal hyperactivity of the amygdala in bipolar patients during articulatory rehearsal in verbal working memory. In the present study, we investigated the dynamic neurofunctional interactions between the right amygdala and the brain systems that underlie verbal working memory in both bipolar patients and healthy controls. In total, 18 euthymic bipolar patients and 18 healthy controls performed a modified version of the Sternberg item-recognition (working memory) task. We used the psychophysiological interaction approach in order to assess functional connectivity between the right amygdala and the brain regions involved in verbal working memory. In healthy subjects, we found significant negative functional interactions between the right amygdala and multiple cortical brain areas involved in verbal working memory. In comparison with the healthy control subjects, bipolar patients exhibited significantly reduced functional interactions of the right amygdala particularly with the right-hemispheric, i.e., ipsilateral, cortical regions supporting verbal working memory. Together with our previous finding of amygdala hyperactivity in bipolar patients during verbal rehearsal, the present results suggest that a disturbed right-hemispheric "cognitive-emotional" interaction between the amygdala and cortical brain regions underlying working memory may be responsible for amygdala hyperactivation and affects verbal working memory (deficits) in bipolar patients.

Dissociating pathomechanisms of depression with fMRI: bottom-up or top-down dysfunctions of the reward system.

Depression is a debilitating psychiatric disorder characterized among other aspects by the inability to properly experience or respond to reward. However, it remains unclear whether patients with depression present impaired reward system due to abnormal modulatory mechanisms. We investigated the activation of the nucleus accumbens (NAcc), a crucial region involved in reward processing, with functional magnetic resonance imaging using the desire-reason-dilemma paradigm. This task allows tracking the activity of the NAcc during the acceptance or the rejection of previously conditioned reward stimuli. Patients were assigned into subgroups of lower (LA) or higher (HA) NAcc activation according to beta weights. LA patients presented significant hypoactivation in the ventral tegmental area in addition to bilateral ventral striatum, confirming impairments in the bottom-up input to the NAcc. Conversely, HA patients presented significant hyperactivation in prefrontal areas such as the rostral anterior cingulate cortex and the anterior ventral prefrontal cortex in addition to bilateral ventral striatum, suggesting disturbances in the top-down regulation of the NAcc. Demographic and clinical differences explaining the abnormal co-activations of midbrain and prefrontal regions were not identified. Therefore, we provide evidence for dysfunctional bottom-up processing in one potential neurobiological subtype of depression (LA) and dysfunctional top-down modulation in another subtype (HA). We suggest that the midbrain and prefrontal regions are more specific pathophysiological substrates for each depression subtype. Above all, our results encourage the segregation of patients by similar dysfunctional mechanisms of the dopaminergic system, which would finally contribute to disentangle more specific pathogeneses and guide the development of more personalized targets for future therapies.