To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Major Depressive Disorder (MDD) is one of the most common mental illnesses worldwide and is strongly associated with suicidality. Commonly used treatments for MDD with suicidality include crisis intervention, oral antidepressants (although risk of suicidal behavior is high among non-responders and during the first 10-14 days of the treatment) benzodiazepines and lithium. Although several interventions addressing suicidality exist, only few studies have characterized in detail patients with MDD and suicidality, including treatment, clinical course and outcomes. Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D)-study is an investigator-initiated trial funded by Janssen-Cilag GmbH.
For population 1 out of 3 OASIS-D populations, to assess the sub-population of patients with suicidality and its correlates in hospitalized individuals with MDD.
The ongoing OASIS-D study consecutively examines hospitalized patients at 8 German psychiatric university hospitals treated as part of routine clinical care. A sub-group of patients with persistent suicidality after >48 hours post-hospitalization are assessed in detail and a sub-group of those are followed for 6 months to assess course and treatment of suicidality associated with MDD. The present analysis focuses on a preplanned interim analysis of the overall hospitalized population with MDD.
Of 2,049 inpatients (age=42.5±15.9 years, females=53.2%), 68.0% had severe MDD without psychosis and 21.2% had moderately severe MDD, with 16.7% having treatment-resistant MDD. Most inpatients referred themselves (49.4%), followed by referrals by outpatient care providers (14.6%), inpatient care providers (9.0%), family/friends (8.5%), and ambulance (6.8%). Of these admissions, 43.1% represented a psychiatric emergency, with suicidality being the reason in 35.9%. Altogether, 72.4% had at least current passive suicidal ideation (SI, lifetime=87.2%), including passive SI (25.1%), active SI without plan (15.5%), active SI with plan (14.2%), and active SI with plan+intent (14.1%), while 11.5% had attempted suicide ≤2 weeks before admission (lifetime=28.7%). Drug-induced mental and behavioral disorders (19.6%) were the most frequent comorbid disorders, followed by personality disorders (8.2%). Upon admission, 64.5% were receiving psychiatric medications, including antidepressants (46.7%), second-generation antipsychotics (23.0%), anxiolytics (11.4%) antiepileptics (6.0%), and lithium (2.8%). Altogether, 9.8% reported nonadherence to medications within 6 months of admission.
In adults admitted for MDD, suicidality was common, representing a psychiatric emergency in 35.9% of patients. Usual-care treatments and outcomes of suicidality in hospitalized adults with MDD require further study.
Refugees and asylum seekers (RAS) in Germany need tailored and resource-oriented mental healthcare interventions.
To evaluate the cost-effectiveness of group psychotherapy for RAS with moderate depressive symptoms.
This is a post hoc cost-effectiveness analysis of Empowerment group psychotherapy that was embedded in a stratified stepped and collaborative care model (SCCM) from the multicentre randomised controlled MEHIRA trial. One hundred and forty-nine participants were randomly assigned to SCCM or treatment as usual (TAU) and underwent Empowerment (i.e. level 3 of the SCCM for adults) or TAU. Effects were measured with the nine-item Patient Health Questionnaire (PHQ-9) and quality adjusted life-years (QALY) post-intervention. Health service and intervention costs were measured. Incremental cost-effectiveness ratios (ICER) were estimated and net monetary benefit (NMB) regressions with 95% confidence intervals were performed. Cost-effectiveness was ascertained for different values of willingness to pay (WTP) using cost-effectiveness acceptability curves for probable scenarios. Trial registration number: NCT03109028 on ClinicalTrials.gov.
Health service use costs were significantly lower for Empowerment than TAU after 1 year. Intervention costs were on average €409.6. Empowerment led to a significant change in PHQ-9 scores but not QALY. Bootstrapped mean ICER indicated cost-effectiveness according to PHQ-9 and varied considerably for QALY in the base case. NMB for a unit reduction in PHQ-9 score at WTP of €0 was €354.3 (€978.5 to −€269.9). Results were confirmed for different scenarios and varying WTP thresholds.
The Empowerment intervention was cost-effective in refugees with moderate depressive symptoms regarding the clinical outcome and led to a reduction in direct healthcare consumption. Concerning QALYs, there was a lack of confidence that Empowerment differed from TAU.
Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.
Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).
Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.
Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.
Background Urban birth, urban living, and ethnic minority status are established risk factors for schizophrenia, but the mechanisms are unclear. Previous evidence suggests a causal role of social exposures and adverse experiences, but experimental evidence is scarce. Methods We combine multimodal neuroimaging with ecological momentary assessment, geolocation and geospatial analysis in an epidemiological longitudinal sample in Germany. Results We find that established risk factors converge on the perigenual cingulate-amygdala-ventral striatal pathway as shown by structural and functional imaging, supporting a role for the ventral-striatal system in psychosis risk. Using a combination of PET and fMRI data in migrants, we suggest a mechanistic link to psychosis by increased dopamine release and synthesis in striatum secondary to prefrontal dysregulation. Importantly, the regulatory system identified overlaps with that implicated in racial stereotyping and prejudice. Moreover, an experiment measuring information flow during an exchange between migrants and non-migrants indicates that during a trust interaction, cultural distance governs the exchange. Conclusions This work shows a convergent risk circuit related to minority position and migration that could guide primary prevention of schizophrenia through reduction of manifestation risk by contextual intervention.
There are many reasons for people with (and without) severe mental illness to exercise regularly. In people with schizophrenia, major depression and bipolar disorder, it has already been shown that regular physical activity as an add-on therapy can improve quality of life and symptom severity. This is particularly important in domains that standard therapy is currently not able to treat sufficiently, such as cognitive deficits. Postulated underlying neurobiological effects include increased volume in hippocampal areas as demonstrated by data of a current clinical trial in people with schizophrenia.
Furthermore, regular exercise is essential to counteract the increased cardiovascular morbidity and mortality of people with severe mental illness. However, most people with severe mental illness do not achieve the recommended amount of physical activity and the potential of exercise as an add-on therapy is currently not even close to being fully realized. On the one hand, it is important that mental health staff also considers the physical condition of patients with mental illnesses and counsels them on their health behavior. On the other hand, there is a need for individually adapted training programs delivered by qualified exercise professionals that incorporate motivational and adherence strategies. Examples of barriers and facilitators for the implementation of exercise as an add-on therapy are discussed on the basis of current local projects.
Disruptive behavior disorders (DBD) are heterogeneous at the clinical and the biological level. Therefore, the aims were to dissect the heterogeneous neurodevelopmental deviations of the affective brain circuitry and provide an integration of these differences across modalities.
We combined two novel approaches. First, normative modeling to map deviations from the typical age-related pattern at the level of the individual of (i) activity during emotion matching and (ii) of anatomical images derived from DBD cases (n = 77) and controls (n = 52) aged 8–18 years from the EU-funded Aggressotype and MATRICS consortia. Second, linked independent component analysis to integrate subject-specific deviations from both modalities.
While cases exhibited on average a higher activity than would be expected for their age during face processing in regions such as the amygdala when compared to controls these positive deviations were widespread at the individual level. A multimodal integration of all functional and anatomical deviations explained 23% of the variance in the clinical DBD phenotype. Most notably, the top marker, encompassing the default mode network (DMN) and subcortical regions such as the amygdala and the striatum, was related to aggression across the whole sample.
Overall increased age-related deviations in the amygdala in DBD suggest a maturational delay, which has to be further validated in future studies. Further, the integration of individual deviation patterns from multiple imaging modalities allowed to dissect some of the heterogeneity of DBD and identified the DMN, the striatum and the amygdala as neural signatures that were associated with aggression.
Aberrant brain connectivity during emotional processing, especially within the fronto-limbic pathway, is one of the hallmarks of major depressive disorder (MDD). However, the methodological heterogeneity of previous studies made it difficult to determine the functional and etiological implications of specific alterations in brain connectivity. We previously reported alterations in psychophysiological interaction measures during emotional face processing, distinguishing depressive pathology from at-risk/resilient and healthy states. Here, we extended these findings by effective connectivity analyses in the same sample to establish a refined neural model of emotion processing in depression.
Thirty-seven patients with MDD, 45 first-degree relatives of patients with MDD and 97 healthy controls performed a face-matching task during functional magnetic resonance imaging. We used dynamic causal modeling to estimate task-dependent effective connectivity at the subject level. Parametric empirical Bayes was performed to quantify group differences in effective connectivity.
MDD patients showed decreased effective connectivity from the left amygdala and left lateral prefrontal cortex to the fusiform gyrus compared to relatives and controls, whereas patients and relatives showed decreased connectivity from the right orbitofrontal cortex to the left insula and from the left orbitofrontal cortex to the right fusiform gyrus compared to controls. Relatives showed increased connectivity from the anterior cingulate cortex to the left dorsolateral prefrontal cortex compared to patients and controls.
Our results suggest that the depressive state alters top-down control of higher visual regions during face processing. Alterations in connectivity within the cognitive control network present potential risk or resilience mechanisms.
Environmental factors and both common and rare genetic variants increasing risk for schizophrenia are being discovered, but the neural mechanisms that mediate their impact are only now coming into focus. We discuss work from a translational genetics approach, with a focus on neuroimaging, delineating mechanisms of genetic risk through interaction of prefrontal cortex with striatum, midbrain and hippocampus. Using social status as an example, we identify dissociable neural responses to perceived social rank using functional magnetic resonance imaging (fMRI) in an interactive, simulated social context. In both stable and unstable social hierarchies, viewing a superior individual differentially engaged perceptual-attentional, saliency, and cognitive systems, notably dorsolateral prefrontal cortex. In the unstable hierarchy setting, additional regions related to emotional processing (amygdala), social cognition (medial prefrontal cortex), and behavioral readiness were recruited. Furthermore, social hierarchical consequences of performance were neurally dissociable and of comparable salience to monetary reward, providing a neural basis for the high motivational value of status. Finally, we discuss GEI impacting on these circuits, with a focus on validating epidemiologically identified GEI on the neural circuit level.
Nowhere in medicine are biomarkers more urgently needed, and more difficult to obtain, than in psychiatry. One the one hand, psychiatric disorders account for a large proportion of the size and burden of disease in Europe and are leading causes of early retirement and sick days at work, pointing to a tremendous unmet medical need. On the other hand, our currently used psychiatric nosology lacks biological validity and is difficult to translate into therapeutic targets and strategies.
Consequently, a large disinvestment of pharmaceutical research and development from psychiatry has happened in the last two years, pointing to an urgent need for reconceptualizing the psychiatric translational enterprise.
In this lecture, we will introduce and review strategies for deriving and using biomarkers in psychiatric translation, using schizophrenia as an example. Our main approach will be to define, using multimodal biological techniques, mechanisms of risk for schizophrenia that can then be interfaced with drug and psychotherapy development at various levels ranging from target detection over better animal models to new approaches to early human studies and finally to personalized medicine.
Epidemiological studies estimated that amongst patients with schizophrenia a large subgroup of up to 25% also suffers from comorbid obsessive compulsive symptoms (OCS). The association between these comorbid OCS and neuropsychological impairment remains unclear and somewhat contradictory. Longitudinal approaches which investigate the stability of OCS related cognitive deficits are missing.
37 patients with schizophrenia and comorbid OCS and 43 schizophrenia patients without OCS were assessed with a comprehensive cognitive test-battery and compared at baseline and again 12 months later.
Schizophrenia patients with comorbid OCS showed significant pronounced deficits with increasing effect sizes over the 12 month assessment period in specific cognitive areas such as visuo-spatial perception and visual memory (WAIS-R block design, Rey-Osterrieth Complex Figure Test), executive functioning (perseveration in the Wisconsin card sorting test) and cognitive flexibility (Trail making test B). These cognitive domains correlated with OCS severity and are known to be candidate domains in obsessive compulsive disorder (OCD).
OCS in schizophrenia is associated longitudinally stable specific cognitive deficits. Prospective studies involving patients with at risk mental states for psychosis are necessary to decipher the interaction of cognitive impairment and the clinical manifestation of schizophrenia and OCS. This might facilitate the definition of patients at high risk for OCS, an early detection of subclinical levels, therapeutic interventions and clinical monitoring.
Limbic-cortical imbalance is an established model for the neurobiology of major depressive disorder (MDD), but imaging genetics studies have been contradicting regarding potential risk and resilience mechanisms. Here, we re-assessed previously reported limbic-cortical alterations between MDD relatives and controls in combination with a newly acquired sample of MDD patients and controls, to disentangle pathology, risk, and resilience.
We analyzed functional magnetic resonance imaging data and negative affectivity (NA) of MDD patients (n = 48), unaffected first-degree relatives of MDD patients (n = 49) and controls (n = 109) who performed a faces matching task. Brain response and task-dependent amygdala functional connectivity (FC) were compared between groups and assessed for associations with NA.
Groups did not differ in task-related brain activation but activation in the superior frontal gyrus (SFG) was inversely correlated with NA in patients and controls. Pathology was associated with task-independent decreases of amygdala FC with regions of the default mode network (DMN) and decreased amygdala FC with the medial frontal gyrus during faces matching, potentially reflecting a task-independent DMN predominance and a limbic-cortical disintegration during faces processing in MDD. Risk was associated with task-independent decreases of amygdala-FC with fronto-parietal regions and reduced faces-associated amygdala-fusiform gyrus FC. Resilience corresponded to task-independent increases in amygdala FC with the perigenual anterior cingulate cortex (pgACC) and increased FC between amygdala, pgACC, and SFG during faces matching.
Our results encourage a refinement of the limbic-cortical imbalance model of depression. The validity of proposed risk and resilience markers needs to be tested in prospective studies. Further limitations are discussed.
Patients with borderline personality disorder frequently show non-suicidal self-injury (NSSI). In these patients, NSSI often serves to reduce high levels of stress.
Investigation of neurobiological mechanisms of NSSI in borderline personality disorder
In total, 21 women with borderline personality disorder and 17 healthy controls underwent a stress induction, followed by either an incision into the forearm or a sham treatment. Afterwards participants underwent resting-state functional magnetic resonance imaging while aversive tension, heart rate and heart rate variability were assessed.
We found a significant influence of incision on subjective and objective stress levels with a stronger decrease of aversive tension in the borderline personality disorder group following incision than sham. Amygdala activity decreased more and functional connectivity with superior frontal gyrus normalised after incision in the borderline personality disorder group.
Decreased stress levels and amygdala activity after incision support the assumption of an influence of NSSI on emotion regulation in individuals with borderline personality disorder and aids in understanding why these patients use self-inflicted pain to reduce inner tension.
Metamemory describes the monitoring and knowledge about one's memory capabilities. Patients with schizophrenia have been found to be less able in differentiating between correct and false answers (smaller confidence gap) when asked to provide retrospective confidence ratings in previous studies. Furthermore, higher proportions of very-high-confident but false responses have been found in this patient group (high knowledge corruption). Whether and how these biases contribute to the early pathogenesis of psychosis is yet unclear. This study thus aimed at investigating metamemory function in the early course of psychosis.
Patients in an at-risk mental state for psychosis (ARMS, n = 34), patients with a first episode of psychosis (FEP, n = 21) and healthy controls (HCs, n = 38) were compared on a verbal recognition task combined with retrospective confidence-level ratings.
FEP patients showed the smallest confidence gap, followed by ARMS patients, followed by HCs. All groups differed significantly from each other. Regarding knowledge corruption, FEP patients differed significantly from HCs, whereas a statistical trend was revealed in comparison of ARMS and FEP groups. Correlations were revealed between metamemory, measures of positive symptoms and working memory performance.
These data underline the presence of a metamemory bias in ARMS patients which is even more pronounced in FEP patients. The bias might represent an early cognitive marker of the beginning psychotic state. Longitudinal studies are needed to unravel whether metacognitive deficits predict the transition to psychosis and to evaluate therapeutic interventions.
In this article, we present data on the analysis of maze-solving behavior as a tool for the investigation of cognitive disturbance in schizophrenic patients. Solving maze tasks efficiently requires both an interaction between and an integration of perceptive and action-oriented processes. Starting from the hypothesis that these domains are preferentially disturbed in schizophrenia, we propose that the maze-solving behavior of schizophrenic patients permits insight into specific impairments in disease-related cognitive processing. We present the results of a maze task study comparing medication-free schizophrenic patients and matched healthy controls. This analysis forms the basis for an investigation of the influence of psychopharmacological treatment strategies on the observed behavior in the maze-solving paradigm. Finally, a third study concerned with improvement over time associated with medication is presented, and possible influences of extrapyramidal motor disturbances on schizophrenic patients' maze performance are discussed.
Epidemiological investigations show that up to 30% of schizophrenic patients suffer from obsessive–compulsive symptoms (OCS) associated with negative impact on the general prognosis. It has been proposed that antiserotonergic second-generation antipsychotics (SGAs) might induce OCS, but investigations of large samples integrating psychopathology, neuropsychology and psychopharmacology are missing.
We stratified 70 patients with schizophrenia according to their mode of antipsychotic treatment: clozapine and olanzapine (group I) compared with aripiprazole and amisulpride (group II). The groups were matched according to age, sex, educational levels and severity of the psychotic disorder (Positive and Negative Syndrome Scale). As the primary endpoint, we evaluated OCS severity (Yale–Brown Obsessive–Compulsive Scale).
OCS were significantly more prevalent and severe in group I, in which OCS severity correlated with dosage of clozapine and duration of treatment. Pronounced cognitive deficits in group I were found in visuospatial perception and visual memory (Wechsler Adult Intelligence Scale-Revised block design, Rey–Osterrieth Complex Figure Test), impulse inhibition (go/no-go test), higher perseveration scores (Wisconsin Card Sorting Test) and reduced set-shift abilities (Trail Making Test Part B, Set-shift Task). These cognitive domains correlated with OCS severity.
OCS in schizophrenia are associated with antiserotonergic SGA treatment, but longitudinal studies have to prove causality. Before starting treatment with antiserotonergic SGAs, specific neurocognitive domains should be evaluated, as visuospatial learning and impulse inhibition performance might allow early detection of OCS secondary to antipsychotic treatment in schizophrenia.
Andreia Santos, Central Institute of Mental Health Mannheim, Germany,
Andreas Meyer-Lindenberg, Department of Psychiatry and Psychotherapy University of Heidelberg and Central Institute of Mental Health Mannheim, Germany
This chapter reviews imaging studies delineating the unique neuropsychiatric features of Williams-Beuren syndrome (WS), as well as recent advances in investigating the neural substrates of the disorder, which have provided significant contributions to unraveling the impact of a specific genetic defect on brain structure and function. It discusses the clinical, behavioral, cognitive and genetic profiles of WS. Studies using high-resolution magnetic resonance imaging (MRI) have found significant brain differences between WS and typically developing individuals. Significant advances in the understanding of the structural basis of WS have come from the application of voxel-based morphometry (VBM), which allows the study of genetic variation without restriction to anatomical boundaries. Findings of the studies reviewed in the chapter offer a systems-level characterization of genetically mediated abnormalities of neural interactions that can be probed for the identification of single-gene effects on brain maturation.
For highly heritable brain disorders, such as schizophrenia and autism, investigating genetic effects on the level of neural systems seems an obvious approach. Nevertheless, the usefulness of the intermediate phenotypes (‘endo’ phenotypes) continues to be debated energetically. We argue that, while not all intermediate phenotypes are created equal, the hypothesis-driven investigation of the translational cascades linking genetic variation to disturbed behavior is a viable and important strategy that should not be supplanted by an exclusive focus on brainless, clinical/categorical phenotypes investigated in very large numbers of participants.
The Holocaust under the Nazi regime is probably the most traumatic catastrophe of our century and even of history in the civilised world. Its deepest abyss consumed the lives of one-third of the world's Jewish population, who were selected and murdered in a cold-blooded industrialised machinery of death in this their ‘Shoa’. The Jewish people represent the victims of the Holocaust more than any other group of human beings who suffered this iniquity. The Holocaust has left in its wake few survivors, and many invalids in body and in mind, who remain compelled to live with a trauma that surpasses any other deliberately caused by fellow humans: and it has left in its wake an entire nation in shame and bewilderment, stigmatised and traumatised by the horrifying crimes that were committed in its name, faced with the task of analysing what happened, so that it may never be repeated, forbidden by the enormity of the horrors from repressing the past, and obliged to integrate deeds that cannot be undone.
Email your librarian or administrator to recommend adding this to your organisation's collection.