Katrin Schroeder

Dissociable systems for gain- and loss-related value predictions and errors of prediction in the human brain.

Midbrain dopaminergic neurons projecting to the ventral striatum code for reward magnitude and probability during reward anticipation and then indicate the difference between actual and predicted outcome. It has been questioned whether such a common system for the prediction and evaluation of reward exists in humans. Using functional magnetic resonance imaging and a guessing task in two large cohorts, we are able to confirm ventral striatal responses coding both reward probability and magnitude during anticipation, permitting the local computation of expected value (EV). However, the ventral striatum only represented the gain-related part of EV (EV+). At reward delivery, the same area shows a reward probability and magnitude-dependent prediction error signal, best modeled as the difference between actual outcome and EV+. In contrast, loss-related expected value (EV−) and the associated prediction error was represented in the amygdala. Thus, the ventral striatum and the amygdala distinctively process the value of a prediction and subsequently compute a prediction error for gains and losses, respectively. Therefore, a homeostatic balance of both systems might be important for generating adequate expectations under uncertainty. Prevalence of either part might render expectations more positive or negative, which could contribute to the pathophysiology of mood disorders like major depression.

Gene-gene interaction associated with neural reward sensitivity.

Reward processing depends on dopaminergic neurotransmission and is modulated by factors affecting dopamine (DA) reuptake and degradation. We used fMRI and a guessing task sensitive to reward-related activation in the prefrontal cortex and ventral striatum to study how individual variation in genes contributing to DA reuptake [DA transporter (DAT)] and degradation [catechol-o-methyltransferase (COMT)] influences reward processing. Prefrontal activity, evoked by anticipation of reward irrespective of reward probability and magnitude, was COMT genotype-dependent. Volunteers homozygous for the Met allele, associated with lower enzyme activity and presumably greater DA availability, showed larger responses compared with volunteers homozygous for the Val allele. A similar COMT effect was observed in the ventral striatum. As reported previously, the ventral striatum was also found to code gain-related expected value, i.e., the product of reward magnitude and gain probability. Individual differences in ventral striatal sensitivity for value were in part explained by an epistatic gene–gene interaction between COMT and DAT. Although most genotype combinations exhibited the expected activity increase with more likely and larger rewards, two genotype combinations (COMT Met/Met DAT 10R and COMT Val/Val 9R) were associated with blunted ventral striatal responses. In view of a consistent relationship between reduced reward sensitivity and addiction, our findings point to a potential genetic basis for vulnerability to addiction.

Subregions of the ventral striatum show preferential coding of reward magnitude and probability

As shown in non-human primate and human fMRI studies the probability and magnitude of anticipated rewards modulate activity in the mesolimbic dopaminergic system. Importantly, non-human primate data have revealed that single dopaminergic neurons code for both probability and magnitude of expected reward, suggesting an identical system. Using a guessing task that allowed the independent assessment of the factors probability and magnitude we were able to assess the impact of reward probability and magnitude in ventral striatal subregions in a large sample (n=98). We observed more anterior and lateral peak activation foci in the ventral striatum for reward probability and a more posterior and medial activation peak for reward magnitude, suggesting a functional segregation at the mesoscopic level. Importantly, this functional bias observed for the group average was also tested in each individual subject, allowing for proper random effects inference for the spatial dissociation. Taken together, our data point toward a functional dissociation of neuronal assemblies suggesting that certain populations of neurons are more sensitive to expected reward probability and other populations are more sensitive to reward magnitude.

Psychotic symptoms in patients with borderline personality disorder: prevalence and clinical management

Purpose of review The aim of this article is to review findings on the prevalence, phenomenology and treatment of psychotic features in borderline personality disorder (BPD), and to discuss factors that might be related to their occurrence. Recent findings Of patients with BPD about 20–50% report psychotic symptoms. Hallucinations can be similar to those in patients with psychotic disorders in terms of phenomenology, emotional impact, and their persistence over time. Although more research is needed on the exact nature of psychotic phenomena in patients with BPD, terms like pseudo-psychotic or quasi-psychotic are misleading and should be avoided. Childhood trauma might play an important role in the development of psychotic symptoms in patients with BPD, as in other populations. More research is necessary on the role of comorbid disorders, especially posttraumatic stress disorder (PTSD). Atypical antipsychotics seem to be beneficial in some patients; evidence on psychotherapy of psychotic symptoms is sparse. Summary Psychotic symptoms, especially hallucinations, seem to be an important feature of BPD. More research on potential mediators and adequate treatment approaches for psychotic symptoms in BPD is needed, and current diagnostic systems might require revision to emphasise psychotic symptoms.

Perinatal mental health service provision in Switzerland and in the UK.

QUESTIONS UNDER STUDY The epidemiology of maternal perinatal-psychiatric disorders as well as their effect on the baby is well recognised. Increasingly well researched specialised treatment methods can reduce maternal morbidity, positively affect mother-baby bonding and empower womens confidence as a mother. Here, we aimed to compare guidelines and the structure of perinatal-psychiatric service delivery in the United Kingdom and in Switzerland from the governments perspective. METHODS Swiss cantons provided information regarding guidelines and structure of service delivery in 2000. A subsequent survey using the same questionnaire was carried out in 2007. In the UK, similar information was accessed through published reports from 2000-2012. RESULTS Guidelines for perinatal psychiatry exist in the UK, whereas in Switzerland in 2000 none of the 26 cantons had guidelines, and in 2007 only one canton did. Joint mother-baby admissions on general psychiatric wards were offered by 92% of the Swiss cantons. In the UK, pregnant women and joint mother-baby admissions are only advised onto specialised perinatal-psychiatric units. In Switzerland, in 2007, three specialised units (max. 24 beds) were in place corresponding to 1 unit per 2.5 million people, while in the UK there were 22 mother-baby units (168 beds) in 2012 (1 unit per 2.8 million). In the UK, less than 50% of trusts provided specialised perinatal-psychiatric health care. CONCLUSIONS The main difference between the UK and Switzerland was the absence of guidelines, regular assessment and plans for future development of perinatal psychiatry in Switzerland. There are still geographical differences in the provision of perinatal-psychiatric services in the UK.

Evidence for an agitated–aggressive syndrome predating the onset of psychosis

BACKGROUND Aggression and suicidality prior to the initiation of treatment are frequent phenomena in psychosis patients. Increased scores in the Brief Psychiatric Rating Scale Excited Component (BPRS-EC) have been shown to predict involuntary treatment, aggression, and suicide in first-episode psychosis (FEP) patients. However, it is unclear if an agitated-aggressive syndrome as measured with the BPRS-EC is already present in at-risk mental state (ARMS). METHODS BPRS-EC scores from 43 ARMS patients, 50 FEP patients, and 25 healthy controls (HC) were analyzed. Multivariate analyses were performed to review if group differences were mediated by potential confounders. In addition, the association of BPRS-EC scores with clinical variables was examined. RESULTS BPRS-EC scores were significantly different across diagnostic groups (H(2)=22.1; p<.001), and post-hoc analyses showed significantly higher BPRS-EC scores for ARMS (p=.001) and for FEP patients (p<.001) compared to HC. Differences remained significant after controlling for gender, years of education, and intelligence. No significant differences emerged between ARMS and FEP patients. BPRS-EC was significantly correlated with lower intelligence (r=-.27; p=.008), reduced level of functioning (r=-.44; p<.001), and with smoking behavior (r=.22; p=.019). CONCLUSIONS ARMS and FEP patients in our sample had significantly higher BPRS-EC scores compared to HC. This may constitute a correlate of an agitated-aggressive syndrome and an increased risk for aggression and suicidality.

Considering DSM-5: Personality Diagnostics in Patients with Schizophrenia Spectrum Disorders

Abstract The aims of this study were to examine the prevalence of personality disorders (PD) in patients with schizophrenia spectrum disorders (SSD), to examine the interaction of axis-I and axis-II symptoms to provide an estimate on the confounding potential of SSD psychopathology in the establishment of DSM-IV PD diagnoses, and to discuss implications concerning the proposed changes in DSM-5. Patients with SSD, aged 18 to 65 years, and being at least partially remitted (PANSS total score < 75) were included. PD was examined categorically and dimensionally using the SCID-II screening questionnaire and interview, and SSD psychopathology was rated using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Forty-five patients (31 with schizophrenia) were included in the current study. Mean age was 37.2 years, and the median duration of illness was 9.5 years. Mean PANSS total score was 42.5. The cumulative prevalence of PD in our collective was 20%, with obsessive-compulsive, antisocial, and borderline PD being the most frequent. There were no cases of cluster A PD diagnoses. In the dimensional analysis, numerous correlations of small to medium effect size emerged between maladaptive personality traits and SSD psychopathology. PD is present in a clinically relevant subgroup of SSD patients and has to be recognized in SSD treatment. Currently, it remains unclear to what extent correlations between personality traits and SSD symptoms can be explained by content overlap or co-variation of SSD psychopathology and PD traits. SSD psychopathology may bias PD diagnostics and lead to a higher percentage of categorical PD diagnoses, especially considering the proposed changes in DSM-5.

Dissociation in patients with schizophrenia spectrum disorders: What is the role of different types of childhood adversity?

AIMS Our study aimed to explore the effects of different types of adverse childhood experiences (e.g. domestic violence, early loss, parental dysfunction, sexual and physical abuse) as well as experiences of sexual and physical abuse in adulthood on dissociative symptoms in adult patients with schizophrenia-spectrum disorders. METHODS 145 patients were examined for psychotic symptoms with the Positive and Negative Syndrome Scale (PANSS), for dissociative symptoms with the German version of the Dissociative Experiences Scale (DES) and for adverse experiences in childhood and adulthood with the Structured Trauma Interview (STI). RESULTS Childhood physical abuse was reported by 32%, childhood sexual abuse by 17% of the patients. Other forms of childhood adversity were also quite common; 18% had witnessed domestic violence, 26% reported early loss, and nearly half of patients reported at least one condition potentially related to parental dysfunction. The DES total score was significantly associated with childhood sexual abuse, witnessing of domestic violence and paternal dysfunction, as well as with physical violence in adulthood. In the final regression model, reports of paternal dysfunction and sexual abuse in childhood were independently associated with adult dissociation. Variance in dissociative symptoms was mainly explained by paternal dysfunction (18%). CONCLUSION Substantial rates of childhood adversity were found and specific associations were evident with adult dissociation amongst psychosis patients who reported sexual abuse or paternal dysfunction in childhood. Therefore, it is important that patients with schizophrenia-spectrum disorders are routinely asked about a broad range of possible adverse childhood experiences in order to provide appropriate interventions.

Diagnostic Validity of ICD-10 Personality Dimensions: A Multitrait-Multimethod Analysis of Two Self-Report Questionnaires and a Structured Interview

Background/Aims: There is growing evidence that the validity of diagnostic methods for personality disorders (PD) may be insufficient. Although the ICD-10 classification system is widely used, there is little data concerning its validity for diagnosing PD. Methods: To examine convergent and discriminant validity of ICD-10 PD, corresponding dimensions were calculated using the Inventory of Clinical Personality Accentuations (self-rating) and the International Personality Disorder Examination ICD-10 module (interview and screening questionnaire). These were administered to 42 psychiatric patients. A multitrait-multimethod analysis of the 2 self-administered questionnaires and the structured interview was conducted. Results: Correspondence between methods is significant at the level of 0.01 for the schizoid, borderline, anankastic, anxious and dependent PD dimensions. The investigation of discriminant validity within and between instruments reveals several strong relationships between different PD dimensions. Conclusion: Convergent validity can be considered sufficient for 5 of the 9 examined PD dimensions. Non-convergence must partly be interpreted as caused by poor discriminant validity inherent in the ICD-10 classification. Conceptualization of PD as completely distinguishable entities may not reflect the clinical reality of a partial overlap between personality disorders.

Subjective well-being, but not subjective mental functioning shows positive associations with neuropsychological performance in schizophrenia-spectrum disorders

OBJECTIVE To assess the association of subjective quality of life as measured by the Subjective Well-being under Neuroleptic Treatment questionnaire (SWN-K) with neuropsychological functioning; to address interactions with the SWN-K domain mental functioning as a measure of subjective cognitive dysfunction; and to examine the interaction of subjective well-being and psychopathology ratings. METHODS Forty-five patients diagnosed with schizophrenia spectrum disorder (SSD) were assessed regarding subjective well-being (SWN-K), neuropsychological impairment, and psychopathology (Brief Psychiatric Rating Scale; BPRS). RESULTS After controlling for multiple comparisons, SWN-K total score showed significant positive correlations with concentration/attention (r=.498), working memory (r=.537), verbal memory (r=.522), and global cognition (r=.459). No correlations of SWN mental functioning and neuropsychological impairment remained significant after Bonferroni correction. Correlations between SWN-K subscales and neuropsychological functioning were generally positive, indicating higher subjective well-being in patients with better neurocognition. In multivariate analyses, global cognition was a significant predictor (p=.011), accounting for 19.7% of SWN total score variance. Adding BPRS total score as predictor (p=.054) explained an additional 6.9% of SWN-K variance. Linear regression analyses with SWN-K mental functioning as dependent variable did not yield statistically significant models. CONCLUSION Subjective well-being and objective neuropsychological functioning show only moderate associations and can be seen as largely independent parameters. In particular, subjective mental functioning cannot serve as a proxy for objective neuropsychological testing.