Influence of mental health professionals' attitudes and personality traits on decision-making around coercion: Results from an experimental quantitative survey using case vignettes.

OBJECTIVE: Research on coercion in mental healthcare has recently shifted to the investigation of subjective aspects, both on the side of the people with mental disorders affected and the staff members involved. In this context, the role of personality traits and attitudes of staff members in decision-making around coercion is increasingly being assessed. This study aimed to examine the role of staff attitudes towards coercion and staff members' personality traits in decision-making around coercion in an experimental setting. METHODS: We assessed the attitudes towards coercion and (general) personality traits of mental health professionals in psychiatric hospitals with a quantitative survey. Furthermore, we developed case vignettes representing cases in a 'grey zone' and included them in the survey to assess staff members' decisions about coercion in specific situations. RESULTS: A general approving attitude towards coercion significantly influenced decisions around coercion in individual cases-resulting in a more likely approval of applying coercion in the cases described in the vignettes. Personality traits did not seem to be relevant in this regard. CONCLUSION: Strategies to reduce coercion in mental healthcare institutions should focus more on the role of staff attitudes and encourage staff members to reflect on them critically.

A German Version of the Staff Attitude to Coercion Scale. Development and Empirical Validation.

Background: Individual staff factors, such as personality traits and attitudes, are increasingly seen as an important factor in the reduction of coercion in mental health services. At the same time, only a few validated instruments exist to measure those factors and examine their influence on the use of coercion. Aim: The present study aimed to develop and validate a German version of the Staff Attitude to Coercion Scale (SACS). Methods: The original English version of the SACS published was translated into German. Subsequently, it was empirically validated on a sample of N = 209 mental health professionals by conducting an exploratory factor analysis. Results: The three-factor structure in the original version of the SACS, consisting of critical, pragmatic and positive attitudes toward the use of coercion, could not be replicated. Instead, the German version revealed one factor ranging from rejecting to approving the use of coercion. Conclusion: The SACS is one of the first instruments created to assess staff attitudes toward coercion in a validated way. The version of the instrument developed in this study allows for a validated assessment of those attitudes in German. Our results highlight the ethical importance of using validated measurements in studies on the role of staff factors in the reduction of coercion.

Predictors of treatment response to psychological interventions in people at clinical high risk of first-episode psychosis.

AIM: Psychological interventions, such as cognitive behavioural therapy (CBT) and supportive counselling (SC), are used to treat people with schizophrenia and people at clinical high risk (CHR) of psychosis. However, little information is available on predictors of treatment response. This study aims to identify such predictors of psychological interventions in CHR. METHODS: A total of 128 help-seeking CHR outpatients were randomized into two groups-integrated psychological intervention (IPI), including CBT, and SC-for 12 months. Multiple regression analysis was used to identify demographic, symptomatic and functional variables that predict improvement in positive (PANSS Positive), negative (PANSS Negative) and basic symptoms (Basic symptom total score) and improvement in functioning (GAF) at 1-year follow up. RESULTS: In the merged group (IPI + SC), people who lived independently, were younger and presented with higher baseline functioning showed more improvement in symptomatic outcomes at follow up. Negative symptoms at baseline predicted less improvement in positive and basic symptoms. Being married or cohabiting and living in the primary family were found to correlate with good functioning at 1-year follow up. CONCLUSIONS: Younger CHR individuals and those who are functioning well may particularly benefit from early intervention. Treatment might need to be modified for low-functioning CHR and those who already display higher scores of negative symptoms. Registration number: NCT00204087.

[Coercion and aggression in psychiatry: the individual psychological dimension of aggressive and coercive acts by therapists]. / Zwang und Gewalt in der Psychiatrie: die individualpsychologische Dimension der Gewaltanwendung auf Seite der Behandler.

There is a long paternalistic tradition in psychiatry and medicine in general. With a view on that, the law has been changed in order to strengthen patients' autonomy and personal rights and also to reduce coercion and violence. Nowadays, medical and therapeutic actions have to take place within stricter and narrower boundaries and the balance between therapists' provision of care and patients' rights of autonomy had to be renegotiated. In the present paper organisational, structural and legal factors which foster the emergence of coercion and violence in psychiatric treatment will be reported along with factors lying within therapists themselves. Individual factors of therapists that foster the emergence of coercion and violence are amongst other factors suggested by partly tremendous differences in prevalence rates of coercion and violence between hospitals and regions. Aggression coming from therapists can be frequently observed in clinical practice and are also reported in the literature. However, this issue nevertheless is a kind of taboo amongst therapists. Aggression, coercion and violence coming from therapists can be explained by their personality, attitudes, level of training and knowledge and also by their individual biography and involvement in cultures and traditions of clinical teams and hospitals. Despite changes in law the prevalence of coercion and violence in psychiatry is still too high. Amongst other factors, also individual factors of therapists can be made responsible for this situation.

Coping as a predictor of treatment outcome in people at clinical high risk of psychosis.

AIM: The concept of coping is relevant to recent models of psychosis, and people with established psychotic disorders have been found to predominately use maladaptive coping strategies. This study aimed to examine the general coping patterns of people at clinical high risk of psychosis (CHR) and to investigate whether pre-therapy coping behaviour plays a role in predicting responsiveness to early interventions. METHODS: One hundred twenty-eight help-seeking CHR outpatients were randomized into two treatment groups: either receiving integrated psychological intervention (IPI), including cognitive behaviour therapy, or supportive counselling (SC) for 12 months. Of those, 91 persons completed a Stress Coping Questionnaire (SCQ) at intake: 45 in the IPI group and 46 in the SC group. General coping behaviour in this sample was analysed and several regressions were conducted separately for each treatment group to examine coping as a predictor of outcome after 12 months of different forms of treatment. RESULTS: Participants relied significantly more on negative than on positive coping strategies, t(90) = -7.185, P < 0.001, and within the positive strategies, stress control was the most preferred one, t(90) = 10.979, P < 0.001. Several pre-therapy coping strategies significantly predicted improvement in symptomatic outcome in both treatment groups, explaining between 16% and 25% of variance. The predictive value of coping was higher in the SC group. CONCLUSIONS: Maladaptive coping behaviours were found to emerge in the early stages of psychosis and coping behaviour contributed significantly to the prediction of post-treatment symptom improvement. These findings indicate a need for psychosocial support and coping strategy enhancement in people at risk of psychosis.

[Neuropsychological Functioning as a Predictor of Treatment Response to Psychoeducational, Cognitive Behavioral Therapy in People at Clinical High Risk of First Episode Psychosis]. / Neuropsychologische Funktionen als Prädiktoren des Therapieerfolgs von psychoedukativer, kognitiv verhaltenstherapeutischer Therapie bei Personen mit erhöhtem Psychoserisiko.

OBJECTIVE: Investigate whether treatment response in people at clinical high risk of psychosis (CHR) is predicted by their cognitive performance. METHOD: 128 CHR outpatients were randomized into two treatment groups, one receiving integrated psychological intervention (IPI), including psychoeducation, the other receiving supportive counselling (SC) for 12 months. Multiple regression analysis was used to identify neurocognitive predictors of treatment response in a subgroup of n = 105, measured by symptomatic and functional improvement at 1-year follow-up. RESULTS: In the IPI, treatment response was associated with performance of executive control and processing speed (R²â€Š= 0.27, p = 0.002). In both treatment groups, performance of working memory/attention was a significant predictor (IPI: R²â€Š= 0.15, p = 0.039, SC: R²â€Š= 0.19, p = 0.012). CONCLUSION: Cognitive performance is associated with treatment response in CHR people. The enhancement of cognitive performance is a useful target of early intervention.

Accelerated brain aging in schizophrenia and beyond: a neuroanatomical marker of psychiatric disorders.

Structural brain abnormalities are central to schizophrenia (SZ), but it remains unknown whether they are linked to dysmaturational processes crossing diagnostic boundaries, aggravating across disease stages, and driving the neurodiagnostic signature of the illness. Therefore, we investigated whether patients with SZ (N = 141), major depression (MD; N = 104), borderline personality disorder (BPD; N = 57), and individuals in at-risk mental states for psychosis (ARMS; N = 89) deviated from the trajectory of normal brain maturation. This deviation was measured as difference between chronological and the neuroanatomical age (brain age gap estimation [BrainAGE]). Neuroanatomical age was determined by a machine learning system trained to individually estimate age from the structural magnetic resonance imagings of 800 healthy controls. Group-level analyses showed that BrainAGE was highest in SZ (+5.5 y) group, followed by MD (+4.0), BPD (+3.1), and the ARMS (+1.7) groups. Earlier disease onset in MD and BPD groups correlated with more pronounced BrainAGE, reaching effect sizes of the SZ group. Second, BrainAGE increased across at-risk, recent onset, and recurrent states of SZ. Finally, BrainAGE predicted both patient status as well as negative and disorganized symptoms. These findings suggest that an individually quantifiable "accelerated aging" effect may particularly impact on the neuroanatomical signature of SZ but may extend also to other mental disorders.

Association between psychopathology and problems of psychosocial functioning in the long-term outcome of patients diagnosed with schizophrenic, schizoaffective and affective disorders.

Mental health problems do significantly impact on a person's functioning. In the past, problems with psychosocial functioning were mainly associated with the diagnoses of schizophrenia. However, nowadays it is clear that impaired psychosocial functioning is also a common phenomenon in people suffering from affective disorders. Only few studies have investigated psychosocial functioning in patients with affective, schizoaffective and schizophrenic disorders in the long-term and in a comparative approach. In the present study, we analysed the association between psychopathology and psychosocial functioning. This question is relevant as symptom remission and sufficient levels of functioning are considered as important indicators of patients' recovery from their mental health problems. The here reported findings refer to the data of a sample of 177 patients with life-time diagnoses belonging to the schizophrenic, schizoaffective or affective spectrum according to the ICD-10 criteria. Psychopathological, socio-demographic and other illness-related variables were assessed at the index hospitalisation and at the 15-year follow-up evaluation. In the present study, psychopathology is focused on data assessed with the PANSS (Positive and Negative Syndrome Scale). Information about patients' psychosocial functioning was assessed by using a modified and extended version of the WHO disability assessment scale (WHO-DAS-M). The association between psychosocial functioning and psychopathology was analysed by correlation analyses with the total sample and diagnostic subsamples. The consistency of correlations across the diagnostic groups and domains of psychosocial functioning was calculated. Findings revealed for all diagnostic groups that higher levels of psychopathology were associated with higher levels of problems in psychosocial functioning in various domains. Though there seem to be some differences between psychopathological dimensions and their effects on different aspects of psychosocial functioning, findings across the three diagnostic categories were fairly consistent. The present findings do highlight the importance of symptom remission in achieving social recovery and preventing impairment in psychosocial functioning in all major psychiatric disorders.

Multivariate patterns of brain-cognition associations relating to vulnerability and clinical outcome in the at-risk mental states for psychosis.

BACKGROUND: Neuropsychological deficits are a core feature of established psychosis and have been previously linked to fronto-temporo-limbic brain alterations. Both neurocognitive and neuroanatomical abnormalities characterize clinical at-risk mental states (ARMS) for psychosis. However, structure-cognition relationships in the ARMS have not been directly explored using multivariate neuroimaging techniques. METHODS: Voxel-based morphometry and partial least squares were employed to study system-level covariance patterns between whole-brain morphological data and processing speed, working memory, verbal learning/IQ, and executive functions in 40 ARMS subjects and 30 healthy controls (HC). The detected structure-cognition covariance patterns were tested for significance and reliability using non-parametric permutation and bootstrap resampling. RESULTS: We identified ARMS-specific covariance patterns that described a generalized association of neurocognitive measures with predominantly prefronto-temporo-limbic and subcortical structures as well as the interconnecting white matter. In the conversion group, this generalized profile particularly involved working memory and verbal IQ and was positively correlated with limbic, insular and subcortical volumes as well as negatively related to prefrontal, temporal, parietal, and occipital cortices. Conversely, the neurocognitive profiles in the HC group were confined to working memory, learning and IQ, which were diffusely associated with cortical and subcortical brain regions. CONCLUSIONS: These findings suggest that the ARMS and prodromal phase of psychosis are characterized by a convergent mapping from multi-domain neurocognitive measures to a set of prefronto-temporo-limbic and subcortical structures. Furthermore, a neuroanatomical separation between positive and negative brain-cognition correlations may not only point to a biological process determining the clinical risk for disease transition, but also to possible compensatory or dysmaturational neural processes.

Menopause and schizophrenia.

We have come a long way from our understanding of the menopause as it was described in the 11th century by Trotula of Salerno, a female gynaecologist who said 'there are older women who give forth blood matter especially as menopause approaches them'. Yet very little is known about the impact menopause has on the mental health of women especially severe and enduring illnesses like schizophrenia. A lot of research has shown that estrogen acts as a protective factor due to its antidopaminergic properties, thus providing an explanation for the increase in risk of a new psychotic disorder during the menopause. This has further led to the hypothesis of hormone replacement therapy providing benefits in the management of these disorders in menopausal women. This review article highlights the importance of a clear understanding of this phase of life in patients suffering from or who present with a risk of developing schizophrenia.

Early recognition and disease prediction in the at-risk mental states for psychosis using neurocognitive pattern classification.

BACKGROUND: Neuropsychological deficits predate overt psychosis and overlap with the impairments in the established disease. However, to date, no single neurocognitive measure has shown sufficient power for a prognostic test. Thus, it remains to be determined whether multivariate neurocognitive pattern classification could facilitate the diagnostic identification of different at-risk mental states (ARMS) for psychosis and the individualized prediction of illness transition. METHODS: First, classification of 30 healthy controls (HC) vs 48 ARMS individuals subgrouped into 20 "early," 28 "late" ARMS subjects was performed based on a comprehensive neuropsychological test battery. Second, disease prediction was evaluated by categorizing the neurocognitive baseline data of those ARMS individuals with transition (n = 15) vs non transition (n = 20) vs HC after 4 years of follow-up. Generalizability of classification was estimated by repeated double cross-validation. RESULTS: The 3-group cross-validated classification accuracies in the first analysis were 94.2% (HC vs rest), 85.0% (early at-risk subjects vs rest), and, 91.4% (late at-risk subjects vs rest) and 90.8% (HC vs rest), 90.8% (converters vs rest), and 89.0% (nonconverters vs rest) in the second analysis. Patterns distinguishing the early or late ARMS from HC primarily involved the verbal learning/memory domains, while executive functioning and verbal IQ deficits were particularly characteristic of the late ARMS. Disease transition was mainly predicted by executive and verbal learning impairments. CONCLUSIONS: Different ARMS and their clinical outcomes may be reliably identified on an individual basis by evaluating neurocognitive test batteries using multivariate pattern recognition. These patterns may have the potential to substantially improve the early recognition of psychosis.

Disease prediction in the at-risk mental state for psychosis using neuroanatomical biomarkers: results from the FePsy study.

BACKGROUND: Reliable prognostic biomarkers are needed for the early recognition of psychosis. Recently, multivariate machine learning methods have demonstrated the feasibility to predict illness onset in clinically defined at-risk individuals using structural magnetic resonance imaging (MRI) data. However, it remains unclear whether these findings could be replicated in independent populations. METHODS: We evaluated the performance of an MRI-based classification system in predicting disease conversion in at-risk individuals recruited within the prospective FePsy (Früherkennung von Psychosen) study at the University of Basel, Switzerland. Pairwise and multigroup biomarkers were constructed using the MRI data of 22 healthy volunteers, 16/21 at-risk subjects with/without a subsequent disease conversion. Diagnostic performance was measured in unseen test cases using repeated nested cross-validation. RESULTS: The classification accuracies in the "healthy controls (HCs) vs converters," "HCs vs nonconverters," and "converters vs nonconverters" analyses were 92.3%, 66.9%, and 84.2%, respectively. A positive likelihood ratio of 6.5 in the converters vs nonconverters analysis indicated a 40% increase in diagnostic certainty by applying the biomarker to an at-risk population with a transition rate of 43%. The neuroanatomical decision functions underlying these results particularly involved the prefrontal perisylvian and subcortical brain structures. CONCLUSIONS: Our findings suggest that the early prediction of psychosis may be reliably enhanced using neuroanatomical pattern recognition operating at the single-subject level. These MRI-based biomarkers may have the potential to identify individuals at the highest risk of developing psychosis, and thus may promote informed clinical strategies aiming at preventing the full manifestation of the disease.

Neuroanatomical correlates of executive dysfunction in the at-risk mental state for psychosis.

Deficits in executive functioning have been described as a core feature of schizophrenia and have been linked to patterns of fronto-temporo-limbic brain alterations. To date, such structure-cognition relationships have not been explored in a clinically defined at-risk mental state (ARMS) for psychosis using whole-brain neuroimaging techniques. Therefore, we used voxel-based morphometry in 40 ARMS and 30 matched healthy control (HC) individuals to investigate whether gray and white matter volumes (1) correlated with the performance in the Trail-Making Test B (TMT-B), an established measure of executive functioning, and (2) were volumetrically linked to the ventromedial prefrontal cortex (VMPFC), found to be associated with TMT-B in the ARMS during the first analysis step. We found the ARMS subjects to be specifically impaired in their TMT-B performance versus HC. Brain-cognition associations involving the insular cortices were observed in the HC, but not in the ARMS individuals. Conversely, TMT-B correlations in the VMPFC, the cerebellum, the fronto-callosal white matter were detected in the ARMS, but not the HC group. The VMPFC was linked to the temporo-limbic cortices in HC, whereas the connectivity pattern in the ARMS involved the left temporal and dorsolateral prefrontal cortex, the cerebellum, the right SMA and extended portions of the fronto-callosal white matter. These findings suggest that executive deficits are already present in the ARMS for psychosis and may be subserved by structurally altered networks of interconnected cortical and subcortical brain regions in line with the disconnectivity hypothesis of schizophrenia.

Use of neuroanatomical pattern regression to predict the structural brain dynamics of vulnerability and transition to psychosis.

BACKGROUND: The at-risk mental state for psychosis (ARMS) has been associated with abnormal structural brain dynamics underlying disease transition or non-transition. To date, it is unknown whether these dynamic brain changes can be predicted at the single-subject level prior to disease transition using MRI-based machine-learning techniques. METHODS: First, deformation-based morphometry and partial-least-squares (PLS) was used to investigate patterns of volumetric changes over time in 25 ARMS individuals versus 28 healthy controls (HC) (1) irrespective of the clinical outcome and (2) according to illness transition or non-transition. Then, the baseline MRI data were employed to predict the expression of these volumetric changes at the individual level using support-vector regression (SVR). RESULTS: PLS revealed a pattern of pronounced morphometric changes in ARMS versus HC that affected predominantly the right prefrontal, as well as the perisylvian, parietal and periventricular structures (p<0.011), and that was more pronounced in the converters versus the non-converters (p<0.010). The SVR analysis facilitated a reliable prediction of these longitudinal brain changes in individual out-of training cases (HC vs ARMS: r=0.83, p<0.001; HC vs converters vs non-converters: r=0.83, p<0.001) by relying on baseline patterns that involved ventricular enlargements, as well as prefrontal, perisylvian, limbic, parietal and subcortical volume reductions. CONCLUSIONS: Abnormal brain changes over time may underlie an elevated vulnerability for psychosis and may be most pronounced in subsequent converters to psychosis. Pattern regression techniques may facilitate an accurate prediction of these structural brain dynamics, potentially allowing for an early recognition of individuals at risk of developing psychosis-associated neuroanatomical changes over time.

The Munich 15-year follow-up study (MUFUSSAD) on first-hospitalized patients with schizophrenic or affective disorders: comparison of psychopathological and psychosocial course and outcome and prediction of chronicity.

Given the limited explanatory power of the available neurobiological findings, results of long-term follow-up studies should still be considered as one criterion among others in the development of psychiatric classification systems regarding schizophrenia and affective disorders. A total of 323 first hospitalized inpatients of the Psychiatric Department of the University Munich were recruited at index time and followed up after 15 years. The full follow-up evaluation including several standardized assessment procedures (AMDP, PANSS, SANS, DAS, GAS) could be performed in 197 patients. The patients originally diagnosed according to ICD-9 were re-diagnosed according to ICD-10 and DSM-IV, using SCID among others. Schizophrenic patients had a much poorer outcome than affective or schizoaffective patients in terms of negative syndrome, deficit syndrome, psychosocial impairments and GAS results, and a higher prevalence of a chronic course. The logistic regression analyses performed to find optimized predictor combinations for the prognosis of a chronic course found, for example, the total Strauss-Carpenter Scale score, male gender and several other psychopathological syndromes to be relevant predictors. The findings reflect some long-term related validity for the differentiation between schizophrenia and affective disorders. The Strauss-Carpenter Scale, male gender as well as several psychopathological syndromes are the most relevant predictors for chronicity.

[Insight into illness: an overview of the concept focusing on schizophrenia]. / Krankheitseinsicht - Eine Ubersicht über das Konzept mit Fokus auf schizophrene Erkrankungen.

OBJECTIVE: Insight into illness is key to successful treatment. Poor insight, especially in schizophrenia, is, however, quite a frequent phenomenon that is also associated with poor adherence to treatment and a variety of unfavorable outcome parameters. On that background, the concept of insight into illness has gained new reseach interest during the last 10 years. The present review aims to report new findings regarding conceptual changes of insight, findings on the etiology, contributing factors as well as the assessment and methods to develop insight. METHODS: Based on a review of the literature, results from more recent studies on insight into illness will be presented. RESULTS: Insight into illness is a complex, multidimensional, strongly culturally embedded phenomenon that is influenced by a variety of factors. The etiology of insight still remains poorly understood but is likely to be multifactorial including psychological, neuropsychological and organic reasons. CONCLUSIONS: Further research is needed, in particularly regarding therapeutical techniques to improve insight into illness.

Social disability in schizophrenic, schizoaffective and affective disorders 15 years after first admission.

BACKGROUND: Interest in social functioning of people suffering from mental illnesses has been increasing over the last few years. Only few studies have investigated differences in social functioning in affective, schizoaffective and schizophrenic patients in the long-term and in a comparative approach. METHOD: The present study is part of a 15 year follow-up study on patients suffering from severe mental illness. The here reported findings refer to the data of a sample of 177 patients with life-time diagnoses belonging to the schizophrenic, schizoaffective or affective spectrum according to the ICD-10 criteria. Psychopathological, socio-demographic and other illness-related variables were assessed at the index hospitalisation and at the 15 year follow-up evaluation by using the assessment system published by the Association for Methodology and Documentation in Psychiatry (AMDP-system). Information about patients' social disability was assessed by using a modified and further developed version of the WHO disability assessment scale, the (Mannheim) Disability Assessment Schedule (DAS-M scale). Prevalence rates of social disability and differences in the severity of social disability between different groups of mental illnesses were evaluated. And the association between social disability, diagnoses and psychopathology was analysed. RESULTS: Compared to affective and schizoaffective patients, schizophrenic patients showed significantly higher levels of social disability in almost all domains. Severe to very severe levels of disability were found in 64% of schizophrenic patients and only in 19% of schizoaffective patients and 5% of affective patients. However, on a descriptive level all three diagnostic groups presented with similar maxima and minima in their profiles of social disability. Multiple regression analyses revealed that the apathy syndrome had the highest impact on the presence of severe social disability with all other psychopathological syndromes, gender, age and diagnosis having no statistically significant influence. CONCLUSION: Findings indicate that patients' disabilities in different diagnostic groups seem to be of a similar quality and nature despite differences in their severity. The impact of psychopathology on disability seems to be more important than the one of diagnosis per se.

Differences in hippocampal volume between major depression and schizophrenia: a comparative neuroimaging study.

Several studies have demonstrated that structural brain change is detectable in the hippocampus in both patients, with schizophrenia and major depression. Only few studies, however, compared both clinical disease entities directly and no larger study has tried to take different disease stages into account. The objectives of this study are to investigate whether hippocampal volumes are reduced in patients with schizophrenia and those with major depression with the same duration of illness compared to healthy controls and to assess further changes at different disease stages. A total of 319 inpatients and healthy controls were enrolled and investigated with magnetic resonance imaging (MRI). Hippocampal volumes were measured using the segmentation software BRAINS. Bilateral hippocampal volume reductions were detected in both schizophrenic and depressed patients compared to healthy control (HC) subjects. Although younger, schizophrenic (SZ) patients showed in their MRI scans significant bilaterally reduced hippocampal volumes compared to patients with major depression. Although the hippocampal reductions were similar at the onset of symptomatic manifestation of both diseases, there was a further significant reduction of the left hippocampus in the recurrently ill SZ subgroup. The data suggest rather dynamic structural brain alterations in schizophrenia compared to major depression. Here, the presented application of the comparative neuroscience approach, by the use of large neuroimaging MRI databases, seems highly valuable. In the field of psychiatry, with its still controversial operationalized descriptive diagnostic entities, the cross-nosological approach provides a helpful tool to better elucidate the still unknown brain pathologies and their underlying molecular mechanisms beyond a single nosological entity.

Neuroanatomical correlates of different vulnerability states for psychosis and their clinical outcomes.

BACKGROUND: Structural brain abnormalities have been described in individuals with an at-risk mental state for psychosis. However, the neuroanatomical underpinnings of the early and late at-risk mental state relative to clinical outcome remain unclear. AIMS: To investigate grey matter volume abnormalities in participants in a putatively early or late at-risk mental state relative to their prospective clinical outcome. METHOD: Voxel-based morphometry of magnetic resonance imaging data from 20 people with a putatively early at-risk mental state (ARMS-E group) and 26 people with a late at-risk mental state (ARMS-L group) as well as from 15 participants with at-risk mental states with subsequent disease transition (ARMS-T group) and 18 participants without subsequent disease transition (ARMS-NT group) were compared with 75 healthy volunteers. RESULTS: Compared with healthy controls, ARMS-L participants had grey matter volume losses in frontotemporolimbic structures. Participants in the ARMS-E group showed bilateral temporolimbic alterations and subtle prefrontal abnormalities. Participants in the ARMS-T group had prefrontal alterations relative to those in the ARMS-NT group and in the healthy controls that overlapped with the findings in the ARMS-L group. CONCLUSIONS: Brain alterations associated with the early at-risk mental state may relate to an elevated susceptibility to psychosis, whereas alterations underlying the late at-risk mental state may indicate a subsequent transition to psychosis.