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Studies investigating cognitive impairments in psychosis and depression have typically compared the average performance of the clinical group against healthy controls (HC), and do not report on the actual prevalence of cognitive impairments or strengths within these clinical groups. This information is essential so that clinical services can provide adequate resources to supporting cognitive functioning. Thus, we investigated this prevalence in individuals in the early course of psychosis or depression.
A comprehensive cognitive test battery comprising 12 tests was completed by 1286 individuals aged 15–41 (mean age 25.07, s.d. 5.88) from the PRONIA study at baseline: HC (N = 454), clinical high risk for psychosis (CHR; N = 270), recent-onset depression (ROD; N = 267), and recent-onset psychosis (ROP; N = 295). Z-scores were calculated to estimate the prevalence of moderate or severe deficits or strengths (>2 s.d. or 1–2 s.d. below or above HC, respectively) for each cognitive test.
Impairment in at least two cognitive tests was as follows: ROP (88.3% moderately, 45.1% severely impaired), CHR (71.2% moderately, 22.4% severely impaired), ROD (61.6% moderately, 16.2% severely impaired). Across clinical groups, impairments were most prevalent in tests of working memory, processing speed, and verbal learning. Above average performance (>1 s.d.) in at least two tests was present for 40.5% ROD, 36.1% CHR, 16.1% ROP, and was >2 SDs in 1.8% ROD, 1.4% CHR, and 0% ROP.
These findings suggest that interventions should be tailored to the individual, with working memory, processing speed, and verbal learning likely to be important transdiagnostic targets.
Clinical high-risk states for psychosis (CHR) are associated with functional impairments and depressive disorders. A previous PRONIA study predicted social functioning in CHR and recent-onset depression (ROD) based on structural magnetic resonance imaging (sMRI) and clinical data. However, the combination of these domains did not lead to accurate role functioning prediction, calling for the investigation of additional risk dimensions. Role functioning may be more strongly associated with environmental adverse events than social functioning.
We aimed to predict role functioning in CHR, ROD and transdiagnostically, by adding environmental adverse events-related variables to clinical and sMRI data domains within the PRONIA sample.
Baseline clinical, environmental and sMRI data collected in 92 CHR and 95 ROD samples were trained to predict lower versus higher follow-up role functioning, using support vector classification and mixed k-fold/leave-site-out cross-validation. We built separate predictions for each domain, created multimodal predictions and validated them in independent cohorts (74 CHR, 66 ROD).
Models combining clinical and environmental data predicted role outcome in discovery and replication samples of CHR (balanced accuracies: 65.4% and 67.7%, respectively), ROD (balanced accuracies: 58.9% and 62.5%, respectively), and transdiagnostically (balanced accuracies: 62.4% and 68.2%, respectively). The most reliable environmental features for role outcome prediction were adult environmental adjustment, childhood trauma in CHR and childhood environmental adjustment in ROD.
Findings support the hypothesis that environmental variables inform role outcome prediction, highlight the existence of both transdiagnostic and syndrome-specific predictive environmental adverse events, and emphasise the importance of implementing real-world models by measuring multiple risk dimensions.
Personalised prediction of functional outcomes is a promising approach for targeted early intervention in psychiatry. However, generalisability and resource efficiency of such prognostic models represent challenges. In the PRONIA study (German Clinical Trials Register: DRKS00005042), we demonstrate excellent generalisability of prognostic models in individuals at clinical high-risk for psychosis or with recent-onset depression, and substantial contributions of detailed clinical phenotyping, particularly to the prediction of role functioning. These results indicate that it is possible that functioning prediction models based only on clinical data could be effectively applied in diverse healthcare settings, so that neuroimaging data may not be needed at early assessment stages.
Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure.
We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry.
(i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains ‘emotional neglect’ and ‘emotional abuse’ were most predictive for CHR and ROP, while in ROD ‘physical abuse’ and ‘sexual abuse’ were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found.
These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.
Clinical high-risk (CHR) for psychosis is indicated by ultra-high risk (UHR) and basic symptom (BS) criteria; however, conversion rates are highest when both UHR and BS criteria are fulfilled (UHR&BS). While BSs are considered the most immediate expression of neurobiological aberrations underlying the development of psychosis, research on neurobiological correlates of BS is scarce.
We investigated gray matter volumes (GMV) of 20 regions of interest (ROI) previously associated with UHR criteria in 90 patients from the Bern early detection service: clinical controls (CC), first-episode psychosis (FEP), UHR, BS and UHR&BS. We expected lowest GMV in FEP and UHR&BS, and highest volume in CC with UHR and BS in-between.
Significantly, lower GMV was detected in FEP and UHR&BS patients relative to CC with no other significant between-group differences. When ROIs were analyzed separately, seven showed a significant group effect (FDR corrected), with five (inferior parietal, medial orbitofrontal, lateral occipital, middle temporal, precuneus) showing significantly lower GM volume in the FEP and/or UHR&BS groups than in the CC group (Bonferroni corrected). In the CHR group, only COGDIS scores correlated negatively with cortical volumes.
This is the first study to demonstrate that patients who fulfill both UHR and BS criteria – a population that has been associated with higher conversion rates – exhibit more severe GMV reductions relative to those who satisfy BS or UHR criteria alone. This result was mediated by the BS in the UHR&BS group, as only the severity of BS was linked to GMV reductions.
The establishment phase of an early detection centre for prodromal psychosis is introduced and characterised, along with its detaining and promoting factors within a universal multi-payer health care system.
Across the first six years (1998–2003), users' characteristics are compared between different diagnostic groups and to the local population statistics; and, for an exemplary 12-months period (3-1-2002 to 2-28-2003), the characteristics of telephone contacts with the service are studied.
Rising steadily in number across the first three years, 872 persons, predominately of German citizenship and higher education, consulted the service until 2003, 326 with first-episode psychosis and 144 not fulfilling criteria for a current or beginning psychosis. Of the 402 putatively prodromal patients, 94% reported predictive basic symptoms, 68.9% attenuated and 20.6% transient psychotic symptoms. Most contacts by persons meeting any prodromal criterion were initiated by mental health professionals (psychiatrists or psychologists) and counselling services.
Supported by public awareness campaigns, an early detection service is well received by its users and private practitioners as reflected by the large proportion of referrals from the latter. However, persons of non-German background as well as of lower education were underrepresented indicating that these sub-groups should be approached by tailored programmes.
Early identification and treatment of schizophrenia may alleviate the symptoms, delay the onset and improve the outcome of psychosis. Thus, detection of individuals at risk during the prodromal phase is an important task. Universal approaches to screen the general population or healthy subjects at risk have not proven possible to-date. However, clinical criteria for detecting ultra-high risk individuals have been developed for specialized settings, with their implementation in interventional studies. This article examines the rationale for early detection and intervention of psychosis, along with a review of some of the current studies. These target prevention using psychological and/or pharmacological intervention strategies have demonstrated promising results in high risk individuals. The German Research Network on Schizophrenia (GRNS) is conducting two multicenter early intervention studies; one with early psychological intervention in subjects who manifest early prodromal symptoms; with the second trial applying clinical management and pharmacological early intervention in subjects experiencing late prodromal symptoms (high risk subjects). Despite the promising results, many of the current studies have small sample sizes with study durations of a short period. The full benefits of early detection and intervention should be revealed once larger and longer studies are conducted.
For the first time, the present study explores pre-episodic disturbances, i.e. self-experienced vulnerability and prodromal symptoms, and related coping strategies preceding schizophrenic and depressive relapses. After complete recovery from the acute episode, 27 patients with recurrent schizophrenic and 24 patients with recurrent depressive episodes were assessed retrospectively for pre-episodic disturbances and related coping strategies with the “Bonn scale for the assessment of basic symptoms—BSABS”. All (100%) of the schizophrenic and 23 (96%) of the depressive patients showed pre-episodic disturbances. Patients with schizophrenia showed significantly more often an increased emotional reactivity and certain perception and thought disturbances. Depressive patients reported significantly more often an impaired tolerance to certain stress and disorders of emotion and affect. Sixty-three percent of the schizophrenics and 87% of the depressives reacted to pre-episodic disturbances with coping strategies. The pre-episodic disturbances in patients with schizophrenia could be described in terms of mild psychotic productivity, those in depressives in terms of mild depressive syndrome. Future studies will have to show if these findings can be replicated in first episode or initial prodromal state samples and if the assessment of mild psychotic productivity and mild depressive syndrome can be used for early diagnosis and early intervention in schizophrenia and depression.
Understanding factors related to poor quality of life (QoL) and self-rated health (SRH) in clinical high-risk (CHR) for psychosis is important for both research and clinical applications. We investigated the associations of both constructs with CHR symptoms, axis-I disorders, and sociodemographic variables in a community sample.
In total, 2683 (baseline) and 829 (3-year follow-up) individuals of the Swiss Canton of Bern (age-at-baseline: 16–40 years) were interviewed by telephone regarding CHR symptoms, using the Schizophrenia Proneness Instrument for basic symptoms, the Structured Interview for Psychosis-Risk Syndromes for ultra-high risk (UHR) symptoms, the Mini-International Neuropsychiatric Interview for current axis-I disorders, the Brief Multidimensional Life Satisfaction Scale for QoL, and the 3-level EQ-5D for SRH.
In cross-sectional structural equation modelling, lower SRH was exclusively significantly associated with higher age, male gender, lower education, and somatoform disorders. Poor QoL was exclusively associated only with eating disorders. In addition, both strongly interrelated constructs were each associated with affective, and anxiety disorders, UHR and, more strongly, basic symptoms. Prospectively, lower SRH was predicted by lower education and anxiety disorders at baseline, while poorer QoL was predicted by affective disorders at baseline.
When present, CHR, in particular basic symptoms are already distressful for individuals of the community and associated with poorer subjective QoL and health. Therefore, the symptoms are clinically relevant by themselves, even when criteria for a CHR state are not fulfilled. Yet, unlike affective and anxiety disorders, CHR symptoms seem to have no long-term influence on QoL and SRH.
Basic symptoms, defined as subjectively perceived disturbances in thought, perception and other essential mental processes, have been established as a predictor of psychotic disorders. However, the relationship between basic symptoms and family history of a transdiagnostic range of severe mental illness, including major depressive disorder, bipolar disorder and schizophrenia, has not been examined.
We sought to test whether non-severe mood disorders and severe mood and psychotic disorders in parents is associated with increased basic symptoms in their biological offspring.
We measured basic symptoms using the Schizophrenia Proneness Instrument – Child and Youth Version in 332 youth aged 8–26 years, including 93 offspring of control parents, 92 offspring of a parent with non-severe mood disorders, and 147 offspring of a parent with severe mood and psychotic disorders. We tested the relationships between parent mental illness and offspring basic symptoms in mixed-effects linear regression models.
Offspring of a parent with severe mood and psychotic disorders (B = 0.69, 95% CI 0.22–1.16, P = 0.004) or illness with psychotic features (B = 0.68, 95% CI 0.09–1.27, P = 0.023) had significantly higher basic symptom scores than control offspring. Offspring of a parent with non-severe mood disorders reported intermediate levels of basic symptoms, that did not significantly differ from control offspring.
Basic symptoms during childhood are a marker of familial risk of psychopathology that is related to severity and is not specific to psychotic illness.
The current study examined the pattern of neurocognitive impairments in a community-recruited sample of clinical high-risk (CHR) participants and established relationships with psychosocial functioning.
CHR-participants (n = 108), participants who did not fulfil CHR-criteria (CHR-negatives) (n = 42) as well as a group of healthy controls (HCs) (n = 55) were recruited. CHR-status was assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Schizophrenia Proneness Instrument, Adult Version (SPI-A). The Brief Assessment of Cognition in Schizophrenia Battery (BACS) as well as tests for emotion recognition, working memory and attention were administered. In addition, role and social functioning as well as premorbid adjustment were assessed.
CHR-participants were significantly impaired on the Symbol-Coding and Token-Motor task and showed a reduction in total BACS-scores. Moreover, CHR-participants were characterised by prolonged response times (RTs) in emotion recognition as well as by reductions in both social and role functioning, GAF and premorbid adjustments compared with HCs. Neurocognitive impairments in emotion recognition accuracy, emotion recognition RT, processing speed and motor speed were associated with several aspects of functioning explaining between 4% and 12% of the variance.
The current data obtained from a community sample of CHR-participants highlight the importance of dysfunctions in motor and processing speed and emotion recognition RT. Moreover, these deficits were found to be related to global, social and role functioning, suggesting that neurocognitive impairments are an important aspect of sub-threshold psychotic experiences and a possible target for therapeutic interventions.
Absent or delayed help-seeking is considered to aggravate the immense personal and societal burden caused by mental disorders. Therefore, we cross-sectionally examined rates and clinical and sociodemographic moderators of early help-seeking for current clinician-assessed non-psychotic mental problems/disorders in the community.
Altogether, 2683 individuals of the Swiss Canton Bern (16–40 years old, response rate 63.4%) were interviewed by telephone for current axis-I problems/disorders using the Mini-International Neuropsychiatric Interview, for psychosocial functioning using the Social and Occupational Functioning Assessment Scale, and for help-seeking for mental problems.
In total, 1122 (41.8%) reported mental problems. Of these, 769 (68.5%) affirmed any one screening question and 353 (31.5%) fulfilled criteria for any current axis-I disorder, and 396 (35.3%) reported any lifetime help-seeking (28.3% sought help in the past and 7.0% were in current treatment). In path analyses, current help-seeking was associated mainly by type and number of mental problems/disorders mediated by functional impairment, in addition to older age, no current partner, and past treatment.
Our cross-sectional data indicate a gap in help-seeking for mental problems/disorders. The relationship between number of mental problems/disorders and help-seeking mediated by functional impairment confirm that individuals commonly do not seek help until problems are severe enough to cause problems in occupational and psychosocial functioning, driving the already immense costs of mental disorders. Thus, campaigns promoting early help-seeking, including early diagnostic clarification of and support for subthreshold mental problems in terms of an indicated prevention, should focus on psychosocial functioning, aside from signs of mental illness.
An efficient indicated prevention of psychotic disorders requires valid risk criteria that work in both clinical and community samples. Yet, ultra-high risk and basic symptom criteria were recently recommended for use in clinical samples only. Their use in the community was discouraged for lack of knowledge about their prevalence, clinical relevance and risk factors in non-clinical, community settings when validly assessed with the same instruments used in the clinic.
Using semi-structured telephone interviews with established psychosis-risk instruments, we studied the prevalence of psychosis-risk symptoms and criteria, their clinical relevance (using presence of a non-psychotic mental disorder or of functional deficits as proxy measures) and their risk factors in a random, representative young adult community sample (N=2683; age 16–40 years; response rate: 63.4%).
The point-prevalence of psychosis-risk symptoms was 13.8%. As these mostly occurred too infrequent to meet frequency requirements of psychosis-risk criteria, only 2.4% of participants met psychosis-risk criteria. A stepwise relationship underlay the association of ultra-high risk and basic symptoms with proxy measures of clinical relevance, this being most significant when both occurred together. In line with models of their formation, basic symptoms were selectively associated with age, ultra-high risk symptoms with traumatic events and lifetime substance misuse.
Psychosis-risk criteria were uncommon, indicating little risk of falsely labelling individuals from the community at-risk for psychosis. Besides, both psychosis-risk symptoms and criteria seem to possess sufficient clinical relevance to warrant their broader attention in clinical practice, especially if ultra-high risk and basic symptoms occur together.
Mental disorders create high individual and societal costs and burden, partly because help-seeking is often delayed or completely avoided. Stigma related to mental disorders or mental health services is regarded as a main reason for insufficient help-seeking.
To estimate the impact of four stigma types (help-seeking attitudes and personal, self and perceived public stigma) on active help-seeking in the general population.
A systematic review of three electronic databases was followed by random effect meta-analyses according to the stigma types.
Twenty-seven studies fulfilled eligibility criteria. Participants' own negative attitudes towards mental health help-seeking (OR = 0.80, 95% CI 0.73–0.88) and their stigmatising attitudes towards people with a mental illness (OR = 0.82, 95% CI 0.69–0.98) were associated with less active help-seeking. Self-stigma showed insignificant association (OR = 0.88, 95% CI 0.76–1.03), whereas perceived public stigma was not associated.
Personal attitudes towards mental illness or help-seeking are associated with active help-seeking for mental problems. Campaigns promoting help-seeking and fighting mental illness-related stigma should target these personal attitudes rather than broad public opinion.
Decline in social functioning occurs in individuals who later develop psychosis.
To investigate whether baseline differences in disability are present in those who do and those who do not make a transition to psychosis in a group clinically at high risk and whether disability is a risk factor for transition.
Prospective multicentre, naturalistic field study with an 18-month follow-up period on 245 help-seeking individuals clinically at high risk. Disability was assessed with the Disability Assessment Schedule of the World Health Organization (WHODAS–II).
At baseline, the transition group displayed significantly greater difficulties in making new friends (z =−3.40, P = 0.001), maintaining a friendship (z =−3.00, P = 0.003), dealing with people they do not know (z =−2.28, P = 0.023) and joining community activities (z =−2.0, P = 0.05) compared with the non-transition group. In Cox regression, difficulties in getting along with people significantly contributed to the prediction of transition to psychosis in our sample (β = 0.569, s.e. = 0.184, Wald = 9.548, P = 0.002, hazard ratio (HR) = 1.767, 95% CI 1.238–2.550).
Certain domains of social disability might contribute to the prediction of psychosis in a sample clinically at high risk.
Anandamide is a bioactive lipid binding to cannabinoid receptors. A homeostatic role for anandamide has been suggested in schizophrenia. We investigated its role in initial prodromal states of psychosis. We measured the levels of anandamide and its structural analog oleoylethanolamide in cerebrospinal fluid and serum of patients in the initial prodromal state (n=27) alongside healthy volunteers (n=81) using high-performance liquid chromatograph/mass spectrometry. Cerebrospinal anandamide levels in patients were significantly elevated. Patients with lower levels showed a higher risk for transiting to psychosis earlier. This anandamidergic up-regulation in the initial prodromal course may suggest a protective role of the endocannabinoid system in early schizophrenia.