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OBJECTIVE: Psychosis spectrum disorders are associated with cerebral changes, but the prognostic value and clinical utility of these findings are unclear. Here, we applied a multivariate statistical model to examine the predictive accuracy of global white matter fractional anisotropy (FA) for transition to psychosis in individuals at ultra-high risk for psychosis (UHR). METHODS: 110 UHR individuals underwent 3 Tesla diffusion-weighted imaging and clinical assessments at baseline, and after 6 and 12 months. Using logistic regression, we examined the reliability of global FA at baseline as a predictor for psychosis transition after 12 months. We tested the predictive accuracy, sensitivity and specificity of global FA in a multivariate prediction model accounting for potential confounders to FA (head motion in scanner, age, gender, antipsychotic medication, parental socioeconomic status and activity level). In secondary analyses, we tested FA as a predictor of clinical symptoms and functional level using multivariate linear regression. RESULTS: Ten UHR individuals had transitioned to psychosis after 12 months (9%). The model reliably predicted transition at 12 months (χ2 = 17.595, p = 0.040), accounted for 15-33% of the variance in transition outcome with a sensitivity of 0.70, a specificity of 0.88 and AUC of 0.87. Global FA predicted level of UHR symptoms (R2 = 0.055, F = 6.084, p = 0.016) and functional level (R2 = 0.040, F = 4.57, p = 0.036) at 6 months, but not at 12 months. CONCLUSION: Global FA provided prognostic information on clinical outcome and symptom course of UHR individuals. Our findings suggest that the application of prediction models including neuroimaging data can inform clinical management on risk for psychosis transition.
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Transtornos Psicóticos , Substância Branca , Anisotropia , Imagem de Difusão por Ressonância Magnética , Humanos , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico por imagem , Reprodutibilidade dos Testes , Fatores de Risco , Substância Branca/diagnóstico por imagemRESUMO
In schizophrenia patients, cognitive functions appear linked to widespread alterations in cerebral white matter microstructure. Here we examine patterns of associations between regional white matter and cognitive functions in individuals at ultra-high risk for psychosis. One hundred and sixteen individuals at ultra-high risk for psychosis and 49 matched healthy controls underwent 3 T magnetic resonance diffusion-weighted imaging and cognitive assessments. Group differences on fractional anisotropy were tested using tract-based spatial statistics. Group differences in cognitive functions, voxel-wise as well as regional fractional anisotropy were tested using univariate general linear modeling. Multivariate partial least squares correlation analyses tested for associations between patterns of regional fractional anisotropy and cognitive functions. Univariate analyses revealed significant impairments on cognitive functions and lower fractional anisotropy in superior longitudinal fasciculus and cingulate gyrus in individuals at ultra-high risk for psychosis. Partial least squares correlation analysis revealed different associations between patterns of regional fractional anisotropy and cognitive functions in individuals at ultra-high risk for psychosis compared to healthy controls. Widespread higher fractional anisotropy was associated with better cognitive functioning for individuals at ultra-high risk for psychosis, but not for the healthy controls. Furthermore, patterns of cognitive functions were associated with an interaction-effect on regional fractional anisotropy in fornix, medial lemniscus, uncinate fasciculus, and superior cerebellar peduncle. Aberrant associations between patterns of cognitive functions to white matter may be explained by dysmyelination.
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Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Imagem de Difusão por Ressonância Magnética/métodos , Transtornos Psicóticos/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Anisotropia , Encéfalo/fisiopatologia , Feminino , Humanos , Masculino , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/psicologia , Fatores de Risco , Substância Branca/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Many psychological treatments have shown effect on reducing self-harm in adults with borderline personality disorder. There is a need of brief psychotherapeutical treatment alternative for suicide prevention in specialized outpatient clinics. METHODS/DESIGN: The DiaS trial was designed as a pragmatic single-center, two-armed, parallel-group observer-blinded, randomized clinical superiority trial. The participants had at least two criteria from the borderline personality disorder diagnosis and a recent suicide attempt (within a month). The participants were offered 16 weeks of dialectical behavior therapy (DBT) versus up to 16 weeks of collaborative assessment and management of suicidality (CAMS) treatment. The primary composite outcome was the number of participants with a new self-harm (nonsuicidal self-injury [NSSI] or suicide attempt) at week 28 from baseline. Other exploratory outcomes were: severity of borderline symptoms, depressive symptoms, hopelessness, suicide ideation, and self-esteem. RESULTS: At 28 weeks, the number of participants with new self-harm in the DBT group was 21 of 57 (36.8%) versus 12 of 51 (23.5%) in the CAMS treatment (OR: 1.90; 95% CI: 0.80-4.40; P = .14). When assessing the effect of DBT versus CAMS treatment on the individual components of the primary outcome, we observed no significant differences in the number of NSSI (OR: 1.60; 95% CI: 0.70-3.90; P = .31) or number of attempted suicides (OR: 2.24; 95% CI: 0.80-7.50; P = .12). CONCLUSION: In adults with borderline personality traits and disorder and a recent suicide attempt, DBT does not seem superior compared with CAMS for reduction of number of self-harm or suicide attempts. However, further randomized clinical trials may be needed.
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Terapia Comportamental/métodos , Transtorno da Personalidade Borderline/terapia , Avaliação de Resultados em Cuidados de Saúde , Comportamento Autodestrutivo/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Ultra-high risk (UHR) is considered a forerunner of psychosis, but most UHR individuals do not later convert, yet remain symptomatic, disabled and help-seeking. Thus, there is an increased recognition of the UHR phenotype as a syndrome in itself, rather than merely a risk syndrome. It is therefore essential to investigate outcomes other than transition to psychosis. For this purpose, perceptual aberration appears to be a distinct, as well as a stable and less state-specific vulnerability indicator. We aimed to investigate perceptual aberration and associations with functional, neuro and social cognitive risk factors in an UHR sample. METHOD: One hundred and twenty UHR and 64 healthy controls were compared on levels of perceptual aberration using the perceptual aberration scale. We further investigated cross-sectional associations between perceptual aberration and CAARMS (as a measure of subthreshold psychotic symptoms) and functional, neuro and social cognitive risk factors within the UHR using Spearmans ρ. RESULTS: Perceptual aberration was significantly higher in UHR than in healthy controls and was associated with social functioning, executive functioning, and emotion recognition. CONCLUSION: Our findings are consistent with a view of perceptual aberration as a stable vulnerability indicator that varies little with clinical state.
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Transtornos Psicóticos , Humanos , Estudos Transversais , Transtornos Psicóticos/psicologia , Fatores de Risco , Função Executiva , Emoções , Escalas de Graduação PsiquiátricaRESUMO
Sleep disturbances are common in individuals at ultra high-risk (UHR) of psychosis and have proven to play a causal role in the occurrence of psychotic symptoms in healthy individuals. Only a few studies have systematically investigated sleep disturbances in UHR individuals. The help-seeking UHR individuals were 18-40 years old, and we included 72 UHR individuals according to the Comprehensive Assessment of At-Risk Mental State criteria (CAARMS) and 36 healthy controls. Sleep was measured with a modified version of the Karolinska Sleep Questionnaire and actigraphy for one night, and melatonin was measured at awakening and bedtime. We compared subjective rated sleep and actigraphy between healthy and UHR individuals (t-test and chi-square test) and examined the association between a CAARMS-composite score (linear regression). UHR individuals subjectively experienced poor sleep, categorised as disturbed sleep- and awakening index compared with healthy controls. We found no differences in actigraphy variables or morning/evening melatonin between UHR and healthy controls (t-test and chi-square). A high CAARMS-composite score was associated with high morning melatonin (B = 0.15, CI 0.02 to 0.27, p = 0.024) and high awakening index (B = 1.86, CI 0.58 to 3.14, p = 0.004) in UHR individuals. The results suggest that UHR individuals with high CAARMS scores have a delayed sleep phase; they have difficulties waking up and feel exhausted at awakening. It might be necessary to evaluate how UHR individuals sleep, and it would be of great interest to follow these patients over time according to the development of psychosis.
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Melatonina , Transtornos Psicóticos , Transtornos do Sono-Vigília , Humanos , Adolescente , Adulto Jovem , Adulto , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/epidemiologia , Fatores de Risco , Transtornos do Sono-Vigília/complicaçõesRESUMO
BACKGROUND: Cognitive impairments are present in individuals at ultra-high risk (UHR) of psychosis and UHR individuals exhibit a hyperactive and dysfunctional HPA-axis. Increasing stress levels could potentially lead to cognitive impairments and no previous studies have examined the association between physiological stress biomarkers and cognition in UHR individuals. This study aims to examine the association between saliva alpha amylase (SAA), heart rate variability (HRV), saliva cortisol, and cognition in UHR individuals. METHOD: We included 72 UHR individuals, aged 18-40, fulfilling criteria of the comprehensive assessment of at-risk mental state (CAARMS). Cognitive tests indexed the 7 core domains as stated by Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS). Physiological stress levels were observed for one day: saliva was collected at awakening, 30 min and 60 min after awakening and at bedtime. HRV was measured during sleep and before awakening. We used generalized linear model and controlled for multiple testing using false discovery rate (FDR). RESULTS: Higher levels of SAA were significantly associated with lower cognitive performance in the domains of verbal and visual learning and memory, sustained attention, working memory and global neurocognition looking at unadjusted data. Controlling for FDR visual memory, sustained attention and global neurocognition remained significant associated with SAA. We discovered no associations between cortisol and cognition. CONCLUSION: Visual learning and memory, sustained attention and global neurocognition remained significantly associated with SAA. This finding supports our hypothesis that an association between abnormal stress biomarkers and impaired cognition might be present in UHR individuals.
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Hidrocortisona , Transtornos Psicóticos , Humanos , Frequência Cardíaca , Saliva , Transtornos Psicóticos/complicações , Transtornos Psicóticos/psicologia , Cognição , Memória de Curto Prazo , Biomarcadores , alfa-AmilasesRESUMO
INTRODUCTION: Individuals at ultra high-risk (UHR) of psychosis exhibit significantly higher stress levels than healthy controls (HC). This study investigates how physiological stress measures differ between HC and UHR individuals and how physiological stress is associated with attenuated psychotic symptoms and changes over time in UHR individuals. Additionally, it examines how the use of medication affects physiological levels of stress. METHOD: The study included 72 UHR individuals and 36 HC. UHR were included according to the comprehensive assessment of at-risk mental state (CAARMS); a total-CAARMS score measured the attenuated psychotic symptoms and was calculated from the four psychosis subscales. HC and UHR were examined at baseline, and 47 UHR individuals were followed up after six months. Physiological stress measures were salivary cortisol, alpha-amylase (SAA) and heart-rate variability (HRV). Saliva was collected at four-time points during the day. RESULTS: There was no significant difference regarding cortisol (awakening response) or SAA measures between HC and UHR individuals. The use of antipsychotics and antidepressants was associated with low HRV in UHR individuals. In an exploratory analysis of 19 UHR individuals, we found an association between the change in total-CAARMS (six months total-CAARMS minus baseline total CAARMS) and the change in HRV during sleep (six months HRV minus baseline HRV). CONCLUSION: Our findings indicate that the use of antipsychotics and antidepressants could be associated with lower HRV in UHR individuals. There might be potential to investigate how HRV develops during the course of illness in UHR individuals.
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Hidrocortisona , Transtornos Psicóticos , Humanos , Estudos Longitudinais , Transtornos Psicóticos/complicações , Risco , Saliva , Fatores de RiscoRESUMO
Premorbid social and academic adjustment are important predictors of cognitive and functional performance in schizophrenia. Whether this relationship is also present in individuals at ultra-high risk (UHR) for psychosis is the focus of the present study. Using baseline data from a randomised clinical trial (N = 146) this study investigated associations between premorbid adjustment and neuro- and social cognition and functioning in UHR individuals aged 18-40 years. Patients were evaluated with the Premorbid Adjustment Scale (PAS) comprising a social and an academic domain. Using validated measures neurocognition was assessed in the domains of processing speed, executive function, attention, verbal learning and memory, visual learning and memory, and working memory along with estimated IQ. Social cognitive domains assessed were theory of mind, emotion recognition, and attributional bias. Functional assessment comprised the domains of social- and role functioning, functional capacity, and quality of life. Linear regression analyses revealed poor premorbid academic adjustment to be associated with poorer performance in processing speed, working memory, attention, full scale IQ, and verbal IQ. Poor premorbid social adjustment was associated with theory of mind deficits. Additionally, both premorbid adjustment domains were associated with social- and role functioning and quality of life. Corroborating evidence from schizophrenia samples, our findings indicate poor premorbid adjustment to correlate with deficits in specific cognitive and functional domains in UHR states. Early premorbid adjustment difficulties may therefore indicate a poor cognitive and functional trajectory associated with significant impairments in early and established psychotic disorders suggesting targets for primary intervention.
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AIM: A significant proportion of individuals at Ultra-High Risk (UHR) for psychosis do not transition to manifest psychosis. Many non-transitioning UHR individuals do, however, display poor long-term outcomes such as persistence of attenuated psychotic symptoms. Evidence is scarce on which variables may predict a better clinical and functional prognosis such as remission from the UHR state. METHODS: A total of 146 UHR individuals were enrolled in a randomized clinical trial (RCT), with this being analyses secondary to the RCT. Participants were assessed on multiple domains of symptoms, functioning, neuro- and social cognition. Regression analyses elucidated on the predictive power of these measures to remission from the UHR status (ie, not meeting UHR criteria) at 12-month follow-up. RESULTS: Of the 91 UHR individuals attending 12-month follow-up, 33 (36%) exhibited remission from the UHR state. Regression analyses revealed baseline functioning to be a significant predictor of risk remission, and this was maintained when controlling for the effect of antipsychotic medication, gender and estimated IQ. The individuals with remission from the UHR state showed lower attenuated psychotic- and depressive symptoms along with better functioning at 12-month follow-up. CONCLUSION: Our findings indicate functioning to be a contributor to the symptomatic recovery of UHR individuals, but a large amount of the variance on risk remission is, however, explained by other factors. Additionally, our findings suggest that UHR individuals with better functioning at ascertainment may present with a better clinical and functional prognosis, which may inform on the need for monitoring and intervention in this subgroup.
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Antipsicóticos , Transtornos Psicóticos , Antipsicóticos/uso terapêutico , Humanos , Prognóstico , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Risco , Fatores de RiscoRESUMO
AIM: Growing evidence suggests that subtle white matter (WM) alterations are associated with psychopathology in individuals at ultra-high risk for psychosis (UHR). However, the longitudinal relationship between symptom progression and WM changes over time remains under-explored. Here, we examine associations between changes in clinical symptoms and changes in WM over six months in a large UHR-cohort. METHODS: 110 UHR-individuals and 59 healthy controls underwent diffusion weighted imaging at baseline and after six months. Group × time effects on fractional anisotropy (FA) were tested globally and in four predefined regions of interest (ROIs) bilaterally using linear modelling with repeated measures. Correlations between the changes in clinical symptoms and FA changes in the ROIs were examined with Pearson's correlation. A partial least squares correlation-technique (PLS-C) explored multivariate associations between patterns of changes in psychopathology, regional FA and additional WM indices. RESULTS: At baseline, UHR-individuals displayed significantly lower FA globally (p = 0.018; F = 12.274), in right superior longitudinal fasciculus (p = 0.02; Adj R2 = 0.07) and in left uncinate fasciculus (p = 0.048; Adj R2 = 0.058) compared to controls (corrected). We identified a group × time interaction in global FA and right superior longitudinal fasciculus, but the finding did not survive multiple comparisons. However, an increase of negative symptoms in UHR-individuals correlated with FA increase in right superior longitudinal fasciculus (p = 0.048, corrected, r = 0.357), and this finding was supported by the multivariate PLS-C. CONCLUSION: We found a positive correlation with a moderate effect between change in negative symptoms and FA change over 6 months in right superior longitudinal fasciculus. This link appeared mainly to reflect a subgroup of UHR-individuals, which already at baseline presented as vulnerable.
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Transtornos Psicóticos , Substância Branca , Anisotropia , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Rede Nervosa/patologia , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaRESUMO
BACKGROUND: Negative symptoms are key features of psychosis-spectrum disorders linked to psychosis development and functional impairments. This study investigated the predictive strength of negative symptoms domains on multiple aspects of real-life functional outcome in individuals at clinical high-risk (CHR) for psychosis. METHODS: A total of 146 UHR individuals were enrolled in a randomized, clinical trial (RCT), with this being analyses secondary to the RCT. The participants were assessed at baseline with the Scale for the Assessment of Negative Symptoms (SANS) encompassing the four domains of affect, alogia, avolition, and anhedonia. Functioning measures, encompassing overall-, social-, and role functioning, self-report social functioning, and quality of life, were obtained at 12-month follow-up. Regression analyses elucidated on the relationship between the four negative symptom domains and functional outcomes. RESULTS: Anhedonia and avolition were the aspects of negative symptoms most predictive of real-life functioning at 12-month follow-up explaining 7-20% of the variance on the outcome measures. Alogia was predictive of social functioning. These findings were maintained when controlling for the effect of neurocognition, antipsychotic medication, and depressive symptoms. DISCUSSION: Our findings show experiential negative symptoms to predict multiple areas of real-life functioning and quality of life, while expressive negative symptoms exert a modest influence on the functional prognosis of CHR individuals. Experiential negative symptoms may therefore constitute an important treatment target in intervention approaches aimed at enhancing the functional outcome of CHR individuals.
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Antipsicóticos , Transtornos Psicóticos , Antipsicóticos/uso terapêutico , Humanos , Sintomas Prodrômicos , Prognóstico , Transtornos Psicóticos/tratamento farmacológico , Qualidade de Vida , Ajustamento SocialRESUMO
There is a scarcity of evidence on subjectively reported cognitive difficulties in individuals at ultra-high risk (UHR) for psychosis and whether these self-perceived cognitive difficulties may relate to objective cognitive deficits, psychopathology, functioning, and adherence to cognitive remediation (CR). Secondary, exploratory analyses to a randomized, clinical trial were conducted with 52 UHR individuals receiving a CR intervention. Participants completed the Measure of Insight into Cognition-Self Report (MIC-SR), a measure of daily life cognitive difficulties within the domains of attention, memory, and executive functions along with measures of neuropsychological test performance, psychopathology, functioning, and quality of life. Our study found participants with and without objectively defined cognitive deficits reported self-perceived cognitive deficits of the same magnitude. No significant relationship was revealed between self-perceived and objectively measured neurocognitive deficits. Self-perceived cognitive deficits associated with attenuated psychotic symptoms, overall functioning, and quality of life, but not with adherence to, or neurocognitive benefits from, a CR intervention. Our findings indicate that UHR individuals may overestimate their cognitive difficulties, and higher levels of self-perceived cognitive deficits may relate to poor functioning. If replicated, this warrants a need for both subjective and objective cognitive assessment in at-risk populations as this may guide psychoeducational approaches and pro-functional interventions. Self-perceived cognitive impairments do not seem to directly influence CR adherence and outcome in UHR states. Further studies are needed on potential mediator between self-perceived cognitive deficits and functioning and quality of life.
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Data (attached) for a focused review and meta-analysis of cerebral levels of glutamate, Glx, and GABA levels assessed with 1H-MRS in high-risk of psychosis states was collected and stored at covidence.org and extracted to The Cochrane Collaboration Review Manager software package (RevMan Version 5.3) for meta-analytical purposes. Meta-analyses were performed with a random-effects, inverse-variance weighted model to calculate the pooled effect size. Heterogeneity was measured using the I2 value. Significance was assessed using two-sided 95% confidence intervals. Potential publication bias was assessed by visual inspection of funnel plots. Supplementary to the co-submitted article are comprehensive meta-analyses of glutamate, Glx, and GABA, as well as the PRISMA flow diagram of included studies and a list of studies included in the review along with available measures and methodological variables. The attached data offers an insight into the included studies and the specified metabolite values for each study and offers possible further investigation for other researchers, as well as an insight into the review and meta-analyses performed. The supplementary material also serves to support findings and interpretations in the main article.
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Disturbances in the brain glutamate and GABA (γ-aminobutyric acid) homeostasis may be markers of transition to psychosis in individuals at high-risk (HR). Knowledge of GABA and glutamate levels in HR stages could give an insight into changes in the neurochemistry underlying psychosis. Studies on glutamate in HR have provided conflicting data, and GABA studies have only recently been initialized. In this meta-analysis, we compared cerebral levels of glutamate and GABA in HR individuals with healthy controls (HC). We searched Medline and Embase for articles published on 1H-MRS studies on glutamate and GABA in HR states until April 9th, 2019. We identified a total of 28 eligible studies, of which eight reported GABA (243 HR, 356 HC) and 26 reported glutamate (299 HR, 279 HC) or Glx (glutamate + glutamine) (584 HR, 632 HC) levels. Sample sizes varied from 6 to 75 for HR and 10 to 184 for HC. Our meta-analysis of 1H-MRS studies on glutamate and GABA in HR states displayed significantly lower (Pâ¯=â¯0.0003) levels of thalamic glutamate in HR individuals than in HC and significantly higher (Pâ¯=â¯0.001) Glx in the frontal lobe of genetic HR individuals (1st-degree relatives) than in HC. No other significant differences in glutamate and GABA levels were found. Subject numbers in the studies on glutamate as well as GABA levels were generally small and the data conflicting. Our meta-analytical findings highlight the need for larger and more homogeneous studies of glutamate and GABA in high-risk states.
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Lobo Frontal/metabolismo , Ácido Glutâmico/metabolismo , Sintomas Prodrômicos , Espectroscopia de Prótons por Ressonância Magnética , Transtornos Psicóticos/metabolismo , Tálamo/metabolismo , Ácido gama-Aminobutírico/metabolismo , Lobo Frontal/diagnóstico por imagem , Humanos , Transtornos Psicóticos/diagnóstico por imagem , Risco , Tálamo/diagnóstico por imagemRESUMO
BACKGROUND: Studies examining glutamate or gamma-aminobutyric acid (GABA) in ultra-high risk for psychosis (UHR) and the association with pathophysiology and cognition have shown conflicting results. We aimed to determine whether perturbed glutamate and GABA levels in the anterior cingulate cortex and glutamate levels in the left thalamus were present in UHR individuals and to investigate associations between metabolite levels and clinical symptoms and cognition. METHODS: We included 122 UHR individuals and 60 healthy control subjects. Participants underwent proton magnetic resonance spectroscopy to estimate glutamate and GABA levels and undertook clinical and cognitive assessments. RESULTS: We found no differences in metabolite levels between UHR individuals and healthy control subjects. In UHR individuals, we found negative correlations in the anterior cingulate cortex between the composite of glutamate and glutamine (Glx) and the Comprehensive Assessment of At-Risk Mental States composite score (p = .04) and between GABA and alogia (p = .01); positive associations in the anterior cingulate cortex between glutamate (p = .01) and Glx (p = .01) and spatial working memory and between glutamate (p = .04), Glx (p = .04), and GABA (p = .02) and set-shifting; and a positive association in the thalamus between glutamate and attention (p = .04). No associations between metabolites and clinical or cognitive scores were found in the healthy control subjects. CONCLUSIONS: An association between glutamate and GABA levels and clinical symptoms and cognition found only in UHR individuals suggests a loss of the normal relationship between metabolite levels and cognitive function. Longitudinal studies with investigation of clinical and cognitive outcome and the association with baseline levels of glutamate and GABA could illuminate whether glutamatergic and GABAergic dysfunction predicts clinical outcome.
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Ácido Glutâmico , Transtornos Psicóticos , Cognição , Glutamina , Humanos , Ácido gama-AminobutíricoRESUMO
BACKGROUND: Individuals at ultra-high risk (UHR) for psychosis have significant cognitive deficits that can impede functional recovery. Applying cognitive remediation (CR) before the onset of frank psychosis may improve the cognitive and functional prognosis of UHR individuals, however, little is known about the feasibility and efficacy of CR for this population. METHODS: In this randomised, clinical trial 146 individuals at UHR for psychosis aged 18-40â¯years were randomly assigned to treatment as usual (TAU) or TAU plus cognitive remediation. The CR targeted neurocognitive and social cognitive remediation. Assessments were carried out at 6- and 12-months post baseline. RESULTS: A total of 73 UHR individuals were assigned to TAU and 73 assigned to TAU + cognitive remediation. Compared to the control group, cognitive remediation did not result in significant improvement on the primary outcome; the Brief Assessment of Cognition in Schizophrenia composite score at 6-month follow-up (bâ¯=â¯-0.125, 95%CI: -0.23 to 0.172, pâ¯=â¯0.41). Nor did the intervention improve secondary outcomes in clinical symptoms or functioning. Exploratory analyses found emotion recognition latencies to be significantly more reduced in the intervention group at 6-months. At 12-months, the intervention group exhibited significantly better performance on two measures of executive function and visual memory. CONCLUSION: The 20-session treatment protocol was not well received in the UHR group, and unsurprisingly global measures did not improve. The benefit found in isolated neuro- and social cognitive measures after even a few sessions points to a potential for cognitive malleability if people can be engaged sufficiently to practice the skills. Trial registration ClinicalTrial.gov identifier: NCT02098408.
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Remediação Cognitiva , Transtornos Psicóticos , Esquizofrenia , Cognição , Função Executiva , Humanos , Transtornos Psicóticos/terapia , Esquizofrenia/complicações , Esquizofrenia/terapiaRESUMO
BACKGROUND: Individuals at ultra-high risk for psychosis (UHR) present with subtle alterations in cerebral white matter (WM), which appear to be associated with clinical and functional outcome. The effect of cognitive remediation on WM organization in UHR individuals has not been investigated previously. METHODS: In a randomized, clinical trial, UHR individuals aged 18 to 40 years were assigned to treatment as usual (TAU) or TAU plus cognitive remediation for 20 weeks. Cognitive remediation comprised 20 x 2-h sessions of neurocognitive and social-cognitive training. Primary outcome was whole brain fractional anisotropy derived from diffusion weighted imaging, statistically tested as an interaction between timepoint and treatment group. Secondary outcomes were restricted to five predefined region of interest (ROI) analyses on fractional anisotropy, axial diffusivity, radial diffusivity and mean diffusivity. For significant timepoint and treatment group interactions within these five ROIs, we explored associations between longitudinal changes in WM and cognitive functions/clinical symptoms. Finally, we explored dose-response effects of cognitive remediation on WM. RESULTS: A total of 111 UHR individuals were included. Attrition-rate was 26%. The cognitive remediation group completed on average 12 h of neurocognitive training, which was considerably lower than per protocol. We found no effect of cognitive remediation on whole-brain FA when compared to treatment as usual. Secondary ROI analyses revealed a nominal significant interaction between timepoint*treatment of AD in left medial lemniscus (P=0.016) which did not survive control for multiple comparisons. The exploratory test showed that this change in AD correlated to improvements of mental flexibility in the cognitive remediation group (p=0.001). We found no dose-response effect of neurocognitive training on WM. CONCLUSIONS: Cognitive remediation comprising 12 h of neurocognitive training on average did not improve global or regional WM organization in UHR individuals. Further investigations of duration and intensity of cognitive training as necessary prerequisites of neuroplasticity-based changes are warranted. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT02098408.
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BACKGROUND: Emotion recognition deficits are essential features of psychotic disorders and the ultra-high risk state of psychosis (UHR), that are known to relate to functional outcome. The potential associations between aspects of emotion recognition deficits and functioning are, however, understudied in UHR individuals. METHOD: Emotion recognition accuracy and latency were assessed in 132 UHR individuals and 60 healthy controls using the CANTAB emotion recognition task along with multiple measures of real life functioning. Multiple regression analyses assessed the potential relations between emotion recognition accuracy, latency, and measures of functioning. RESULTS: A consistent finding was that emotion recognition latency, but not accuracy, was associated with the four observer-rated measures of functioning (ß in the range -1.57 to -16.20), which remained significant on one measure after controlling for neurocognitive processing speed. Neither emotion recognition accuracy, nor latency related to real life functioning in healthy controls. DISCUSSION: The results suggest that processing speed of social cognitive information is an important correlate to real-life functioning in UHR individuals which may be a relevant target in social cognitive remediation programs for patients at risk for psychosis.
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Disfunção Cognitiva/fisiopatologia , Emoções/fisiologia , Expressão Facial , Reconhecimento Facial/fisiologia , Transtornos Psicóticos/fisiopatologia , Percepção Social , Adolescente , Adulto , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino , Transtornos Psicóticos/complicações , Reconhecimento Psicológico/fisiologia , Risco , Adulto JovemRESUMO
OBJECTIVE: Patients at ultra-high risk (UHR) for psychosis show significant impairments in functioning. It is essential to determine which factors influence functioning, as it may have implications for intervention strategies. This study examined whether social cognitive abilities and clinical symptoms are associated with functioning and social skills. METHODS: The study included 65 UHR patients and 30 healthy controls. Social cognitive function, social skills, and a broad range of functioning measures were assessed. RESULTS: The UHR patients demonstrated significant decrements on The Awareness of Social Inferences Task total score (p = .046, d = .51), and on the CANTAB emotion recognition task total percent correct (p = .023, d = .54) displaying particular difficulties in negative affect recognition. The patients exhibited significant impairments in social skills measured with the High Risk Social Challenge (pË.001, d = 1.05). Aspects of emotion recognition were associated with role functioning and social skill performance. The level of attributional bias was associated with overall functioning, and theory of mind ability was associated with self-reported functioning. Negative symptoms were associated with all measures of functioning (p ≤ .05). CONCLUSION: Significant impairments in social cognition and social skills were found in UHR patients. The patients' social cognitive function was associated with overall functioning and social skills. Negative symptoms appear to play an important role for functioning. Research is needed to investigate how the relations between social cognition, social skills and functioning develop from the UHR state to the stage of manifest illness. Research into how deficits in social cognition and social skills can be ameliorated in UHR patients is warranted.
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BACKGROUND: Cognitive deficits are a distinct feature among people at ultra-high risk (UHR) for psychosis and pose a barrier to functional recovery. Insufficient evidence exists on how to ameliorate these cognitive deficits in patients at UHR for psychosis and hence improve daily living and quality of life. The aim of the trial is to investigate whether cognitive remediation can improve cognitive and psychosocial function in patients at UHR for psychosis. METHODS: The FOCUS trial (Function and Overall Cognition in Ultra-high risk States) is a randomised, parallel group, observer-blinded clinical trial enrolling 126 patients meeting the standardised criteria of being at UHR for psychosis. Patients are recruited from psychiatric in- and outpatient facilities in the Copenhagen catchment area. Patients are randomised to one of the two treatment arms: cognitive remediation plus standard treatment versus standard treatment. The cognitive remediation consists of 24 weekly group-based and manualised sessions targeting neurocognition and social cognition. In addition to the group sessions, the patients will be offered 12 individual sessions aiming at maximising the transfer of the effects of the cognitive training to their everyday lives. Follow-up assessments will be conducted at 6 and 12 months after randomisation. The primary outcome is the composite score on the Brief Assessment of Cognition in Schizophrenia at cessation of treatment after 6 months. Secondary outcomes are social and daily functioning, psychosis-like symptoms, negative symptomatology, and depressive symptomatology as measured with the Personal and Social Performance Scale, Brief Psychiatric Rating Scale-Expanded Version, Scale for the Assessment of Negative Symptoms, and the Montgomery-Åsberg Depression Rating Scale. DISCUSSION: This is the first trial to evaluate the effects of neurocognitive and social cognitive remediation in UHR patients. The FOCUS trial results will provide evidence on the effect of targeted and comprehensive cognitive rehabilitation on cognition, daily living, and symptomatology as well as long-term outcome in preventing transition to psychosis in UHR patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT 02098408 . Date of registration 18 March 2014.