Psychosis Onset In Individuals Research Articles

Importance of Early Detection in Early Psychosis

Early psychosis is the term coined in the hope that early intervention and treatment would benefit the long-term clinical outcomes of patients with psychosis. According to the clinical staging of psychosis, clinical high risk for psychosis and first-episode psychosis are allocated to early psychosis. Here, we described several clinical issues regarding the importance of early detection in early psychosis. As for clinical high risk for psychosis, we addressed the prevalence and clinical courses of clinical high risk for psychosis and whether early intervention services can lower the risk of psychosis onset in individuals with clinical high risk for psychosis. Regarding first-episode psychosis, we showed the prevalence of first-episode psychosis, the patterns, definitions, and clinical implications of the duration of untreated psychosis, and whether early intervention services can reduce the duration of untreated psychosis. With further research, we hope to achieve convincing evidence that early intervention can provide longterm benefits to patients with psychosis.

Speech characteristics yield important clues about motor function: Speech variability in individuals at clinical high-risk for psychosis

Background and hypothesis: Motor abnormalities are predictive of psychosis onset in individuals at clinical high risk (CHR) for psychosis and are tied to its progression. We hypothesize that these motor abnormalities also disrupt their speech production (a highly complex motor behavior) and predict CHR individuals will produce more variable speech than healthy controls, and that this variability will relate to symptom severity, motor measures, and psychosis-risk calculator risk scores. Study design: We measure variability in speech production (variability in consonants, vowels, speech rate, and pausing/timing) in N = 58 CHR participants and N = 67 healthy controls. Three different tasks are used to elicit speech: diadochokinetic speech (rapidly-repeated syllables e.g., papapa…, pataka…), read speech, and spontaneously-generated speech. Study results: Individuals in the CHR group produced more variable consonants and exhibited greater speech rate variability than healthy controls in two of the three speech tasks (diadochokinetic and read speech). While there were no significant correlations between speech measures and remotely-obtained motor measures, symptom severity, or conversion risk scores, these comparisons may be under-powered (in part due to challenges of remote data collection during the COVID-19 pandemic). Conclusion: This study provides a thorough and theory-driven first look at how speech production is affected in this at-risk population and speaks to the promise and challenges facing this approach moving forward.

Pineal morphology of the clinical high-risk state for psychosis and different psychotic disorders

BackgroundPineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-risk (CHR) of psychosis or if pineal atrophy is specific to schizophrenia among different psychotic disorders. MethodsThis magnetic resonance imaging study examined the volume of and cyst prevalence in the pineal gland in 135 individuals at CHR of psychosis [52 (38.5%) subsequently developed psychosis], 162 with first-episode psychosis (FEP), 89 with chronic schizophrenia, and 87 healthy controls. The potential contribution of the pineal morphology to clinical characteristics was also examined in the CHR and FEP groups. ResultsPineal volumes did not differ significantly between the CHR, FEP, and chronic schizophrenia groups, but were significantly smaller than that in healthy controls. However, pineal volumes were not associated with the later onset of psychosis in the CHR group or FEP sub-diagnosis (i.e., schizophrenia, schizophreniform disorder, affective psychosis, and other psychoses). No significant differences were observed in the prevalence of pineal cysts between the groups, and it also did not correlate with clinical characteristics in the CHR and FEP groups. ConclusionThese results suggest that pineal atrophy is a general vulnerability marker of psychosis, while pineal cysts do not appear to contribute to the pathophysiology of psychosis.

Construct validity for computational linguistic metrics in individuals at clinical risk for psychosis: Associations with clinical ratings

Language deficits are prevalent in psychotic illness, including its risk states, and are related to marked impairment in functioning. It is therefore important to characterize language impairment in the psychosis spectrum in order to develop potential preventive interventions. Natural language processing (NLP) metrics of semantic coherence and syntactic complexity have been used to discriminate schizophrenia patients from healthy controls (HC) and predict psychosis onset in individuals at clinical high-risk (CHR) for psychosis. To date, no studies have yet examined the construct validity of key NLP features with respect to clinical ratings of thought disorder in a CHR cohort. Herein we test the association of key NLP metrics of coherence and complexity with ratings of positive and negative thought disorder, respectively, in 60 CHR individuals, using Andreasen's Scale of Assessment of Thought, Language and Communication (TLC) Scale to measure of positive and negative thought disorder. As hypothesized, in CHR individuals, the NLP metric of semantic coherence was significantly correlated with positive thought disorder severity and the NLP metrics of complexity (sentence length and determiner use) were correlated with negative thought disorder severity. The finding of construct validity supports the premise that NLP analytics, at least in respect to core features of reduction of coherence and complexity, are capturing clinically relevant language disturbances in risk states for psychosis. Further psychometric study is required, in respect to reliability and other forms of validity.

Volume Reduction of the Dorsal Lateral Prefrontal Cortex Prior to the Onset of Frank Psychosis in Individuals with an At-Risk Mental State.

Although some individuals with at-risk mental states (ARMS) develop overt psychosis, surrogate markers which can reliably predict a future onset of psychosis are not well established. The dorsal lateral prefrontal cortex (DLPFC) is thought to be involved in psychotic disorders such as schizophrenia. In this study, 73 ARMS patients and 74 healthy controls underwent 1.5-T 3D magnetic resonance imaging scans at three sites. Using labeled cortical distance mapping, cortical thickness, gray matter (GM) volume, and surface area of DLPFC were estimated. These measures were compared across the diagnostic groups. We also evaluated cognitive function among 36 ARMS subjects to clarify the relationships between the DLPFC morphology and cognitive performance. The GM volume of the right DLPFC was significantly reduced in ARMS subjects who later developed frank psychosis (ARMS-P) relative to those who did not (P = 0.042). There was a positive relationship between the right DLPFC volume and the duration prior to the onset of frank psychosis in ARMS-P subjects (r = 0.58, P = 0.018). Our data may suggest that GM reduction of the DLPFC might be a potential marker of future onset of psychosis in individuals with ARMS.

Abnormal Function in Dentate Nuclei Precedes the Onset of Psychosis: A Resting-State fMRI Study in High-Risk Individuals.

The cerebellum serves a wide range of functions and is suggested to be composed of discrete regions dedicated to unique functions. We recently developed a new parcellation of the dentate nuclei (DN), the major output nuclei of the cerebellum, which optimally divides the structure into 3 functional territories that contribute uniquely to default-mode, motor-salience, and visual processing networks as indexed by resting-state functional connectivity (RsFc). Here we test for the first time whether RsFc differences in the DN, precede the onset of psychosis in individuals at risk of developing schizophrenia. We used the magnetic resonance imaging (MRI) dataset from the Shanghai At Risk for Psychosis study that included subjects at high risk to develop schizophrenia (N = 144), with longitudinal follow-up to determine which subjects developed a psychotic episode within 1 year of their functional magnetic resonance imaging (fMRI) scan (converters N = 23). Analysis used the 3 functional parcels (default-mode, salience-motor, and visual territory) from the DN as seed regions of interest for whole-brain RsFc analysis. RsFc analysis revealed abnormalities at baseline in high-risk individuals who developed psychosis, compared to high-risk individuals who did not develop psychosis. The nature of the observed abnormalities was found to be anatomically specific such that abnormal RsFc was localized predominantly in cerebral cortical networks that matched the 3 functional territories of the DN that were evaluated. We show for the first time that abnormal RsFc of the DN may precede the onset of psychosis. This new evidence highlights the role of the cerebellum as a potential target for psychosis prediction and prevention.

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis

The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk. To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020. Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group). Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001). This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.

Cortical and Subcortical Brain Morphometry Abnormalities in Youth at Clinical High Risk for Psychosis and Individuals With Early Illness Schizophrenia

Many longitudinal structural brain imaging studies have reported progressive worsening of morphometric brain abnormalities in schizophrenia over the illness course, consistent with an underlying progressive pathophysiology. Although morphometric abnormalities in chronic schizophrenia are well-documented, less is known about brain morphometry abnormalities prior to psychosis onset in individuals at clinical high risk for psychosis (CHR), and how they compare with abnormalities early in the course of schizophrenia (ESZ).

Lower speech connectedness linked to incidence of psychosis in people at clinical high risk

BackgroundFormal thought disorder is a cardinal feature of psychotic disorders, and is also evident in subtle forms before psychosis onset in individuals at clinical high-risk for psychosis (CHR-P). Assessing speech output or assessing expressive language with speech as the medium at this stage may be particularly useful in predicting later transition to psychosis. MethodSpeech samples were acquired through administration of the Thought and Language Index (TLI) in 24 CHR-P participants, 16 people with first-episode psychosis (FEP) and 13 healthy controls. The CHR-P individuals were then followed clinically for a mean of 7 years (s.d. = 1.5) to determine if they transitioned to psychosis. Non-semantic speech graph analysis was used to assess the connectedness of transcribed speech in all groups. ResultsSpeech was significantly more disconnected in the FEP group than in both healthy controls (p < .01) and the CHR-P group (p < .05). Results remained significant when IQ was included as a covariate. Significant correlations were found between speech connectedness measures and scores on the TLI, a manual assessment of formal thought disorder. In the CHR-P group, lower scores on two measures of speech connectedness were associated with subsequent transition to psychosis (8 transitions, 16 non-transitions; p < .05). ConclusionThese findings support the utility and validity of speech graph analysis methods in characterizing speech connectedness in the early phases of psychosis. This approach has the potential to be developed into an automated, objective and time-efficient way of stratifying individuals at CHR-P according to level of psychosis risk.

Models Predicting Psychosis in Patients With High Clinical Risk: A Systematic Review.

ObjectiveThe present study reviews predictive models used to improve prediction of psychosis onset in individuals at clinical high risk for psychosis (CHR), using clinical, biological, neurocognitive, environmental, and combinations of predictors.MethodsA systematic literature search on PubMed was carried out (from 1998 through 2019) to find all studies that developed or validated a model predicting the transition to psychosis in CHR subjects.ResultsWe found 1,406 records. Thirty-eight of them met the inclusion criteria; 11 studies using clinical predictive models, seven studies using biological models, five studies using neurocognitive models, five studies using environmental models, and 18 studies using combinations of predictive models across different domains. While the highest positive predictive value (PPV) in clinical, biological, neurocognitive, and combined predictive models were relatively high (all above 83), the highest PPV across environmental predictive models was modest (63%). Moreover, none of the combined models showed a superiority when compared with more parsimonious models (using only neurocognitive, clinical, biological, or environmental factors).ConclusionsThe use of predictive models may allow high prognostic accuracy for psychosis prediction in CHR individuals. However, only ten studies had performed an internal validation of their models. Among the models with the highest PPVs, only the biological and neurocognitive but not the combined models underwent validation. Further validation of predicted models is needed to ensure external validity.

What Causes the Onset of Psychosis in Individuals at Clinical High Risk? A Meta-analysis of Risk and Protective Factors.

Twenty percent of individuals at clinical high risk for psychosis (CHR-P) develop the disorder within 2 years. Extensive research has explored the factors that differentiate those who develop psychosis and those who do not, but the results are conflicting.The current systematic review and meta-analysis comprehensively addresses the consistency and magnitude of evidence for non-purely genetic risk and protective factors associated with the risk of developing psychosis in CHR-P individuals. Random effects meta-analyses, standardized mean difference (SMD) and odds ratio (OR) were used, in combination with an established stratification of evidence that assesses the association of each factor and the onset of psychotic disorders (from class I, convincing evidence to class IV weak evidence), while controlling for several types of biases.A total of 128 original controlled studies relating to 26 factors were retrieved. No factors showed class I-convincing evidence. Two further factors were associated with class II-highly suggestive evidence: attenuated positive psychotic symptoms (SMD = 0.348, 95% CI: 0.280, 0.415) and global functioning (SMD = −0.291, 95% CI: −0.370, −0.211). There was class III-suggestive evidence for negative psychotic symptoms (SMD = 0.393, 95% CI: 0.317, 0.469). There was either class IV-weak or no evidence for all other factors.Our findings suggest that despite the large number of putative risk factors investigated in the literature, only attenuated positive psychotic symptoms, global functioning, and negative psychotic symptoms show suggestive evidence or greater for association with transition to psychosis. The current findings may inform the refinement of clinical prediction models and precision medicine in this field.

Disorganized Gyrification Network Properties During the Transition to Psychosis

There is urgent need to improve the limited prognostic accuracy of clinical instruments to predict psychosis onset in individuals at clinical high risk (CHR) for psychosis. As yet, no reliable biological marker has been established to delineate CHR individuals who will develop psychosis from those who will not. To investigate abnormalities in a graph-based gyrification connectome in the early stages of psychosis and to test the accuracy of this systems-based approach to predict a transition to psychosis among CHR individuals. This investigation was a cross-sectional magnetic resonance imaging (MRI) study with follow-up assessment to determine the transition status of CHR individuals. Participants were recruited from a specialized clinic for the early detection of psychosis at the Department of Psychiatry (Universitäre Psychiatrische Kliniken [UPK]), University of Basel, Basel, Switzerland. Participants included individuals in the following 4 study groups: 44 healthy controls (HC group), 63 at-risk mental state (ARMS) individuals without later transition to psychosis (ARMS-NT group), 16 ARMS individuals with later transition to psychosis (ARMS-T group), and 38 antipsychotic-free patients with first-episode psychosis (FEP group). The study dates were November 2008 to November 2014. The dates of analysis were March to November 2017. Gyrification-based structural covariance networks (connectomes) were constructed to quantify global integration, segregation, and small-worldness. Group differences in network measures were assessed using functional data analysis across a range of network densities. The extremely randomized trees algorithm with repeated 5-fold cross-validation was used to delineate ARMS-T individuals from ARMS-NT individuals. Permutation tests were conducted to assess the significance of classification performance measures. The 4 study groups comprised 161 participants with mean (SD) ages ranging from 24.0 (4.7) to 25.9 (5.7) years. Small-worldness was reduced in the ARMS-T and FEP groups and was associated with decreased integration and increased segregation in both groups (Hedges g range, 0.666-1.050). Using the connectome properties as features, a good classification performance was obtained (accuracy, 90.49%; balanced accuracy, 81.34%; positive predictive value, 84.47%; negative predictive value, 92.18%; sensitivity, 66.11%; specificity, 96.58%; and area under the curve, 88.30%). These findings suggest that there is poor integration in the coordinated development of cortical folding in patients who develop psychosis. These results further suggest that gyrification-based connectomes might be a promising means to generate systems-based measures from anatomical data to improve individual prediction of a transition to psychosis in CHR individuals.

Coping styles in individuals at ultra-high risk for psychosis: Associations with cognitive appraisals

Maladaptive coping may play an important role in the manifestation of symptoms, functioning, and overt psychosis onset in individuals at ultra-high risk (UHR) for psychosis. To determine the factors associated with coping strategies, the relationships between cognitive appraisals and coping styles were investigated in UHR individuals. Sixty-five UHR individuals and 83 healthy controls were assessed for coping styles and cognitive appraisals of attribution bias as a primary appraisal and self-efficacy and perceived social support as a secondary appraisal. UHR participants relied more on a passive, tension-reduction coping style and less on an active, problem-focused coping style. These maladaptive coping styles in UHR individuals were significantly associated with their cognitive appraisals of stress. Aberrant attribution style of hostility perception and composite blaming bias were associated with problem-focused coping and tension-reduction, respectively. Perceived social support was related to problem-focused coping, seeking social support, and wishful thinking. General self-efficacy was associated with problem-focused coping. Our findings suggest that cognitive appraisals themselves may be the major determinants of coping styles in UHR individuals. The identified attribution styles, perceived social support, and self-efficacy may provide some clues regarding specialized interventions for the buildup of adaptive coping strategies in UHR individuals.

White matter abnormalities in 22q11.2 deletion syndrome patients showing cognitive decline.

Decline in cognitive functioning precedes the first psychotic episode in the course of schizophrenia and is considered a hallmark symptom of the disorder. Given the low incidence of schizophrenia, it remains a challenge to investigate whether cognitive decline coincides with disease-related changes in brain structure, such as white matter abnormalities. The 22q11.2 deletion syndrome (22q11DS) is an appealing model in this context, as 25% of patients develop psychosis. Furthermore, we recently showed that cognitive decline also precedes the onset of psychosis in individuals with 22q11DS. Here, we investigate whether the early cognitive decline in patients with 22q11DS is associated with alterations in white matter microstructure. We compared the fractional anisotropy (FA) of white matter in 22q11DS patients with cognitive decline [n = 16; -18.34 (15.8) VIQ percentile points over 6.80 (2.39) years] to 22q11DS patients without cognitive decline [n = 18; 17.71 (20.17) VIQ percentile points over 5.27 (2.03) years] by applying an atlas-based approach to diffusion-weighted imaging data. FA was significantly increased (p < 0.05, FDR) in 22q11DS patients with a cognitive decline in the bilateral superior longitudinal fasciculus, the bilateral cingulum bundle, all subcomponents of the left internal capsule and the left superior frontal-occipital fasciculus as compared with 22q11DS patients without cognitive decline. Within 22q11DS, the early cognitive decline is associated with microstructural differences in white matter. At the mean age of 17.8 years, these changes are reflected in increased FA in several tracts. We hypothesize that similar brain alterations associated with cognitive decline take place early in the trajectory of schizophrenia.

Deconstructing Pretest Risk Enrichment to Optimize Prediction of Psychosis in Individuals at Clinical High Risk

Pretest risk estimation is routinely used in clinical medicine to inform further diagnostic testing in individuals with suspected diseases. To our knowledge, the overall characteristics and specific determinants of pretest risk of psychosis onset in individuals undergoing clinical high risk (CHR) assessment are unknown. To investigate the characteristics and determinants of pretest risk of psychosis onset in individuals undergoing CHR assessment and to develop and externally validate a pretest risk stratification model. Clinical register-based cohort study. Individuals were drawn from electronic, real-world, real-time clinical records relating to routine mental health care of CHR services in South London and the Maudsley National Health Service Trust in London, United Kingdom. The study included nonpsychotic individuals referred on suspicion of psychosis risk and assessed by the Outreach and Support in South London CHR service from 2002 to 2015. Model development and validation was performed with machine-learning methods based on Least Absolute Shrinkage and Selection Operator for Cox proportional hazards model. Pretest risk of psychosis onset in individuals undergoing CHR assessment. Predictors included age, sex, age × sex interaction, race/ethnicity, socioeconomic status, marital status, referral source, and referral year. A total of 710 nonpsychotic individuals undergoing CHR assessment were included. The mean age was 23 years. Three hundred ninety-nine individuals were men (56%), their race/ethnicity was heterogenous, and they were referred from a variety of sources. The cumulative 6-year pretest risk of psychosis was 14.55% (95% CI, 11.71% to 17.99%), confirming substantial pretest risk enrichment during the recruitment of individuals undergoing CHR assessment. Race/ethnicity and source of referral were associated with pretest risk enrichment. The predictive model based on these factors was externally validated, showing moderately good discrimination and sufficient calibration. It was used to stratify individuals undergoing CHR assessment into 4 classes of pretest risk (6-year): low, 3.39% (95% CI, 0.96% to 11.56%); moderately low, 11.58% (95% CI, 8.10% to 16.40%); moderately high, 23.69% (95% CI, 16.58% to 33.20%); and high, 53.65% (95% CI, 36.78% to 72.46%). Significant risk enrichment occurs before individuals are assessed for a suspected CHR state. Race/ethnicity and source of referral are associated with pretest risk enrichment in individuals undergoing CHR assessment. A stratification model can identify individuals at differential pretest risk of psychosis. Identification of these subgroups may inform outreach campaigns and subsequent testing and eventually optimize psychosis prediction.

Comparing time use in individuals at different stages of psychosis and a non-clinical comparison group

Social functioning difficulties are a common and disabling feature of psychosis and have also been identified in the prodromal phase. However, debate exists about how such difficulties should be defined and measured. Time spent in structured activity has previously been linked to increased psychological wellbeing in non-clinical samples and may provide a useful way of assessing social functioning in clinical settings.The current study compared hours in structured activity, assessed with the Time Use Survey, in three clinical groups at different stages of psychosis: individuals with at-risk mental states (N=199), individuals with first-episode psychosis (N=878), and individuals with delayed social recovery following the remission of psychotic symptoms (N=77). Time use in the three clinical groups was also compared with norms from an age-matched non-clinical group (N=5686) recruited for the Office for National Statistics UK 2000 Time Use Survey. Cutoff scores for defining social disability and recovery were examined.All three clinical groups spent significantly fewer hours per week in structured activity than individuals in the non-clinical group. Reduced activity levels were observed before the onset of psychosis in individuals with at-risk mental states. Additional reductions in activity were observed in the first-episode psychosis and delayed recovery groups compared to the at-risk mental state group. Assessing time spent in structured activity provides a useful way to assess social disability and recovery across the spectrum of psychosis.

Psychotherapy for adolescents and young adults at high risk for psychosis: a systematic review

Unlike medication treatment, which may confer an unfavourable risk-benefit ratio, psychosocial intervention has been an emerging target of recent randomized controlled trials (RCTs) assessing its efficacy in delaying or preventing the onset of psychosis in individuals identified at 'clinical high risk'. Literature comparing qualitative differences in these psychotherapeutic interventions is scarce. The aim of the current study was to conduct a PRISMA systematic review evaluating the efficacy of psychotherapeutic interventions in reducing the rates of conversion to psychosis in clinical high-risk individuals. RCTs were identified in PubMed, Medline and PsycINFO databases up to 30 November 2013. Six studies (comprising 800 participants) met review inclusion criteria. Three investigators performed data extraction independently by using a pre-structured selection form, and conducted risk of bias assessment employing the Cochrane approach. All six studies employed cognitive behaviour therapy as a core element. Three trials achieved a significant effect. The two trials that employed cognitive behaviour therapy enhanced for the specialized needs of clinical high-risk patients maintained significant effects at post-treatment follow up. Evidence from recent trials suggest that cognitive behaviour therapy may be beneficial in delaying or preventing onset of psychosis in clinical high-risk individuals, although effect sizes to date appear small. Further research is needed in larger samples to establish whether cognitive behaviour therapy is efficacious, and if additional intervention components can enhance established psychotherapies.

S.21.04 Intensive intervention in first episode of psychosis – does it make a difference in the long term and for whom?

Social functioning difficulties are a common and disabling feature of psychosis and have also been identified in the prodromal phase. However, debate exists about how such difficulties should be defined and measured. Time spent in structured activity has previously been linked to increased psychological wellbeing in non-clinical samples and may provide a useful way of assessing social functioning in clinical settings.The current study compared hours in structured activity, assessed with the Time Use Survey, in three clinical groups at different stages of psychosis: individuals with at-risk mental states (N = 199), individuals with first-episode psychosis (N = 878), and individuals with delayed social recovery following the remission of psychotic symptoms (N = 77). Time use in the three clinical groups was also compared with norms from an age-matched non-clinical group (N = 5686) recruited for the Office for National Statistics UK 2000 Time Use Survey. Cutoff scores for defining social disability and recovery were examined.All three clinical groups spent significantly fewer hours per week in structured activity than individuals in the non-clinical group. Reduced activity levels were observed before the onset of psychosis in individuals with at-risk mental states. Additional reductions in activity were observed in the first-episode psychosis and delayed recovery groups compared to the at-risk mental state group. Assessing time spent in structured activity provides a useful way to assess social disability and recovery across the spectrum of psychosis.

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Reduced prepulse inhibition (PPI) of the auditory startle reflex is a hallmark feature of attention-processing deficits in patients with schizophrenia and other psychotic disorders. Recent evidence suggests that these deficits may also be present before the onset of psychosis in individuals at ultra-high risk (UHR) and become progressively worse as psychosis develops. We conducted a longitudinal follow-up study to observe the development of PPI over time in UHR adolescents and healthy controls. Two-year follow-up data of PPI measures were compared between UHR adolescents and a matched control group of typically developing individuals. We included 42 UHR adolescents and 32 matched controls in our study. Compared with controls, UHR individuals showed reduced PPI at both assessments. Clinical improvement in UHR individuals was associated with an increase in PPI parameters. A developmental increase in startle magnitude partially confined the interpretation of the association between clinical status and PPI. Furthermore, post hoc analyses for UHR individuals who became psychotic between assessments had limited power owing to a low transition rate (14%). Deficits in PPI are present before the onset of psychosis and represent a stable vulnerability marker over time in UHR individuals. The magnitude of this marker may partially depend on the severity of clinical symptoms.