Ashleigh Lin

Neurocognitive predictors of functional outcome two to 13 years after identification as ultra-high risk for psychosis

BACKGROUND AND AIMnLittle is known about the relationship between neurocognitive performance and functional outcome before the onset of frank psychosis. This longitudinal study aimed to investigate neurocognitive predictors of poor functional outcome in a group identified as ultra-high risk (UHR) for psychosis between two and 13 years prior.nnnMETHODnIndividuals (N=230) identified as UHR for psychosis at the PACE Clinic in Melbourne completed assessment of psychopathology, functioning and neurocognition at baseline and follow-up. The mean length of follow-up was 7.26 years (SD 3.05).nnnRESULTSnForty-one individuals with the poorest functional outcome were identified. Only 48.8% of this group had transitioned to psychosis. Poor functional outcome was associated with reduced performance at baseline in the specific neurocognitive domains of verbal learning and memory, processing speed and attention, and verbal fluency, but not global cognitive impairment. Reduced performance on a verbal story recall task, in combination with higher negative symptoms at baseline, was the best predictor of later poor outcome. Baseline positive psychotic symptoms and GAF scores were not associated with later poor outcome.nnnDISCUSSIONnTo date, this is the longest follow-up study of an UHR sample. Poor functional outcome was associated with specific neurocognitive decrements, regardless of transition to psychosis. The detection of individuals with poor functioning at follow-up, against a background of previously identified risk factors for psychotic disorder, may yield a valid group in which to study biomarkers and treatment of schizophrenia.

Volumetric Abnormalities Predating the Onset of Schizophrenia and Affective Psychoses: An MRI Study in Subjects at Ultrahigh Risk of Psychosis

It remains unclear whether brain structural abnormalities observed before the onset of psychosis are specific to schizophrenia or are common to all psychotic disorders. This study aimed to measure regional gray matter volume prior to the onset of schizophreniform and of affective psychoses. We investigated 102 subjects at ultrahigh risk (UHR) of developing psychosis recruited from the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia. Twenty-eight of these subjects developed psychosis subsequent to scanning: 19 schizophrenia, 7 affective psychoses, and 2 other psychoses. We examined regional gray matter volume using 1.5 mm thick, coronal, 1.5 Tesla magnetic resonance imaging and voxel-based morphometry methods of image analysis. Subjects were scanned at presentation and were followed up clinically for a minimum of 12 months, to detect later transition to psychosis. We found that both groups of subjects who subsequently developed psychosis (schizophrenia and affective psychosis) showed reductions in the frontal cortex relative to UHR subjects who did not develop psychosis. The subgroup that subsequently developed schizophrenia also showed smaller volumes in the parietal cortex and, at trend level, in the temporal cortex, whereas those who developed an affective psychosis had significantly smaller subgenual cingulate volumes. These preliminary findings suggest that volumetric abnormalities in UHR individuals developing schizophrenia vs affective psychoses comprise a combination of features that predate both disorders and others that may be specific to the nature of the subsequent disorder.

The relationship between coping and subclinical psychotic experiences in adolescents from the general population – a longitudinal study

BACKGROUNDnSubclinical psychotic experiences during adolescence may represent liability for developing psychotic disorder. Both coping style and the degree of persistence of psychotic experiences may play a role in the progression to clinical psychotic disorder, but little is known about the causal relationship between the two.nnnMETHODnPath modelling was used to examine longitudinal relationships between subclinical positive psychotic experiences and three styles of coping (task-, emotion- and avoidance-oriented) in an adolescent general population sample (n=813) assessed three times in 3 years. Distinct developmental trajectories of psychotic experiences, identified with growth mixture modelling, were compared on the use of these coping styles.nnnRESULTSnOver time, emotion-oriented coping in general was bi-directionally related to psychotic experiences. No meaningful results were found for task- or avoidance-oriented coping. Females reported using a wider range of coping styles than males, but the paths between coping and psychotic experiences did not differ by gender. Persistence of psychotic experiences was associated with a greater use of emotion-oriented coping, whereas a decrease in experiences over time was associated with an increased use of task-orientated coping.nnnCONCLUSIONSnEmotion-oriented coping is the most important coping style in relation to psychotic experiences, as it may contribute to a vicious cycle and is associated with persistence of experiences. In addition, more task-oriented coping may result in a decrease in psychotic experiences. Results suggest that opportunities for intervention may already be present at the level of subclinical psychosis.

Subclinical psychosis and depression: Co-occurring phenomena that do not predict each other over time

BACKGROUNDnThe path from subclinical psychotic experiences to clinical disorder is thought to be mediated by the persistence of subclinical psychotic experiences. One of the factors that is likely associated with this persistence is depression. Although commonly viewed as interrelated concepts, the exact relationship between subclinical psychosis and depression is not clear.nnnMETHODSnCross-lagged path modeling was used to explore the relationship between subclinical psychosis and depression across and over time in an adolescent population seeking assistance for non-psychotic disorders (N=138), measured at four occasions over a two-year period.nnnRESULTSnSubclinical psychosis and depression were related to each other at every cross-sectional measurement, but did not predict each other over time. Subclinical psychotic experiences and depressive symptom levels were highest at baseline, when participants presented to the clinical service for help. In addition, the relationship between them was also strongest at baseline and decreased significantly over time.nnnCONCLUSIONnThe results suggest that psychosis and depression are interrelated phenomena that strongly co-occur in time, but longitudinally, one does not predict change in the other. Both psychopathological dimensions should be addressed when treatment is provided to adolescent help-seekers.

Neurocognitive predictors of transition to psychosis: medium- to long-term findings from a sample at ultra-high risk for psychosis

BACKGROUNDnIndividuals at ultra-high risk (UHR) for psychosis show reduced neurocognitive performance across domains but it is unclear which reductions are associated with transition to frank psychosis. The aim of this study was to investigate differences in baseline neurocognitive performance between UHR participants with (UHR-P) and without transition to psychosis (UHR-NP) and a healthy control (HC) group and examine neurocognitive predictors of transition over the medium to long term.nnnMETHODnA sample of 325 UHR participants recruited consecutively from the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne and 66 HCs completed a neurocognitive assessment at baseline. The UHR group was followed up between 2.39 and 14.86 (median = 6.45) years later. Cox regression was used to investigate candidate neurocognitive predictors of psychosis onset.nnnRESULTSnThe UHR group performed more poorly than the HC group across a range of neurocognitive domains but only performance on digit symbol coding and picture completion differed between the groups. The risk of transition was only significantly associated with poorer performance on visual reproduction [hazard ratio (HR) 0.919, 95% confidence interval (CI) 0.876-0.965, p = 0.001] and matrix reasoning (HR 0.938, 95% CI 0.883-0.996, p = 0.037). These remained significant even after controlling for psychopathology at baseline.nnnCONCLUSIONSnThis study is the longest follow-up of an UHR sample to date. UHR status was associated with poorer neurocognitive performance compared to HCs on some tasks. Cognition at identification as UHR was not a strong predictor of risk for transition to psychosis. The results suggests the need to include more experimental paradigms that isolate discrete cognitive processes to better understand neurocognition at this early stage of illness.

A longitudinal study of obsessive-compulsive disorder in individuals at ultra-high risk for psychosis

BACKGROUNDnWe evaluated whether (1) a diagnosis of obsessive-compulsive disorder (OCD) at baseline, or (2) the persistence, remission or emergence of de novo OCD at follow-up, were associated with the development of different psychotic disorders in a cohort of individuals at ultra-high risk (UHR) for psychosis.nnnMETHODSnPatients were assessed for OCD at baseline and after a mean of 7.4 years follow-up and classified into: (i) Non-OCD group - patients without OCD both at baseline and follow-up (nxa0=xa0269; 86.2%), (ii) Incident OCD group - patients without OCD at baseline but with OCD at follow-up (nxa0=xa017; 5.4%), (iii) Remitting OCD group - patients with OCD at baseline but without OCD at follow-up (nxa0=xa020; 6.4%), (iv) Persistent OCD group - patients with OCD both at baseline and at follow-up (nxa0=xa06; 1.9%). Rates of different DSM-IV psychotic disorders at follow-up were compared across these groups.nnnRESULTSnPatients who displayed remitting OCD were not related to the development of any DSM-IV psychotic disorder. A diagnosis of incident OCD was associated with greater rates of psychotic disorders at follow-up, particularly mood disorders with psychotic features and psychotic disorders not otherwise specified (PDNOS), and greater baseline severity of general psychopathology, alogia, and avolition-apathy. Two of the six patients (40%) with persistent OCD developed schizophrenia, while only 12.5%, 5.0%, and 9.7% of incident, remitting, and non-OCD groups, respectively, exhibited the same condition at follow-up. Rates of antipsychotic use in the previous two years were not significantly different between the groups.nnnCONCLUSIONSnOur findings suggest that, in a cohort of individuals at UHR for psychosis, remission of OCD does not increase the risk of psychosis, while de novo OCD was associated with development of mood disorders with psychotic features and PDNOS.

Effects of NRG1 and DAOA genetic variation on transition to psychosis in individuals at ultra-high risk for psychosis

Prospective studies have suggested genetic variation in the neuregulin 1 (NRG1) and D-amino-acid oxidase activator (DAOA) genes may assist in differentiating high-risk individuals who will or will not transition to psychosis. In a prospective cohort (follow-up=2.4–14.9 years) of 225 individuals at ultra-high risk (UHR) for psychosis, we assessed haplotype-tagging single-nucleotide polymorphisms (htSNPs) spanning NRG1 and DAOA for their association with transition to psychosis, using Cox regression analysis. Two NRG1 htSNPs (rs12155594 and rs4281084) predicted transition to psychosis. Carriers of the rs12155594 T/T or T/C genotype had a 2.34 (95% confidence interval (CI)=1.37–4.00) times greater risk of transition compared with C/C carriers. For every rs4281084 A-allele the risk of transition increased by 1.55 (95% CI=1.05–2.27). For every additional rs4281084-A and/or rs12155594-T allele carried the risk increased ∼1.5-fold, with 71.4% of those carrying a combination of ⩾3 of these alleles transitioning to psychosis. None of the assessed DAOA htSNPs were associated with transition. Our findings suggest NRG1 genetic variation may improve our ability to identify UHR individuals at risk for transition to psychosis.

Follow-up factor structure of schizotypy and its clinical associations in a help-seeking sample meeting ultra-high risk for psychosis criteria at baseline

BACKGROUNDnSchizotypy is a multidimensional construct indexing psychometric risk for schizophrenia. This study investigated the factor structure and clinical associations of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) short scales, assessed at follow-up in an originally help-seeking sample identified as ultra-high risk for psychosis.nnnMETHODnParticipants were 228 help-seeking individuals identified as ultra-high risk for psychosis between 2 and 14 years previously (mean, 7.09; SD, 3.17; median, 6.41). The 43-item O-LIFE short scales (Unusual Experiences, Introvertive Anhedonia, Cognitive Disorganization, Impulsive Nonconformity) and indices of depression, anxiety, positive and negative psychotic symptoms, functioning, and quality of life were administered at follow-up. Structural equation modeling was used.nnnRESULTSnImpulsive Nonconformity was shown to be an unstable factor and was excluded. A 3-factor model of Unusual Experiences, Cognitive Disorganization, and Introvertive Anhedonia was found to be the best description of the data, compared with a 1-factor model. Unusual Experiences factor was associated with positive psychotic symptoms; Cognitive Disorganization was associated with depression and anxiety; and Introvertive Anhedonia was associated with positive and negative psychotic symptoms, quality of life, and functioning.nnnCONCLUSIONSnThe Impulsive Nonconformity factor of the O-LIFE short scales should be interpreted with caution. A well-fitting 3-factor model provides support for a dimensional structure in schizotypy that is similar to that of schizophrenia. Separate dimensions were differentially associated with psychopathology, functioning, and quality of life. The interpersonal dimension of schizotypy was the only dimension associated with poorer functioning and quality of life and may be a sensitive indicator of need for care.

Dynamic Association Between Interpersonal Functioning and Positive Symptom Dimensions of Psychosis Over Time: A Longitudinal Study of Healthy Adolescents

BACKGROUNDnCross-sectional studies have indicated that alterations in social functioning, particularly interpersonal functioning, are associated with the occurrence of psychotic symptoms and experiences at different levels of the extended psychosis phenotype (ranging from population psychometric expression of liability to overt psychotic disorder). However, more research is needed on the development of this association over time.nnnMETHODSnCross-lagged path modeling was used to analyze bidirectional, longitudinal associations between 4 dimensions of subclinical psychotic experiences (persecutory ideation, bizarre experiences, perceptual abnormalities, and magical thinking) and interpersonal functioning in an adolescent general population sample (N = 881 at T1, N = 652 at T2, and N = 512 at T3) assessed 3 times in 3 years.nnnRESULTSnAll symptom dimensions showed some association with interpersonal functioning over time, but only bizarre experiences and persecutory ideation were consistently and longitudinally associated with interpersonal functioning. Poorer interpersonal functioning predicted higher levels of bizarre experiences and persecutory ideation at later measurement points (both T1 to T2 and T2 to T3).nnnCONCLUSIONSnPoor interpersonal functioning in adolescence may reflect the earliest expression of neurodevelopmental alterations preceding expression of psychotic experiences in a symptom-specific fashion.

Markers of vulnerability to obsessive-compulsive disorder in an ultra-high risk sample of patients who developed psychosis.

Aims: The study aims to identify markers of vulnerability to obsessive–compulsive disorder (OCD) in an ultra‐high risk sample of patients who developed psychosis.