In the current study, findings were similar in a 1-year repeated measures analysis that allowed for intraperson variation.Within the United States alone, the economic burden has been estimated around 60 billion dollars annually and is a direct consequence of reduced productivity, high direct medical costs , and high non-health care costs. Recent work has highlighted the exacerbation of such costs by longer duration of untreated psychosis , which has been linked to more severe symptomatology, poorer global outcomes, decreased social functioning, and lower likelihood of remission. The additional correlation between longer DUP and increased delays in accessing mental health services emphasizes the need for early intervention and detection to minimize such morbidity. Over the last two decades, a multitude of research has emerged focusing early detection efforts on the “clinical high-risk ” state , which refers to individuals identified as having pre-psychotic clinical symptoms and functioning. In particular, the comparison between CHR individuals who ultimately develop fully psychotic features and those who do not suggests a potentially fruitful way of ascertaining distinct risk factors for the emergence of overt psychotic-spectrum disorders, as well as possible intervention targets. With new literature on this population emerging daily, it seems prudent to draw attention to the most current work, and how it is shaping our understanding of psychosis prediction and the underlying mechanisms leading to illness onset. To that effect, this article aims to provide a comprehensive review of recent progress in the early detection and prediction of psychosis. As referenced above,vertical growing rack the CHR construct is broadly defined in terms of operationally defined thresholds of pre-psychotic or subthreshold symptoms.
Although the diagnostic tool varies slightly across sites , the criteria are typically defined as the presence of one or more of the following: attenuated positive symptoms , brief intermittent psychotic symptoms , and familial genetic risk or schizotypal personality disorder combined with prominent deterioration in functioning . Positive, negative, general, and disorganized symptoms are typically rated on a scale addressing typical/healthy ranges, prodromal ranges, and psychotic ranges. Other work has focused on basic symptoms, or cognitive abnormalities in domains such as language, perception, motivation, and/or thought processing that may reflect earlier stages of risk. The criteria for conversion to psychosis typically converge on the presence of at least one fully psychotic symptom occurring several times a week for at least one week to one month, depending on the interview. For recent, comprehensive reviews of CHR criteria and diagnostic instruments, readers are directed elsewhere. Studies of the validity of the CHR state and research classification system have revealed some evidence of convergent, discriminant, and predictive power. Specifically, recent work from the North American Prodromal Longitudinal Study Consortium found that individuals who continue to meet CHR criteria over time as compared to symptomatic remitters were reported to have worse long-term functioning. CHR status appeared distinct from symptoms meeting criteria for Major Depressive Disorder; and those that met criteria for CHR status progression were more likely to convert to overt psychosis than those with stable CHR classification or those who remit.As compared to healthy controls , CHR individuals were found to have significantly greater impaired stress tolerance, despite similar rates of self-reported life events; in the CHR cohort, impaired stress tolerance was linked to poorer long-term global functioning and increases in depression, anxiety, conceptual disorganization and total negative symptoms over a four-year follow-up period, independent of the number of stressful life events.
Social and role functioning in CHR youth has also been separately predicted by negative symptoms and a composite neurocognitive factor within the multi-site NAPLS cohort, with negative symptoms mediating the effects of neurocognition. CHR individuals, those diagnosed with schizophrenia , and those with a first-degree family member with schizophrenia all perform similarly on tasks of emotion perception, and more poorly than HC. However, patients with SZ performed more poorly than CHR individuals on tasks of emotion differentiation , suggesting some emotion-based deficits may develop later in the course of illness. Yong et al. found that this decreased ability to recognize and label facial affect among CHRs, as well as deficits in theory of mind ability, were correlated with neurocognitive deficits in attention and working memory. However, no control group was included in this study, limiting interpretability of the results. Research on retrospective risk factors leading to the emergence and progression of psychosis has converged on premorbid social dysfunction. Poor adolescent social functioning has been shown to predict psychosis emergence over a 2.5-year follow-up, with high specificity and positive predictive power when combined with baseline-rated suspiciousness. This relationship was observed irrespective of both early childhood social functioning and severity of most positive and negative symptoms at baseline. However, baseline disorganized communication, suspiciousness, social anhedonia, and reduced ideational richness mediated this relationship. Interestingly, observed decreases in role and global functioning over time did not predict conversion. Additionally, in this cohort poor adolescent social functioning was more likely to predict onset of schizophrenia as opposed to other psychotic disorders, suggesting some diagnostic specificity. Further supporting this possibility, premorbid social functioning seems to differentiate future schizophreniaspectrum disorders from other psychiatric conditions even when rated by school teachers of 10 to 13-year-old children at genetic high risk for psychosis.
Other research using predictive models of observed long-term social and role deficits have confirmed the above findings. Both clinical and neuropsychological measures appear relevant; Carrion et al. found that baseline-evaluated social functioning, global disorganized symptomatology, and decreased processing speed predicted impaired social functioning at three to five year follow-up. Similarly, poor role functioning, motor disturbances , and verbal memory deficits at baseline predicted later role outcome. However, only impaired social outcome significantly correlated with conversion to psychosis, while predictors of role outcome were independent of conversion. Therefore, while poor functioning in both domains persists among CHR patients, early social deficits again seem to confer specific vulnerability for psychosis. Gender differences may also be relevant to these findings, as Walder and colleagues found that baseline social functioning and overall positive symptom severity predicted conversion in male CHR patients only . However, given that females were rated to have higher overall functioning at baseline in this study, and the fact that males demonstrated an association between greater deficits in childhood social adjustment and severity of later symptoms, these findings will need to be confirmed in an independent study. In addition to the significance of early social dysfunction,cannabis vertical grow racks the above work highlights the focus on baseline-rated features in the prediction of subsequent psychosis outcome. To investigate this further, one European study used latent class analysis to determine if certain baseline factors distinguished future CHR converters from non-converters. While latent class membership failed to separate anything other than overall CHR participants and healthy controls, the baseline SIPS factor score was significantly higher in subsequent converters than non-converters. Specifically, higher total positive symptom scores indicated later conversion in an independent sample. In a related investigation, baseline and three- to six-year follow-up ratings of global functioning ; Quality of Life Scale were split at the median, resulting in ‘good’ and ‘poor’ functioning groups. Individuals were additionally characterized as ‘deterioriating’ or ‘improving’ based on functioning changes from baseline to a three- to six year follow-up. Those meeting criteria for poor functioning at baseline and deteriorating function over time demonstrated the highest likelihood of converting to psychosis, with the deteriorating factor proving to be the most predictive . This suggests that investigation of progressive changes in social and role functioning over time may be a better predictor of psychosis risk than is functioning at a single time point. Substance use has also been investigated as a risk factor for conversion; in the Enhancing the Prospective Prediction of Psychosis study, reduced use of alcohol was a predictor of later psychosis. However, this may be a proxy for increased social withdrawal as indicated by reduced social drinking, rather than a distinct predictor. A more comprehensive review of ten studies found that while CHR participants commonly reported use of cannabis, alcohol, and nicotine/tobacco, only two of the ten studies found a positive association between substance use and subsequent conversion to psychosis.
One found that nicotine and cannabis abuse were predictive, and the other found that general substance abuse was associated with conversion when included in a multivariate prediction model. However, as the authors highlight, most of the included studies analyzed only baseline or lifetime levels of substance use, rather than changes in usage over time throughout the study. Neuroimaging work has additionally proposed a schizophrenia-specific vulnerability to the effects of cannabis due to the correlation between structural brain changes and substance use observed in CHRs only . Additionally, some researchers have found that the presence of sexual abuse during childhood or adolescence, rather than broad presence of abuse or neglect, was associated with conversion. Specifically, high sexual abuse scores on a self-report questionnaire led to a two- to four-fold increase in the rate of conversion as compared to those with low scores. This suggests that trauma-related stress may confer additional vulnerability for psychosis emergence, though additional work on abuse severity and frequency/duration is warranted.Neuropsychological studies have revealed differences in the overall cognitive functioning of CHR youth as compared to HCs. For example, in comparison to individuals who recently experienced their first psychotic episode and non-CHR help-seeking patients , Magaud and colleagues found that CHRs do not show significant differences in overall IQ, nor on specific sub-scales, based on conventional statistical approaches. However, analyses examining differences within sub-tests of an index revealed a higher proportion of diverse verbal comprehension profiles among CHR versus both FE and HS individuals. CHR individuals therefore appear to demonstrate specific patterns of subtle, early changes in their verbal cognition that may be best detected by investigating sub-scales rather than global index scores using classic analytic techniques. Global intelligence has also been evaluated for its ability to predict psychosis emergence in conjunction with SIPS positive symptoms, with the combination producing slightly more accurate prediction of conversion than SIPS positive symptoms alone. In this study, both high severity of symptoms and low IQ were deemed the only factors to independently forecast psychosis from among a wide range of clinical and neurocognitive variables, over a six-year follow-up period. Although both clinical and neurocognitive measures were assessed in conjunction with global functioning , only increased disorganization symptoms at baseline significantly correlated with poorer functioning at follow-up, suggesting a greater ability of clinical measures over neuropsychological ones to predict transition and long-term outcome. This has been affirmed through other work in which a best fit prediction model assessing several variables was created based on CHR APS criteria, basic symptoms of cognitive disturbances and delayed processing speed. Although the combination of clinical and neuropsychological features conferred the highest risk for conversion, individually, APS + COGDIS alone predicted conversion above and beyond the presence of processing speed deficits alone. Studies examining neurocognitive predictors independent of positive or other symptoms have similarly been conducted with mixed findings. In a recent meta-analytic review, broad cognitive deficits were observed in CHR and GHR individuals as compared to healthy controls, with more severe cognitive deficits in all areas save sustained attention predicting conversion. However, modest effect sizes for baseline group differences between CHR+ and CHR− again suggest a limited generalizability of baseline cognitive factors as stand-alone predictors of psychosis. In contrast, another study examining pattern of changes in CHR neurocognitive ability over one year revealed that, among a large number of neuropsychological variables assessed, a significantly larger effect size for verbal memory deficits alone was found for converters versus non-converters. No differences were found in overall neuropsychological impairment or effect sizes for executive functioning scores at follow-up between CHR+ and CHR− groups. However, overall CHR neurocognitive functioning was reduced at a one-year follow-up relative to baseline, with executive function and verbal memory ability significantly below healthy control performance. No evidence was found for progressive changes in IQ in the CHR group, nor were group differences found between CHRs and HC in the domains of sustained attention and motor functioning. This work suggested that only progressive verbal memory impairments may be related to psychosis emergence, though the sample size and conversion rate here were notably small, especially given the short follow-up time period.