Pediatric population-based studies with longitudinal study designs may be helpful for defining normative growth charts of diverse disease dimensions that in turn may aid in developing individual risk predictions . Here, we review different aspects of population-based studies with regard to the psychosis spectrum; we discuss neurodevelopmental underpinnings of psychosis spectrum symptoms, brain morphometric and functional alterations in individuals experiencing psychotic symptoms in the general population, and the role of genetic liability for psychosis. Given the overwhelming evidence offered by this body of recent work that even sub-clinical psychotic symptoms pose a risk for severe mental illnesses, we highlight promising strategies that facilitate access to mental health services for adolescents, a group highly vulnerable to mental health problems. Even though further research is needed, in particular to understand risk and resilience factors for longitudinal symptom progression, policy making should take available data into account to further reduce mental health stigma and to invest in prevention and early intervention programs. Despite the longstanding conceptualization of a continuum of psychotic symptoms ,cultivation grow rack this is not reflected in current diagnostic manuals . Recent findings in both help-seeking individuals experiencing PS, and studies on PS in the general population have further emphasized this notion .
Presumably, the psychosis continuum is characterized by qualitatively similar PS that vary in levels of conviction and duration, ranging from sub-clinical schizotypal symptoms to severe psychosis spectrum disorders such as schizophrenia. PS, as typically studied in population-based cohorts, include positive symptoms such as hallucinations and delusions. Sometimes negative symptoms such as flat affect are also considered when establishing sub-clinical psychosis categories for detailed discussion on psychometric issues. The concept of a psychosis continuum has further facilitated the adoption of a clinical staging model . Symptoms typically observed in the general population refer to stage 1a, nonspecific general psychopathologies such as depressive and anxiety symptoms alongside sub-threshold PS, and stage 1b with more specific PS, i.e., commonly termed clinical- or ultra-high risk state . Stage 0 in this model is defined by a genetic risk through a positive family history of severe mental illness and other states are characterized by above-threshold PS , persistence of symptoms , and severe, non-remitted psychotic disorders . Importantly, individuals do not necessarily change stages with time but may remain in their initially assigned stage. Similarly, studies on clinical high-risk cohorts specifically examining conversion to full-blown psychosis, i.e., changes of clinical stages, find low transition rates of approximately 20-35% over 2 years . Furthermore, the clinical staging model is primarily based on retrospective studies and requires further prospective validation.
The fact that the majority of individuals with a first episode of psychosis have not sought help before their ‘psychotic break’ highlights the necessity to broaden the target symptoms and audience of early intervention strategies for psychosis spectrum disorders. Population based studies have become an important strategy to validate the concept of a psychosis continuum, and may be helpful to tailor future primary prevention strategies to the general population by examining longitudinal trajectories of PS development across childhood and adolescence to detect early predictors . Studies on PS in the general population can further be viewed as an alternative to the CHR approach, an enrichment sampling focused on help-seeking individuals fulfilling certain diagnostic criteria . Studies applying CHR criteria to date have focused primarily on psychosis spectrum outcomes . Given that clinical ascertainment is required, CHR cohorts may not reflect the broader population experiencing PS, which may at least partially explain higher pluripotentiality of PS observed in population-based studies relative to CHR samples .Similar to overt psychotic disorders, PS in the general population are often accompanied by cognitive impairments , reduced quality of life , higher rates of substance use, functional disability, suicidality , and alterations in brain structure and function , rendering PS an important public health issue. In accordance with a clinical staging model, PS pose an elevated risk for the later development of overt mental illness; not only severe psychosis spectrum disorders but also depression, anxiety disorder, and bipolar disorder , amplifying the significance as a public health concern.
However, recent epidemiological and genetic findings highlight the complex relationship between PS and severe mental illnesses : overt psychotic disorders may exhibit diverse psychopathological precursors and similarly, PS in childhood and adolescence do not always foreshadow persistent psychosis and/or schizophrenia later in life. For example, in the Philadelphia Neurodevelopmental Cohort a positive predictive value of 0.51 was reported for initial screening of PS , but in a small Irish youth sample childhood PS had a positive predictive value of >0.59 for adolescent externalizing and internalizing problems . Population-based longitudinal studies on sub-clinical/ sub-threshold PS in children and adolescents offer promise for identifying disease biomarkers that predict progression to overt mental illness . Ultimately, these efforts aim at improving early identification of at-risk youth in order to improve long-term functional outcomes. Risk factors for sub-threshold PS and overt psychotic disorders, include genetic risk, both family history and high impact copy number variations such as 22q11.2 deletion syndrome , exposure to drugs as well as childhood adversities/trauma, obstetric complications, and socioeconomic difficulties, including ethnic minority and immigrant status . Importantly, all forms of prevention, i.e., universal, selective, and indicated , can be tailored to these risk factors . For example, universal prevention targets the general population and could involve destigmatization and anti-bullying campaigns to improve mental well-being overall. Selective preventions for people with increased risk for developing psychiatric disorders could be implemented in clinics by providing services for families of patients with severe mental illnesses, and indicated prevention is aimed at improving outcome in CHR individuals . Overall, general population studies allow for larger and unbiased samples, without typical confounders in clinical populations such as medication and illness duration. Such studies can therefore inform and shape policy making for preventive measures of severe mental illnesses. Table 1 provides an overview of population-based studies cited in this review.A pressing question, requiring longitudinal study, is whether sub-clinical PS in youth in the general population are in fact associated with the onset of overt psychosis later in life. One such study is the Dunedin Multidisciplinary Health and Development study, a birth cohort study out of New Zealand that followed the initial cohort over 38 years. A recent follow-up of this cohort reported that PS at age 11 were associated not only with a diagnosis of schizophrenia at age 38 7. but also with diagnoses of Post Traumatic Stress Disorder , substance dependence , depression , and anxiety . Higher rates of PS at age 11 further predicted suicide/ suicide attempts at age 38,greenhouse grow racks even when controlling for other psychiatric disorders at age 11 [the 15-year follow-up study of the Dunedin cohort at age 26 reported very similar findings ]. It is important to note, however, that PS were assessed with the Diagnostic Interview Schedule for Children, an instrument that includes only 5 questions on positive PS. The Avon Longitudinal Study of Parents and Children , with over 13,000 study participants, includes a total of 68 assessment points between birth and age 18.
Niarchou et al. reported that, similar to results from the Dunedin cohort, PS at age 12 were predictive of a psychotic disorder at age 18. Interestingly, nonspecific symptoms such as depersonalization and sub-psychotic unusual experiences were predictive of a psychotic disorder and depression at age 18 . Even though, ALSPaC also assessed only positive PS, the semi-structured PLIKSi instrument covers the three major domains of positive PS, i.e., hallucinations, delusions, and bizarre thinking, and therefore reflects a broader spectrum of PS . Overall, in the general population it appears that PS during childhood and adolescence increase the risk of later development of a broad range of psychiatric illnesses . PS in help-seeking individuals fulfilling CHR criteria may be more specific in terms of predicting psychosis onset even though rates of co-occurring non-psychotic disorders are also higher in these cohorts relative to the general population . Although their etiology is not well understood, PS throughout life are often preceded and accompanied by emotional and behavioral problems, which in turn are often associated with life adversities. Findings from the ALSPaC sample further confirmed previously described risk factors. In particular, early neurodevelopmental problems such as autism spectrum symptoms, asphyxia during birth, lower IQ, and delayed early motor development were specifically associated with PS in adolescence . Bolhuis et al.highlighted emotional and behavioral problems at age 3 and 6 as the earliest significant predictors of PS at age 10. These encompassed depressive symptoms, aggressive behavior, anxiety, sleep difficulties, attention problems, and somatic complaints. Interestingly, emotional and behavioral problems also partially explained the association between previously described risk factors such as autistic traits and childhood adversities and PS, rendering it likely that emotional problems are a core risk factor or precursor for later PS. Further, the authors hypothesize that PS can manifest differently across the lifespan, ranging from emotional problems in early childhood to sub-clinical PS in late childhood and adolescence, and severe mental illness in adulthood. However, difficulties in validly assessing PS in younger children could lead to a distortion of the true association between childhood emotional problems and PS . A twin study further supports an association between childhood emotional and behavioral problems and adolescent PS by showing a modest genetic overlap across these phenotypes . Further, lack of certain personal resources such as low optimism, low self-esteem, and high avoidance, in addition to emotional problems, have been reported as significant predictors of PS during adolescence . Early life stress and childhood adversities are associated with emotional and behavioral problems not only in childhood and adolescence but across the lifespan . In the largest population-based study to date, the World Health Organization Mental Health Survey , McGrath and colleagues confirmed that childhood adversities are associated with an at least two-fold increased risk for developing PS, in a dose-response relationship . Childhood adversities characterizing ‘maladaptive family functioning’ posed a somewhat stronger association with later onset of PS than ‘other childhood adversities’ . Interestingly, when adjusting for other mental illnesses with onset prior to PS, the association between childhood adversities and PS onset during adolescence became non-significant. This finding suggests that childhood adversities are not only a risk factor for adolescent-onset PS, but also other psychopathological symptoms with onset prior to adolescence, which in turn may lead to PS. Finally, an often-discussed risk factor for the consecutive development of PS is cannabis use; longitudinal results from the Netherlands Mental Health and Incidence Study reported that baseline cannabis use predicted PS at follow-up . Recent publications conclude that the evidence for this association is sufficient for policy makers to take this risk into consideration when further discussing legalizing cannabis . Recently, genetic studies have made great progress in elucidating the genetic architecture of severe mental illnesses. In the majority of cases, risk for severe mental illnesses appears to be attributable to the cumulative impact of multiple genes, where each gene individually explains only a small amount of variance, but the sum of risk alleles across all identified variants accounts for up to 18% of variance in schizophrenia diagnosis . As such, investigation of polygenic risk scores , based on effect sizes of common variants associated with schizophrenia and other disorders has become increasingly common in population-based studies. Studies applying PRS to developmental cohorts have recently emerged. For example, in the ALSPaC cohort schizophrenia PRS was significantly associated with negative symptoms and anxiety during adolescence, but not with positive symptoms, again suggesting that the genetic basis of PS may present differently across development . In line with behavioral studies, Riglin et al. highlighted associations between schizophrenia PRS and diverse problems of childhood development at ages 7 to 9, such as lower IQ and poor social and language skills . A recent study combined three major population-based cohorts [ALSPaC, TEDS , and CATSS ], identifying significant associations between schizophrenia PRS and different symptom domains: hallucinations and paranoia , anhedonia, cognitive disorganization, and parent-rated negative symptoms . Interestingly, bipolar disorder PRS was also significantly associated with hallucinations and paranoia, even when including individuals who scored zero on this scale.