As a result of the high risk perspective, interventions have often been provided in the prodromal phase of schizophrenia (Brew, Shannon, Storey, Boyd, & Mulholland, 2017; Fusar-Poli, Yung, McGorry, & van Os, 2014). It may be more effective to investigate predictors in earlier stages of life in order to prevent development of the disorder. Previous evidence suggests that this earlier identification should be done prior to the advent of significant disability characterizing the prodrome and without restriction to those accessing health services (Laurens & Cullen, 2016; Scott, 2016). A number of researchers maintain that psychotherapeutic, psychosocial, or mastering-oriented interventions should be directed towards children and adolescents who are potentially in premorbid phases of the disorder (Laurens & Cullen, 2016; Liu, Keshavan, Tronick, & Seidman, 2015; Scott, 2016; Seidman & Nordentoft, 2015; Sommer et al., 2016). Neurocognitive impairments (Bora et al., 2014; Seidman et al., 2016) and reduced social skills (Addington & Heinssen, 2012) are often already established when subclinical symptoms emerge (Sommer et al., 2016). Multiple preventive and treatment strategies have been proposed for children with proven genetic vulnerability and children with transient psychotic symptoms (Sommer et al., 2016).
Relatively robust evidence indicates that children who present social, emotional, and behavioural problems as well as psychosis-related symptoms in childhood or adolescence have an increased risk of developing schizophrenia spectrum disorders later in life (Cornblatt et al., 2015; Golembo-Smith et al., 2012; Rapado-Castro, McGorry, Yung, Calvo, & Nelson, 2015; Welham, Isohanni, Jones, & McGrath, 2009). Previous studies have identified the developmental antecedents of schizophrenia prior to the prodromal phase, such as greater exposure and responsiveness to stressors, impaired performance on measures of general intelligence, specific cognitive functions, brain structure and functional abnormalities, and neuromotor dysfunction (Dickson, Laurens, Cullen, & Hodgins, 2012; Rund, 2018; Welham et al., 2009).
A fairly large number of studies have focused on retrospective information from peers, teachers, and relatives, while few prospective studies have investigated the subjects’ own experiences (Seidman & Nordentoft, 2015). Results from longitudinal studies of general populations as well as familial high risk in cases of individuals at increased genetic risk of developing schizophrenia may not be generalizable. That is because most people with the disorder do not have affected family members (Laurens & Cullen, 2016).
It is important to expand the knowledge of early antecedents of schizophrenia in order to develop specific interventions aimed at identification and prevention of early psychotic symptoms (Scott, 2016). Prospective data on antecedents are not widely available because many studies have investigated retrospective data (Laurens et al., 2015). However, there is evidence that self-report measures are reliable in premorbid phases of schizophrenia (Brill et al., 2007). Prospective data from individuals who later developed psychotic illness and who have described their subjective experiences and premorbid characteristics in terms of health-related variables help preclude biased recollections of historical behaviour. They could also be a useful contribution to the field of early detection and prevention of psychotic illness (Lancefield, Raudino, & Downs, 2016).
The aim of the study
The aim of the study was to compare self-reported health and function in premorbid participants who later developed schizophrenia with healthy controls. We hypothesized that those in the premorbid phase of schizophrenia would report poorer self-perceived mental and psychosocial health compared to the controls.
Method
Design
The study had a prospective case-control design based on premorbid data from the Young-HUNT1 survey, which was part of the Nord-Trøndelag Health Study (Helseundersøkelsen i Nord-Trøndelag, HUNT). This longitudinal population study was conducted by the Norwegian University of Science and Technology (NTNU).
The Young-HUNT1 survey
The Young-HUNT1 survey was conducted in Nord-Trøndelag County in the period spanning 1995 to 1997 (Holmen et al., 2014) (https://www.ntnu.edu/hunt). Nord-Trøndelag is in Central Norway and currently has a stable population size of around 130,000 inhabitants (Holmen et al., 2014). The county is considered to be representative of Norway as a whole in terms of geography, economy, industry, and sources of income, age distribution, morbidity, and mortality. The study presented in this article was based on the Young-HUNT1 survey, which is the adolescent part of The HUNT Study (age range 13–19 years). The cohort consisted of 8,984 persons, about 90% of the youth population in Nord-Trøndelag. The data collection was performed in schools by trained nurses, and the methods included self-report questionnaires, structured interviews, and clinical measurements. The questionnaires covered major public health issues, including somatic and mental health, quality of life, and health behaviours.
Procedure
Based on a list of persons registered with a diagnosis of schizophrenia (F.20.0–F.20.9) in the Patient Administrative System (PAS) at the Department of Psychiatry of Nord-Trøndelag Hospital Trust, we identified people born in Nord-Trøndelag between 1977 and 1983 and thus eligible for participation in Young-HUNT1. Two study members examined the medical records of the PAS cohort based on the following inclusion criteria (Figure 1): 1) residence during the Young-HUNT1 survey period; 2) plausible schizophrenia diagnosis based on patient records; and 3) the absence of prodromal and manifest psychotic symptoms during Young-HUNT1 data collection. Prodromal symptoms were considered present in cases where marked changes in behaviour or thought patterns were reported at the time of participation in Young-HUNT1. The included cases were then invited to participate in the study.
Two external experienced psychiatrists validated the included cohorts’ diagnoses and estimated onset of disease based on the participants’ medical records. Inclusion was dependent upon fulfilment of the diagnostic criteria according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) criteria (World Health Organisation, 2016). Each case was grouped in one of the following categories: (a) certain diagnosis; (b) probable diagnosis; and (c) uncertain diagnosis. If there was at least one ‘uncertain diagnosis’ score, then the respondents’ data were excluded. The project members confirmed the respondents’ participation in the Young-HUNT1 survey based on the HUNT database. An application for this procedure was granted by the NTNU administrators of The HUNT Study (Nord-Trøndelag Health Study, 2015).
The informed consent procedure was undertaken by project members in collaboration with the individual’s therapist, primarily in the clinic or at his or her home. When individuals were prevented from using this approach, they were contacted by telephone. When necessary, required information was obtained from medical records held at clinics for children and adolescents and from former therapists.
Individuals who fulfilled the inclusion criteria and gave their consent to participate in the study were included in the study case group. The case group consisted of patients from the Psychiatric Department in the Nord-Trøndelag Hospital Trust.
Sample
The study dataset consisted of responses to the self-reported Young-HUNT1 questionnaires from a case group of 15 youths (Table 1), of whom 12 were boys and three were girls. Mean age at the time of Young-HUNT1 data collection was 16 years and one month, ranging from 13 years and 11 months to 18 years and eight months. The time of first reported prodromal symptoms varied from six months to eight years after Young-HUNT1. Later, four subgroups of schizophrenia were identified among the case group subjects.
From the HUNT sample (n = 8,984), we excluded respondents who had reported reduced mobility, reduced hearing, physical illness, severe mental illness, epilepsy, diabetes, migraine, or other somatic conditions lasting more than three months. From the remaining cohort, we identified a comparison group of healthy controls, matched 3:1 (n = 45) on gender and age.
Measures
To measure topics relevant to this study, we selected the questions in Young-HUNT1 regarding psychiatric conditions such as anxiety and depression, self-esteem, personality, and well-being. In addition, we included questions related to alcohol use, tobacco use, physical activity, school problems, social function, help-seeking behaviour, and leisure-time activity. (For the questionnaire see Young-HUNT1; ‘Junior high school (age 13–16)’ and ‘High school (age 16–19)’).
Some of the questions were single items, but most of the independent variables were composite scores constructed by the administrators of HUNT from a set of questions (examples: school function (14), friends (7), alcohol (5), and tobacco use (10) as well as help-seeking behaviour (6)). Other HUNT Study questions were based on structured, validated scales like The Hopkins Symptom Checklist version SCL-5 (Tambs & Moum, 1993). This checklist was used to assess symptoms of anxiety and depression. Four questions from Rosenberg’s Self-Esteem Scale were used to assess self-esteem (Rosenberg, 1965). ‘General well-being’ is a three-item quality-of-life scale validated in earlier HUNT studies (Storksen, Roysamb, Holmen, & Tambs, 2006). Moreover, an 18-item short version of the Eysenck Personality Questionnaire (EPQ) assesses extraversion, neuroticism, and psychoticism (Eysenck & Eysenck, 1977). Psychoticism has been difficult to interpret in theory (Gudbergsson, Fosså, Sanne, & Dahl, 2007) and was therefore excluded from our analyses. Each item on the EPQ-18 was scored as 0 (no) and 1 (yes), and the six-item scores on each dimension were summed, giving a total score ranging from zero to six on each dimension. We present results on all the sum scores but also for each question.
This dual presentation was done since some of the single questions, such as “often worried,” might be particularly important considering the subjects’ risk of potentially experiencing emotional problems prior to schizophrenia development (Rapado-Castro et al., 2015; Welham et al., 2009).
The question ‘Do you smoke?’ had five items ranging from ‘Yes, I smoke about xx cigarettes daily’ to ‘No, I don’t smoke’. The responses were dichotomized between ‘smoking daily’ and ‘not smoking daily’. Similar dichotomizations have been used in other Young-HUNT studies (Bratberg, Nilsen, Holmen, & Vatten, 2007; Mangerud, Bjerkeset, Holmen, Lydersen, & Indredavik, 2014). Schizophrenia is associated with an increased risk of daily smoking (Compton et al., 2009). Activities during the past week were dichotomized into ‘inactivity’ and ‘activity’. Inactivity was defined as ‘less than one day or one hour or less per week’ in accordance with recommendations in other studies (Rangul, Holmen, Kurtze, Cuypers, & Midthjell, 2008). Self-reported alcohol use was assessed with two questions: (1) ‘Have you ever tried drinking alcohol?’ with the response options ‘Yes’, ‘No’, and ‘Don’t know’; and (2) ‘Have you ever drunk so much alcohol that you felt intoxicated (drunk)?’, which was measured on a scale with five response options (‘Never’, ‘Once’, ‘2–3 times’, ‘4–10 times’, and ‘> 10 times’). None of the participants answered ‘Don’t know’ to the first question, which was dichotomized into ‘Yes’ or ‘No’. The second question was dichotomized between ‘Never’ and ‘Once or more’. Similar dichotomizations have been used in other Young-HUNT studies (Bratberg et al., 2007; Mangerud et al., 2014).
Lacking existing dichotomization procedures in the Young-HUNT1 dataset, we divided the groups based on their absence or presence of the element asked for in the questions. The question ‘How often have you been to the school health centre?’, which had three values – ‘Not at all’, ‘One to three times’, and More than three times’– the variables were dichotomized between ‘Not at all’ and ‘One or more times’.
Leisure time was assessed with the question: ‘How often have you done any of these activities in the past week?’ Since problems related to social activities are found to be a potentially important risk factor for schizophrenia, we present only those five of the nine sub-questions related to social activities (Derdikman-Eiron, Hjemdal, Lydersen, Bratberg, & Indredavik, 2013; Liu et al., 2015; Tarbox & Pogue-Geile, 2008; Michalska da Rocha, Rhodes, Vasilopoulou, & Hutton, 2017).
Fourteen sub-questions about school were gathered under the main question: ‘Do any of the following things happen to you at school/concerning school, or have any of them happened?’ The school questions were grouped into three separate domains: (1) problems related to concentration and academic achievement (Academic); (2) behavioural problems (Conduct); and (3) well-being problems (Dissatisfaction) (Storksen, Roysamb, Holmen, & Tambs, 2006). A specific single question, ‘Are you teased/harassed by other students?’, formed a single question domain. All of these are presented in the results section.
Adding to the already referred items, we used three single-item questions that investigated participants’ experience of loneliness, number of friends, and self-assessed health status.
Statistical methods
Data analyses were performed with IBM’s SPSS, version 23 (IBM, 2013). Differences in means were analysed with independent samples’ t-tests. Associations between case and controls and the categorical variables were analysed by estimating odds ratios from standard binary logistic regressions and by chi-square or Fisher’s exact tests. All tests were two-tailed.
Ethical considerations
The study was approved by the Regional Committee for Medical and Health Research Ethics and was conducted in accordance with the Helsinki Declaration (The World Medical Association, 2013). All participants had the required competence to give an informed consent to participate in the study.
Results
Participants in the case group reported significantly poorer scores on the ‘General well-being’ scale compared with those reported by the healthy controls (p = .002). The estimated mean difference was −2.5. On two of three items, the case group reported significantly poorer well-being compared with the healthy controls (satisfaction with life (p = .007) and feeling strong and vital (p = .001)).
The scores on the SCL-5 scale showed no significant differences between the two groups. However, the case group scored significantly lower on one of the items, having been more dejected, down, or sad compared with the healthy controls (p = .01), and the mean difference was –.59. The participants in the case group experienced more nervousness (during the last month) than the controls (p = .004). With regard to the EPQ, there were no differences on the two scales for neuroticism and extraversion, but there were differences on two single items: ‘more often worried’ (p = .004) and not liking ‘meeting ahead of schedule to appointments’ (p = .013). We did not find any significant differences between the groups in terms of self-esteem as measured with the short version of Rosenberg`s Self-Esteem Scale.
Compared with healthy controls, those in the case group reported having fewer close friends (p = .034), feeling lonelier (p = .003), and spending fewer hours (p = .002) and days per week (p =.009) engaged in sports or exercise.
The case group reported daily smoking more often than the healthy controls (p = .001), but there were no differences between the groups on the question ‘Have you tried smoking?’
No differences were identified regarding the use of school health services or help-seeking behaviour based on the question about initiating contact with school health services. Those in the case group had more often been to a general practitioner (p = .011) and to a psychologist in the last year (p = .046) than had the healthy controls. There were no differences between the cases and controls in terms of patterns of alcohol use or the question about their present state of health (p = .251).
No differences were identified concerning school (concentration/school conduct and academic achievement).
Discussion
The study hypothesis was that, as a group, young people who later suffered from schizophrenia would report significantly poorer self-perceived health than would the control group. We found this was the case for some health-related themes. In many areas, there were no differences. None of the results indicated that the case group had better health than the healthy controls.
The findings suggest that the main differences between the case group and the control group were that the case group’s subjects had elevated premorbid levels of negative affect in terms of poorer subjective well-being and a higher degree of nervousness. They reported themselves more dejected and sad compared with the healthy controls. These findings correspond closely with results from previous research on emotional problems, which showed that, for example, social anxiety (Johnstone, Ebmeier, Miller, Owens, & Lawrie, 2005; Jones, Rodgers, Murray, & Marmot, 1994) and depressive symptoms (Fusar-Poli et al., 2017; Fusar-Poli, Nelson, Valmaggia, Yung, & McGuire, 2014; Häfner et al., 1998) were generally highly prevalent in early stages of non-affective psychotic disorders (Thompson et al., 2015).
To our knowledge, few studies have examined subjective well-being in people in phases prior to the onset of schizophrenia. When asked about both intrapsychic and functional conditions, young people who were considered vulnerable to developing psychosis reported lower subjective quality of life than control groups (Bechdolf & Pukrop et al., 2005; Bechdolf & Ruhrmann et al., 2005; Svirskis et al., 2007). Low level of well-being is associated with less resilience in people with mental illnesses (Uzenoff et al., 2010), and it is an important topic to investigate in people in transition to psychosis (Brew et al., 2017). For many of our participants, their experiences of poor levels of well-being appear to have existed for quite some time before the onset of schizophrenia. Therefore, the low well-being scores can hardly be explained by annoying psychotic symptoms or by negative mental and social consequences associated with having a diagnosis.
The participants reported being more affected by worrying compared to the healthy controls. The concept of worry is documented as a factor in theoretical models for the establishment and continuation of psychopathological processes (Wells & Matthews, 1996). A thinking style characterized by worry has been identified as one among other specific proximal causal factors in persecutory delusions (Freeman & Garety, 2014). Worry leads to implausible ideas (Freeman et al., 2012; Freeman & Garety, 2014). Antecedent worry and rumination may predict delusional and hallucinatory experiences and associated distress (Hartley, Haddock, e Sa, Emsley, & Barrowclough, 2014). An elevated level of worry may contribute to a longer duration of paranoid thoughts (Startup, Freeman, & Garety, 2007). Treatment aimed at reducing concern may improve paranoid symptoms (Freeman et al., 2015). Our findings indicate that worrying processes were present in premorbid phases for the case group subjects. This finding may serve as a contribution to the ongoing discussion of the phenomenon’s significance in the development of schizophrenia.
The case group reported poorer social functioning compared with healthy controls regarding the following: feeling lonelier, having fewer close friends, not following up on appointments, and having a tendency to receive fewer visits. Studies have indicated that the frequency of meeting friends and the experience of low subjective well-being are the strongest adolescent predictors of reduced psychosocial functioning in young adulthood (Derdikman-Eiron et al., 2013). A number of studies have shown that a history of poor childhood social functioning during critical developmental stages is a sensitive predictor for schizophrenia later in life (Liu et al., 2015; Tarbox & Pogue-Geile, 2008). Loneliness is not only associated with manifest psychotic disorders but is also likely to be already present in subclinical stages (Michalska da Rocha et al., 2017). For a number of our cases, the experience of loneliness was reported before the onset of schizophrenia, indicating that such an experience was potentially a contributing factor in the development of the disorder.
Based on the responses they gave, the participants of the Young-HUNT1 survey were dissatisfied with their lives, often did not feel strong and vital, did not like school breaks, and felt lonelier than their peers. From this information, we can assume that many of them who later developed schizophrenia experienced struggles in daily life. A connection between low subjective well-being, depression, and experienced social support has previously been identified in individuals with first-episode psychosis (Uzenoff et al., 2010). Furthermore, previous research suggests that greater sensitivity to everyday stress is an indicator of both later development of psychosis (Myin-Germeys & van Os, 2007; Van Winkel, Stefanis, & Myin-Germeys, 2008) and experiences of social defeat (Selten & Cantor-Graae, 2007). The aforementioned dissatisfaction with life could indicate that at the time of participation the case subjects experienced what Myin-Germeys & Van Os (2007) describe as the ‘emotional pathway to psychosis’.
There were no differences between the case and control groups on the variables ‘self-esteem’ and ‘school function’ (concentration and academic achievement). The homogeneous response on self-esteem is interesting, given that the case group reported a higher degree of emotional and social problems. The lack of significant differences on reported school function differs from studies that have shown an association between schizophrenia in the premorbid phase and IQ reduction, cognitive deficits (Agnew-Blais et al., 2015; Welham et al., 2009), lower grades at school, and more negative academic assessments from teachers (Ullman, Levine, Reichenberg, & Rabinowitz, 2012).
Our study showed that individuals diagnosed with schizophrenia were less physically active in the premorbid phase of their disease compared with the healthy controls. In an earlier study, we found a relationship between inactivity and a diagnosis of schizophrenia (Okkenhaug et al., 2016). The reduced physical activity in the premorbid phases of schizophrenia development in this study confirm the findings from three linked studies of physical activity in adolescents who later developed psychosis (Sormunen et al., 2017).
The majority of the case group subjects reported that they smoked daily. There is a strong association between nicotine use and schizophrenia (Gurillo, Jauhar, Murray, & MacCabe, 2015; McCreadie, 2003), especially with daily smoking (Compton et al., 2009). Earlier studies have documented that smoking is overrepresented among people in the pre-clinical phases of schizophrenia (Myles et al., 2012) and at the onset of first-episode psychoses (Gurillo et al., 2015). Smoking is also associated with the earlier debut of symptoms (Gurillo et al., 2015). That many in the case group reported smoking before onset of disease supports the current argument that smoking is not necessarily a cause of schizophrenia. Smoking could represent one of many risk factors for disease development (Gurillo et al., 2015) by contributing to symptoms such as anxiety and depression (Alderson & Lawrie, 2015).
Studies have shown that alcohol abuse starts in early adolescence and that there are no differences in such abuse between healthy youths and youths in premorbid phases of schizophrenia (Buchy et al., 2015; Hambrecht, Lotz, Häfner-Ranabauer, & Waschkowski, 1996; Mangerud et al., 2014). Our findings support the findings of these studies.
Some case group subjects reported that they had more often attended appointments with general practitioners or psychologists. However, we found no difference between the groups as to whether they had taken the initiative to seek help from their school health services. Moreover, none of the participants reported the need for additional help of that type. Previous research has shown that people with first-episode psychosis do not initiate help-seeking for themselves, particularly those who have a relative who is affected by mental illness (O’Callaghan et al., 2010). This lack of help-seeking increases the challenge of implementing early identification and intervention strategies. Identification of adolescent premorbid function should rely on information not only from health services but also from peers, teachers, or significant others.
Limitations and strengths
The clinical sample in the present study was small. This tendency may have increased the risk of reduced external validity and generalizability. The sample size also excluded the possibility of conducting multiple regression analysis and justified the choice to analyse dichotomous variables. Furthermore, the sample had considerable gender skewness, with more males than females, which might have affected the results. There was also a risk of reduced reliability associated with the reporting of self-reported data, but there is no reason to suspect that participants with a later diagnosis of schizophrenia would differ from others regarding the validity of such data (Brill et al., 2007). The risk of bias regarding data derived from self-assessments stemming from participants’ long-term deficient memories or subjective distortions of their childhood was minimized by the data being prospective.
The case group participants had well-validated diagnoses, and people with short, single psychotic episodes (< 1 month) were excluded. The case group subjects were also considered representative of the total population of people who developed schizophrenia in the cohort born between 1977 and 1983 in Nord-Trøndelag. Compared with other studies where respondents were selected on the basis of genetic risk factors, the self-reported premorbid data limited potentially biased responses compared with other retrospective methods.
Conclusions
Adolescents in the premorbid phase of schizophrenia reported poorer self-perceived mental and psychosocial health in several areas compared with healthy controls. Compared with the healthy controls, they reported poorer subjective well-being, they felt more nervous, less happy, and sad, and they described themselves as more worried. Additionally, they had fewer friends, and they reported feeling lonely more often. Almost 50% smoked nicotine daily, and they were less physically active than their healthy peers.
The task of identifying subjects at risk of developing schizophrenia is challenging.
The task of identifying subjects at risk of developing schizophrenia is challenging because such individuals may not seek help for their psychological problems. It can be assumed that data from broad national health surveys, such as Young-HUNT1, will continue to be an important source of knowledge. The variety of questions on multiple domains provides the opportunity to construct a comprehensive knowledge base for the heterogeneous premorbid characteristics of people at risk of developing schizophrenia. More prospective data from larger cohorts are needed to be able to generalize such knowledge.
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