Developing services for the early detection of psychosis - Springer Link

Eur Child Adolesc Psychiatry (2007) 16:96–103 DOI 10.1007/s00787-006-0579-7

Andor E. Simon Binia Roth Solange Zmilacher Emanuel Isler Daniel Umbricht

Accepted: 3 July 2006 Published online: 8 September 2006

The contents of this paper were presented at the 48th Annual Conference of the Swiss Society of Child and Youth Psychiatry, Mu¨nsterlingen, Switzerland, 4th November 2005 A.E. Simon, MD (&) Specialized Outpatient Clinic for Early Psychosis Psychiatric Outpatient Services Department of Psychiatry 4101 Bruderholz, Switzerland Tel.: +41-61/425-45 45 Fax: +41-61/425-45 46 E-Mail: [email protected] B. Roth Æ S. Zmilacher Æ E. Isler Child and Adolescent Psychiatric Department Department of Psychiatry 4101 Bruderholz, Switzerland D. Umbricht Translational Medicine Neuroscience Exploratory Development Novartis Pharma AG 4056 Basel, Switzerland

ORIGINAL CONTRIBUTION

Developing services for the early detection of psychosis A critical consideration of the current state of the art

j Abstract Recent research has

attempted to improve the identification of individuals at-risk of developing schizophrenia to permit targeted early prevention. Two sets of criteria, one characterized by a subgroup of ‘basic symptoms’ [Klosterko¨tter, Hellmich, Steinmeyer, Schultze-Lutter (2001) Arch Gen Psychiat 58:158– 164] and one by the ultra high-risk model [Miller, McGlashan, Woods, Stein, Driesen, Corcoran, Hoffman, Davidson (1999) Psychiatr Q 70:273–287; Yung, McGorry, McFarlane, Jackson, Patton, Rakkar (1996) Schizophr Bull 22:283–303], have been associated with positive predictive values for later schizophrenia. This paper is a critical discussion of these predictive values. In the first part, the paper demonstrates that the predictive values of at-risk criteria are mediated by a strong

ECAP 579

Introduction Over recent years, the goal to intervene during the initial prodrome of schizophrenia has drawn great interest both in clinical psychiatry and in research. To some extent, this interest has been driven by findings that a shortened duration of untreated psychosis may be associated with better illness outcome [1, 2]. As a result, a vast number of services have been established across the continents to deliver more appropriate care to patients in early phases of schizophrenia [3].

enrichment effect and depend considerably on the structure of early detection systems. Further, it shows that these predictive values do not apply to the general population level, where subclinical psychosis shows high prevalence and incidence rates, and that these values may be less predictive in adolescents. In the second part, the paper discusses the need for specific sensitization on several levels of an early detection system and proposes a selected overview of prototypical models already applied in this field.

j Key words prodrome – basic symptoms – at-risk state – ultra high-risk – early detection

Early intervention requires an accurate definition of at-risk states for schizophrenia. A few groups have attempted to define criteria which best describe the initial schizophrenia prodrome [4, 5]. These definitions tend to emphasize attenuated or intermittent positive symptoms and are referred to as the ultra high-risk (UHR) criteria. Naturalistic studies using these criteria were able to show high transition rates to schizophrenia [6, 7], thus suggesting strong predictive values of the UHR criteria. These results furthered enthusiasm in the field of schizophrenia prevention. However, it may be argued

A.E. Simon et al. Service development in early psychosis

that the UHR criteria – due to the focus on attenuated and intermittent positive symptoms – only capture a subgroup of prodromal individuals, very likely those closest to manifest schizophrenia. Indeed, earlier studies have commonly found high prevalence rates of social disability and negative symptoms up to 2–4 years before the onset of psychotic symptoms in individuals who developed schizophrenia [8]. Moreover, cognitive impairment has also been shown in at-risk patients [9–12] long before the onset of a first episode of schizophrenia. Thus, from a clinical point of view, the focus on positive symptoms seems to have significant limitations. A substantial number of at-risk individuals may not present attenuated or intermittent psychotic symptoms, but may be characterized by sustained negative symptoms and/or impaired social and cognitive functioning. This paper is a critical discussion of the commonly applied prodromal criteria and their interpretation in present research. First, we argue that the predictive values of prodromal criteria are mediated by the structure of the early detection services in which they are embedded and applied. Further, we discuss future directions, which attempt to address the shortcoming of the criteria revealed in this paper and present some results of our ongoing prospective study on patients at putative risk for psychosis. Finally, we underline the importance of collaboration between youth and adult psychiatry. The present paper, however, does not include a discussion of childhood-onset schizophrenia, as childhood-onset schizophrenia, a rare disorder that begins before the child’s 13th birthday, has a low prevalence of one child in 10,000 [13–15].

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cognition in patients with emerging, manifest and remitting schizophrenia. As they express experiences that are not observable from the outside, ‘basic symptoms’ are thought to already characterize the early phases of the prodrome. ‘Basic symptoms’ are central to the behavioral disturbances and functional disability of these patients [22]. In a recent publication, Klosterko¨tter et al. [23] reported a follow-up study of 160 adult individuals (mean age: 29.3 years, SD ± 10.0) who were considered to be at-risk of developing schizophrenia and enrolled in the Cologne Early Recognition (CER) study. The presence of any of the baseline ‘basic symptoms’ was used as a test to predict the onset of schizophrenia over a mean follow-up period of 9.6 years. For a subgroup of 10 ‘basic symptoms’ (see Table 1), a reasonable sensitivity and positive predictive values of 70% and higher for later schizophrenia were reported [23]. On the other hand, only 4% of patients without any of these ‘basic symptoms’ went on to develop schizophrenia [23]. However, studies on adolescents revealed less specific results. For instance, a cross-sectional study on 36 schizophrenic and 75 non-schizophrenic adolescent psychiatric inpatients (mean age: 16.4 years, SD ± 1.2) was performed to assess the specificity of prodromal signs in early age groups. This study retrospectively covered the last 6 months before admission. The occurrence of any single basic symptom did not show schizophrenic specificity in adolescents, but the number of ‘basic symptoms’ was increased in schizophrenic patients compared with subjects with other diagnoses [24].

j The ultra high-risk criteria

The schizophrenia prodrome Over the past decades, a number of attempts were undertaken to refine the criteria of the initial prodrome of schizophrenia [4, 5, 16, 17]. Two approaches have received significant attention: the ‘basic symptom’ and the UHR approach. Because they may lie on a continuum along the schizophrenia prodrome, these two approaches have recently been combined in a number of studies of the early phases of schizophrenia, such as the German Research Network on Schizophrenia (GRNS) [18], the European Prediction of Psychosis Study (EPOS) [19], and the Swiss Bruderholz Study [20, 21].

j Basic symptoms Long before the introduction of the UHR criteria, the so-called ‘basic symptoms’ were described as the subjective experiences of altered inner perception and

The UHR criteria include mostly observable signs and symptoms and are thought to describe the late prodrome of schizophrenia. Two groups, the Melbourne group [5] and the Yale group [4], have described three UHR groups (see Table 1): brief intermittent positive symptoms not meeting the DSMIV [25] duration criterion for schizophrenia; attenuated positive psychotic symptoms and a genetic risk/ deterioration syndrome (first degree relative with any psychotic disorder and/or patient meeting DSM-IV Schizotypal Personality Disorder criteria AND a 30% or greater drop in the Global Assessment of Functioning (GAF) [25] score during the last month compared to 12 months ago). Levels of negative symptom scores are not included into the UHR definition. In naturalistic studies, both groups showed considerable transition rates to schizophrenia, ranging between 34.6 % (mean patient age: 19.4, SD ± 3.5) [7] and 54 % (mean patient age: 17.8 years, SD ± 6.1) [6] during the first year after initial assessment.

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Table 1 Predictive ‘Basic Symptoms’ according to Klosterko¨tter et al., 2001 [23] Thought interference Thought perseveration Thought pressure Thought blockages Disturbances of receptive language Decreased ability to discriminate between ideas and perception, fantasy and true memory Unstable ideas of reference Derealization Visual perception disturbances Acoustic perception disturbances Ultra High-Risk (UHR) criteria according to Miller et al., 1999 [4] Brief Intermittent Psychotic Syndrome Any SOPS positive symptom score of 6 that does not last for at least one hour per day at an average frequency of four days per week over one month. Attenuated Positive Prodromal Syndrome Any SOPS positive symptom score between 3 and 5 that occured at this level at an average frequency of at least once per week in the past month [SOPS positive symptoms: unusual thought content/delusional ideas; suspiciousness/persecutory ideas; grandiose ideas; perceptual abnormalities/hallucinations; disorganized communication] Genetic Risk and Deterioration Syndrome First degree relative with any psychotic disorder and/or patient meeting DSM-IV Schizotypal Personality Disorder criteria AND a 30% or greater drop in the GAF score during the last month compared to 12 months ago [GAF = Global Assessment of Functioning, American Psychiatric Association APA, 1994]. Suggested Further Clinical Criteria for Future Detection Systems Sustained functional decline Social withdrawal Attenuated and sustained negative symptoms such as affective flattening anhedonia avolition decreased ideational richness

j How predictive are the predictive values really? Both the transition rates using the ‘basic symptoms’ and the UHR approach suggest that these criteria are of fairly high predictive value. However, a number of caveats need to be addressed. Most importantly, population-based studies on the prevalence and incidence of subclinical psychosis shed a critical light on these predictive values. These studies suggest that the psychosis phenotype exists in nature in a much more continuous state than suggested in the diagnostic manuals [26, 27]. They have been able to show prevalence rates of up to 20% [28–30] and incidence rates of up to 1–2% of so-called subthreshold, psychosis-like symptoms in the general population [31, 32]. Against the assumed lifetime prevalence of 1% and incidence rate of 0.01–0.02% for non-affective psychosis [33], these findings can be used as a proxy to calculate the diagnostic and predictive values of subthreshold psychotic symptoms in the general population. The significance of the high prevalence

and incidence rates of subclinical psychotic experiences is that the ratio of subclinical/clinical is necessarily going to be very high: about 1:20 for prevalence and 1:100 for incidence. In other words, for each 20 individuals who have ever had a subclinical psychotic experience in their lives, only one is also going to have a lifetime diagnosis of non-affective psychotic disorder. Thus, the diagnostic value is only 5%. Similarly, for each 100 new onset cases of subclinical psychosis, only one case of non-affective psychotic disorder is going to result, leading to a predictive value of only 1%. In other words, if prevalent subclinical psychotic experiences were going to be used as a test to screen for prevalent psychotic disorder, 95% would be rated false–positive. If incident subclinical psychotic experiences were going to be used as a test to screen for incident psychotic disorder in the general population, 99% would be rated false–positive. The comparison of these findings with the above reported transition rates of ‘basic symptoms’ [23] and the UHR [4, 5] criteria is of critical importance. Firstly, it reveals that in the general population the reported predictive values of these criteria are not nearly as high as in the investigated patient samples. It is noteworthy that to date no study has been conducted to explore the prevalence and incidence of ‘basic symptoms’ in the general population. Furthermore, the divergent findings from the Klosterko¨tter [23] and the Resch [24] studies suggest that whereas ‘basic symptom’ scores in non-psychotic adult patients seem to have a predictive power for later schizophrenia, this may not hold true for adolescent patients, who may present with prodromal-like features, identity problems, depersonalization and signs of irritation due to adaptive problems of their age group [34]. This may need to be taken into account even more critically against the background of the very low prevalence of adolescent schizophrenia of 0.23% [35]. Secondly, it shows that the patient samples investigated in the Cologne, Melbourne and Yale groups are highly enriched patient samples with predominant prevalence of the target criteria. While it was never the aim of these groups to attempt identification as early as in the general population, the inclusion of an enriched patient sample thus seems to present a substantial limitation. For example, in the CER study, the authors succeeded in creating a series of sophisticated selection processes that led to a final enriched sample of individuals who were mainly referred by other specialists for further assessment [23]. The proximity of UHR criteria to the positive symptom dimension and the strong overlap in this dimension between the Structured Interview for Prodromal Symptoms (SIPS) [36], developed to define patients with UHR criteria, and the Positive and


Negative Symptom Scale (PANSS) [37] suggest a similar selection effect.

j The forgotten insidious features of psychosis Another caveat that needs to be addressed is the focus on positive symptoms and the non-inclusion of negative symptoms and signs of functional disability. For example, in the SIPS [36] only the five items on the positive symptom scale are used to classify UHR patients in the attenuated or the intermittent psychotic symptom subgroups, whereas the six negative symptom items are not applied for this purpose. As early as 1903, Diem described a subgroup of schizophrenia with no positive symptoms and coined the term ‘schizophrenia simplex’ [38]. Furthermore, Ha¨fner et al. [8] reported high prevalence of negative symptoms, social decline and depression up to 2– 4 years prior to onset of psychotic symptoms in individuals who later developed schizophrenia. Other authors described the ‘deficit syndrome’ of schizophrenia and referred to the high rates of negative symptoms as well as functional disability in a subgroup of patients with schizophrenia [39]. The wellknown association of such insidious features with young age and poor prognosis [14, 40, 41] clearly warrants a wider focus beyond the positive symptom dimension. Along this line of thought, Cornblatt et al. [10] have recently expanded the UHR model by adding a group of criteria to capture patients who lack any of the SIPS positive symptoms [36], but who are characterized by attenuated negative symptoms.

Improving the early detection system j The help-seeking criterion Against the background of these limitations, early recognition systems face the challenge of finding their way between ‘‘Scylla and Charybdis’’: narrowing the focus to the most specific at-risk criteria and limiting prevention to the most visible at-risk patients, on the one hand; while, on the other, widening the focus towards a broad spectrum of carriers of isolated potential at-risk symptoms that may never go on to develop into full-blown schizophrenia. It is very likely that one of the major discriminators in this difficult task is the ‘help-seeking criterion’. Accordingly, while many individuals with sub-threshold psychotic symptoms may never need treatment and never become help-seeking, others may experience distress at some point and become help-seeking patients. The ‘help-seeking criterion’ may thus serve as a sensitive discriminator between individuals that may not need

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to receive at-risk assessment and those who do. It could thus be suggested that the reported at-risk criteria carry an increased predictive value by the bare fact that some individuals are help-seeking and will end up in early prevention services simply because they are suffering from a specific symptom.

j Sensitization and sample enrichment Help-seeking patients need to be provided appropriate help early in the course of the disease. Besides patient-related factors, which account for delayed application of appropriate help [42], dismissed recognition of at-risk patients can potentially occur at each level of the health system. Thus, ideally, each one of these levels – general population, primary care groups, and specialists – would need to receive appropriate sensitization and education on early warning signs and symptoms of schizophrenia. This strategy would ensure that not only the most symptomatic patients such as the UHR patients would be referred to the next level of a prevention system, but also those patients with less prominent states such as enduring negative symptoms or sustained functional disability. In the following chapters we describe a small selection of sensitization models. This account, however, is limited to prototypical models and does not cover the entire field.

j Population-based sensitization In one of the most successful population-based prevention campaigns in an early detection project in South-western Norway, a large sensitization campaign was presented to the public and, simultaneously, early detection teams were provided for fast and lowthreshold assessment of help-seeking patients. The group was able to show a significant reduction in the DUP (duration of untreated psychosis) as compared to a historic control sample [43]. This model supported the idea that for help-seeking individuals and their families, population-based sensitization can lead to faster and more direct referrals for further assessment. This results in shorter help-seeking trajectories and may have a beneficial impact on clinical status [43].

j Primary care-based sensitization Ideally, in the next step, the most commonly contacted professional groups would need to be sensitized to the early warning signs of psychosis [44]. Pathways analyses strongly contributed to the better understanding of the help-seeking trajectories of patients with emerging psychosis. Typically, patients

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often seek help from their general practitioners (GPs) before they are referred to more specialized services [45, 46]. However, a recent survey among 1089 Swiss GPs was able to show that while GPs showed satisfactory detection abilities of psychotic symptoms, they underidentified the insidious features of emerging psychosis [47]. These findings were more recently replicated in the International GP Study on Early Psychosis (IGPS), a 10-country-study among 3042 GPs [48]. These results corroborate the difficult task of GPs in detecting psychosis early in the course. Most importantly, a recent analysis of the help-seeking pathways of 104 patients referred to a specialized prodromal outpatient service revealed that it was those patients with predominant insidious features that commonly contacted GPs [49]. Furthermore, both the Swiss GP and the IGPS study revealed that GPs only saw between 1 and 2 patients per year in whom they suspected an emerging psychosis, and that GPs clearly favored specialized, low-threshold assessment services for fast referrals [47, 48]. Based on the findings of the Swiss GP survey, a sensitization model for GPs was launched in North Western Switzerland in 2002 as part of the Bruderholz Study, a prospective study on at-risk patients, which was expanded to collaboration between youth and adult psychiatric departments in April 2004. First, a modified version of the Swiss GP questionnaire was sent to all GPs in order to assess levels of diagnostic knowledge and needs of GPs [47]. Second, all GPs (n = 240) of the catchment area (300,000 population) were sensitized to the most important early warning signs of emerging psychosis. For this purpose, about half of all GPs were visited individually in their practice and another half educated in small groups. Education focused on the insidious features of emerging psychosis such as sustained functional decline and social withdrawal, and also drew attention to psychotic or psychotic-like symptoms. GPs were encouraged to contact the specialized outpatient service for early psychosis that had newly been established whenever patients with these features were identified. Sensitization continued throughout 2003 with 3-monthly newsletters, telephone contacts and continuous medical education. Continuous medical education again focused on the insidious features of emerging psychosis and included psychotic or psychotic-like symptoms. Third, after the one-year sensitization, the survey was repeated with an identical questionnaire. A total of 234 GPs responded across both surveys (n = 141 in each survey; total response rate = 96%). Preliminary analyses suggested that GPs showed a significant increase in the overall diagnostic knowledge score in the second survey. The increase was accounted for by an increased awareness among GPs of functional decline as a potential early

warning sign of psychosis [20]. Although neither investigated in the Swiss GP survey nor in the Bruderholz Study, it can be assumed that similar findings would have been revealed in other primary care groups such as pediatricians, as these groups play an equally pivotal role in the early detection of psychosis [50]. Along this line of thought, the 3-monthly newsletters were also sent to pediatricians when collaboration with youth psychiatry was established within the Bruderholz Study. The results of the Bruderholz Study document the advantage of continuous sensitization in primary care professionals as opposed to mere continuous medical education, which has regularly failed to show a sustained influence on GPs’ knowledge and detection abilities of mental illnesses [51]. This is particularly the case in disorders which present with rather unspecific features [52]. As beginning psychosis is a low-prevalence disorder in general practice [47], it has to be assumed that continuous sensitization is warranted in order to maintain elevated awareness of this disorder. The finding that GPs did not favor continuous medical education in neither the Swiss GP nor the IGPS studies [47, 48] mirrors the need for a regular and continuous approach. As GPs show satisfactory detection abilities of psychotic symptoms, but underidentify the insidious features of emerging psychosis [47], this continuous approach needs to focus primarily on these insidious features. Given the satisfactory knowledge of GPs on psychotic or psychotic-like symptoms, a primary focus on these symptoms would not enable GPs to identify a wider range of at-risk patients.

j Specialized outpatient services It must be expected that an increase in GPs’ diagnostic knowledge and detection abilities would be paralleled with considerable referrals of patients with these exact features into a specialized outpatient service. Indeed, of the 2-years-referrals to the Bruderholz Study, 45 out of 104 patients (43%) did not present any psychotic or psychosis-like features as measured with the SIPS [36] and the PANSS [37]. Also, 93% of all patients showed considerable levels of negative symptoms as measured by these two scales [21]. These findings reflect the sensitization and education effect towards a lower specificity, but higher sensitivity of the referred patient sample in terms of at-risk states for psychosis. Thus, such a model has a clear advantage of not only including the most symptomatic patients, but also a broad range of perhaps equally at-risk patients. However, given the prospective design of studies such as the Bruderholz study, it remains unclear


whether these patients, and in particular those without psychotic or psychotic-like symptoms, are really at-risk for psychosis. Therefore, in order to refine the prodromal criteria for the initial assessment procedures, we were recently able to show that adding the ‘basic symptom’ criteria [23] to the UHR criteria [4] resulted in a stronger homogeneity between the at-risk groups defined by the ‘basic symptom’ and the UHR criteria and patients suffering from a first psychotic episode [21]. This broader approach suggests that, as opposed to specialized outpatient services such as the Personal Assistance and Crisis Evaluation; Melbourne (PACE) and the Prevention through Risk Identification, Management and Education; Yale/New Haven (PRIME) clinics, which only apply the UHR criteria, more patients that may be at true risk for later schizophrenia can be monitored and assessed prospectively.

Conclusions and future directions This paper critically reconsiders the published data on the predictive values of prodromal criteria for later schizophrenia. It suggests that it is not so much these criteria that have good predictive values, but rather that this property strongly depends on the early detection system in which these criteria are embedded. Thus, a selective detection system that aims for high specificity will necessarily result in including only patients with characteristics that have yielded relatively high transition rates to schizophrenia [4, 5]. However, such a system is not likely to have enough sensitivity and is likely to miss out on subgroups of patients that may not present with psychotic or psychotic-like symptoms, but may equally be at-risk for developing schizophrenia. These may be patients with sustained functional decline, social withdrawal, marked and prolonged negative symptoms as well as cognitive deficits. For patients with these characteristics who have already developed schizophrenia, the terms ‘schizophrenia simplex’ and ‘deficit syndrome’ have been coined [38, 39]. In order to include patients with these characteristics before onset of schizophrenia, a broader early detection system is warranted (see Table 1 ). Necessarily, such an early detection system would face a number of challenges. The first pertains to the potential risk of unnecessarily stigmatizing individuals with subthreshold psychotic symptoms who may never go on to develop full-blown psychosis and may not need any professional help. The high ratio between subclinical and clinical psychosis in the general population suggests that subthreshold psychotic symptoms may only need further care and assessment if they lead to help-seeking behavior in

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these individuals. Early detection systems would thus need to be focused on help-seeking individuals. The second challenge pertains to assuring sustained awareness and knowledge among health professionals of early warning signs of psychosis. Low-prevalence disorders such as emerging psychosis warrant continuous sensitization among primary care groups such as GPs, pediatrics and school psychologists. Our paper provides prototypical examples of successful enrichment strategies that were able to increase awareness of the general population [43] and the detection abilities of GPs [20]. A third challenge evolves directly from an early detection system model that aims for higher sensitivity. Such systems will necessarily be contacted by more help-seeking individuals. This is particularly the case in systems where adolescents and young adults are included into the assessments. In this age range, individuals present with a range of developmental processes that can resemble the schizophrenia prodrome [24]. On the other hand, it is also in this age range where the early onset cases of schizophrenia evolve [14] which is associated with poorer prognosis [14, 40]. Thus, in order to reassure appropriate prevention of schizophrenia, early detection systems need to encompass the entire age range of increased risk for incident psychosis and be undertaken as collaboration between youth and adult psychiatry. The Bruderholz Study is the first Swiss early detection system for psychosis, which was established to assess at-risk individuals systematically as part of such collaboration [53]. Subsequently, given the higher sensitivity and lower specificity, transition rates to full-blown psychosis will be lower than in more selective, enriched samples. However, a critical mass of transitions to psychosis is necessary in order to prospectively disentangle which characteristics can discriminate between those patients who will develop schizophrenia and those who will not. Against the background of limited incidences of schizophrenia within each catchment area, such a task may only yield appropriate data and knowledge if early detection systems are linked together within networks that reach beyond the boarders of each catchment area. Such networks have been launched in Germany [18], and in the U.K., 50 early intervention teams have been established at a cost of £70 million under the National Health Service Plan [54]. Similarly, the Swiss Early Psychosis Project (SWEPP) has conducted a nationwide continuous medical education program and has initiated teaching workshops for several psychiatric institutions for the assessment of ‘basic symptoms’ and UHR criteria [53]. These networks are important in order to answer a number of crucial questions, e.g. how long to observe someone with a diagnosed at-risk state; how long sustained negative symptoms have to

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last before a diagnosis of an at-risk state or even schizophrenia must be established. In summary, to overcome the pitfalls of schizophrenia prevention, optimal early detection systems need to be modeled as collaboration between youth and adult psychiatry and as networks across catchment areas. Failure to successfully combine the two areas would result in the prevention system again becoming highly selective. Collaboration between specialists of both youth and adult psychiatry would

therefore provide a promising basis for the improvement of schizophrenia prevention. j Acknowledgements We gratefully acknowledge Frauke SchultzeLutter, University of Cologne, Germany, for training in ‘basic symptoms’ and UHR ratings. The Bruderholz Study is supported by an educational grant from the Freiwillige Akademische Gesellschaft Basel (FAG), Switzerland, and from the Stiftung fu¨r Gesundheitsfo¨rderung, Baselland, Switzerland. The pilot phase of this study was supported by an unrestricted grant from Astra Zeneca, Switzerland.

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