Background Little is understood about the conceptual relationship of depression and quality of life (QoL). Judgments concerning both, implicitly or explicitly, involve a time perspective. The aim of this study was to test de Leval's theoretical model linking depression and QoL with a time perspective. The model predicts that changes in cognitions about one's past, present and future QoL, will be associated with changes in depressive symptomatology.
Background
Little is understood about the conceptual relationship of depression and quality of life (QoL). Judgments concerning both, implicitly or explicitly, involve a time perspective. The aim of this study was to test de Leval's theoretical model linking depression and QoL with a time perspective. The model predicts that changes in cognitions about one's past, present and future QoL, will be associated with changes in depressive symptomatology.Methods Eighteen psychiatric in-patients with a clinically confirmed diagnosis of depression were assessed on commencing treatment and 12 weeks later. QoL was assessed by the Schedule for Evaluation of Individual Quality of Life (SEIQoL), depression by the Beck Depression Inventory (BDI-II) and hopelessness by the Beck Hopelessness Scale (BHS). Time perspective was incorporated by asking QoL questions about the past, present and future.
Methods
Eighteen psychiatric in-patients with a clinically confirmed diagnosis of depression were assessed on commencing treatment and 12 weeks later. QoL was assessed by the Schedule for Evaluation of Individual Quality of Life (SEIQoL), depression by the Beck Depression Inventory (BDI-II) and hopelessness by the Beck Hopelessness Scale (BHS). Time perspective was incorporated by asking QoL questions about the past, present and future.Results Depression and hopelessness were associated with a poorer present QoL. Depression lowered present QoL but did not alter future QoL, as these remained consistently high whether participants were depressed or recovering. However, depressed individuals had a larger gap between their actual present QoL and future (aspired to) QoL. Changes in QoL were influenced by depression and hopelessness. Contrary to the model, perception of "past" QoL was not affected by depression or hopelessness.
Results
Depression and hopelessness were associated with a poorer present QoL. Depression lowered present QoL but did not alter future QoL, as these remained consistently high whether participants were depressed or recovering. However, depressed individuals had a larger gap between their actual present QoL and future (aspired to) QoL. Changes in QoL were influenced by depression and hopelessness. Contrary to the model, perception of "past" QoL was not affected by depression or hopelessness.Conclusions de Leval's model was largely confirmed. Thus depression and hopelessness influence a person's present and future QoL. The analysis of a temporal horizon was helpful in understanding the link between depression and QoL.
Conclusions
de Leval's model was largely confirmed. Thus depression and hopelessness influence a person's present and future QoL. The analysis of a temporal horizon was helpful in understanding the link between depression and QoL.

Background Assessment of quality of life (QoL) has become increasingly important in health care, particularly as an evaluative method to measure outcomes of the impact of disease and interventions. To date it is unclear how research on QoL relates to other psychological constructs such as depression and anxiety. Many clinical studies assess a number of related psychosocial dimensions but without a theoretical basis for the unique contribution of each. On an intuitive level, QoL and depression can appear as opposing phenomena – crudely representing all the positive and negative aspects of well-being. Poor QoL is sometimes seen as a consequence of depression [ 1 - 3 ]. On the other hand, poor QoL may also be a precursor to depression. In other formulations, depression can be seen as a component of QoL. Whatever the implicit models of their interrelationships, there has been little theoretical attention or research to understand the relationship between depression and QoL. A theoretical approach developed by de Leval [ 4 , 5 , 8 ] tries to capture and highlight possible relationships between depression and QoL in a "three-time-dimension" theory. This theory links depression and QoL on a timeline of the past-present-future. Time can be perceived objectively and subjectively. It consists of three dimensions: past, present and future. The presence of psychopathology, e.g. depression has been found to influence time perception. For instance, individuals who are depressed have been reported as finding that time passes more slowly [ 11 ]. In comparison to others, depressed individuals also have a temporal focus, which is less future directed and more focused on the past. The "three-time-dimension" theory describes the dislocated temporal horizon of the depressed patient. It situates both depression and quality of life as part of a continuum in time rather than as independent phenomena. De Leval proposes that, for the depressed individual, time passes slowly, the present is dissociated from the past and the potential for the future is lost or viewed with hopelessness [ 4 ]. During the course of their depression, individuals want to go back to their past when things were perceived as better. This searching for the past becomes the individual's future. According to de Leval, depressed individuals have two pasts: the actual past when they were well and the past as a position they wish to regain or aspire to, i.e. the 'therapeutic future', when things were better than they are in the present. In the proposed model by de Leval, in accordance with DSM-III-R criteria, depression is referred to as "ill-being". Ill-being is the current or present state of the patient experiencing depression. De Leval uses the term depression for "phenomenological-depression", i.e., depression as perceived by the individual in question and it is placed on the past-present timeline. She proposes that this "phenomenological-depression" is related to the perception of a gap between a healthy past and a present ill-being. The greater the gap between past and present, the greater the phenomenological-depression. In de Leval's theory, QoL is perceived as the gap between actual experience and future aspirations. Whereas depression is placed on the past-present timeline, QoL is placed along the timeline using present and future. QoL according to this model is defined as being "the appropriateness of future aspirations to the present" or "the making present of the future". The larger the gap, the lower the QoL of the individual (Figure  1 ). Although not included explicitly in de Leval's theory, the concept of hopelessness as described by Beck [ 2 ] is worth considering given its timeline focus on negative evaluations of the future. Figure 1 Illustration of de Leval's model In a cross-sectional study, de Leval [ 5 ] examined the three-time-dimension theory in a group of 110 clinically depressed psychiatric patients. They completed a 30-item questionnaire – the Three-Time-dimension Synoptic Scale (3TSS – French version) developed by the author [ 6 ]. Questions were chosen to reflect the content of existing mental health scales and each question asked about their feelings now, their feelings in the past (before being depressed) and what they wanted to feel in the future. Findings indicated preliminary support for the theory. No other study has to our knowledge tested Leval's theory empirically. The present study sought to advance the understanding about the conceptual relationship of depression and QoL by empirically testing de Leval's model in a longitudinal study. It also sought to assess the model using a previously developed individualised system for assessing QoL. If de Leval's proposals concerning the centrality of the temporal assessment are correct, then any QoL assessment instrument which measures the present can be adapted to measure the past and the future as aspired to. In this study, the model was operationalised as follows: scores on standardised depression measures were taken to demonstrate an individual's level of depression, i.e., 'present ill-being'. QoL was the gap between an individual's present status (' present ill-being ' in the case of depression) and anticipated status (i.e ' therapeutic future ') and was measured by the discrepancy between  present  and  future  actual QoL scores. The level of  phenomenological depression  – i.e. the gap between a person's perceived  past  and  present  " ill-being " was measured by the discrepancy between the past and present actual QoL scores. These gaps are referred to as time comparisons gaps. The full model is displayed in Figure  1 . In addition to components of de Leval's model, aspirational QoL was measured and assessed for all three time periods: past, present and future. This was included to provide further information about the gap between where an individual is and where he/she would like to be. These gaps are referred to as preference comparisons gaps. It was hypothesized that the greater the gap between actual and aspirational scores at any time (past/present/future), the worse the QoL and vice versa. This reflects Calmans definition of QoL. He defines QoL as the gap between actual QoL and preferred QoL [ 3 ]. As an additional measure of an individual's perception of the future hopelessness was included . The model was tested at two time points: when individuals were clinically depressed (time 1) and approximately three months later when their progress towards recovery could be estimated (time 2). The following hypotheses were tested in order to validate de Leval's model and additional components: Hypothesis 1: The size of the gap between actual and past QoL scores is larger when patients are depressed, in comparison to when they are less/not depressed. Hypothesis 1a: The therapeutic future is the view of a healthy past. Therefore scores for past and future QoL are equal. Hypothesis 2: The change in depression scores (present "ill-being") from time 1 to time 2 predicts the change in the gap between  actual  and  aspirational  QoL scores. Hypothesis 3: The change in hopelessness scores from time 1 to time 2 predicts the change in the gap between  actual  and  aspirational  QoL scores. Hypothesis 4: A reduction in depression narrows the gap between the past and present, and enhances QoL by narrowing the gap between present and future QoL.
Background
Assessment of quality of life (QoL) has become increasingly important in health care, particularly as an evaluative method to measure outcomes of the impact of disease and interventions. To date it is unclear how research on QoL relates to other psychological constructs such as depression and anxiety. Many clinical studies assess a number of related psychosocial dimensions but without a theoretical basis for the unique contribution of each. On an intuitive level, QoL and depression can appear as opposing phenomena – crudely representing all the positive and negative aspects of well-being. Poor QoL is sometimes seen as a consequence of depression [ 1 - 3 ]. On the other hand, poor QoL may also be a precursor to depression. In other formulations, depression can be seen as a component of QoL. Whatever the implicit models of their interrelationships, there has been little theoretical attention or research to understand the relationship between depression and QoL.A theoretical approach developed by de Leval [ 4 , 5 , 8 ] tries to capture and highlight possible relationships between depression and QoL in a "three-time-dimension" theory. This theory links depression and QoL on a timeline of the past-present-future. Time can be perceived objectively and subjectively. It consists of three dimensions: past, present and future. The presence of psychopathology, e.g. depression has been found to influence time perception. For instance, individuals who are depressed have been reported as finding that time passes more slowly [ 11 ]. In comparison to others, depressed individuals also have a temporal focus, which is less future directed and more focused on the past.The "three-time-dimension" theory describes the dislocated temporal horizon of the depressed patient. It situates both depression and quality of life as part of a continuum in time rather than as independent phenomena. De Leval proposes that, for the depressed individual, time passes slowly, the present is dissociated from the past and the potential for the future is lost or viewed with hopelessness [ 4 ]. During the course of their depression, individuals want to go back to their past when things were perceived as better. This searching for the past becomes the individual's future. According to de Leval, depressed individuals have two pasts: the actual past when they were well and the past as a position they wish to regain or aspire to, i.e. the 'therapeutic future', when things were better than they are in the present. In the proposed model by de Leval, in accordance with DSM-III-R criteria, depression is referred to as "ill-being". Ill-being is the current or present state of the patient experiencing depression. De Leval uses the term depression for "phenomenological-depression", i.e., depression as perceived by the individual in question and it is placed on the past-present timeline. She proposes that this "phenomenological-depression" is related to the perception of a gap between a healthy past and a present ill-being. The greater the gap between past and present, the greater the phenomenological-depression.In de Leval's theory, QoL is perceived as the gap between actual experience and future aspirations. Whereas depression is placed on the past-present timeline, QoL is placed along the timeline using present and future. QoL according to this model is defined as being "the appropriateness of future aspirations to the present" or "the making present of the future". The larger the gap, the lower the QoL of the individual (Figure  1 ). Although not included explicitly in de Leval's theory, the concept of hopelessness as described by Beck [ 2 ] is worth considering given its timeline focus on negative evaluations of the future.In a cross-sectional study, de Leval [ 5 ] examined the three-time-dimension theory in a group of 110 clinically depressed psychiatric patients. They completed a 30-item questionnaire – the Three-Time-dimension Synoptic Scale (3TSS – French version) developed by the author [ 6 ]. Questions were chosen to reflect the content of existing mental health scales and each question asked about their feelings now, their feelings in the past (before being depressed) and what they wanted to feel in the future. Findings indicated preliminary support for the theory. No other study has to our knowledge tested Leval's theory empirically.The present study sought to advance the understanding about the conceptual relationship of depression and QoL by empirically testing de Leval's model in a longitudinal study. It also sought to assess the model using a previously developed individualised system for assessing QoL. If de Leval's proposals concerning the centrality of the temporal assessment are correct, then any QoL assessment instrument which measures the present can be adapted to measure the past and the future as aspired to. In this study, the model was operationalised as follows: scores on standardised depression measures were taken to demonstrate an individual's level of depression, i.e., 'present ill-being'. QoL was the gap between an individual's present status (' present ill-being ' in the case of depression) and anticipated status (i.e ' therapeutic future ') and was measured by the discrepancy between  present  and  future  actual QoL scores. The level of  phenomenological depression  – i.e. the gap between a person's perceived  past  and  present  " ill-being " was measured by the discrepancy between the past and present actual QoL scores. These gaps are referred to as time comparisons gaps. The full model is displayed in Figure  1 . In addition to components of de Leval's model, aspirational QoL was measured and assessed for all three time periods: past, present and future. This was included to provide further information about the gap between where an individual is and where he/she would like to be. These gaps are referred to as preference comparisons gaps. It was hypothesized that the greater the gap between actual and aspirational scores at any time (past/present/future), the worse the QoL and vice versa. This reflects Calmans definition of QoL. He defines QoL as the gap between actual QoL and preferred QoL [ 3 ]. As an additional measure of an individual's perception of the future hopelessness was included . The model was tested at two time points: when individuals were clinically depressed (time 1) and approximately three months later when their progress towards recovery could be estimated (time 2).present ill-beingtherapeutic futurepresentfuturephenomenological depressionpastpresentill-beingThe following hypotheses were tested in order to validate de Leval's model and additional components:Hypothesis 1: The size of the gap between actual and past QoL scores is larger when patients are depressed, in comparison to when they are less/not depressed.Hypothesis 1a: The therapeutic future is the view of a healthy past. Therefore scores for past and future QoL are equal.Hypothesis 2: The change in depression scores (present "ill-being") from time 1 to time 2 predicts the change in the gap between  actual  and  aspirational  QoL scores.actualaspirationalHypothesis 3: The change in hopelessness scores from time 1 to time 2 predicts the change in the gap between  actual  and  aspirational  QoL scores.actualaspirationalHypothesis 4: A reduction in depression narrows the gap between the past and present, and enhances QoL by narrowing the gap between present and future QoL.Methods Consecutive psychiatric in-patients (N = 27) were approached to participate in a longitudinal study of depression. Study inclusion criteria were age ≥ 18 years, diagnosis of moderate to severe uni-polar depression (DSM-IV-criteria), a moderate or severe depression rating on the Beck Depression Inventory II [ 1 ], no cognitive disabilities (Mini Mental State Exam, [ 7 ]). Exclusion criteria were diagnosis of severe psychopathology or borderline personality disorder, more than two previous episodes of depression that were of more than three months duration and history of prolonged substance abuse or use of psychotropic medication, which would impede participation in a research interview. Patients were recruited as soon after admission as was deemed appropriate by medical staff. Instruments Quality of life (QoL) QoL was assessed by the Schedule for the Evaluation of Individual Quality of Life (SEIQoL) [ 12 ], a well-established method of assessing QoL which incorporates the value system of the individual participant. To reduce interview demands for depressed participants, the shorter direct weighting (SEIQoL-DW) procedure was applied [ 9 ]. In the first step of the standard SEIQoL procedure, participants are asked to nominate the five areas of their life (cues) that are most important to them. In the second step, participants rate their current status or level of functioning on each cue. Ratings are against a vertical axis anchored from "worst possibly" to "best possibly". The final assessment step in SEIQoL involves quantifying the relative importance (weight) of each cue to the judgment of participants' overall QoL. This is obtained by using a weighting disk, consisting of five interlocking coloured disks that can be rotated around a central point to form a pie chart. These disks are labelled with the five nominated cues and are adjusted by participants until they are satisfied that the proportion of the pie chart displayed by each life area accurately reflects the relative importance they attach to these life areas. The SEIQoL Index score is calculated by multiplying each cue weight with the relevant level of functioning. These five scores then are summed. The scale of the SEIQoL Index score ranges from worst possible (0) to best possible (100). This was done for each time anchor and point. Time perspective To measure the temporal nature of the gap in terms of perceptions of their actual and aspirational past, present and future QoL according to the Leval's theory and Calman's definition of QoL, participants were asked to rate the status of each nominated SEIQoL cue (i.e. how were you doing?) based on the following questions: Past: - Where were you before you got depressed? (actual past) - Where would you have liked to have been? (aspirational past) Present:  - Where are you now? (actual present) - Where would you like to be? (aspirational present) Future: - Where do you expect to be in a year’s time? (actual future) - Where would you like to be in a year’s time? (aspirational future) Thus scores were taken for actual present, aspirational present, actual past, aspirational past and actual future, aspirational future. Depression The Beck Depression Inventory (BDI), a 21 item self-report instrument for measuring the severity of depression in adults, was developed for the assessment of symptoms corresponding to criteria for diagnosing depressive disorders based on the DSM-IV. In this study an updated version is used (BDI-II) [ 1 ]. The BDI-II requires about 10 minutes to complete and has a two week time-frame including today. Items are rated on a four point scale ranging from 0 to 3, with higher scores reflecting more severe depression. A cut-off score of 20 was used. The psychometric properties have been well established [ 1 ]. Hopelessness The Hopelessness Scale [ 2 ] is a 20 item self-report instrument designed to assess pessimistic expectations. Items are rated true (1) or false (0), with a higher score indicating hopelessness. Internal consistency (split-half reliability) exceeds .90 in a range of samples and concurrent validity has been established [ 2 ].
Methods
Consecutive psychiatric in-patients (N = 27) were approached to participate in a longitudinal study of depression. Study inclusion criteria were age ≥ 18 years, diagnosis of moderate to severe uni-polar depression (DSM-IV-criteria), a moderate or severe depression rating on the Beck Depression Inventory II [ 1 ], no cognitive disabilities (Mini Mental State Exam, [ 7 ]). Exclusion criteria were diagnosis of severe psychopathology or borderline personality disorder, more than two previous episodes of depression that were of more than three months duration and history of prolonged substance abuse or use of psychotropic medication, which would impede participation in a research interview. Patients were recruited as soon after admission as was deemed appropriate by medical staff.Instruments Quality of life (QoL) QoL was assessed by the Schedule for the Evaluation of Individual Quality of Life (SEIQoL) [ 12 ], a well-established method of assessing QoL which incorporates the value system of the individual participant. To reduce interview demands for depressed participants, the shorter direct weighting (SEIQoL-DW) procedure was applied [ 9 ]. In the first step of the standard SEIQoL procedure, participants are asked to nominate the five areas of their life (cues) that are most important to them. In the second step, participants rate their current status or level of functioning on each cue. Ratings are against a vertical axis anchored from "worst possibly" to "best possibly". The final assessment step in SEIQoL involves quantifying the relative importance (weight) of each cue to the judgment of participants' overall QoL. This is obtained by using a weighting disk, consisting of five interlocking coloured disks that can be rotated around a central point to form a pie chart. These disks are labelled with the five nominated cues and are adjusted by participants until they are satisfied that the proportion of the pie chart displayed by each life area accurately reflects the relative importance they attach to these life areas. The SEIQoL Index score is calculated by multiplying each cue weight with the relevant level of functioning. These five scores then are summed. The scale of the SEIQoL Index score ranges from worst possible (0) to best possible (100). This was done for each time anchor and point. Time perspective To measure the temporal nature of the gap in terms of perceptions of their actual and aspirational past, present and future QoL according to the Leval's theory and Calman's definition of QoL, participants were asked to rate the status of each nominated SEIQoL cue (i.e. how were you doing?) based on the following questions: Past: - Where were you before you got depressed? (actual past) - Where would you have liked to have been? (aspirational past) Present:  - Where are you now? (actual present) - Where would you like to be? (aspirational present) Future: - Where do you expect to be in a year’s time? (actual future) - Where would you like to be in a year’s time? (aspirational future) Thus scores were taken for actual present, aspirational present, actual past, aspirational past and actual future, aspirational future. Depression The Beck Depression Inventory (BDI), a 21 item self-report instrument for measuring the severity of depression in adults, was developed for the assessment of symptoms corresponding to criteria for diagnosing depressive disorders based on the DSM-IV. In this study an updated version is used (BDI-II) [ 1 ]. The BDI-II requires about 10 minutes to complete and has a two week time-frame including today. Items are rated on a four point scale ranging from 0 to 3, with higher scores reflecting more severe depression. A cut-off score of 20 was used. The psychometric properties have been well established [ 1 ]. Hopelessness The Hopelessness Scale [ 2 ] is a 20 item self-report instrument designed to assess pessimistic expectations. Items are rated true (1) or false (0), with a higher score indicating hopelessness. Internal consistency (split-half reliability) exceeds .90 in a range of samples and concurrent validity has been established [ 2 ].
Instruments
Quality of life (QoL) QoL was assessed by the Schedule for the Evaluation of Individual Quality of Life (SEIQoL) [ 12 ], a well-established method of assessing QoL which incorporates the value system of the individual participant. To reduce interview demands for depressed participants, the shorter direct weighting (SEIQoL-DW) procedure was applied [ 9 ]. In the first step of the standard SEIQoL procedure, participants are asked to nominate the five areas of their life (cues) that are most important to them. In the second step, participants rate their current status or level of functioning on each cue. Ratings are against a vertical axis anchored from "worst possibly" to "best possibly". The final assessment step in SEIQoL involves quantifying the relative importance (weight) of each cue to the judgment of participants' overall QoL. This is obtained by using a weighting disk, consisting of five interlocking coloured disks that can be rotated around a central point to form a pie chart. These disks are labelled with the five nominated cues and are adjusted by participants until they are satisfied that the proportion of the pie chart displayed by each life area accurately reflects the relative importance they attach to these life areas. The SEIQoL Index score is calculated by multiplying each cue weight with the relevant level of functioning. These five scores then are summed. The scale of the SEIQoL Index score ranges from worst possible (0) to best possible (100). This was done for each time anchor and point.
Quality of life (QoL)
QoL was assessed by the Schedule for the Evaluation of Individual Quality of Life (SEIQoL) [ 12 ], a well-established method of assessing QoL which incorporates the value system of the individual participant. To reduce interview demands for depressed participants, the shorter direct weighting (SEIQoL-DW) procedure was applied [ 9 ]. In the first step of the standard SEIQoL procedure, participants are asked to nominate the five areas of their life (cues) that are most important to them. In the second step, participants rate their current status or level of functioning on each cue. Ratings are against a vertical axis anchored from "worst possibly" to "best possibly".The final assessment step in SEIQoL involves quantifying the relative importance (weight) of each cue to the judgment of participants' overall QoL. This is obtained by using a weighting disk, consisting of five interlocking coloured disks that can be rotated around a central point to form a pie chart. These disks are labelled with the five nominated cues and are adjusted by participants until they are satisfied that the proportion of the pie chart displayed by each life area accurately reflects the relative importance they attach to these life areas. The SEIQoL Index score is calculated by multiplying each cue weight with the relevant level of functioning. These five scores then are summed. The scale of the SEIQoL Index score ranges from worst possible (0) to best possible (100). This was done for each time anchor and point.Time perspective To measure the temporal nature of the gap in terms of perceptions of their actual and aspirational past, present and future QoL according to the Leval's theory and Calman's definition of QoL, participants were asked to rate the status of each nominated SEIQoL cue (i.e. how were you doing?) based on the following questions: Past: - Where were you before you got depressed? (actual past) - Where would you have liked to have been? (aspirational past) Present:  - Where are you now? (actual present) - Where would you like to be? (aspirational present) Future: - Where do you expect to be in a year’s time? (actual future) - Where would you like to be in a year’s time? (aspirational future) Thus scores were taken for actual present, aspirational present, actual past, aspirational past and actual future, aspirational future.
Time perspective
To measure the temporal nature of the gap in terms of perceptions of their actual and aspirational past, present and future QoL according to the Leval's theory and Calman's definition of QoL, participants were asked to rate the status of each nominated SEIQoL cue (i.e. how were you doing?) based on the following questions:Past:- Where were you before you got depressed? (actual past)- Where would you have liked to have been? (aspirational past)Present:- Where are you now? (actual present)- Where would you like to be? (aspirational present)Future:- Where do you expect to be in a year’s time? (actual future)- Where would you like to be in a year’s time? (aspirational future)Thus scores were taken for actual present, aspirational present, actual past, aspirational past and actual future, aspirational future.Depression The Beck Depression Inventory (BDI), a 21 item self-report instrument for measuring the severity of depression in adults, was developed for the assessment of symptoms corresponding to criteria for diagnosing depressive disorders based on the DSM-IV. In this study an updated version is used (BDI-II) [ 1 ]. The BDI-II requires about 10 minutes to complete and has a two week time-frame including today. Items are rated on a four point scale ranging from 0 to 3, with higher scores reflecting more severe depression. A cut-off score of 20 was used. The psychometric properties have been well established [ 1 ].
Depression
The Beck Depression Inventory (BDI), a 21 item self-report instrument for measuring the severity of depression in adults, was developed for the assessment of symptoms corresponding to criteria for diagnosing depressive disorders based on the DSM-IV. In this study an updated version is used (BDI-II) [ 1 ]. The BDI-II requires about 10 minutes to complete and has a two week time-frame including today. Items are rated on a four point scale ranging from 0 to 3, with higher scores reflecting more severe depression. A cut-off score of 20 was used. The psychometric properties have been well established [ 1 ].Hopelessness The Hopelessness Scale [ 2 ] is a 20 item self-report instrument designed to assess pessimistic expectations. Items are rated true (1) or false (0), with a higher score indicating hopelessness. Internal consistency (split-half reliability) exceeds .90 in a range of samples and concurrent validity has been established [ 2 ].
Hopelessness
The Hopelessness Scale [ 2 ] is a 20 item self-report instrument designed to assess pessimistic expectations. Items are rated true (1) or false (0), with a higher score indicating hopelessness. Internal consistency (split-half reliability) exceeds .90 in a range of samples and concurrent validity has been established [ 2 ].Results Of 27 patients approached, 24 gave written consent and took part in the study (89% response rate). Over the three month follow-up period, six patients dropped out (75% follow-up rate). Information on the complete sample of 18 patients was analysed. Sociodemographic and clinical details are presented in table  1 . Table 1 Sociodemographic and clinical profile of recruited sample (N = 24) Mean ± SD % Min Max Gender (% male) 50 Age (years) 36.7 ± 14.4 18 72 Marital status   Married/partner 42   Single 54   Separated 4 Occupation:   Employed 50   Unemployed/retired 16   Student 21   Homemaker 13 Residence (% urban) 71 Time since hospital admission (days) 5 ± 2.7 1 9 No. of previous episodes of depression 0.7 ± 0.7 0 2 Duration of previous episodes of depression (weeks) 2.6 ± 3.6 <1 12 Baseline scores of the depression measure (BDI-II) showed high levels of severity, which were reduced significantly after three months (p < .001, table  2 ). While at baseline all 18 patients scored above 20, only six patients remained above this threshold at three months follow-up. The mean hopelessness score (BHS) of 10 at baseline dropped significantly by 5 (p < .002). Table 2 Profile of mental health at baseline and three month follow-up (N = 18) Baseline three months Mean SD Mean SD t p Depression   BDI-II 34.0 9.5 15.0 11.4 4.8 <.001 Hopelessness   BHS 10.0 5.8 5.0 4.9 3.2 .002 The five most commonly mentioned cues for the SEIQoL at time 1 were: mental health, family of origin, work marriage/relationship, friends and leisure. There were no new cues introduced at time 2. This is consistent with previous research on cue profiles across varying populations. The actual present level of overall QoL was very low at baseline (time 1, see table  3 ). This increased significantly over three months. Aspirational level of present QoL (where one would like to be now) was significantly higher at both baseline and three months then the actual present level. QoL did not change significantly over time (p = .102). Table 3 Quality of life (QoL) over time and actual and aspirational "gaps" at baseline and three months measured by SEIQoL Index Score Actual t p Aspirational t p t p Present Baseline 35.4 ± 19.1 88.2 ± 11.4 10.5 <.001 3.2 .002 1.3 .102 three months 61.1 ± 22.8 88.5 ± 8.5 5.5 <.001 Past Baseline 70.2 ± 13.7 87.0 ± 10.5 4.8 <.001 .2 .411 1.5 .07 three months 68.7 ± 18.8 83.7 ± 8.4 4.4 <.001 Future Baseline 66.8 ± 21.0 90.8 ± 10.5 5.1 <.001 .3 .362 .2 .396 three months 74.4 ± 23.6 91.5 ± 7.5 3.6 .001 Actual past level of overall QoL did not change from baseline to three months later. Aspirational past QoL (where one would have liked to be then) was significantly higher at baseline and three months than actual past and this did not change over time (table  3 ). Actual future QoL did not change significantly over the three months follow-up. Actual future QoL was significantly lower at baseline and three months than the aspirational future QoL. Aspirational future QoL was consistently high over time. The gap between actual and aspirational QoL is presented in table  4 . The biggest gap was perceived between baseline actual present level of QoL and aspirational present QoL. This large gap was significantly reduced after three months. This confirms hypothesis 1. Other gaps remained unchanged (figure  2 ). Correlations between the preference comparison QoL gaps for present, past and future assessments with the severity of depression (d) showed significant high correlations for the present (p) and future (f) gap at baseline (1) and three months (2) (r pd1  = .468, r fd1  = .475, both p < .05, r pd2  = .815, r fd2  = .730, both p < .01). In addition, correlations between the QoL preference comparison gaps for present, past and future assessment and hopelessness (h) were statistically significant at baseline for the present (p) gap and at three months (2) for present (p) and future (f) gaps (r ph1  = .567, r ph2  = .586, r fh2  = .422, all p < .05). There was no difference between actual past and actual future QoL scores at baseline and three months (p = .475, p = .528). This confirms hypothesis 1a. Table 4 Differences between actual and aspirational QoL "gaps" at baseline and three months as measured by the SEIQoL Index Score Time Baseline actual/aspirational gap (M ± SD) Three months actual/aspirational gap (M ± SD) F Time Present 52.7 ± 21.0 27.6 ± 21.2 9.21 .007 Past 16.8 ± 14.7 14.9 ± 14.9 .154 .699 Future 23.9 ± 19.6 17.0 ± 17.9 2.86 .109 Figure 2 Illustration of the preference comparison gaps (actual/aspirational QoL) for the three time points (past, present and future) at baseline and three months. Δ represents the change from baseline to three months for the time anchor "present" ** p < .001 Multiple regression was conducted to investigate whether depression and hopelessness contribute to the change in the size of the gap of actual and aspirational QoL over time. Changes in depression and hopelessness scores over time were entered as independent variables in a multiple regression, while the change in gap scores was entered as the dependent variable. A significant amount of variance was explained by changes in the present and future gaps for actual and aspirational QoL (52.4%, 59,9% respectively both p < 0.01). Change in depression contributed to change (reduction) in the gap between present actual and aspirational Qol (β =.676). Change in hopelessness (β =.589) was the significant contributing factor for change (reduction) in the gap between actual and aspirational future QoL (table  5 ). This confirms hypothesis 2 and 3 in parts. Table 5 Multiple regression analyses to explain the change in the actual/aspirational gap by change in Beck Depression Inventory (BDI) and Beck Hopelessness Scale (BHS) change scores from time 1 to time 2. Δ in actual/aspirational Gap Variable name 1 R 2 p-value β p Present .524 .004 Δ BDI 12 .676 .020 Δ BHS 12 .063 .813 Past .043 .720 Δ BDI 12 .053 .888 Δ BHS 12 .165 .661 Future .599 .001 Δ BDI 12 .230 .352 Δ BHS 12 .589 .026 1 Change of Beck Depression Inventory (BDI) and change of Beck Hopelessness Scale (BHS) were entered as predicting variables in these analyses In table  6 , the differences of present and past (phenomenological-depression) and present and future QoL (quality of life) are assessed according to de Leval's model. As already reported, baseline actual present QoL scores were considerably lower than actual past scores (35.4 ± 19.1 vs. 70.2 ± 13.7, p <.001). This significant gap (34.8 ± 22.5) between present and past QoL was significantly reduced over three months to a gap of 7.6 ± 30.9 (p = .011). At the three month follow-up, there was no statistical difference in the gap between actual present and past QoL perception (figure  3 ). The gap between present and future QoL was large and significant at baseline (31.3 ± 27.2, p < .001). Differences remained significant at the 3 month follow-up (13.3 ± 13.5, p = .001) with higher QoL levels for the future. However, the reduction in the gap over time was also significant (p = .010). Table 6 Testing de Leval's model: time gap comparison for actual QoL scores measured by SEIQoL Index Score QoL at Baseline t p QoL at three months t p Past 70.2 ± 13.7 68.7 ± 18.8 6.5 p < .001 1.0 .310 Present 35.4 ± 19.1 61.1 ± 22.8 Present 35.4 ± 19.1 61.1 ± 22.8 4.8 p < .001 4.2 .001 Future 66.8 ± 21.0 74.4 ± 23.6 Figure 3 Illustration of the time comparison gaps (past-present/present-future QoL; shaded areas) for the three time points (past, present and future) at baseline and three months. Δ represents the change from baseline to three months for the time anchor "past" and "future" ** p < .001; ns ... not significant To investigate how depression and hopelessness may influence the change in the size of the gaps proposed by de Leval, multiple regression analysis was conducted. Change in depression and hopelessness scores over time were entered as independent variables in a multiple regression, while the change in the gap over time, was entered as the dependent variable. Changes in the size of the two time comparison gaps (past/present; present/future) were not influenced by change in depression or hopelessness scores (R 2  = .281, p = .09; R 2  = .162, p = .266). This partly disconfirms hypothesis 4
Results
Of 27 patients approached, 24 gave written consent and took part in the study (89% response rate). Over the three month follow-up period, six patients dropped out (75% follow-up rate). Information on the complete sample of 18 patients was analysed. Sociodemographic and clinical details are presented in table  1 .Sociodemographic and clinical profile of recruited sample (N = 24)Baseline scores of the depression measure (BDI-II) showed high levels of severity, which were reduced significantly after three months (p < .001, table  2 ). While at baseline all 18 patients scored above 20, only six patients remained above this threshold at three months follow-up. The mean hopelessness score (BHS) of 10 at baseline dropped significantly by 5 (p < .002).Profile of mental health at baseline and three month follow-up (N = 18)The five most commonly mentioned cues for the SEIQoL at time 1 were: mental health, family of origin, work marriage/relationship, friends and leisure. There were no new cues introduced at time 2. This is consistent with previous research on cue profiles across varying populations. The actual present level of overall QoL was very low at baseline (time 1, see table  3 ). This increased significantly over three months. Aspirational level of present QoL (where one would like to be now) was significantly higher at both baseline and three months then the actual present level. QoL did not change significantly over time (p = .102).Quality of life (QoL) over time and actual and aspirational "gaps" at baseline and three months measured by SEIQoL Index ScoreActual past level of overall QoL did not change from baseline to three months later. Aspirational past QoL (where one would have liked to be then) was significantly higher at baseline and three months than actual past and this did not change over time (table  3 ). Actual future QoL did not change significantly over the three months follow-up. Actual future QoL was significantly lower at baseline and three months than the aspirational future QoL. Aspirational future QoL was consistently high over time.The gap between actual and aspirational QoL is presented in table  4 . The biggest gap was perceived between baseline actual present level of QoL and aspirational present QoL. This large gap was significantly reduced after three months. This confirms hypothesis 1. Other gaps remained unchanged (figure  2 ). Correlations between the preference comparison QoL gaps for present, past and future assessments with the severity of depression (d) showed significant high correlations for the present (p) and future (f) gap at baseline (1) and three months (2) (r pd1  = .468, r fd1  = .475, both p < .05, r pd2  = .815, r fd2  = .730, both p < .01). In addition, correlations between the QoL preference comparison gaps for present, past and future assessment and hopelessness (h) were statistically significant at baseline for the present (p) gap and at three months (2) for present (p) and future (f) gaps (r ph1  = .567, r ph2  = .586, r fh2  = .422, all p < .05). There was no difference between actual past and actual future QoL scores at baseline and three months (p = .475, p = .528). This confirms hypothesis 1a.Differences between actual and aspirational QoL "gaps" at baseline and three months as measured by the SEIQoL Index ScoreMultiple regression was conducted to investigate whether depression and hopelessness contribute to the change in the size of the gap of actual and aspirational QoL over time. Changes in depression and hopelessness scores over time were entered as independent variables in a multiple regression, while the change in gap scores was entered as the dependent variable. A significant amount of variance was explained by changes in the present and future gaps for actual and aspirational QoL (52.4%, 59,9% respectively both p < 0.01). Change in depression contributed to change (reduction) in the gap between present actual and aspirational Qol (β =.676). Change in hopelessness (β =.589) was the significant contributing factor for change (reduction) in the gap between actual and aspirational future QoL (table  5 ). This confirms hypothesis 2 and 3 in parts.Multiple regression analyses to explain the change in the actual/aspirational gap by change in Beck Depression Inventory (BDI) and Beck Hopelessness Scale (BHS) change scores from time 1 to time 2.1 Change of Beck Depression Inventory (BDI) and change of Beck Hopelessness Scale (BHS) were entered as predicting variables in these analysesIn table  6 , the differences of present and past (phenomenological-depression) and present and future QoL (quality of life) are assessed according to de Leval's model. As already reported, baseline actual present QoL scores were considerably lower than actual past scores (35.4 ± 19.1 vs. 70.2 ± 13.7, p <.001). This significant gap (34.8 ± 22.5) between present and past QoL was significantly reduced over three months to a gap of 7.6 ± 30.9 (p = .011). At the three month follow-up, there was no statistical difference in the gap between actual present and past QoL perception (figure  3 ). The gap between present and future QoL was large and significant at baseline (31.3 ± 27.2, p < .001). Differences remained significant at the 3 month follow-up (13.3 ± 13.5, p = .001) with higher QoL levels for the future. However, the reduction in the gap over time was also significant (p = .010).Testing de Leval's model: time gap comparison for actual QoL scores measured by SEIQoL Index ScoreTo investigate how depression and hopelessness may influence the change in the size of the gaps proposed by de Leval, multiple regression analysis was conducted. Change in depression and hopelessness scores over time were entered as independent variables in a multiple regression, while the change in the gap over time, was entered as the dependent variable. Changes in the size of the two time comparison gaps (past/present; present/future) were not influenced by change in depression or hopelessness scores (R 2  = .281, p = .09; R 2  = .162, p = .266). This partly disconfirms hypothesis 4Discussion In this study the relationship of QoL and depression was investigated in two ways. First the preference comparison gaps were assessed, i.e. where patients perceive themselves to be and where they wish to be. This was done for all three time dimensions (past, present and future). Secondly, the time comparison gap was assessed, i.e. where patients see themselves now in comparison to the past, and in comparison to the future. Both approaches were carried out on the basis of de Leval's model linking depression to all three time dimensions. Our findings are consistent with previous results, showing that people use their current affective state as a basis for making judgments of how happy and satisfied they are with their lives. A depressed person will usually see his or her well-being, social functioning and living conditions as worse than they appear to an independent observer or to patients themselves after recovery – the so called "affective fallacy" [ 10 ]. Clinically depressed patients were assessed at two time points before and three months after admission to a psychiatric hospital. Clinical measures (depression and hopelessness) showed significant improvements for all 18 patients, indicating successful treatment. Alongside the reduction in depression, actual present QoL improved significantly over time. In contrast, actual past QoL did not change over time. Successful treatment of depression had no influence of the individual's perception of the past. In addition, there was no significant change in actual future QoL, i.e. how patients realistically estimated their QoL to be one year from now. Thus assessments of the past and of the expected future did not change when patients recovered from a depressive episode. Aspirational QoL was the same between the three time dimensions and remained constant over time. There was always a preference comparisons gap over time – independent of depression or recovering depression. Our findings suggest the larger the present preference comparison gap, the greater the depression. While the preference comparison gap of the past did not change over time with the decrease of depression, there was a trend for the future preference comparison gap that might become statistically significant with a larger sample size. However, aspirations were not affected by depression, since they remained the same for past, present and future from baseline in hospital to three months later. Overall these findings may indicate that a reduction in the present preference gap should be the main goal for therapeutic actions for depressed patients. An achievable target may be to keep the same preference comparison gap between and over time points to maintain a healthy homeostasis and a good QoL (figure  2 ). Interestingly, the mean level of aspirational QoL was not at the top of the possible scale (100). This may reflect an individual "QoL set-point" as discussed by Seligman [ 14 ]. He proposes that an individual might be genetically predetermined, to a particular set-point, to which he/she might return after both ups and downs. In therapy then the goal might be to help an individual actively work to return to his/her set point as soon as possible. Successful treatment of depression, indicated by a significant change of BDI-II and BHS scores, was accompanied by a significant reduction in the gap between present actual and aspirational QoL. A reduction in the gap between actual present QoL with the aspirational QoL ("where one would like to be right here and now") reflects a more positive view of the present and is accompanied by significant improvements in QoL. Depression was consistently correlated with the time comparison gap between present and future QoL assessments. However, depression was more highly associated with the present and future preference comparison gap at three months. This suggests, that depression may be more highly associated with the actual/aspirational gap when people are less depressed. In contrast, hopelessness was consistently correlated with the preference comparison future gaps and only at baseline with the gap of present actual/aspirational QoL. The gap between the actual past and aspirational past QoL was not explained by either depression or hopelessness. Change in depression or hopelessness was important in reducing the preference comparison gap for present and future QoL assessments. Change in depression was important in reducing the size of the present gap. Change in hopelessness significantly contributed to reducing the size of the future gap. Given that present "ill-being" is seen as depression, while hopelessness is future orientated and directed, this finding makes sense. This has implications for therapy: to improve the QoL of patients with depression, relief from depression must be provided. Hopelessness needs to be tackled in addition to achieving a realistic future QoL perspective. To a large extend this study confirms de Leval's theory. The assessment of de Leval's model: present and future QoL (quality of life) and past and present (phenomenological-depression) showed interesting results. The theoretical time comparison gap between a "healthy past" and present "ill-being" was confirmed by the significant difference between patients' perceptions of actual present and future QoL, at baseline. Over time, following appropriate treatment, this time comparison gap should close and QoL should improve, if the treatment is considered to be successful. The significant reduction of the past-present gap over time, and the loss in significance in size of this gap three months later, further confirms de Leval's model. This reduction of the time comparison gap between the present "ill-being" and a "healthy past" resulted in an improvement in QoL. The reduction was achieved by a change in the actual view of the present, leaving the view of the past unchanged (figure  3 ). According to de Leval's model, recovery from depression is achieved when the appraisal of present and past QoL are very close, i.e. a very narrow gap. This means that a reduction of the gap between present and future QoL should improve current QoL. Although this study showed a decrease in depression over time by standard measures of depression and the size of the time comparison gap was significantly reduced between the two time points, the size of the gap did remain significant between the present and future at three months follow up. This finding may either indicate that the patients were still depressed at three months, or this part of the model could not be confirmed (figure  3 ). de Leval argues that therapeutic future is the view of a healthy past. Therefore one would expect similar scores for past and future QoL. This was supported by our findings for both time points. The change in the size of the time comparison gaps was not predicted by the change in either hopelessness or depression scores over time. This suggests that the change in time comparison gap's may be influenced by other variables, not assessed in this study. Depression lowered a person's actual QoL, but not their aspirational QoL. This was consistent whether a person was depressed or improving and for each of the time dimensions (past-present-future). The recollection of the past, either actual or aspirational did not change for the depressed or recovering person, neither did their view of the future. Thus for this patient group, the perception of the past and the future was not altered by depression status, which might be linked to individual QoL set points. Limitations Since we tested the model in a small and specialised sample, the findings are not generalisable. However, our study did test de Leval's model in a clinically depressed sample which is the focus of the most likely benefit of understanding the interplay of the two phenomena of depression and quality of life. It is also a challenging group to recruit, engage with and maintain in a research project.
Discussion
In this study the relationship of QoL and depression was investigated in two ways. First the preference comparison gaps were assessed, i.e. where patients perceive themselves to be and where they wish to be. This was done for all three time dimensions (past, present and future). Secondly, the time comparison gap was assessed, i.e. where patients see themselves now in comparison to the past, and in comparison to the future. Both approaches were carried out on the basis of de Leval's model linking depression to all three time dimensions.Our findings are consistent with previous results, showing that people use their current affective state as a basis for making judgments of how happy and satisfied they are with their lives. A depressed person will usually see his or her well-being, social functioning and living conditions as worse than they appear to an independent observer or to patients themselves after recovery – the so called "affective fallacy" [ 10 ]. Clinically depressed patients were assessed at two time points before and three months after admission to a psychiatric hospital. Clinical measures (depression and hopelessness) showed significant improvements for all 18 patients, indicating successful treatment. Alongside the reduction in depression, actual present QoL improved significantly over time. In contrast, actual past QoL did not change over time. Successful treatment of depression had no influence of the individual's perception of the past. In addition, there was no significant change in actual future QoL, i.e. how patients realistically estimated their QoL to be one year from now. Thus assessments of the past and of the expected future did not change when patients recovered from a depressive episode. Aspirational QoL was the same between the three time dimensions and remained constant over time. There was always a preference comparisons gap over time – independent of depression or recovering depression.Our findings suggest the larger the present preference comparison gap, the greater the depression. While the preference comparison gap of the past did not change over time with the decrease of depression, there was a trend for the future preference comparison gap that might become statistically significant with a larger sample size. However, aspirations were not affected by depression, since they remained the same for past, present and future from baseline in hospital to three months later. Overall these findings may indicate that a reduction in the present preference gap should be the main goal for therapeutic actions for depressed patients. An achievable target may be to keep the same preference comparison gap between and over time points to maintain a healthy homeostasis and a good QoL (figure  2 ). Interestingly, the mean level of aspirational QoL was not at the top of the possible scale (100). This may reflect an individual "QoL set-point" as discussed by Seligman [ 14 ]. He proposes that an individual might be genetically predetermined, to a particular set-point, to which he/she might return after both ups and downs. In therapy then the goal might be to help an individual actively work to return to his/her set point as soon as possible.Successful treatment of depression, indicated by a significant change of BDI-II and BHS scores, was accompanied by a significant reduction in the gap between present actual and aspirational QoL. A reduction in the gap between actual present QoL with the aspirational QoL ("where one would like to be right here and now") reflects a more positive view of the present and is accompanied by significant improvements in QoL. Depression was consistently correlated with the time comparison gap between present and future QoL assessments. However, depression was more highly associated with the present and future preference comparison gap at three months. This suggests, that depression may be more highly associated with the actual/aspirational gap when people are less depressed. In contrast, hopelessness was consistently correlated with the preference comparison future gaps and only at baseline with the gap of present actual/aspirational QoL. The gap between the actual past and aspirational past QoL was not explained by either depression or hopelessness. Change in depression or hopelessness was important in reducing the preference comparison gap for present and future QoL assessments. Change in depression was important in reducing the size of the present gap. Change in hopelessness significantly contributed to reducing the size of the future gap. Given that present "ill-being" is seen as depression, while hopelessness is future orientated and directed, this finding makes sense. This has implications for therapy: to improve the QoL of patients with depression, relief from depression must be provided. Hopelessness needs to be tackled in addition to achieving a realistic future QoL perspective.To a large extend this study confirms de Leval's theory. The assessment of de Leval's model: present and future QoL (quality of life) and past and present (phenomenological-depression) showed interesting results. The theoretical time comparison gap between a "healthy past" and present "ill-being" was confirmed by the significant difference between patients' perceptions of actual present and future QoL, at baseline. Over time, following appropriate treatment, this time comparison gap should close and QoL should improve, if the treatment is considered to be successful. The significant reduction of the past-present gap over time, and the loss in significance in size of this gap three months later, further confirms de Leval's model. This reduction of the time comparison gap between the present "ill-being" and a "healthy past" resulted in an improvement in QoL. The reduction was achieved by a change in the actual view of the present, leaving the view of the past unchanged (figure  3 ).According to de Leval's model, recovery from depression is achieved when the appraisal of present and past QoL are very close, i.e. a very narrow gap. This means that a reduction of the gap between present and future QoL should improve current QoL. Although this study showed a decrease in depression over time by standard measures of depression and the size of the time comparison gap was significantly reduced between the two time points, the size of the gap did remain significant between the present and future at three months follow up. This finding may either indicate that the patients were still depressed at three months, or this part of the model could not be confirmed (figure  3 ). de Leval argues that therapeutic future is the view of a healthy past. Therefore one would expect similar scores for past and future QoL. This was supported by our findings for both time points. The change in the size of the time comparison gaps was not predicted by the change in either hopelessness or depression scores over time. This suggests that the change in time comparison gap's may be influenced by other variables, not assessed in this study. Depression lowered a person's actual QoL, but not their aspirational QoL. This was consistent whether a person was depressed or improving and for each of the time dimensions (past-present-future). The recollection of the past, either actual or aspirational did not change for the depressed or recovering person, neither did their view of the future. Thus for this patient group, the perception of the past and the future was not altered by depression status, which might be linked to individual QoL set points.Limitations Since we tested the model in a small and specialised sample, the findings are not generalisable. However, our study did test de Leval's model in a clinically depressed sample which is the focus of the most likely benefit of understanding the interplay of the two phenomena of depression and quality of life. It is also a challenging group to recruit, engage with and maintain in a research project.
Limitations
Since we tested the model in a small and specialised sample, the findings are not generalisable. However, our study did test de Leval's model in a clinically depressed sample which is the focus of the most likely benefit of understanding the interplay of the two phenomena of depression and quality of life. It is also a challenging group to recruit, engage with and maintain in a research project.Conclusion This study showed that depression influenced individual QoL by lowering the person's actual QoL. Thus depression was associated with a larger gap between current reality (actual perceptions) and patient aspirations and realistic expectations. Aspirations for past, present and future QoL remained the same over time. However, patients actual appraisal of their present QoL improved with successful treatment of depression, reflected by a closure of the present preference gap. de Leval's model was largely confirmed. Thus depression and hopelessness influence a person's present and future QoL. The analysis of a temporal horizon was very helpful in understanding the link between depression and QoL. Therapeutic interventions can be considered as closing the gap between a person's present QoL and their present aspirations and realistic expectations for the future. This could be achieved, according to the data presented here, by changing the view of the present and not necessarily by changing the level of expected future QoL. Knowing the persons aspirational QoL level may be a helpful guide for the therapist in that it provides important information about a depressed person's position in the progress towards what he or she considers to be recovery.
Conclusion
This study showed that depression influenced individual QoL by lowering the person's actual QoL. Thus depression was associated with a larger gap between current reality (actual perceptions) and patient aspirations and realistic expectations. Aspirations for past, present and future QoL remained the same over time. However, patients actual appraisal of their present QoL improved with successful treatment of depression, reflected by a closure of the present preference gap.de Leval's model was largely confirmed. Thus depression and hopelessness influence a person's present and future QoL. The analysis of a temporal horizon was very helpful in understanding the link between depression and QoL. Therapeutic interventions can be considered as closing the gap between a person's present QoL and their present aspirations and realistic expectations for the future. This could be achieved, according to the data presented here, by changing the view of the present and not necessarily by changing the level of expected future QoL. Knowing the persons aspirational QoL level may be a helpful guide for the therapist in that it provides important information about a depressed person's position in the progress towards what he or she considers to be recovery.Authors' contributions Margaret Moore contributed to conception and design, acquisition, analysis and interpretation of the data and revised the article. Stefan Höfer drafted the article and contributed to the analysis and interpretation of the data. Hannah McGee contributed to the conception and design and interpretation of the data and revised the article. Lena Ring contributed to the interpretation and revised the article. All authors have given final approval of the version to be published
Authors' contributions
Margaret Moore contributed to conception and design, acquisition, analysis and interpretation of the data and revised the article. Stefan Höfer drafted the article and contributed to the analysis and interpretation of the data. Hannah McGee contributed to the conception and design and interpretation of the data and revised the article. Lena Ring contributed to the interpretation and revised the article.All authors have given final approval of the version to be published


Background Plexiform neurofibromas (PNF) are benign tumors of the peripheral nerve which mostly develop in patients with neurofibromatosis type 1 (NF1). Surgical interventions are usually not applied to children with small tumors. These are rather restricted to debulking of larger tumors in adults that cause clinical complications or aesthetic disfigurement. In most cases, a total resection of PNF is not possible due to the network-like growth of the tumors.
Background
Plexiform neurofibromas (PNF) are benign tumors of the peripheral nerve which mostly develop in patients with neurofibromatosis type 1 (NF1). Surgical interventions are usually not applied to children with small tumors. These are rather restricted to debulking of larger tumors in adults that cause clinical complications or aesthetic disfigurement. In most cases, a total resection of PNF is not possible due to the network-like growth of the tumors.Patients and methods Early surgical intervention was carried out for 9 small PNFs in 7 NF1 children. Tumor resection was performed following the graphical delineation of the affected skin and according the MRI findings.
Patients and methods
Early surgical intervention was carried out for 9 small PNFs in 7 NF1 children. Tumor resection was performed following the graphical delineation of the affected skin and according the MRI findings.Results Total resection was achieved for all 9 PNF without causing any neurological or organic deficit. Annual magnetic resonance tomography over a period of four years did not reveal any relapse of the tumors.
Results
Total resection was achieved for all 9 PNF without causing any neurological or organic deficit. Annual magnetic resonance tomography over a period of four years did not reveal any relapse of the tumors.Conclusions Early surgical intervention for small superficial PNFs in NF1 children have various advantages and may especially be considered a strategy to prevent progression.
Conclusions
Early surgical intervention for small superficial PNFs in NF1 children have various advantages and may especially be considered a strategy to prevent progression.

Background Plexiform neurofibromas (PNF) are benign tumors originating from nerve sheath cells, subcutaneous, or visceral peripheral nerves and can involve multiple fascicles [ 1 ]. PNF occur almost exclusively in patients with NF1, an autosomal dominant disorder caused by defect of one allele of the tumor suppressor gene,  NF1  on 17q [ 2 - 5 ]. At least 30% of NF1 patients suffer from PNF [ 2 , 6 , 7 ], which are often present at birth and progress during the first years of life. The growth rate and pattern of PNF vary to a large extent and their growth spurts are unpredictable. PNF can arise in various parts of the body, for example as anterior mediastinal masses, sciatic nerve lesions with pelvic extension, or perirectal plexiform and uterine tumors, often leading to severe clinical complications [ 7 ]. Especially tumors occurring in the head and neck area often lead to facial disfigurement and functional deficits. Due to large size of the tumors and involvement of multiple fascicles of nerves and tissues, the risk of neurological and functional destruction upon tumor resection is high. Surgical interventions are thus commonly postponed as long as possible. In addition, most surgical interventions are limited to debulking and rests of tumors often re-grow afterwards leading to the requirement of repeated intervention [ 8 - 10 ]. Previously we reported that PNF can be distinguished into three growth categories using magnetic resonance imaging (MRI): superficial, displacing and invasive. Superficial PNF arise from subcutaneous or cutaneous nerves and may remain within the upper layer of the skin – usually not involving major nerves [ 10 ]. Subtotal and total resection without functional destruction is often possible for superficial PNF, as demonstrated in our recent study [ 11 ]. In contrast, invasive PNF infiltrate multiple tissue planes and are thus much more difficult or impossible to resect. Superficial PNF show progressive growth and it is unknown whether or not a superficial PNF may change to displacing or invasive types. Early resection of small superficial PNF may thus be considered as an advantageous treatment option. In this study, we present the results of early intervention for 9 PNFs in 7 NF1 children aged 3 to 15 years.
Background
Plexiform neurofibromas (PNF) are benign tumors originating from nerve sheath cells, subcutaneous, or visceral peripheral nerves and can involve multiple fascicles [ 1 ]. PNF occur almost exclusively in patients with NF1, an autosomal dominant disorder caused by defect of one allele of the tumor suppressor gene,  NF1  on 17q [ 2 - 5 ]. At least 30% of NF1 patients suffer from PNF [ 2 , 6 , 7 ], which are often present at birth and progress during the first years of life. The growth rate and pattern of PNF vary to a large extent and their growth spurts are unpredictable. PNF can arise in various parts of the body, for example as anterior mediastinal masses, sciatic nerve lesions with pelvic extension, or perirectal plexiform and uterine tumors, often leading to severe clinical complications [ 7 ]. Especially tumors occurring in the head and neck area often lead to facial disfigurement and functional deficits. Due to large size of the tumors and involvement of multiple fascicles of nerves and tissues, the risk of neurological and functional destruction upon tumor resection is high. Surgical interventions are thus commonly postponed as long as possible. In addition, most surgical interventions are limited to debulking and rests of tumors often re-grow afterwards leading to the requirement of repeated intervention [ 8 - 10 ].NF1Previously we reported that PNF can be distinguished into three growth categories using magnetic resonance imaging (MRI): superficial, displacing and invasive. Superficial PNF arise from subcutaneous or cutaneous nerves and may remain within the upper layer of the skin – usually not involving major nerves [ 10 ]. Subtotal and total resection without functional destruction is often possible for superficial PNF, as demonstrated in our recent study [ 11 ]. In contrast, invasive PNF infiltrate multiple tissue planes and are thus much more difficult or impossible to resect. Superficial PNF show progressive growth and it is unknown whether or not a superficial PNF may change to displacing or invasive types. Early resection of small superficial PNF may thus be considered as an advantageous treatment option.In this study, we present the results of early intervention for 9 PNFs in 7 NF1 children aged 3 to 15 years.Patients and methods The 7 children were examined in our NF-Clinic in the Department of Maxillofacial Surgery, University Hospital Eppendorf, Hamburg. Diagnosis of NF1 was based on the NIH criteria [ 6 ]. Informed consent was obtained from parents of these children. All patients received dermatological, neurological and ophthalmological examinations as well as an ultrasound of abdominal organs. PNF were diagnosed based on the following indications: subcutaneous location on palpation, associated with thickening of the skin, local hypertrophy, hair excess and hyperpigmentation on inspection, and prepubertal occurrence from the medical report. Magnetic resonance image (MRI) was done for the tumor regions at 1.5 Tesla with T1- and T2- weighted sequences including a short-tau inversion-recovery (STIR) sequence. Ultra rapid half Fourier single-shot turbo spin-echo (HASTE) sequences were used for imaging the trunk. Intravenous contrast medium was given to all patients. Tumor resection was performed following the graphical delineation of the affected skin and according the MRI findings. Tumor resection included the epidermal and subcutaneous layer with safety margins of 1 cm in all directions. Exploration of the underlying muscles was mandatory.
Patients and methods
The 7 children were examined in our NF-Clinic in the Department of Maxillofacial Surgery, University Hospital Eppendorf, Hamburg. Diagnosis of NF1 was based on the NIH criteria [ 6 ]. Informed consent was obtained from parents of these children. All patients received dermatological, neurological and ophthalmological examinations as well as an ultrasound of abdominal organs. PNF were diagnosed based on the following indications: subcutaneous location on palpation, associated with thickening of the skin, local hypertrophy, hair excess and hyperpigmentation on inspection, and prepubertal occurrence from the medical report. Magnetic resonance image (MRI) was done for the tumor regions at 1.5 Tesla with T1- and T2- weighted sequences including a short-tau inversion-recovery (STIR) sequence. Ultra rapid half Fourier single-shot turbo spin-echo (HASTE) sequences were used for imaging the trunk. Intravenous contrast medium was given to all patients. Tumor resection was performed following the graphical delineation of the affected skin and according the MRI findings. Tumor resection included the epidermal and subcutaneous layer with safety margins of 1 cm in all directions. Exploration of the underlying muscles was mandatory.Results Seven NF1 children, five boys and two girls, aged 3 to 15 years were included in this study. All of them met the NIH diagnostic criteria for NF1 [ 6 ]. PNF was initially diagnosed clinically and further ascertained by MRI (Figs.  1 ,  2 ,  3 ,  4 ,  5 ,  6 ,  7 ). Five tumors were histologically confirmed as PNF (Fig.  8 ). Other four were reported as diffuse neurofibromas due to lack of nerve fascicle in the examined sections. However, these tumors were parts of PNF. Five PNF in four children exhibited hyperpigmentation while the other two had hair excess in the tumor area. Two children had two and the other five had one PNF each. Size of tumors varied from 2 cm to 8 cm in greatest diameter (table  1 ). All PNF were superficial based on MRI. The tumor location was variable (table  1 ). Neither functional deficit nor pain was caused by the tumors at the time of surgery. Neither was there significant aesthetic disfigurement caused by the tumors. Figure 1 1A: Pre-surgical T2-weighted STIR-sequence, axial section: in right ventral chest wall bright superficial thickening of cutis and subcutis without involvement of muscles. 1B: Pre-surgical T2-weighted STIR-sequence, axial section: very bright, flat superficial cutaneous PNF in proximal part of right upper arm. 1C: Pre-surgical clinical frontal view of both PNF on right upper arm and thorax wall. 1D: Post-surgical T1-weighted sequence, axial section: small defect in cutis and subcutis, no PNF visible anymore. 1E: Post-surgical T2-weighted STIR-sequence, axial section: complete removal of tumor with hypointensive induration. 1F: Post-surgical clinical frontal view of both scars on right upper arm and thorax wall. Figure 2 2A: Pre-surgical T2-weighted STIR-sequence, axial section: superficial tumor covering the laryngeal prominence. 2B: Pre-surgical clinical frontal view of PNF of ventral neck. 2C: Post-surgical T2-weighted STIR-sequence, axial section: scar tissue praelaryngeal visible. 2D: Post-surgical clinical frontal view of laryngeal scar. Figure 3 3A: Pre-surgical T2-weighted STIR sequence of left ventral abdominal wall, paraumbilical. Bright plexiform neurofibroma with thickening of cutis without involvement of muscle. 3B: Pre-surgical T2-weighted STIR sequence, axial section of left ventral abdominal wall, costal margin. Small bright plexiform neurofibroma in cutis and subcutis ventral left. 3C: Pre-surgical clinical frontal view of abdomen with both superficial plexiform neurofibromas visible. 3D: Post-surgical MRI control from A. Complete removal of plexiform neurofibroma. 3E: Post-surgical MRI control from B. Complete removal of plexiform neurofibroma. 3F: Post-surgical clinical frontal view of abdomen. Only two visible scars left after surgery. Figure 4 4A: Pre-surgical T2-weighted STIR-sequence, axial section: discrete signs of flat funicular, cutaneous and subcutaneous PNF near the left iliac crest with involvement of soft tissue, but without visible infiltration of abdominal muscles. 4B: Pre-surgical clinical view of PNF in the left flank. 4C: Post-surgical T2-weighted Haste-sequence: complete resection of tumor, only a smooth fibrous post-surgical induration and small scar can be identified. 4D: Post-surgical clinical view of hypertrophic scar. Figure 5 5A: Pre-surgical T2-weighted STIR-sequence, axial section; small nodular hyperintensive PNF in the cutis and subcutis on left ventral chest wall. 5B: Pre-surgical clinical view of PNF in left chest wall, parasternal. 5C: Post-surgical T2-weighted Turbo Spin Echo-sequence, axial section: tumor no longer visible, only adipose tissue visible in the subcutis. 5D: Post-surgical clinical view of scar. Figure 6 6A: Pre-surgical T2-weighted STIR-sequence, transversal section: bright, flat cutaneous and subcutaneous PNF of right back without involvement of abdominal wall and muscles. 6B: Pre-surgical clinical view of PNF on right back with hypertrichosis. 6C: Post-surgical T2-weighted Turbo Spin Echo-sequence, axial section: complete removal of PNF, thin scar, no subcutaneous fatty tissue visible in scan. 6D: Post-surgical clinical view of scar after tumor removal on back. Figure 7 7A: Pre-surgical T2-weighted STIR-sequence, transversal section: Cutaneous and subcutaneous PNF of forearm, bright signal without involvement of muscles or fascia. 7B: Pre-surigcal clinical view of hyperpigmented PNF of left forearm. 7C: Post-surgical T2-weighted STIR-sequence, axial section: complete removal of tumor. 7D: Post-surgical clinical view of scar on left forearm. Figure 8 Photomicrograph of PNF.  Plexiform neurofibroma WHO grade I invading fascicles of a peripheral nerve. Tumor growth is primarily confined to the endoneurial space; the perineurium (arrow) forms a natural border for the tumor. Note the loose myoxid texture of the tumor tissue Table 1 Clinical information Patient number Sex Age at surgery Tumor location Hyper pigmentation hair growth Size (greatest diameter) Histology post-operative MRI Annual MRI follow up 1 f 5 upper arm right no no 4 cm PNF yes yes 5 thorax right yes no 4 cm PNF yes yes 2 m 15 Adams apple no no 5 cm PNF no yes 3 f 14 rib bow left no no 4 cm PNF no yes 14 paraumbilical left no no 3 cm PNF no yes 4 m 3 thigh left yes yes 7 cm PNF no yes 5 m 4 thorax left yes no 2 cm PNF yes yes 6 m 7 back right yes yes 8 cm PNF yes yes 7 m 11 lower arm left yes no 5 cm PNF no only 2003 In 2001, all seven children underwent surgical intervention for their nine PNF. During the mobilization of the underlying skin layers, three patients showed enlarged nerves running from subcutis to superficial muscle layers, which were identified and additionally resected. These enlarged nerves were proven to be PNF in all cases. Primary wound closure was achieved following the mobilization of the marginal skin. Healing followed without complications in all cases. The scars are relatively small and no hypertrophy was observed. The intervention was well tolerated by all children and recovery occurred within a few days. Postoperative MRI was done for three children. Six children underwent follow-up examinations annually by MRI for three years. One child was only examined in 2003, two years after the operation. MRI revealed successful total resection for all 9 tumors (Figs.  1 ,  2 ,  3 ,  4 ,  5 ,  6 ,  7 ). So far, no tumor re-growth has been detected in any of the children.
Results
Seven NF1 children, five boys and two girls, aged 3 to 15 years were included in this study. All of them met the NIH diagnostic criteria for NF1 [ 6 ]. PNF was initially diagnosed clinically and further ascertained by MRI (Figs.  1 ,  2 ,  3 ,  4 ,  5 ,  6 ,  7 ). Five tumors were histologically confirmed as PNF (Fig.  8 ). Other four were reported as diffuse neurofibromas due to lack of nerve fascicle in the examined sections. However, these tumors were parts of PNF. Five PNF in four children exhibited hyperpigmentation while the other two had hair excess in the tumor area. Two children had two and the other five had one PNF each. Size of tumors varied from 2 cm to 8 cm in greatest diameter (table  1 ). All PNF were superficial based on MRI. The tumor location was variable (table  1 ). Neither functional deficit nor pain was caused by the tumors at the time of surgery. Neither was there significant aesthetic disfigurement caused by the tumors.Clinical informationPatient numberSexAge at surgeryTumor locationHyper pigmentationhair growthSize (greatest diameter)Histologypost-operative MRIAnnual MRI follow upIn 2001, all seven children underwent surgical intervention for their nine PNF. During the mobilization of the underlying skin layers, three patients showed enlarged nerves running from subcutis to superficial muscle layers, which were identified and additionally resected. These enlarged nerves were proven to be PNF in all cases. Primary wound closure was achieved following the mobilization of the marginal skin. Healing followed without complications in all cases. The scars are relatively small and no hypertrophy was observed. The intervention was well tolerated by all children and recovery occurred within a few days.Postoperative MRI was done for three children. Six children underwent follow-up examinations annually by MRI for three years. One child was only examined in 2003, two years after the operation. MRI revealed successful total resection for all 9 tumors (Figs.  1 ,  2 ,  3 ,  4 ,  5 ,  6 ,  7 ). So far, no tumor re-growth has been detected in any of the children.Discussion In this study we demonstrated that small superficial PNF can be completely resected, leaving scars without hypertrophy. Operation is relatively uncomplicated, allows healing by primary intention, requires only a few days of hospitalization and is thus no burden for even the youngsters. Within the clinical and radiological follow-up period of three years there was no re-growth of the tumors. However, it cannot be excluded that all tumor cells have been resected. Therefore those patients warrant further annual clinical examination. The scars in some children may seem more obvious and disfiguring after the operation. However, in comparison to the complications the tumors may cause later, they are only of minor concern. Furthermore, these scars may be corrected later surgically. Without resection, these small PNF are likely to grow continuously to a large or even very large size which often causes aesthetic disfigurement, functional deficits and pain. Resection of large tumors is much more difficult and total resection is usually not possible any more. Currently it is not clarified whether or not growth patterns of PNF might possibly change from superficial to displacing or to invasive types over time. Early surgical intervention of small superficial PNF may thus be considered as a preventive strategy for later disfigurement and functional deficits. Adequate diagnosis of NF1 and thus small PNF in the pediatric age group is challenging. Children usually do not complain about subtle pain or discomfort in the affected skin region. Even in the presence of some symptoms parents are often not aware of the origin of the tumor. Only small PNF of the face and neck causing disfigurement in children tend to be recognized early. On the other hand, small PNF of the trunk and extremities which present with subtle hyperpigmentation, hair excess and palpable tumor tissue are frequently not noticed by the physicians. These tumors are rarely diagnosed correctly as PNF. In our cohort only one child received the diagnosis of a PNF correctly by the referring family physician. For better management and adequate treatment, efforts should be made to diagnose NF1 and PNF in their early stage.
Discussion
In this study we demonstrated that small superficial PNF can be completely resected, leaving scars without hypertrophy. Operation is relatively uncomplicated, allows healing by primary intention, requires only a few days of hospitalization and is thus no burden for even the youngsters. Within the clinical and radiological follow-up period of three years there was no re-growth of the tumors. However, it cannot be excluded that all tumor cells have been resected. Therefore those patients warrant further annual clinical examination.The scars in some children may seem more obvious and disfiguring after the operation. However, in comparison to the complications the tumors may cause later, they are only of minor concern. Furthermore, these scars may be corrected later surgically.Without resection, these small PNF are likely to grow continuously to a large or even very large size which often causes aesthetic disfigurement, functional deficits and pain. Resection of large tumors is much more difficult and total resection is usually not possible any more. Currently it is not clarified whether or not growth patterns of PNF might possibly change from superficial to displacing or to invasive types over time. Early surgical intervention of small superficial PNF may thus be considered as a preventive strategy for later disfigurement and functional deficits.Adequate diagnosis of NF1 and thus small PNF in the pediatric age group is challenging. Children usually do not complain about subtle pain or discomfort in the affected skin region. Even in the presence of some symptoms parents are often not aware of the origin of the tumor. Only small PNF of the face and neck causing disfigurement in children tend to be recognized early. On the other hand, small PNF of the trunk and extremities which present with subtle hyperpigmentation, hair excess and palpable tumor tissue are frequently not noticed by the physicians. These tumors are rarely diagnosed correctly as PNF. In our cohort only one child received the diagnosis of a PNF correctly by the referring family physician. For better management and adequate treatment, efforts should be made to diagnose NF1 and PNF in their early stage.Conclusions Early surgical intervention of small superficial PNFs is uncomplicated, without burden for even the youngsters and enables total resection of the tumors. It may be considered as a preventive strategy for later disfigurement and functional deficits.
Conclusions
Early surgical intervention of small superficial PNFs is uncomplicated, without burden for even the youngsters and enables total resection of the tumors. It may be considered as a preventive strategy for later disfigurement and functional deficits.Competing interests The authors declare that they have no competing interests.
Competing interests
The authors declare that they have no competing interests.Authors' contributions REF  and  RS  carried out the surgical intervention for the tumors and post-operational care of the patients. CF  carried out the MRI and was involved in the diagnosis of PNF. MH  and  VFM  did the diagnosis and were responsible for management and consulting of the patients. REF  and  VFM  designed the study and prepared the manuscript. All authors read and approved the final version of the manuscript.
Authors' contributions
REF  and  RS  carried out the surgical intervention for the tumors and post-operational care of the patients.REFRSCF  carried out the MRI and was involved in the diagnosis of PNF.CFMH  and  VFM  did the diagnosis and were responsible for management and consulting of the patients.MHVFMREF  and  VFM  designed the study and prepared the manuscript.REFVFMAll authors read and approved the final version of the manuscript.


Microbes are arguably the most adaptable organisms on Earth, inhabiting nearly every crevice of nearly every corner of the globe. Some invade the cavities of a wide variety of insects and other invertebrates while others colonize the skin, blood, eyes, and internal organs of animals. Still others thrive in such inhospitable places as the hydrothermal vents of the ocean floor and the Dry Valleys of Antarctica. These “simple” single-celled organisms have evolved unique molecules and strategies over some 3.5 billion years that suit life on the edge. With the sequenced genomes of nearly 140 microbial species in hand, scientists are gaining valuable insights into the nature of this adaptive diversity.Adapting to such radically different niches, it appears, has produced genes with diverse functions that evolve at very different rates. Genes that code for molecules essential for fundamental cellular functions like maintaining cell metabolism and structure tend to evolve rather slowly, while genes that make proteins charged with mediating cellular responses to internal or external changes often evolve relatively quickly. Pathogenic microbes in particular rely on a flexible genome to keep a step ahead of their hosts' similarly evolving defenses in the never-ending struggle to gain adaptive advantage. This adaptability underlies the increasing antibiotic resistance of diseases like tuberculosis, as selective pressures favor the expansion of resistant bacterial populations.Combating such problems requires a molecular understanding of bacterial infections, yet function has been ascribed to only a fraction of the genes found in microbial genomes. One approach to improve functional analyses of genome sequences combines bioinformatics with experimental methods. With such collaborations in mind, Yu Zheng, Richard Roberts, and Simon Kasif have developed a computational approach to help filter out the genetic noise and home in on genomic regions likely to contain clues to gene function. Their method relies on a novel way of classifying genes that flags sequences likely to reward biochemical and genetic efforts to analyze gene function.Many comparative genomic studies have focused on looking for sequence “motifs” that correlate with well-characterized protein sequences (that is, the amino acid sequence) and predicting function based on their similarity to the known protein sequences. Zheng, Roberts, and Kasif took a different approach, classifying genes based on their sequence variation. The researchers analyzed 43 fully sequenced microbial genomes and, after determining the degree of conservation or divergence among similar genes in different species, divided the genes into three broad categories: rapidly evolving genes unique to a particular species; highly conserved genes; and “segmentally variable,” or mosaic, genes. Stipulating that the boundaries between the categories are somewhat blurred, Zheng et al. define segmentally variable genes as regions that show a mosaic pattern of one or more rapidly evolving, variable regions interspersed with conserved regions. Based on evidence suggesting that retained variable regions tend to serve a function, the researchers predicted that these mosaic genes, with their highly variable, fast-evolving regions, would shed light on the forces that shape genome diversity and adaptation.For most of the microbes analyzed, mosaic genes accounted for about 8–20% of their genomes. Selecting several large families of mosaic genes, Zheng et al. explored the relationship between genes with known function and the structure of their variable regions. Noting an overabundance of particular functional categories in different species—such as signaling proteins that come into either direct or indirect contact with the cell's environment—the researchers speculate that the variable regions may constitute an adaptive layer for the microbe, as they not only “play a key role in mediating interactions with other molecules” but also support a microbe's ability to adapt to its particular niche. Several bacteria species, for example, contain roughly 40% more mosaic sensor genes involved in cell motility, which the authors attribute to the microbes' “expanded ability to detect different chemical signals and find favorable environments.”This regional variability appears to reflect the influence of selective pressures that fuel diversity through ongoing interactions with other rapidly evolving molecules in the environment, adding another source of genetic adaptability as cells adjust to new environments and outmaneuver pathogenic threats. While many of the mosaic genes identified encode proteins involved in host-pathogen interactions, defense mechanisms, and intracellular responses to external changes, their function is only broadly understood. While Zheng et al. cannot say to what extent variability affects function—Is extreme variability required for diversity or can modest variation suffice?—they are refining their classification of segmentally variable genes to address such questions. Until then, the authors' “mosaic” approach to understanding gene function promises to improve efforts to annotate the volumes of sequenced genomes on hand, offering biologists a much-needed tool to sift through the mountains of genomic datasets and identify promising targets for further study.