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Developmental Psychiatry Section, University of Cambridge, Cambridge, UK
Correspondence: V. Dunn, Developmental Psychiatry Section, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge CB2 2AH, UK.Tel: +44 (0)1223 746053; e-mail: vjd20{at}cam.ac.uk
Declaration of interest None. Funding detailed in Acknowledgements.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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Aims To investigate long-term psychiatric outcome of school-age depression in community and clinic samples.
Method A group of 113 young adults were followed up after a mean of 7.8 years (s.e.=15).
Results Groups with persistent and recurrent depression were identified. Recurrence of affective disorder was similar in clinic and community groups. The clinic group had significantly longer index episodes; these were predicted by an early psychiatric history, longer episode duration before treatment and greater impairment. Being female, having higher self-report depression scores and comorbidity at index episode predicted earlier recurrence. Males were more likely to have persistentdepression.
Conclusions Prognosis is similar in young people with depression from community and clinical samples. Boys from a clinical sample are at higher risk than girls of becoming persistently and severely mentally ill.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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METHOD |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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Clinic and control groups
The clinic group comprised patients aged 8–16 years attending two
child and adolescent mental health clinics in the Cambridge area: 92 were
recruited in 1991–2 and 28 in 1995–6. The 38 well controls (no
psychiatric disorder), from the same geographical area, were recruited through
general practitioners in 1991–2 and were matched for age and gender to
every third patient with depression. Participants were interviewed at study
entry and 36 weeks later. For this study, information from these assessments,
together with details from clinical notes, was pooled to designate the
‘index’ episode.
Community group
The 35 community participants, aged 12–17 years, were recruited from
Cambridge-shire schools to participate in a large community depression study
in 1994–5. All were illness-free at entry. After 1 year a proportion of
these young people were either depressed or had been depressed in the interim:
these provided the sample for follow-up.
Measures
Psychopathology
Baseline assessment. Original diagnoses were assigned according to
DSM–III–R (American Psychiatric
Association, 1987), using the Schedule for Affective Disorders and
Schizophrenia for School-Age Children (K–SADS) Present state
(Chambers et al, 1985;
Kolvin et al, 1991)
for clinic patients and the K–SADS Present and Lifetime version
(Kaufman et al, 1997)
for those from the community.
Follow-up assessment. Current and lifetime diagnoses were generated using the Structured Clinical Interview for DSM–IV Axis I Disorders (SCID–I; American Psychiatric Association, 1994), Patient Edition (First et al, 1997). We screened for antisocial and borderline personality disorders using an adapted screen from the Structured Clinical Interview for DSM–IV Axis II Disorders (SCID–II; Spitzer et al, 1990). Positive responses were followed up using the relevant section of the SCID–II interview.
Note ondiagnosis. At baseline, a proportion of people in the clinic group had experienced an episode of major depressive disorder within an episode of dysthymia (double depression). It was impossible to distinguish accurately the onset and offset of major depression within the dysthymic episode. Therefore, index episodes of depression are rated from onset to offset of significant depressive symptoms, with no attempt to delineate full major depressive disorder from dysthymia.
Self-reports
Baseline assessment. All participants completed the Mood and
Feelings Questionnaire (MFQ; Costello &
Angold, 1988; Wood et
al, 1995). This 33-item questionnaire covers the symptom
areas specified in DSM–IV for major depressive disorder.
Test–retest reliability (4 weeks) is highly satisfactory
(r=0.85).
Follow-up assessment. Current level of depressed mood in adulthood was assessed using the Beck Depression Inventory (BDI; Beck et al, 1961).
Puberty
Baseline assessment. Participants in the clinic group were shown
gender-appropriate sketches relating to the five standard Tanner stages of
pubertal development (Tanner,
1962) and asked to select which looked ‘most like
them’. Participants were grouped as pre-/early puberty (Tanner stages I
and II) or mid/late puberty (Tanner stages III–V). The stage of puberty
was not assessed in the community group.
Timeline
Follow-up assessment. The use of a timeline proved invaluable in
orienting participants to the lengthy follow-up period. A timeline was drawn
from the date of the last interview to the current interview. Interviewee and
interviewer chronologically mapped significant life events on the timeline,
for example school leaving, examinations, relationships, losses, followed by
episodes of illness, good health, treatment and medication.
Data collection
Tracing procedure
Recorded deaths since baseline were checked using the
‘list-cleaning’ service provided by the Office for National
Statistics. Participants were contacted by letter through their family of
origin or through their general practitioner by way of their strategic health
authority.
Follow-up interview
Participants were interviewed as soon after their 22nd birthday as
possible. The eldest were approached first, from July 2000. Follow-up
interviewing lasted for 31 months. Follow-up time was calculated from the date
of each participant’s last baseline interview (in adolescence) to the
date of their follow-up interview (as young adults). Interviews were conducted
by four trained research staff, masked to baseline diagnoses and ascertainment
group. Diagnoses were reached by consensus with a clinician (I.G.).
Reliability was acceptable (
> 0.8). Participants gave written
consent to both the interview and access to clinical notes. Participants were
seen either at home or at the Developmental Psychiatry Section in Cambridge. A
small remuneration was offered. The study received the full approval of the
local and regional ethics committees.
Statistical procedures
Analysis was carried out using the Statistical Package for the Social
Sciences, version 10.0 for Windows. Mann–Whitney U-tests were
used on non-parametric data and t-tests on parametric data. Time to
full remission (defined as a minimum of 2 months free of depressive symptoms
and functional impairment) of the index episode of depression and time from
full remission to first depressive recurrence (defined as a new depressive
episode following a period of full remission) were examined using
Kaplan–Meier survival analysis. (This method takes into account the
assessment periods of people for whom the event of interest has not occurred
by the end-point of the study, defining them as ‘censored’. Here,
these are participants whose index episode of depression had not fully
remitted and those who had not experienced a depressive recurrence by the time
of their follow-up interview.) As those interviewed were unable to reliably
pinpoint onsets and offsets accurately, times were recorded and entered to the
nearest 0.25 of a year. Survival curves were compared using the log-rank test.
In the clinic group, Cox regression was used to examine baseline factors
thought to influence time to full remission and time to first depressive
recurrence.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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2=8.47, d.f.=2, P=0.014). Participants
and nonparticipants were compared on a number of baseline variables.
Significant differences were found only within the clinic group:
non-participants were significantly younger at the onset of their index
episode of depression (mean 12.1 years v. 13.5 years,
z=72.72, P=0.006), more likely to have been pre-pubertal or
in the early stages of puberty (v. mid to late puberty) (28 (61%)
v. 26 (35%), 2=7.59, d.f.=1, P=0.006), have
less psychiatric illness among first-degree relatives (27 (56%) v. 23
(36%), 2=4.58, d.f.=1, P=0.032) and have parents who
had completed their education by age 16 years: mothers 37 (64%) v. 15
(27%), 2=15.16, d.f.=1, P<0.001; fathers 29 (63%)
v. 22 (36%), 2=7.65, d.f.=1, P=0.006.
Success of tracing, sample response and exclusions
Table 1 compares
participation according to ascertainment group. Of the original 193
participants, 191 were traced (99%). Of these, 121 (63%) were interviewed, 29
(15%) refused, 38 (20%) did not respond and 3 (2%) were out of the UK. Of the
121 interviewed, 8 were subsequently excluded: 1 for medical reasons and 7
because their index episodes were nonaffective.
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Final sample
Data reported here are based on 113 participants: 58 clinic and 25
community participants all with depression (major depression, minor depression
or dysthymia) in childhood or adolescence, and 30 depression-free controls.
Mean follow-up times differed significantly between groups: 8.1 years
(s.d.=1.3), 5.8 years (s.d.=0.6) and 9.2 years (s.d.=0.81) for clinic,
community and control groups respectively (Kruskal–Wallis
2=59.86, d.f.=2, P<0.001). Univariate comparisons
(Mann–Whitney) showed differences were significant between all three
groups (clinic v. controls z=3.78, P<0.001;
clinic v. community z=6.43, P<0.001; community
v. controls z=76.34, P<0.001).
Mean age at follow-up interview was 23 years (s.d.=1.66), 22 years (s.d.=0.79) and 23.5 years (s.d.=1.6) for the clinic, community and control groups respectively (clinic v. community t=2.88, P=0.005; community v. controls t=4.07, P<0.001).
Baseline characteristics
Table 2 gives the
characteristics of the sample at baseline. Compared with the community group,
participants in the clinic group were more severely impaired, had higher rates
of attempted suicide and self-harm, more psychotic symptoms, were
significantly younger at onset of depression, received more treatment and
medication and had significantly more psychiatric illness among first-degree
relatives. Self-report depression scores were no different between the clinic
and the community groups; both were significantly higher than controls.
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Subsequent disorder
Figure 1 compares subsequent
psychiatric illness in the ascertainment groups. By the time of their
follow-up interview 24 of 30 controls (80%) had remained illness-free compared
with 16 of 58 clinic patients (28%) (Fisher’s exact test
P=0.001) and 10 of 25 young people from the community (40%)
(Fisher’s exact test P=0.005). As the focus of this report is
depression we do not report on those who had exclusively non-affective
illness.
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In the clinic group with subsequent affective disorder (33, consisting of 10 men and 23 women), men were more likely than women to be persistently depressed: 7 (70%) v. 6 (26%); whereas women were more likely to have recurrent episodes, 17 (74%) v. 3 (30%): (Fisher’s exact test P=0.026).
No completed suicide was recorded during the follow-up period. There was a trend for more suicidal ideation and attempts in the intervening years among the clinic group (19 of 58; 33%) compared with the community group (3 of 25; 12%); Fisher’s exact test P=0.06. In the control group, one person experienced suicidal ideation but there was no suicide attempt.
Index depression
The index episode of depression fully remitted in 45 clinic patients (78%)
and 23 from the community (92%). Kaplan–Meier survival analysis was
carried out to examine predictors of time to full remission. The 13 clinic
patients (22%) and the 2 from the community (8%) in whom the index episode did
not remit are censored in the analysis. (‘Full remission’ refers
to depression; comorbid symptoms might have persisted.)
Figure 2 compares the
cumulative survival times to full remission. The median time to full remission
in clinic patients was 2 years (95% CI 0.83–3.17) v. 3 months
in the community. By 3 months after onset, remission had occurred in 3 clinic
patients (5%) compared with 17 (68%) in the community. By the end of the first
year numbers in remission were 16 (28%) and 22 (88%) and by 2 years 29 (50%)
and 23 (92%) for clinic and community groups respectively. Remission rates
were clearly different (log-rank test 2=25.1, d.f.=1,
P<0.001) and so further analysis was made of the two groups
separately.
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Owing to small numbers, missing data and skewed distribution, Cox regression analysis of the community sample was not possible.
First recurrence of depression
Clinic group
Survival analysis explored time from full remission to first recurrence of
depression, necessarily including only those whose index episode of depression
had remitted (n=45). Of these, 20 (44%) experienced at least one
recurrence of depression. The 25 (56%) whose depression did not recur are
censored in the analysis. Figure
3 shows the cumulative recurrence rate. The median time to first
recurrence was 9.25 years (95% CI 8.64–9.86). By 1 year after remission
only 1 (2%) had experienced recurrence, after 2 years 5 (11%), after 3 years 8
(18%), 4 years 9 (20%), 5 years 13 (29%) and 6 years 15 (34%). In 3 instances
the person was well for 9 years before the depression recurred. Recurrence
peaked at 9% in years 1–2 and 4–5.
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Community group
Small numbers made survival analysis impossible. Calculated in the standard
way, mean time to first recurrence (n=12) was 3.4 years (s.d.=1.5).
The mean duration of first recurrence was 44 weeks (s.d.=53.3) with a mean age
at onset of 19.5 years (s.d.=2).
Controls
The mean age at onset of new episodes was 19 years, and the mean duration
was 41 weeks (s.d.=42.2).
Group with persistent depression
The mean duration of depression, from onset in adolescence through to
follow-up in young adult life, was 9.6 years (s.d.=2, range 7–13.8). The
original diagnoses of the 15 people with non-remitted depression were 3 (20%)
pure depression, 7 (47%) depression/anxiety, 5 (33%) multiple comorbidity.
Most had complex diagnostic profiles with persistent depression remaining a
core feature. One individual was subsequently diagnosed as having
schizophrenia; one had bipolar affective disorder (also substance dependency);
three people experienced other psychotic episodes (two also
substance-dependent); three became dysthymic (one also substance-dependent);
three had persistent anxiety symptoms (one also substance-dependent); and four
had ‘pure’ persistent depression. Five participants (33%) had
repeated in-patient stays during the follow-up period. Non-adherence to
treatment (defined as a pattern of missed appointments, withdrawal from
treatment, discharging self from hospital and refusing prescribed medication)
was significantly higher in this group than among those with recurrent
depression: 8 of 15 (53%) compared with 6 of 31 (19%; Fisher’s exact
test P=0.04).
There were significantly more suicide attempts and suicidal ideation among the group with persistent depression than among the recurrent depression group: 13 of 15 (87%) v. 6 of 32 (19%; Fisher’s exact test P=0.001).
Substance and alcohol use
During follow-up
Recreational use or no use of substances and alcohol was reported by 36
(63%), 19 (76%) and 23 (77%) of the clinic, community and control groups
respectively. However, many of these reported regular, high levels of
recreational use. Commonly, cannabis, amphetamines and/or alcohol were used
2–3 times per week, with use increasing over time. However, little or no
functional impairment was reported. Dependence was coded according to
DSM–IV criteria. At least one episode of prolonged, daily (or near-daily
for more than 6 months) substance or alcohol misuse was reported by 15 people
in the clinic group (26%), 4 in the community group (16%) and 7 in the control
group (23%) (NS). Prolonged polysubstance/alcohol misuse or dependence was
absent in the control group but was reported by 6 (11%) of the clinic sample
and 2 (8%) of the community sample (missing data on 1 clinic patient;
n=57).
Current use
At follow-up, dependency rates in the clinic and community groups were 5
(9%) and 1 (4%) respectively: in the clinic group 2 persons were dependent on
heroin, 2 on prescribed medication (with substantial overuse) and 1 on
alcohol; the person from the community group was alcohol-dependent. All were
depressed. There was no dependence among the controls. A further 3 clinic
(5%), 1 community (4%) and 2 control (7%) participants reported current, daily
cannabis use or alcohol use for at least 6 months, but only one of the clinic
group met impairment criteria.
Current psychiatric status
Clinic group
At follow-up, 22 (38%) from the clinic group had a current diagnosis: 17
affective disorder (11 major depressive disorder, 4 dysthymia, 2 bipolar
disorder); 1 schizophrenia (also with depression); 1 attention-deficit
hyperactivity disorder; 3 probable personality disorders disorders (1
antisocial and 2 borderline; both with depression and 1 alcohol-dependent). In
17 instances (29%) the participant was receiving treatment (9 out-patient
care, 1 counselling, 6 general practitioner care, 1 other) and 15 participants
(26%) were taking psychotropic medication. The mean BDI score was 11
(s.d.=0.3, range 0–37).
Community group
Eight participants (32%) had a current diagnosis at follow-up interview: 6
affective disorder (4 major depressive disorder, 1 dysthymia, 1 bipolar
disorder) and 2 anxiety disorder. In 3 instances (12%) the participant was
currently receiving treatment (1 out-patient care, 2 general practitioner
care) and were taking psychotropic medication. The mean BDI score was 8
(s.d.=5.6, range 0–19). Community participants were as likely as clinic
patients to have a current diagnosis.
Controls
Three people in the control group (10%) were diagnosed with an affective
disorder at follow-up interview: 1 bipolar disorder, 1 depression and 1 minor
depression with comorbid eating disorder symptoms (eating disorder not
otherwise specified). Both those with bipolar and major depression were
receiving psychiatric treatment and psychotropic medication. The mean BDI
score was 5 (s.d.=5.1, range 0–25).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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Persistent depression
To our knowledge, previous studies have not identified a group whose
adolescent depression continued, unabated, into young adulthood. This may be
for methodological reasons. For example, Weissman et al
(1999a,
b) left an arbitrary
gap of 12 months between baseline and follow-up in an attempt not to confuse
index and subsequent episodes. Similarly, others, whose primary focus was
adult recurrence, recorded baseline data at around 13 years and follow-up data
from 17 years (Harrington et al,
1990; Fombonne et al,
2001). This strategy runs the risk of misclassification, with
persistent depression being incorrectly classified as recurrent. Our study
overcame this by collecting data continuously from baseline throughout the
follow-up period. The result is the identification of a small group (more
males than females) with unremitting mental illness. These patients are
characterised by more severe impairment than those described in previous
studies, in which partial remissions occurred with ongoing residual symptoms
(reviewed by Birmaher et al,
2002).
For most of those with persistent depression (80%), the index episode of depression was accompanied by at least one comorbid disorder. Complex diagnostic profiles evolved, including high rates of psychotic illness (30%), dependence (30%) and suicidal thoughts or attempts (87%). In over half (53%), the patient regularly did not adhere to treatment. The Cox regression suggested that, as adolescents, these individuals had been depressed for long periods before starting treatment and had been severely impaired. Within the clinic group, first-onset depression may exert a more deleterious effect on males compared with females, but neither age nor pubertal status at first episode contributed to the outcome. These patients might benefit from early, long-term and more intensive clinical intervention than is currently given.
Remission and recurrence in the community group
The adolescents ascertained from the community on the whole achieved
remission from their first depressive episode: 68% by 3 months and 92% by 3
years. This may be explained by less severe index episodes characterised by
the absence of suicide attempts and psychotic features, a near-absence of
self-harm and only moderate impairment. Despite this, almost half (48%)
experienced recurrence of their depression, which is consistent with the 45%
recurrence rate reported by Lewinsohn et al
(1999). First recurrences were
similar in length to those experienced in the clinic group. The small size of
this community group means that the results should be treated with caution.
They suggest that the probability of recurrence is high despite the moderate
nature of the original depressive episode. A small proportion of individuals
from the community may suffer persistent depression, with no remission, into
young adulthood. Young people in the community with depression, therefore,
might benefit from early detection and robust intervention.
Remission and recurrence in the clinic group
Remission of the index episode of depression was slower among clinic
patients: only 5% had achieved remission by 3 months, less than a third by 12
months and only half by 3 years. Median time to full remission was 2 years,
with 13 (22%) having no remission by follow-up. This contrasts with previous
studies which have reported rates of 92% remission by 18 months
(Kovacs et al,
1984)–our 18-month figure was 38% – and 80% after 12
months (McCauley et al,
1993). This may be a result, in part, of our not differentiating
between dysthymia and major depressive disorder at the index assessment.
Kovacs et al (1984)
reported a pattern in dysthymia that more closely resembles that reported
here: a median duration of around 3 years, low annual remission rates and a
maximal remission of 89% after 6 years.
Longer index episodes were associated with more severe impairment, being depressed for longer before starting treatment and having an early psychiatric episode. In those with higher self-report depression (MFQ) scores and comorbidity at index assessment the depression tended to recur sooner, and recurrence was earlier in females than in males. There was no effect of puberty or age. Confidence intervals were wide in our Cox regression, indicating a less-than-perfect fit which could be a result of the wide distribution of times to first recurrence (6 months to 9.75 years) and the small number of males (n=3) who experienced recurrence compared with females (n=17).
Females with depression were more likely to have a recurrent pattern of depressive disorder, whereas more males developed persistent mental illness. The non-participants in the follow-up constituted 45% of the original clinic group, were younger and had less psychiatric illness among first-degree relatives. Thus, the above findings should be treated cautiously.
Substance and alcohol use
The 9% dependency rate in the clinic group (all participants currently
depressed and 3 with psychotic illness) was lower than the 29% reported by
Fombonne et al
(2001). This may be owing to
our comparatively young follow-up age (mean 23 years), compared with a mean of
35 years in the Fombonne study. The high thresholds we set for diagnosis might
have resulted in an underestimate.
Deaths during follow-up
Although 46% of those from the clinic group had either self-harmed or
attempted suicide at the time of the index episode, there was no recorded
suicide during the follow-up period. This is somewhat surprising as the
strongest predictor of suicide is previous self-harm
(Safinofsky, 2000;
Hawton et al, 2003).
Other studies have reported moderate suicide rates. For example, Weissman
et al
(1999a) reported a
7.7% suicide rate; Harrington et al
(1990) reported 4 deaths (3%),
3 of which were suicide; and Fombonne et al
(2001) reported 8 deaths (3%),
6 of which were suicide. Our absence of suicides may be explained by our
cohort being relatively young at follow-up: mean age 23 years, compared with
means of 26 years, 31 years and 35 years respectively in the other
studies.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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Received for publication July 27, 2004. Revision received February 2, 2005. Accepted for publication March 23, 2005.
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, n=58, 45
remitted (78%), 13 (22%) censored/unremitted at 7–13.7 years) and the
community group (-------, n=25, 23 remitted (92%), 2 (8%)
censored/unremitted, both at 6 years).