Seminar

Depression in young people

Anita Thapar, Olga Eyre, Vikram Patel, David Brent

Depression rates in young people have risen sharply in the past decade, especially in females, which is of concern Published Online
because adolescence is a period of rapid social, emotional, and cognitive development and key life transitions. Adverse August 5, 2022
https://doi.org/10.1016/
outcomes associated with depression in young people include depression recurrence; the onset of other psychiatric S0140-6736(22)01012-1
disorders; and wider, protracted impairments in interpersonal, social, educational, and occupational functioning.
Wolfson Centre for Young
Thus, prevention and early intervention for depression in young people are priorities. Preventive and early intervention People’s Mental Health and
strategies typically target predisposing factors, antecedents, and symptoms of depression. Young people who have a Child and Adolescent
family history of depression, exposure to social stressors (eg, bullying, discordant relationships, or stressful life Psychiatry Section, Division of
Psychological Medicine and
events), and belong to certain subgroups (eg, having a chronic physical health problem or being a sexual minority) are Clinical Neurosciences,
at especially high risk of depression. Clinical antecedents include depressive symptoms, anxiety, and irritability. School of Medicine,
Evidence favours indicated prevention and targeted prevention to universal prevention. Emerging school-based and Cardiff University, Cardiff, UK
community-based social interventions show some promise. Depression is highly heterogeneous; therefore, a stepwise (Prof A Thapar MBBCh,
O Eyre MBChB); Department of
treatment approach is recommended, starting with brief psychosocial interventions, then a specific psychological Global Health and Social
therapy, and then an antidepressant medication. Medicine, Harvard Medical
School, Boston, MA, USA
Introduction fifth edition of the Diagnostic and Statistical Manual of (Prof V Patel MD);
Department of Psychiatry,
Depression is a leading contributor to the global burden Mental Disorders (DSM-5),6 and as mood disorders in the University of Pittsburgh,
of disease and is associated with personal, societal, and 11th revision of the International Classification of Diseases Pittsburgh, PA, USA
economic burden.1 Depression in young people is an (ICD-11).7 Most of this Seminar will focus on major (Prof D Brent MD)
increasing concern not only because it occurs during a depressive disorder, although in some instances, when Correspondence to:
period of rapid social, emotional, and cognitive relevant (eg, for public health and for low-income and Prof Anita Thapar, Wolfson
Centre for Young People’s Mental
development, and key life transitions,2 but because its middle-income countries [LMICs]), we include research Health and Child and Adolescent
prevalence in young people (ie, ages 10–24 years) has with broader definitions of depressive disorder and Psychiatry Section, Division of
risen sharply in the past decade, especially in females.3 depressive symptoms. Although more than 80% of the Psychological Medicine and
Depression describes a variety of mood related concepts world’s young people live in LMICs, most of the research Clinical Neurosciences, School of
Medicine, Cardiff University,
and a spectrum of difficulties (figure 1). At one end of the we identified was done in high-income countries; thus, we Cardiff CF24 4HQ, UK
spectrum, depression can refer to a mood state in the have identified studies from LMICs to supplement this thapar@cf.ac.uk
context of normative mood fluctuations. The presence of evidence, especially regarding interventions.
depressive symptoms that do not meet full diagnostic Our primary focus is on adolescence (10–19-year-olds).
criteria for major depressive disorder is known as However, we also consider childhood (ie, younger than
subthreshold depression,4 which has negative effects on 10 years) because of its relevance to later adolescence and
quality of life and is a risk indicator of a later depressive transitions to young adult life (ie, up to age 25 years)
disorder. Depressive or mood disorders are at the other because of growing calls to define adolescence more
extreme of the spectrum. A diagnosis of major depressive broadly between 10 years and 24 years of age.2
disorder is characterised by depressed mood that is
present nearly every day for most of the day, for at least Epidemiology
2 weeks, or loss of interest or enjoyment in all, or The prevalence of major depressive disorder is low
almost all activities (known as anhedonia) and a range of in children (reported to be 0·6–1·1%),8,9 but increases
other symptoms (figure 2), including irritability in
children and adolescents younger than 18 years. These
depression symptoms need to interfere with daily life Search strategy and selection criteria
functioning and represent a change from how the person We searched MEDLINE via Ovid using the search term
functioned before symptom onset. However, even using “depression” combined with “child”, “adolescent”,
these diagnostic criteria, major depressive disorder is or “teenager”. We combined these terms with search terms
highly heterogeneous. There is variability in the different covering epidemiology, cause, pathophysiology, assessment,
depressive symptom combinations; clinical severity diagnosis, treatment, outcomes, prevention, and
(captured by the descriptors mild, moderate, or severe intervention. We restricted the search to papers in English
depression); age at first onset; comorbidities; and published between Jan 1, 2011, and Aug 13, 2021, and
outcomes. Depression can spontaneously remit, recur, or primary research papers in English published between
persist (known as persistent depressive disorder), but also Jan 1, 2018, and Aug 13, 2021. We focused on meta-analyses
signal the onset of later bipolar disorder or schizophrenia. and systematic reviews when available and included primary
Along with other diagnoses associated with depression, research papers for relevant recent findings. A full list of
major depressive disorder and persistent depressive search terms used can be found in the appendix (p 1). See Online for appendix
disorder are classified as depressive disorders in the

www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1 1

 Seminar
Low mood Subthreshold depression Depressive disorder
Low mood and additional depressive Persistent low mood and Persistent, recurrent,
symptoms (eg, loss of interest, enjoyment additional depressive or psychotic depression
but not reaching diagnostic threshold) symptoms
Coping Distress and concern Interference with daily Severe or chronic
life impairment
Risks including self-harm, suicide, and self-neglect
Figure 1: The spectrum of depression
Core clinical symptoms of major depressive disorder
• Depressed mood or, for children and adolescents, irritable mood
• Diminished interest or pleasure
• Significant increase or reduction in weight or appetite*
• Insomnia or hypersomnia*
• Psychomotor agitation or retardation
• Loss of energy or fatigue*
• Feelings of excessive or inappropriate guilt or worthlessness
• Loss of concentration, reduced ability to think, or indecisiveness
• Recurrent thoughts of death, suicidal ideas, or suicide attempt
Figure 2: Core clinical symptoms of major depressive disorder5
*Symptoms that were found to be more common in adolescents than adults
with depression in a two generation study.
sharply in adolescents and young adults, especially in
females.10,11 The rise in incidence might be due to
increased social demands and stressors, hormonal
changes, and brain development.12 Exact prevalence rates
of depression vary depending on the age sampled and
how broadly depression has been defined.
A 2015 meta-analysis of 41 population-based studies
of children and adolescents done across 27 countries
from every world region,13 suggests a worldwide 1-year
prevalence rate of 1·3% (95% CI 0·7–2·3) for major
depressive disorder. However, significant heterogeneity
was observed due to sample representativeness,
sampling frame, and the diagnostic instrument used. A
systematic review and meta-analysis of children and
adolescents, published in 2022, gave a similar
prevalence of 1·3% (95% CI 0·6–2·9) in high-income
countries.14 Although the 1-year prevalence rates of
major depressive disorder are quite low, these studies
cover a wide age range and depression typically first
arises during adolescence and early adulthood. For
example, a 2017 mental health survey in England
showed that the prevalence of an emotional disorder
(including anxiety disorders, mania or bipolar affective
disorder, and depressive disorders) was 9% in
11–16-year-olds and 14·9% in 17–19-year-olds.9 In the
older age group, a quarter of women (22·4%) had an
emotional disorder. For narrowly defined major
depressive disorder, this survey observed an overall
prevalence of 2·1% in 5–19-year-olds; in the oldest age
group (17–19-year-olds), the prevalence of major
depressive disorder was 4·8%.
2 www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1
A current concern is that the prevalence of major
depressive disorder, broadly defined depression, and
emotional disorders, including anxiety and depression,
has risen sharply in young people over the past decade
(figure 3), especially in females. The 1·5 to 2·0-times rise
in prevalence of these difficulties was observed before
the COVID-19 pandemic; the prevalence of depression
appears to have risen subsequently.16
The annual cross-sectional US National Survey on Drug
Use and Health that was published in 2019 reported that
the 1-year prevalence of broadly defined depression
increased from 8·3% to 12·9% in 12–17-year-olds
between 2011 and 2016 (figure 3).11 This trend was
paralleled by increased use of adolescent mental health
services between 2005 and 2018, with the greatest increase
in demand on specialist mental health services being for
emotional problems (anxiety, depressive symptoms, and
suicidal behaviour).17 England’s Mental Health of Children
and Young People Survey showed a similar increased rate
of probable emotional disorders from 3·9% in 2004
to 5·8% in 5–15-year-olds in 2017 (figure 3). With the use
of broader indicators of mental health in young adults,
the UK Office of National Statistics found that 31% of
women aged 16–24 years reported some evidence of
depression or anxiety, showing an increase from the
previous year (26%) and 5 years earlier (26%).18
These surveys all suggest that depression, no matter
how it is defined, is becoming more common in later
adolescence and early adulthood than in previous years,
especially in females. Prevalence of depression is
particularly high in people who have special educational
needs or a chronic health problem, and in
people who come from socioeconomically disadvantaged
households.9
Depression is approximately twice as common in
females than in males;19 this gender gap is observed
across the life span, but it first arises after puberty,19 and
it appears to be mediated by increases in oestradiol and,
in some studies, testosterone.20 A meta-regression of
studies published between 1980 and 2019 showed that,
despite substantial societal changes, while the gender
gap across a person’s lifespan in the USA has stayed the
same, the gender gap has increased for depression
(disorder and symptoms) in 10–19-year-olds.19 Social
changes, such as increased loneliness, academic strain,
widening socioeconomic inequality, or an increased
willingness to disclose mental health difficulties, might
account for the rise in the number of people with
depression3 and increased gender gap, but the factors
that affect the gender gap remain unknown.
Outcomes
Depression in adolescence and early adulthood is
associated with recurrence in later life. Approximately
50% of adolescents will have another episode of
depression,21,22 with a nearly 3-times higher risk of
depression in adulthood compared with those who did

not have depression in adolescence.23,24 Factors increasing
the risk of recurrence include female sex, multiple
depressive episodes in adolescence, poor parental
mental health, family history of depression recurrence,
chronic interpersonal stress, poor relationships with
peers, and comorbid anxiety disorder.25–27
Adolescents with depression have an elevated risk of
other psychopathology, including later anxiety
disorders22,28 and increased rates of conversion from
depression to bipolar affective disorder.29 Symptoms of
depression have been found to be associated with eating
disorders30 and functional somatic symptoms.31 High-
risk behaviours associated with depression in young
people include an increase in suicide attempts,23 alcohol,
nicotine, and drug use,32 and high-risk sexual behaviours
(eg, non-use of contraception or a high number of
sexual partners).33,34 Physical health outcomes associated
with depression in young people include increased risk
of cardiovascular disease and obesity.35,36 In addition
to adverse mental and physical health outcomes,
depression in young people has widespread negative
effects on psychosocial functioning, including lower
educational attainment and higher welfare dependence
and unemployment in adulthood than young people
without depression.24,37,38 Some evidence suggests that
depression in young people affects future interpersonal
difficulties, including marital functioning,39 increased
loneliness,40 and an increased need for social support.41
Conversely, preventing the onset or recurrence of
depression, at least in adolescence, predicts better adult
functioning.42 To date, longitudinal research has focused
on outcomes into early adulthood (up to age 35 years),
with little information for the years after. However,
persistent depressive disorder in adolescence has been
shown to predict use of health-care resources up to the
age of 40 years; this suggests that the effect of adolescent
depression continues after early adulthood.43
Although depression in young people is associated
with a broad range of adverse outcomes, long-term
outcomes vary between individuals.44 Outcomes might
differ depending on the number and severity of
depressive episodes.44 Studies on the trajectories of
depression across adolescence and early adulthood
have found that people with more persistent depression
over time have particularly poor adult outcomes in
terms of mental health difficulties, self-harm, substance
use, and physical health, and have an increased
probability of not being in education, employment, or
training at age 25 years.45–47 Having comorbid disorders
also affects later outcomes. For example, comorbid
neurodevelopmental disorders (such as attention-
deficit hyperactivity disorder [ADHD] and autism
spectrum disorder) are associated with an earlier
onset and more persistent course of depression.48
Comorbid conduct disorder increases the risk for
later drug use, alcoholism, and antisocial personality
disorder,49 and comorbid alcohol and substance use
www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1 3
Seminar
A B
100 100
7 14
6 12
5 10
Frequency (%)
4 8
3 6
2 4
1 2
0 0
2004 2017 2011 2016
Year Year
Figure 3: Rate of emotional disorders and depression over time in two
countries9,11,15
(A) Emotional disorders in England in 5–15-year-olds. (B) Broadly defined
depression in the USA in 12–17-year-olds.
increases the future risk of suicidality and suicide.50
Other factors are associated with improved outcomes;
for example, positive attributional style and good
parent–child relationships are associated with better
outcomes.22
Treatment trials often use the absence of diagnosis or
reduction in depressive symptoms as evidence of good
outcomes, typically relying on clinician reports.51
However, service users have described a need to
measure outcomes beyond symptoms, including
interpersonal relationships and the ability to cope with
problems, factors which are considered infrequently in
existing studies.51 Measuring what matters most to
young people and their families and what leads to
optimal interpersonal, educational, and occupational
outcomes, are important considerations for deciding
which interventions provide the most benefit for
patients, families, and society.
Risk factors and antecedents
Depression is explained by multiple different risk
factors that have probabilistic risk effects; no single risk
factor is necessary or sufficient to explain the causes of
depression. Recognising common risk factors and
clinical antecedents of depression can be helpful in
guiding prevention and surveillance efforts (figure 4).
Individual-level risk factors
Pooled twin studies suggest that approximately 40% of
the variance in depression is explained by genetic
factors, with an increased genetic risk, for more severe,
recurrent, and early-onset depression.52,53 Of note,
genetic liability for depression is correlated with
exposure to social stressors. This gene–environment
correlation means that people with a higher genetic
loading are also more likely to be exposed to stressors,
thereby creating a double risk effect.54
 Seminar
Genetic studies of adult depression have identified
more than a hundred common genetic risk variants,
each of small effect size.55 Rare, large effect size copy
number variants (chromosomal deletions and
duplications) also contribute risk.56 The genetic risk
variants for depression are highly pleiotropic and also
are associated with a number of disorders, including
schizophrenia, bipolar disorder, ADHD, and autism
spectrum disorder.57 A composite of common genetic
risk variants (polygenic risk scores) predicts depression
in adolescents58 and adults, although prediction is too
weak to have clinical use. Depression polygenic risk
scores are also associated with exposure to mal­
treatment and bullying,59,60 showing gene–environment
correlation, although gene–environment interactions
did not withstand meta-analyses or replications.61
Other individual risk factors include temperament (eg,
negative and positive emotionality),62 personality (eg,
neuroticism)63 and particular styles of thinking and
behaving (eg, cognitive rumination).64 More proximal
cognitive behavioural mechanisms have long been
considered important mediators of risk and are the target
of many psychological interventions for depression.
Depression typically onsets from adolescence onwards.
However, for many people, the first episode is preceded
by clinical antecedents, including extended periods of
subthreshold depressive symptoms or different mental
or neurodevelopmental disorders. Anxiety in childhood
and early adolescence is the most common antecedent.65
Another consistent finding is that childhood irritability
also predicts future depression in adolescence.66 In
DSM-5, disruptive mood dysregulation disorder—
defined by early onset and severe irritability characterised
by recurrent temper outbursts—is grouped with
depressive disorders, but in ICD-11 irritability remains a
feature of oppositional defiant disorder, which is a
behavioural problem. Another group at elevated risk for
Chronic physical illness
Childhood anxiety
Neurodevelopmental disorder
Irritability
Early adversity
Exposure to parent depression
or mental disorder
Depression in adolescence
and young adulthood
Multiple psychosocial stressors
Severe acute stressors
Chronic social adversity
Substance use and lifestyle factors
Genetic liability
Maturation
Figure 4: Causes and development
4 www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1
adolescent depression are people with a neurodevelop­
mental disorder,67,68 specifically ADHD and autism
spectrum disorder. It is not clear whether these
antecedents represent a prodrome to illness, have causal
risk effects on later depression, or whether they simply
reflect overlapping causes. If causal, early treatment of
antecedents where possible should reduce risks for
adolescent depression. Some evidence suggests that
effective treatment of anxiety69 and ADHD70 could reduce
risks for depression, but no definitive evidence yet shows
that treatment of other antecedents prevents later
depression.71
Another important risk group is people with a history
of chronic physical illness, particularly illnesses that
affect the CNS (eg, migraine or epilepsy).72 Because
undetected depression can lead to non-adherence to
treatment, risky behaviours (eg, drug or alcohol use),
and decreased engagement with health services, the
possibility of depression in people with a physical
health condition needs to be considered by professionals
working in both primary and secondary care.
Some evidence suggests small effect size associations
between sleep disruption and adolescent depression,73
with similar findings for obesity and depression. However,
the relationships between both sleep and obesity with
depression could be bidirectional and explained by
confounders.74 Links between sedentary behaviour and
adolescent depression have also been found. This
behaviour is closely related to body-mass index and screen
time; prospective studies suggest that sedentary behaviour
is a risk factor and exercise is protective.75
Family-level, school-level, and peer-level risk factors
One particularly common risk factor is having a parent
with depression. Approximately 40% of people with an
affected parent develop depression,76 with risks being
highest for children of parents who have a history of
multigenerational, recurrent, severe, and early-onset
depression. Intergenerational transmission appears to
be explained by both inherited and social mechanisms,
including offspring exposure to current parent
depression.77–79 Some adolescents are resilient to the
effect of parental depression, protected by high-quality
relationships with the other parent and friends,
connection to school, and participation in sports and
exercise.80 Social stressors associated with subsequent
adolescent depression include exposure to mal­
treatment,81 early life trauma, and adversities, such as
disrupted caregiving,82 bullying,83 social isolation,84
discordant relationships, and stressful life events (eg,
death of a loved one or loss of a romantic relationship).82
Current evidence, which is far from definitive, suggests
that although there are some benefits of digital
technology (eg, increased self-esteem and perceived
social support),85 it comes with some risks, such as
cyberbullying, interference with sleep, unfavourable
social comparison, and addiction.86

Group-level and population-level risk factors
The most widely studied community-level stressors
associated with an increased prevalence of depression
across age groups include:87 living in poverty or violent
neighbourhoods; homelessness; being a refugee or
displaced; exposure to war or terrorism; and the near
universal exposure to the COVID-19 pandemic, which
has had a disproportionate effect on young people.88
These stressors and traumas disproportionately affect
some racial groups or minority ethnic groups, thereby
increasing the risk for depression. However, illustrating
the wide variability in the effect of ethnicity and culture
on depression, UK studies have reported lower rates of
adolescent depression in some minority ethnic groups
(such as people of south Asian origin) than in White
children and adolescents in the UK, suggesting either
differences in reporting or cultural effects.9 Young
people who are members of minority sexual or gender
groups show increased rates of depression, which can
be partly attributed to peer victimisation, family
conflict, and rejection.89
Pathophysiology
Although there are multiple studies on the processes by
which environmental stressors are translated to
depressive symptoms (eg, hormonal, autonomic, and
epigenetic processes), the most coherent findings
informing depression pathophysiology come from
studies that probe neurocircuitry and cognitive
behavioural processes. Neuroimaging studies of
adolescents who have depression have documented a
neural basis for long-standing observations about the
roles that impairments in reward response, impaired
top-down cognitive control of emotions, selective over-
attention to negative emotional stimuli, and negative,
ruminative self-scrutiny have played in the causes of
depression.90,91
A blunted response to rewarding stimuli predicts the
onset of depression and is associated with increased
anhedonia and depressive severity. Adolescents with
depression show hypoactivation of the ventral striatum
when anticipating reward, and reduced response in the
orbital prefrontal cortex and other prefrontal structures
with reward receipt. The reward response network,
consisting of frontal and striatal structures has shown
increased connectivity within the network early in
depression, and reduced connectivity in children and
adolescents— especially in those who have had multiple
depressive episodes.90,92,93 The reward network has been
reported to be highly heritable, but reward function is
also disrupted by early life trauma, particularly related
to deprivation (eg, low levels of cognitive and social
stimulation during development).94
Adolescents with depression show difficulty with
top-down cognitive control of emotion (ie, emotion
regulation), and so they are less effective at attenuating
a negative emotional response to a distressing situation
www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1 5
Seminar
or probe than adolescents without depression. In
response to such negatively valanced probes, children
and adolescents with depression show altered activation
of frontocingulate, parietal, and subgenual and dorsal
anterior cingulate cortical regions.90,95 The cognitive
control network, comprised of these regions, most
commonly shows increased connectivity. Early life
stress, particularly involving impaired caregiving, is
associated with these psychological and attendant
neural alterations.96 Conversely, the development of
medial prefrontal cortex-amygdala connectivity in
adolescents exposed to adverse caregiver experiences
could make them more resilient to depression;
connectivity that might be facilitated by later positive
interactions with caregivers.97 Prefrontal cortex-
amygdala connectivity appears to be primarily
accounted for by environmental effects.98
People with depression selectively attend to negatively
valanced stimuli that reinforce depressive symptoms.91
Accordingly, in response to negative emotional stimuli
(eg, social rejection), adolescents with depression show
increased activation in the amygdala, supragenual
anterior cingulate cortex, and the orbitofrontal cortex.
Increased connectivity is observed in young people
with depression within the affective circuitry and in the
broader salience network, which includes the dorsal
anterior cingulate cortex, anterior insula, amygdala,
and the ventrolateral prefrontal cortex. Exposure to
threat increases the likelihood of developing these
cognitive biases.94
People with depression show a tendency for self-
referential thinking, manifested by rumination,
frequent use of first person pronouns, and alterations
in autobiographical memory.90 The circuitry that
supports introspection and self-reflection, commonly
referred to as the default mode network, consists of
the precuneus, posterior cingulate cortex, medial
prefrontal cortex, and the inferior parietal cortex. The
different circuits described also show altered
interrelationships in adolescents with depression. For
example, consistent with the view that depression is
related to impaired top-down cognitive control of
emotion, adolescents with depression show decreased
connectivity between the cognitive control and affective
networks.90
Prevention
Preventive interventions can act at an entire population
level (universal), a targeted subgroups level (selective),
or an individual level (indicated). When considering the
strength of evidence on prevention, it is important to
acknowledge that the evidence is heavily biased towards
proximal targets, which can be modified at the
individual level (eg, with cognitive behavioural
principles) because random assignment of participants
in clinical trials to one of these interventions is more
feasible than for interventions for more distal targets.
 Seminar
Individual level
Universal interventions targeting social–emotional
competencies that are based on cognitive behavioural
principles have been delivered via school systems, such
as the Penn Resilience Program in the USA.99 Other
interventions have been based on psychoeducation,
mindfulness, interpersonal therapy,100 and psychosocial
support. A systematic review of all school-based
universal interventions focused solely on preventing
depression concluded that there is little evidence to
show that any of the interventions are effective,101
including in LMICs,102 and recommended multilevel,
systems-based interventions in the future.
Indicated interventions typically include principles of
cognitive behavioural therapy, or, in a few instances,
interpersonal therapy. Systematic reviews report small
to moderate effects of interventions such as cognitive
behavioural therapy in reducing subthreshold
depression, corresponding to a number-needed-to-treat
of 8·4 to prevent major depression in one patient.103
Meta-analyses of inter­vention programmes delivered in
schools find that effects are only observed in the short
term,104,105 and might not prevent future major depressive
disorder. However, one indicated cognitive behavioural
therapy prevention programme delivered in health-care
settings resulted in better adult functioning 6 years
later, suggesting that delayed onset of depression might
have benefits.42 Digital interventions are potentially
more scalable than other types of interventions (ie,
those that are not delivered digitally), but digital
interventions require better quality evaluation.106 The
rate of non-completion of digitally delivered
interventions is high; of note, engagement is enhanced
by coaching support. Digitally delivered interventions
seem to be more effective in adolescents with less
frequent substance use and whose parents do not have
depression.107
Selective prevention targets individuals in high-risk
groups, exposed to recognised depression risk factors.108
Prevention programmes for children whose parents
have depression are effective, but less so if the parent is
currently depressed.109 Evidence on the long-term
benefits of selective prevention interventions is
varied.108,110
Schools and community level
An alternative approach to preventing depression is
to target systems, such as the school environment,
rather than individual people. Systematic reviews have
shown that school-based interventions have relatively
small effects, but evidence from LMICs is very
scarce.101,102 One successful example is the Strengthening
Evidence base on school-based interventions for
promoting adolescent health programme (SEHER).
SEHER is a school-based intervention, with universal,
group, and individual targeted strategies. A trial in
rural India showed large reductions in depressive
6 www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1
symptoms when the intervention was delivered by
lay counsellors (defined in this study as members of
the local community aged 21 years or older, who
had completed at least a high school education, and
had no professional health training).111,112 However,
the same intervention when delivered by school
staff was ineffective, a finding also observed in other
trials,113 suggesting a moderating role of the person who
delivers the intervention. Another school-based
intervention in the UK that targeted the social
environment showed improvements in some outcomes
but not depression.114
At the population level, interventions targeting
messaging that encourages skewed body image
preferences, gender inequality, and discrimination
against some groups (eg, sexual minority adolescents)
through appropriate legislation, public campaigns, and
peer support programmes, might all contribute to
reduced risk for depression. Similarly, programmes
that target early parenting and known risk factors, such
as bullying, and provide income support through cash
transfers to families and young people, might also
contribute to reducing suicide and improving mental
health.115
Screening, diagnostic assessment and
measures
Screening
Depression in adolescents is under-recognised, leaving
it often undertreated.116 Although routine screening has
the potential to improve identification of depression,
international guidelines differ, with US guidelines
supporting universal screening for depression in
adolescents,117 whereas both the Canadian guidelines118
and UK guidelines119 view the existing data as not
supportive of universal screening. Broadly, there is
moderate sensitivity and specificity across screening
measures, but positive predictive values are poor: a
high proportion of people screening positive do not
meet the criteria for a diagnosis of depression. In
resource scarce settings—in which clinical assessment
of people who screen as positive might not be possible—
the threshold for a positive screen should be increased.
In primary care, because the diagnosis of depression is
often missed, screening might be useful if follow-up
assessment is possible. Within specialist child and
adolescent mental health services (CAMHS),
depression screening tools perform similarly to when
they are used in primary care,120 but false positives
might be less problematic because systems are in place
for additional assessments. Guidelines from the
National Institute for Health and Care Excellence
(NICE) recommend screening young people aged
11 years or older who have been referred to CAMHS
without a diagnosis of depression.119 To date, there is
little evidence to support universal adolescent
depression screening programmes; therefore,

screening should only be implemented if there are
systems in place for additional assessment, diagnosis,
and treatment.
Young people with depressive symptoms should be
screened for current and recent suicidal ideation,
suicide intent, and a history of previous suicidal
behaviour; a safety plan for coping with suicidal
thoughts should be developed with the young person
and their family. NICE guidance recommends that
children and young people with suspected severe
depression who are at a high risk of suicide are assessed
by a CAMHS professional within 24 h of referral.119
Diagnostic assessment
The first key step when doing a diagnostic assessment
is to establish a trusting relationship with the young
person, which can require time and effort—especially if
the young person has been reluctant to seek help.
Dysphoria, sadness, and short-lived depression
(figure 1) are common in adolescence,45,121 and most
adolescents with these symptoms do not require
referral to a mental health specialist. UK guidelines119
suggest that health-care professionals in primary care,
schools, and other community settings should be
trained to detect symptoms of depression and assess
young people at risk. Referral from primary to
secondary care CAMHS is recommended if the young
person has severe depressive symptoms, complex
symptomatology, or comorbidity (eg, mania, substance
abuse, or at high risk of suicide); if symptoms or
distress persist despite appropriate support; if there is
continued interference with social, educational, and
other important areas of functioning; or if the patient
has indicators that make the likelihood of depressive
onset high (eg, personal or family history of
depression).119,122
Gathering information, such as descriptions and
contexts in which these symptoms affect daily
functioning, not just about specific depression
symptoms (figure 2), is helpful in informing the
diagnostic assessment. Identifying the functional
consequences of depression in collaboration with the
young person can help identify what outcomes matter
most to them and what they seek to change.123 Caregiver
report is important to complement the information
taken from young people about their depression
symptoms, especially younger adolescents, and liaison
with schools is important when depression affects
functioning at school.
Depression in adolescence and early adult life might
increase the normative tendency for risk taking to
result in increased risk-taking behaviours, which
highlights the importance of assessing suicidal and
other risks.124 Irritability might be a more prominent
feature of depression in adolescents than in adults.
Recognising comorbidities in people with major
depressive disorder (eg, anxiety or ADHD) is also
www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1 7
Seminar
important because comorbidities are associated with
worse depression outcomes, and they might require
adjustments to the support or intervention package.
Anxiety is the most common comorbidity, but
disordered eating is increasingly common,10 and
neurodevelopmental disorders (such as ADHD and
autism spectrum disorder) are easily missed in females.
Differential diagnosis needs to include the
consideration of whether depression is the initial
presenting feature of another condition, such as bipolar
disorder or schizophrenia. Although most young
people with depression do not progress to these major
mental disorders, careful assessment should be done
so that they are not missed; obtaining a family history
can indicate risks of transition to these disorders and
suggest a more cautious approach to treatment,
monitoring, and follow-up. Complex post-traumatic
stress disorder also needs to be considered as a
differential diagnosis because of overlapping symptoms
and comorbidity with depression.
Assessment and treatment of depression require
clinicians to characterise the social, familial (including
romantic partner), educational, or work contexts of the
young person. Some guidelines also recommend
profiling risk in community settings as well as in
specialist settings.119 Assessing the quality of
interpersonal relationships and support networks is
especially important, as is identifying risk exposures,
such as bullying, maltreatment, life events, a history of
trauma, lifestyle factors, and whether the young person
belongs to a high-risk group (eg, special educational
needs, sexual or gender minority, or chronic physical
illness). Identifying a young person’s strengths and
protective factors (eg, family support) and investigating
how the young person manages mood and suicidal
urges is important for shaping the different components
of a collaborative intervention package.
Depression measures
Questionnaires can be used for screening, assessment
of depression symptoms, and monitoring response to
treatment. Some general questionnaires incorporate
depression items, whereas others specifically measure
symptoms of depression. When selecting a question­
naire to use, there are numerous considerations,
including its psychometric properties, recommended
age range, and practical issues (eg, the time taken to
complete or cost). The most commonly used
depression questionnaires for children and adolescents
are summarised in the table. Because of the large
number of questionnaires, there have been efforts to
streamline their use. The Revised Child Anxiety and
Depression Scale has been recommended by the
international consortium for health outcomes
measurement for assessing depression symptom
response to clinical care.134 The Mood and Feelings
Questionnaire is a commonly used measure with good
 Seminar

psychometric properties, and it is recommended for
assessment and treatment monitoring of adole­scents
with depression.141 With regards to screening, the
Patient Health Question­naire-Adolescent and Beck’s
Depression Inventory have been suggested
as appropriate measures.133 Although semi-structured
diagnostic interviews (eg, Schedule for Affective
Disorders and Schizophrenia for School-Age Children)
and structured diagnostic interviews (eg, the
Development and Well-Being Assessment)144,145 are
important research tools, which can be helpful in
some secondary care clinics (eg, for diagnostic
dilemmas), a flexible approach to recording a patient’s
history and assessing their mental state while
including the rigour and detail of these instruments is
generally preferred in routine practice.

Beck’s Depression Center for Children’s Mood and Feelings Patient Health Reynolds Adolescent Revised Children’s
Inventory (BDI)125 Epidemiologic Depression Questionnaire Questionnaire-9 Depression Scale Anxiety and Depression
Studies Depression Inventory (CDI)127 (MFQ)128 (PHQ-9)129 (RADS)130 Scale (RCADS)131
Scale (CES-D)126
Summary
Age, years 13–80 Designed for adults, 7–18 8–18 Suitable for use in 13–18 years 8–18
but suitable for use in adolescents132
adolescents126
Rater Self-report Self-report Self, parent, teacher Self and parent Self-report Self-report Self and parent
Scale 21 items, scoring 20 items, scoring 0–3, 27 items, scoring 33 items (parent 9 items, scoring 0–3, 30 items, scoring 1–4, 47 items, grouped into
0–3, range 0–63 range 0–60 0–2, range 0–54 report 34 items), range 0–27 range 30–120 6 subscales; 1 subscale
scoring 0–2, range measures depression
0–66 symptom (10 items),
each item rated 0–4
Time 10 min 5–20 min 15 min 10 min 5 min 10 min 5–10 min
Related scales BDI-Y and BDI-PC CES-DC CDI-2 SMFQ PHQ-2, PHQ-A129 RADS-2 RCADS-25
and RCADS-25-P
Recommended Recommended by ·· ·· Recommended by PHQ-A recommended by ·· Recommended by
the US Preventive NICE guidance on the US Preventive Wellcome and the National
Services Task Force depression in Services Task Force to Institute of Mental Health
for screening for children and young screen depression in for use in research relating
depression in people to monitor adolescents aged to young people with
adolescents133 clinical progress119 12–18133 depression and anxiety,
and by the International
Consortium for Health
Outcomes Measurement
for assessing depression
symptoms in response to
clinical care134
Internal α 0·86 α 0·88120 α 0·86120 α 0·94135 α 0·86–0·89129 α 0·93120 α 0·82137
consistency
Validity ·· ·· High predictive, Good content and Good criterion and Good construct Good convergent and
convergent and criterion validity138 construct validity129 validity139 concurrent validity131
construct validity137
Cutoff Optimal cutoffs Optimal cutoffs vary Optimal cutoffs Optimal cutoffs vary Optimal cutoffs vary Cutoff of 77 A t-score for the
vary across across samples. Range vary across samples. across samples: across samples. Range suggested141 appropriate grade level
samples, but range from 12 to 24.120,140 Range from ≥27 to ≥29 for self- from ≥5 to ≥15.140 Cutoff is calculated from a raw
from ≥11 to 24120,140 Cutoff of 16 suggested 11 to 19.120 report135,142,143 and of 10 often used in score. Clinical threshold
for moderate Suggested cutoff ≥21 to ≥27 for parent adults, recommended is top 2% of scores
depression141 >20 report135,143 cutoff of 11 in (t-score of ≥70)
adolescents140
Sensitivity 84–100140 70–84140 83120 63–84135,142,143 72–89140 ·· 74131
Specificity 98–100140 45–75140 84120 61–88135,142,143 78–95140 ·· 77131
Positive predictive 10–86140 8–21140 21–90120 67142 15–65140 ·· ··
value
Negative predictive 98–100140 88–99140 63–100120 86142 97–99140 ·· ··
value
Area under the 0·92120 0·83120 0·83120 0·82 (self), 0·69 0·88140 ·· ··
curve (parent)135
BDI-Y=Beck’s Depression Inventory-youth. BDI-PC=Beck’s Depression Inventory-primary care. CDI-2=Children’s Depression Inventory. CES-DC=Center for Epidemiological Studies Depression Scale for Children.
NICE=National Institute for Health and Care Excellence. PHQ-2=Patient Health Questionnaire, first two questions. PHQ-A=Patient Health Questionnaire 9 modified for adolescents. RADS-2=Reynolds Adolescent
Depression Scale, 2nd edn. RCADS-25=The Revised Children’s Anxiety and Depression Scale, 25-item version. RCADS-25-P=The Revised Children’s Anxiety and Depression Scale, 25-item version (parent version).
SMFQ=Short Mood and Feelings Questionnaire.

Table: Questionnaires commonly used to measure depression symptoms in young people

8 www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1


Treatment
General approach
Guidelines in many countries cover depression in
children and adolescents up to age 18 years, and they
suggest a stepwise approach to treating depression and
to avoid prescribing antidepressants alone.119 For mild
depression, NICE recommends that support and
psychoeducation include making changes to lifestyle
(eg, sleep, diet, and use of drugs); this might be sufficient
intervention, with continued monitoring.119 Recognising
and assessing the contribution of risk and traumatic
exposures (eg, intimate partner violence) to distress is
an important first step. NICE119 recommends watchful
waiting of up to 4 weeks for people with mild depression.
For people who do not spontaneously go into remission,
referral for supportive and psychological interventions
in the community (eg, schools and tier 2 CAMHS) is
recommended. The addition of exercise and behaviour
activation to a person’s daily routine could be helpful at
all stages of intervention. Single session interventions
for adolescents that focus on self-efficacy and a growth
mindset have been shown to result in significant
reductions in depressive symptoms,146,147 and the sessions
could be an important first step for treatment of mild
depression in the community. Meta-analyses and
individual trials from LMICs find that adaptations of
extant and culturally adapted psychological and
psychosocial interventions that focus on problem
solving148 or positive human attributes (eg, growth
mindset and gratitude), including single session and
group sessions led by a lay person (ie, someone who
does not have a clinical background),149,150 can effectively
reduce depressive symptoms. For example, a randomised
controlled trial found that a group intervention led by a
lay person with a focus on teaching growth mindset,
gratitude, and value affirmation for 60 min per week for
4 weeks reduced anxiety and depression in adolescents
from Kenya for up to 7 months.150 The studies from
LMICs highlight the potential effectiveness of low-cost
interventions in countries where resources are scarce,
and could be relevant to many high-income countries in
which resources are constrained.
Specialist care is usually indicated for moderate-to-
severe depression, for people with comorbidities or
suicide ideation. For moderate depression, treatment
with an evidence-based psycho­ therapy or combined
treatment with medication is recommended first. UK
NICE guidance119 suggests that there is little clear
evidence to favour one psychotherapy over another. For
chronic or severe depression, a combination of
medication and psychotherapy is recommended, after
ruling out the presence of bipolar disorder in the patient
or first degree relatives. If the young person does not
improve within 4–6 weeks, they should be reassessed to
make sure that there are no other factors that could be
contributing to their clinical presentation, such as peer
victimisation, poor sleep, problems from a comorbid
www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1 9
Seminar
condition (eg, anxiety or ADHD), family conflict, same-
sex attraction, and past or current trauma. If no
psychosocial contributor to non-response is identified,
for adolescents receiving psychotherapy alone combined
treatment should be provided. For adolescents receiving
medication, trying an alternative psychotherapy or
increasing the dose of the antidepressants is reasonable.
If a young person does not respond to an adequate dose
of medication and psychotherapy, switching to another
antidepressant is reasonable. When faced with a partial
response to an antidepressant plus psychotherapy,
augmentation with another drug is a reasonable
next step.
Specific psychological therapies for depression
Although direct comparisons of cognitive behavioural
therapy and interpersonal therapy are few and
equivocal, meta-analyses suggest that interpersonal
therapy has stronger effects than cognitive behavioural
therapy relative to control interventions.151,152 Cognitive
behavioural therapy that includes behaviour activation,
caregiver involvement, and challenging cognitive
distortions, is more effective than cognitive behavioural
therapy that exclusively focuses on cognitive distortions.
Higher severity of depression, a history of maltreatment,
and the presence of non-suicidal self-injury decrease
the likelihood of patients responding to cognitive
behavioural therapy.153,154 An initial course of either
interpersonal therapy or cognitive behavioural therapy
is 8–16 sessions over 3–4 months. A meta-analysis155
showed that the effects of cognitive behavioural therapy
on symptoms of depression delivered online with high
involvement from the therapist was more effective than
in people who had low involvement from the therapist
(Cohen’s d 0·52 vs 0·16).
In a large, pragmatic trial of adolescent depression
based in the UK, cognitive behavioural therapy was
compared with a brief problem-solving intervention and
short-term psychodynamic therapy. The brief problem-
solving intervention targeted behaviour activation,
problem-solving, and interpersonal effectiveness. All
three interventions resulted in a 50% decline in
depressive symptoms, with no group differences;
therefore, the brief problem-solving intervention was
viewed as the most cost-effective.156
Other promising interventions that have shown
efficacy in single trials include a modification of parent–
child interaction therapy, with an additional module on
emotion regulation for 3–7-year-olds with depression
and family-focused therapy for preadolescents (aged
7–14 years) with depression.157,158
Modular and transdiagnostic approaches
A modular approach to treatment involves prioritising
and sequencing interventions to address what the
parent and young person view as the most challenging
mental health issues; this approach has been shown to
 Seminar
be effective in improving mental health. A trial with a
modular approach to treatment done in schools shows
improvements in functioning, anxiety, depression, and
behavioural problems compared with usual care;
however, attempts at replication have been equivocal.159
Medication
Most treatment trials either span ages 18–65 years or
focus on individuals younger than 18 years. Thus, there
is much less known about the 18–24 years age group
specifically. For adolescents younger than 18 years, a
network meta-analysis of clinical trials found that
fluoxetine, either alone, or in combination with cognitive
behavioural therapy, is more effective than a pill placebo;
fluoxetine in combination with cognitive behavioural
therapy was not more effective than fluoxetine.151
Venlafaxine showed the highest risk for suicidal events
compared with pill placebo, whereas fluoxetine did not
show a statistically significant elevation in suicidal
events.151 There is modest evidence for efficacy of
escitalopram, sertraline, and duloxetine in adolescents
with depression.160 NICE guidelines119 recommend
against the use of paroxetine and venlafaxine.
Although a high dose of an antidepressant is not
associated with an increased likelihood of response in
adults, this might not be the case in adolescents with
treatment-resistant depression.161 Maternal depression,
increased symptom severity, and sleep difficulties, are
associated with a poorer response to antidepressants.153,162
Continued treatment with antidepressants after
recovery from depression for an additional 6 months
results in a much lower rate of relapse and recurrence
than treatment with placebo for 6 months.163 The
addition of cognitive behavioural therapy to
antidepressant treatment has resulted in even more
complete protection against relapse compared with
continued antidepressant treatment alone in the 1-year
follow-up period.164 Studies of treatment-resistant
depression have shown that in adolescents who have
not responded to an initial trial with a selective
serotonin reuptake inhibitor a switch to another
selective serotonin reuptake inhibitor with the addition
of cognitive behavioural therapy results in the highest
response rate compared with a medication switch
alone.165 UK NICE guidance119 suggests intensive
psychological therapy with or without fluoxetine,
sertraline, and citalopram and augmentation with an
antipsychotic. Ketamine shows promise in adolescents
with treatment-resistant depression, but there are no
large trials or long-term follow-up data to document
efficacy or long-term benefits or risks.166 Although safe
and well tolerated, rapid transmagnetic stimulation is
not more effective for the relief of treatment-resistant
depression than sham treatment.167 Although there are
no clinical trials of electroconvulsive therapy for
adolescent depression, open data and clinical
experience suggest that electroconvulsive therapy is
10 www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1
advised for adolescents who have not responded to at
least three antidepressants, especially in the face of
psychotic depression, a history of mania, and
psychomotor retardation.
Conclusion
More than a decade has passed since the last Lancet
Seminar on depression in adolescents, and during this
time its prevalence has sharply increased, especially in
females during late adolescence and early adult life.
There is greater appreciation that research and clinical
services are immensely restricted by the rigid aged
18-years boundaries between adolescence and
adulthood. The gap between adolescence and adulthood
needs to be addressed going forward and we welcome
the growing interest in youth psychiatry.168 Although
there are multiple meta-analyses of risk factors, the
reasons why the prevalence of depression in young
people has risen and what needs to be done to reduce
depression at a population level are unknown and are a
priority for the next generation of research. Prevention
and early intervention are important and appear most
effective when targeted at the highest risk groups. How
these interventions are best delivered requires more
research and innovation. Moreover, more distal public
health strategies also require evaluation even if
randomised controlled trials are not possible. Although
treatment recommendations have not substantially
changed in the past decade, a broader set of psychological
and behavioural interventions are now available to
clinicians. However, there are remarkably few new
treatment trials to guide clinicians managing more
severe forms of depression. In conclusion, depression is
highly heterogeneous, more so in young people, and
spans a spectrum of severity. Neuroscience and genetic
discoveries coupled with social and clinical data could
be used to personalise treatment and improve outcomes.
Contributors
AT led the organisation of the paper; drafted the introduction,
conclusion, epidemiology, risk factors, antecedents, and assessment
sections; drafted the figures; and did the final editing. OE drafted the
outcomes, screening and measures, and the table of measures
sections; and oversaw the literature search. VP drafted the prevention
section and oversaw sections about low-income and middle-income
countries. DB drafted sections on pathophysiology and interventions.
All authors did additional literature reviews and contributed to editing
all sections.
Declaration of interests
AT receives a salary from Cardiff University; honoraria that go to
Cardiff University from speaker contributions to international
scientific meetings, from Wellcome Trust for serving on an interview
panel, and from Wiley for textbook royalties; research grant funding to
her university from Wolfson Foundation, Wellcome Trust, and Medical
Research Council (MRC); and serves on the board of the UK charity
ADHD Foundation (unpaid). VP reports personal fees from Johnson
and Johnson and Librum; current grants from the National Institute of
Mental Health (NIMH), Grand Challenges Canada, MRC, and
Wellcome Trust; and serves as an adviser to Modern
Health. DB reports grants from NIMH, American Foundation for
Suicide Prevention (ASFP), Once Upon a Time Foundation, and
Beckwith Foundation; royalties from eResearch Technology, UptoDate,

Guilford Press, and Healthwise; honorarium for membership on the
Scientific Advisory Board of the Klingenstein Third Generation
Foundation and AFSP, outside the submitted work; and intellectual
property, currently with no financial interest, supported by funding
from NIMH for the development of BRITE (a safety planning web-
based mobile application), the As Safe As Possible intervention (a brief
intervention for suicidal youth), the Computerized Adaptive Screen for
Suicidal Youth measure (ie, a screen designed to estimate the risk for a
suicide attempt in the subsequent 3 months), a suicide risk machine
learning algorithm (for which DB has also received funding from the
Beckwith Institute), and the Screening Wizard screening tool (ie, a
support tool for primary care physicians to aid in assessment and
referral of patients who screen positive for depression and suicidal
risk). OE receives a salary from Cardiff University, funded by Wolfson
Foundation.
References
1 GBD 2017 Disease and Injury Incidence and Prevalence
Collaborators. Global, regional, and national incidence, prevalence,
and years lived with disability for 354 diseases and injuries for
195 countries and territories, 1990–2017: a systematic analysis for
the Global Burden of Disease Study 2017. Lancet 2018;
392: 1789–858.
2 Patton GC, Sawyer SM, Santelli JS, et al. Our future: a Lancet
commission on adolescent health and wellbeing. Lancet 2016;
387: 2423–78.
3 Collishaw S. Annual research review: secular trends in child
and adolescent mental health. J Child Psychol Psychiatry 2015;
56: 370–93.
4 Bertha EA, Balázs J. Subthreshold depression in adolescence:
a systematic review. Eur Child Adolesc Psychiatry 2013; 22: 589–603.
5 Rice F, Riglin L, Lomax T, et al. Adolescent and adult differences
in major depression symptom profiles. J Affect Disord 2019;
243: 175–81.
6 American Psychiatric Association. Diagnostic and statistical manual
of mental disorders, 5th edn. Washington, DC: American Psychiatric
Association, 2013.
7 WHO. ICD-11. International Classification of Diseases 11th revision.
2019. https://icd.who.int/en (accessed Sept 8, 2021).
8 Vasileva M, Graf RK, Reinelt T, Petermann U, Petermann F.
Research review: a meta-analysis of the international prevalence
and comorbidity of mental disorders in children between 1 and
7 years. J Child Psychol Psychiatry 2021; 62: 372–81.
9 National Health Service. Mental health of children and young people
in England, 2017 [PAS]. 2017. https://digital.nhs.uk/data-and-
information/publications/statistical/mental-health-of-children-and-
young-people-in-england/2017/2017#summary (accessed
Jan 16, 2019).
10 National Health Service. Mental health of children and young people
in England, 2021 - wave 2 follow up to the 2017 survey. 2021. https://
digital.nhs.uk/data-and-information/publications/statistical/mental-
health-of-children-and-young-people-in-england/2021-follow-up-to-
the-2017-survey (accessed Dec 3, 2021).
11 Lu W. Adolescent depression: national trends, risk factors, and
healthcare disparities. Am J Health Behav 2019; 43: 181–94.
12 Blakemore S-J. Adolescence and mental health. Lancet 2019;
393: 2030–31.
13 Polanczyk GV, Salum GA, Sugaya LS, Caye A, Rohde LA. Annual
research review: a meta-analysis of the worldwide prevalence of
mental disorders in children and adolescents.
J Child Psychol Psychiatry 2015; 56: 345–65.
14 Barican JL, Yung D, Schwartz C, Zheng Y, Georgiades K, Waddell C.
Prevalence of childhood mental disorders in high-income countries:
a systematic review and meta-analysis to inform policymaking.
Evid Based Ment Health 2022; 25: 36–44.
15 National Health Service. Mental health of children and young people
in Great Britain, 2004. 2005. https://digital.nhs.uk/data-and-
information/publications/statistical/mental-health-of-children-and-y
oung-people-in-england/mental-health-of-children-and-young-
people-in-great-britain-2004 (accessed Dec 6, 2021).
16 Ford T, John A, Gunnell D. Mental health of children and young
people during pandemic. BMJ 2021; 372: n614.
17 Mojtabai R, Olfson M. National trends in mental health care for US
adolescents. JAMA Psychiatry 2020; 77: 703–14.
www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1 11
Seminar
18 Office for National Statistics. Young people’s well-being in the UK:
2020. 2020. https://www.ons.gov.uk/peoplepopulationand
community/wellbeing/bulletins/youngpeopleswellbeingintheuk/
2020#main-points (accessed March 25, 2022).
19 Platt JM, Bates L, Jager J, McLaughlin KA, Keyes KM. Is the US
gender gap in depression changing over time? A meta-regression.
Am J Epidemiol 2021; 190: 1190–206.
20 Stumper A, Alloy LB. Associations between pubertal stage and
depression: a systematic review of the literature.
Child Psychiatry Hum Dev 2021; published online Sept 16.
https://doi.org/10.1007/s10578-021-01244-0.
21 Kessler RC, Avenevoli S, Ries Merikangas K. Mood disorders
in children and adolescents: an epidemiologic perspective.
Biol Psychiatry 2001; 49: 1002–14.
22 Costello EJ, Maughan B. Annual research review: optimal
outcomes of child and adolescent mental illness.
J Child Psychol Psychiatry 2015; 56: 324–41.
23 Johnson D, Dupuis G, Piche J, Clayborne Z, Colman I. Adult
mental health outcomes of adolescent depression: a systematic
review. Depress Anxiety 2018; 35: 700–16.
24 Harris IM, Beese S, Moore D. Predicting future self-harm or
suicide in adolescents: a systematic review of risk assessment
scales/tools. BMJ Open 2019; 9: e029311.
25 Lewinsohn PM, Rohde P, Seeley JR, Klein DN, Gotlib IH. Natural
course of adolescent major depressive disorder in a community
sample: predictors of recurrence in young adults. Am J Psychiatry
2000; 157: 1584–91.
26 Curry J, Silva S, Rohde P, et al. Recovery and recurrence following
treatment for adolescent major depression. Arch Gen Psychiatry
2011; 68: 263–69.
27 Sheets ES, Craighead WE. Comparing chronic interpersonal
and noninterpersonal stress domains as predictors of depression
recurrence in emerging adults. Behav Res Ther 2014; 63: 36–42.
28 McLeod GFH, Horwood LJ, Fergusson DM. Adolescent
depression, adult mental health and psychosocial outcomes at
30 and 35 years. Psychol Med 2016; 46: 1401–12.
29 Uchida M, Serra G, Zayas L, et al. Can manic switches be
predicted in pediatric major depression? A systematic literature
review. J Affect Disord 2015; 172: 300–06.
30 Puccio F, Fuller-Tyszkiewicz M, Ong D, Krug I. A systematic
review and meta-analysis on the longitudinal relationship between
eating pathology and depression. Int J Eat Disord 2016; 49: 439–54.
31 Campo JV. Annual research review: functional somatic symptoms
and associated anxiety and depression – developmental
psychopathology in pediatric practice. J Child Psychol Psychiatry
2012; 53: 575–92.
32 Groenman AP, Janssen TWP, Oosterlaan J. Childhood psychiatric
disorders as risk factor for subsequent substance abuse:
a meta-analysis. J Am Acad Child Adolesc Psychiatry 2017; 56: 556–69.
33 Lehrer JA, Shrier LA, Gortmaker S, Buka S. Depressive symptoms
as a longitudinal predictor of sexual risk behaviors among US
middle and high school students. Pediatrics 2006; 118: 189–200.
34 Foley JD, Vanable PA, Brown LK, et al. Depressive symptoms
as a longitudinal predictor of sexual risk behaviors among
African-American adolescents. Health Psychol 2019; 38: 1001–09.
35 Goldstein BI, Korczak DJ. Links between child and adolescent
psychiatric disorders and cardiovascular risk. Can J Cardiol 2020;
36: 1394–405.
36 Mannan M, Mamun A, Doi S, Clavarino A. Prospective
associations between depression and obesity for adolescent males
and females - a systematic review and meta-analysis of
longitudinal studies. PLoS One 2016; 11: e0157240.
37 Clayborne ZM, Varin M, Colman I. Systematic review and meta-
analysis: adolescent depression and long-term psychosocial
outcomes. J Am Acad Child Adolesc Psychiatry 2019; 58: 72–79.
38 Wickersham A, Sugg HVR, Epstein S, Stewart R, Ford T, Downs J.
Systematic review and meta-analysis: the association between
child and adolescent depression and later educational attainment.
J Am Acad Child Adolesc Psychiatry 2021; 60: 105–18.
39 Kessler RC, Bromet EJ. The epidemiology of depression across
cultures. Annu Rev Public Health 2013; 34: 119–38.
40 Allen JP, Chango J, Szwedo D, Schad M. Long-term sequelae of
subclinical depressive symptoms in early adolescence.
Dev Psychopathol 2014; 26: 171–80.
 Seminar
41 Giaconia RM, Reinherz HZ, Paradis AD, Hauf AM, Stashwick CK.
Major depression and drug disorders in adolescence: general
and specific impairments in early adulthood.
J Am Acad Child Adolesc Psychiatry 2001; 40: 1426–33.
42 Brent DA, Brunwasser SM, Hollon SD, et al. Effect of a cognitive-
behavioral prevention program on depression 6 years after
implementation among at-risk adolescents: a randomized clinical
trial. JAMA Psychiatry 2015; 72: 1110–18.
43 Ssegonja R, Alaie I, Philipson A, et al. Depressive disorders in
adolescence, recurrence in early adulthood, and healthcare usage
in mid-adulthood: a longitudinal cost-of-illness study.
J Affect Disord 2019; 258: 33–41.
44 Colman I, Wadsworth ME, Croudace TJ, Jones PB. Forty-year
psychiatric outcomes following assessment for internalizing
disorder in adolescence. Am J Psychiatry 2007; 164: 126–33.
45 Weavers B, Heron J, Thapar AK, et al. The antecedents and
outcomes of persistent and remitting adolescent depressive
symptom trajectories: a longitudinal, population-based English
study. Lancet Psychiatry 2021; 8: 1053–61.
46 Schubert KO, Clark SR, Van LK, Collinson JL, Baune BT.
Depressive symptom trajectories in late adolescence and early
adulthood: a systematic review. Aust N Z J Psychiatry 2017;
51: 477–99.
47 Wickrama KAS, Wickrama T, Lott R. Heterogeneity in youth
depressive symptom trajectories: social stratification and
implications for young adult physical health. J Adolesc Health
2009; 45: 335–43.
48 Rice F, Riglin L, Thapar AK, et al. Characterizing developmental
trajectories and the role of neuropsychiatric genetic risk variants
in early-onset depression. JAMA Psychiatry 2019; 76: 306–13.
49 Fombonne E, Wostear G, Cooper V, Harrington R, Rutter M.
The Maudsley long-term follow-up of child and adolescent
depression. 1. Psychiatric outcomes in adulthood. Br J Psychiatry
2001; 179: 210–17.
50 Tuisku V, Kiviruusu O, Pelkonen M, Karlsson L, Strandholm T,
Marttunen M. Depressed adolescents as young adults - predictors
of suicide attempt and non-suicidal self-injury during an 8-year
follow-up. J Affect Disord 2014; 152–154: 313–19.
51 Krause KR, Bear HA, Edbrooke-Childs J, Wolpert M. Review: what
outcomes count? A review of outcomes measured for adolescent
depression between 2007 and 2017.
J Am Acad Child Adolesc Psychiatry 2019; 58: 61–71.
52 McIntosh AM, Sullivan PF, Lewis CM. Uncovering the genetic
architecture of major depression. Neuron 2019; 102: 91–103.
53 Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of
major depression: review and meta-analysis. Am J Psychiatry 2000;
157: 1552–62.
54 Rutter M. Some of the complexities involved in gene-environment
interplay. Int J Epidemiol 2015; 44: 1128–29.
55 Howard DM, Adams MJ, Clarke TK, et al. Genome-wide meta-
analysis of depression identifies 102 independent variants and
highlights the importance of the prefrontal brain regions.
Nat Neurosci 2019; 22: 343–52.
56 Kendall KM, Rees E, Bracher-Smith M, et al. Association of rare
copy number variants with risk of depression. JAMA Psychiatry
2019; 76: 818–25.
57 Lee PH, Anttila V, Won H, et al. Genomic relationships, novel
loci, and pleiotropic mechanisms across eight psychiatric
disorders. Cell 2019; 179: 1469–82.e11.
58 Musliner KL, Mortensen PB, McGrath JJ, et al. Association of
polygenic liabilities for major depression, bipolar disorder, and
schizophrenia with risk for depression in the Danish population.
JAMA Psychiatry 2019; 76: 516–25.
59 Warrier V, Kwong ASF, Luo M, et al. Gene–environment
correlations and causal effects of childhood maltreatment on
physical and mental health: a genetically informed approach.
Lancet Psychiatry 2021; 8: 373–86.
60 Schoeler T, Choi SW, Dudbridge F, et al. Multi-polygenic score
approach to identifying individual vulnerabilities associated with
the risk of exposure to bullying. JAMA Psychiatry 2019; 76: 730–38.
61 Peyrot WJ, Van der Auwera S, Milaneschi Y, et al. Does childhood
trauma moderate polygenic risk for depression? A meta-analysis
of 5765 subjects from the Psychiatric Genomics Consortium.
Biol Psychiatry 2018; 84: 138–47.
12 www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1
62 Khazanov GK, Ruscio AM. Is low positive emotionality a specific
risk factor for depression? A meta-analysis of longitudinal studies.
Psychol Bull 2016; 142: 991–1015.
63 Hakulinen C, Elovainio M, Pulkki-Råback L, Virtanen M,
Kivimäki M, Jokela M. Personality and depressive symptoms:
individual-participant meta-analysis of 10 cohort studies.
Depress Anxiety 2015; 32: 461–70.
64 Rood L, Roelofs J, Bögels SM, Nolen-Hoeksema S, Schouten E.
The influence of emotion-focused rumination and distraction on
depressive symptoms in non-clinical youth: a meta-analytic
review. Clin Psychol Rev 2009; 29: 607–16.
65 Rice F, Sellers R, Hammerton G, et al. Antecedents of new-onset
major depressive disorder in children and adolescents at high
familial risk. JAMA Psychiatry 2017; 74: 153–60.
66 Vidal-Ribas P, Brotman MA, Valdivieso I, Leibenluft E, Stringaris A.
The status of irritability in psychiatry: a conceptual and quantitative
review. J Am Acad Child Adolesc Psychiatry 2016; 55: 556–70.
67 Ghaziuddin M, Ghaziuddin N, Greden J. Depression in persons
with autism: implications for research and clinical care.
J Autism Dev Disord 2002; 32: 299–306.
68 Meinzer MC, Pettit JW, Viswesvaran C. The co-occurrence of
attention-deficit/hyperactivity disorder and unipolar depression in
children and adolescents: a meta-analytic review. Clin Psychol Rev
2014; 34: 595–607.
69 Keeton CP, Caporino NE, Kendall PC, et al. Mood and suicidality
outcomes 3–11 years following pediatric anxiety disorder
treatment. Depress Anxiety 2019; 36: 930–40.
70 Chang Z, D’Onofrio BM, Quinn PD, Lichtenstein P, Larsson H.
Medication for attention-deficit/hyperactivity disorder and risk for
depression: a nationwide longitudinal cohort study. Biol Psychiatry
2016; 80: 916–22.
71 Garber J, Brunwasser SM, Zerr AA, Schwartz KTG, Sova K,
Weersing VR. Treatment and prevention of depression and
anxiety in youth: test of cross-over effects. Depress Anxiety 2016;
33: 939–59.
72 Pinquart M, Shen Y. Depressive symptoms in children and
adolescents with chronic physical illness: an updated meta-
analysis. J Pediatr Psychol 2011; 36: 375–84.
73 Marino C, Andrade B, Campisi SC, et al. Association between
disturbed sleep and depression in children and youths:
a systematic review and meta-analysis of cohort studies.
JAMA Netw Open 2021; 4: e212373.
74 Rao WW, Zong QQ, Zhang JW, et al. Obesity increases the risk of
depression in children and adolescents: results from a systematic
review and meta-analysis. J Affect Disord 2020; 267: 78–85.
75 Chaplin AB, Daniels NF, Ples D, et al. Longitudinal association
between cardiovascular risk factors and depression in young
people: a systematic review and meta-analysis of cohort studies.
Psychol Med 2021; published online June 25. https://doi.
org/10.1017/S0033291721002488.
76 Maciejewski D, Hillegers M, Penninx B. Offspring of parents with
mood disorders: time for more transgenerational research,
screening and preventive intervention for this high-risk
population. Curr Opin Psychiatry 2018; 31: 349–57.
77 McAdams TA, Rijsdijk FV, Neiderhiser JM, et al. The relationship
between parental depressive symptoms and offspring
psychopathology: evidence from a children-of-twins study and an
adoption study. Psychol Med 2015; 45: 2583–94.
78 Lewis G, Rice F, Harold GT, Collishaw S, Thapar A.
Investigating environmental links between parent depression
and child depressive/anxiety symptoms using an assisted
conception design. J Am Acad Child Adolesc Psychiatry 2011;
50: 451–59.e1.
79 Tully EC, Iacono WG, McGue M. An adoption study of parental
depression as an environmental liability for adolescent depression
and childhood disruptive disorders. Am J Psychiatry 2008;
165: 1148–54.
80 Collishaw S, Hammerton G, Mahedy L, et al. Mental health
resilience in the adolescent offspring of parents with depression:
a prospective longitudinal study. Lancet Psychiatry 2016; 3: 49–57.
81 Norman RE, Byambaa M, De R, Butchart A, Scott J, Vos T.
The long-term health consequences of child physical abuse,
emotional abuse, and neglect: a systematic review and meta-
analysis. PLoS Med 2012; 9: e1001349.

82 LeMoult J, Humphreys KL, Tracy A, Hoffmeister JA, Ip E,
Gotlib IH. Meta-analysis: exposure to early life stress and risk for
depression in childhood and adolescence.
J Am Acad Child Adolesc Psychiatry 2020; 59: 842–55.
83 Moore SE, Norman RE, Suetani S, Thomas HJ, Sly PD, Scott JG.
Consequences of bullying victimization in childhood and
adolescence: a systematic review and meta-analysis.
World J Psychiatry 2017; 7: 60–76.
84 Achterbergh L, Pitman A, Birken M, Pearce E, Sno H, Johnson S.
The experience of loneliness among young people with
depression: a qualitative meta-synthesis of the literature.
BMC Psychiatry 2020; 20: 415.
85 Best P, Manktelow R, Taylor B. Online communication, social
media and adolescent wellbeing: a systemic narrative review.
Child Youth Serv Review 2014; 41: 27–36.
86 Ivie EJ, Pettitt A, Moses LJ, Allen NB. A meta-analysis of the
association between adolescent social media use and depressive
symptoms. J Affect Disord 2020; 275: 165–74.
87 Stirling K, Toumbourou JW, Rowland B. Community factors
influencing child and adolescent depression: a systematic review
and meta-analysis. Aust N Z J Psychiatry 2015; 49: 869–86.
88 Racine N, McArthur BA, Cooke JE, Eirich R, Zhu J, Madigan S.
Global prevalence of depressive and anxiety symptoms in children
and adolescents during COVID-19: a meta-analysis. JAMA Pediatr
2021; 175: 1142–50.
89 Amos R, Manalastas EJ, White R, Bos H, Patalay P. Mental health,
social adversity, and health-related outcomes in sexual minority
adolescents: a contemporary national cohort study.
Lancet Child Adolesc Health 2020; 4: 36–45.
90 Chahal R, Gotlib IH, Guyer AE. Brain network connectivity
and the heterogeneity of depression in adolescence - a precision
mental health perspective. J Child Psychol Psychiatry 2020;
61: 1282–98.
91 LeMoult J, Gotlib IH. Depression: a cognitive perspective.
Clin Psychol Rev 2019; 69: 51–66.
92 Rappaport BI, Kandala S, Luby JL, Barch DM. Brain reward
system dysfunction in adolescence: current, cumulative, and
developmental periods of depression. Am J Psychiatry 2020;
177: 754–63.
93 Whalen DJ, Gilbert KE, Kelly D, et al. Preschool-onset major
depressive disorder is characterized by electrocortical deficits in
processing pleasant emotional pictures. J Abnorm Child Psychol
2020; 48: 91–108.
94 McLaughlin KA, Weissman D, Bitrán D. Childhood adversity
and neural development: a systematic review.
Annu Rev Dev Psychol 2019; 1: 277–312.
95 Barch DM, Harms MP, Tillman R, Hawkey E, Luby JL. Early
childhood depression, emotion regulation, episodic memory,
and hippocampal development. J Abnorm Psychol 2019; 128: 81–95.
96 Tottenham N. Neural meaning making, prediction, and
prefrontal-subcortical development following early adverse
caregiving. Dev Psychopathol 2020; 32: 1563–78.
97 Tottenham N, Hare TA, Casey BJ. Behavioral assessment of
emotion discrimination, emotion regulation, and cognitive
control in childhood, adolescence, and adulthood. Front Psychol
2011; 2: 39.
98 Achterberg M, Bakermans-Kranenburg MJ, van Ijzendoorn MH,
van der Meulen M, Tottenham N, Crone EA. Distinctive
heritability patterns of subcortical-prefrontal cortex resting state
connectivity in childhood: a twin study. Neuroimage 2018;
175: 138–49.
99 Bastounis A, Callaghan P, Banerjee A, Michail M. The effectiveness
of the Penn Resiliency Programme (PRP) and its adapted versions
in reducing depression and anxiety and improving explanatory
style: a systematic review and meta-analysis. J Adolesc 2016;
52: 37–48.
100 Filia K, Eastwood O, Herniman S, Badcock P. Facilitating
improvements in young people’s social relationships to prevent or
treat depression: a review of empirically supported interventions.
Transl Psychiatry 2021; 11: 305.
101 Caldwell DM, Davies SR, Hetrick SE, et al. School-based
interventions to prevent anxiety and depression in children and
young people: a systematic review and network meta-analysis.
Lancet Psychiatry 2019; 6: 1011–20.
www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1 13
Seminar
102 Bradshaw M, Gericke H, Coetzee BJ, Stallard P, Human S,
Loades M. Universal school-based mental health programmes in
low- and middle-income countries: a systematic review and
narrative synthesis. Prev Med 2021; 143: 106317.
103 Cuijpers P, Pineda BS, Ng MY, et al. A meta-analytic review:
psychological treatment of subthreshold depression in children
and adolescents. J Am Acad Child Adolesc Psychiatry 2021;
60: 1072–84.
104 Gee B, Reynolds S, Carroll B, et al. Practitioner review: effectiveness
of indicated school-based interventions for adolescent depression
and anxiety - a meta-analytic review. J Child Psychol Psychiatry 2020;
61: 739–56.
105 Rasing SPA, Creemers DHM, Janssens JMAM, Scholte RHJ.
Depression and anxiety prevention based on cognitive behavioral
therapy for at-risk adolescents: a meta-analytic review. Front Psychol
2017; 8: 1066.
106 Clarke AM, Kuosmanen T, Barry MM. A systematic review of online
youth mental health promotion and prevention interventions.
J Youth Adolesc 2015; 44: 90–113.
107 Conejo-Cerón S, Bellón JÁ, Motrico E, et al. Moderators of
psychological and psychoeducational interventions for the
prevention of depression: a systematic review. Clin Psychol Rev 2020;
79: 101859.
108 Loechner J, Starman K, Galuschka K, et al. Preventing depression
in the offspring of parents with depression: a systematic review and
meta-analysis of randomized controlled trials. Clin Psychol Rev 2018;
60: 1–14.
109 Garber J, Clarke GN, Weersing VR, et al. Prevention of depression
in at-risk adolescents: a randomized controlled trial. JAMA 2009;
301: 2215–24.
110 Havinga PJ, Maciejewski DF, Hartman CA, Hillegers MHJ,
Schoevers RA, Penninx BWJH. Prevention programmes for
children of parents with a mood/anxiety disorder: systematic review
of existing programmes and meta-analysis of their efficacy.
Br J Clin Psychol 2021; 60: 212–51.
111 Shinde S, Weiss HA, Varghese B, et al. Promoting school climate
and health outcomes with the SEHER multi-component secondary
school intervention in Bihar, India: a cluster-randomised controlled
trial. Lancet 2018; 392: 2465–77.
112 Shinde S, Weiss HA, Khandeparkar P, et al. A multicomponent
secondary school health promotion intervention and adolescent
health: an extension of the SEHER cluster randomised controlled
trial in Bihar, India. PLoS Med 2020; 17: e1003021.
113 Werner-Seidler A, Perry Y, Calear AL, Newby JM, Christensen H.
School-based depression and anxiety prevention programs for
young people: a systematic review and meta-analysis.
Clin Psychol Rev 2017; 51: 30–47.
114 Bonell C, Allen E, Warren E, et al. Effects of the Learning Together
intervention on bullying and aggression in English secondary
schools (INCLUSIVE): a cluster randomised controlled trial. Lancet
2018; 392: 2452–64.
115 Machado DB, Williamson E, Pescarini JM, et al. The impact
of a national cash transfer programme on reducing suicide: a study
using the 100 million Brazilian cohort. SSRN 2021; published
online Jan 14. https://doi.org/10.2139/ssrn.3766234 (preprint).
116 Merikangas KR, He JP, Burstein M, et al. Service utilization for
lifetime mental disorders in U.S. adolescents: results of the
National Comorbidity Survey-Adolescent Supplement (NCS-A).
J Am Acad Child Adolesc Psychiatry 2011; 50: 32–45.
117 Siu AL. Screening for depression in children and adolescents:
US Preventive Services Task Force recommendation statement.
Pediatrics 2016; 137: e20154467.
118 Roseman M, Saadat N, Riehm KE, et al. Depression screening and
health outcomes in children and adolescents: a systematic review.
Can J Psychiatry 2017; 62: 813–17.
119 National Institute for Health and Care Excellence. Depression in
children and young people: identification and management.
National Institute for Health and Care Excellence. 2019. https://
www.nice.org.uk/guidance/ng134 (accessed Nov 10, 2021).
120 Stockings E, Degenhardt L, Lee YY, et al. Symptom screening
scales for detecting major depressive disorder in children
and adolescents: a systematic review and meta-analysis of
reliability, validity and diagnostic utility. J Affect Disord 2015;
174: 447–63.
 Seminar
121 Kovacs M, Yaroslavsky I. Practitioner review: dysphoria and its
regulation in child and adolescent depression.
J Child Psychol Psychiatry 2014; 55: 741–57.
122 Hopkins K, Crosland P, Elliott N, Bewley S. Diagnosis and
management of depression in children and young people:
summary of updated NICE guidance. BMJ 2015; 350: h824.
123 Krause K, Midgley N, Edbrooke-Childs J, Wolpert M.
A comprehensive mapping of outcomes following psychotherapy
for adolescent depression: the perspectives of young people,
their parents and therapists. Eur Child Adolesc Psychiatry 2021;
30: 1779–91.
124 Pozuelo JR, Desborough L, Stein A, Cipriani A. Systematic review
and meta-analysis: depressive symptoms and risky behaviors
among adolescents in low- and middle-income countries.
J Am Acad Child Adolesc Psychiatry 2022; 61: 255–76.
125 Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J.
An inventory for measuring depression. Arch Gen Psychiatry 1961;
4: 561–71.
126 Radloff LS. The use of the Center for Epidemiologic Studies
Depression Scale in adolescents and young adults. J Youth Adolesc
1991; 20: 149–66.
127 Kovacs M. The Children’s Depression Inventory (CDI).
Psychopharmacol Bull 1985; 21: 995–98.
128 Angold A, Costello EJ. Mood and Feelings Questionnaire (MFQ).
1987. https://devepi.duhs.duke.edu/measures/the-mood-and-
feelings-questionnaire-mfq/ (accessed Dec 2, 2021).
129 Kroenke K, Spitzer RL, Williams JBW. The PHQ-9: validity of a
brief depression severity measure. J Gen Intern Med 2001;
16: 606–13.
130 Reynolds WM. Reynolds Adolescent Depression Scale. Odessa, FL:
Psychological Assessment Resources, 1987.
131 Chorpita BF, Moffitt CE, Gray J. Psychometric properties of the
Revised Child Anxiety and Depression Scale in a clinical sample.
Behav Res Ther 2005; 43: 309–22.
132 Richardson LP, McCauley E, Grossman DC, et al. Evaluation of the
Patient Health Questionnaire-9 item for detecting major depression
among adolescents. Pediatrics 2010; 126: 1117–23.
133 Forman-Hoffman V, McClure E, McKeeman J, et al. Screening for
major depressive disorder in children and adolescents: a systematic
review for the U.S. preventive services task force. Ann Intern Med
2016; 164: 342–49.
134 Krause KR, Chung S, Adewuya AO, et al. International consensus
on a standard set of outcome measures for child and youth anxiety,
depression, obsessive-compulsive disorder, and post-traumatic
stress disorder. Lancet Psychiatry, 8: 76–86.
135 Wood A, Kroll L, Moore A, Harrington R. Properties of the Mood
and Feelings Questionnaire in adolescent psychiatric outpatients:
a research note. J Child Psychol Psychiatry 1995; 36: 327–34.
136 Piqueras JA, Martín-Vivar M, Sandin B, San Luis C, Pineda D.
The Revised Child Anxiety and Depression Scale: a systematic
review and reliability generalization meta-analysis. J Affect Disord
2017; 218: 153–69.
137 Carnevale T. An integrative review of adolescent depression
screening instruments: applicability for use by school nurses.
J Child Adolesc Psychiatr Nurs 2011; 24: 51–57.
138 Thabrew H, Ruppeldt P, Sollers JJ 3rd. Systematic review of
biofeedback interventions for addressing anxiety and depression in
children and adolescents with long-term physical conditions.
Appl Psychophysiol Biofeedback 2018; 43: 179–92.
139 Myers K, Winters NC. Ten-year review of rating scales. II: scales for
internalizing disorders. J Am Acad Child Adolesc Psychiatry 2002;
41: 634–59.
140 Roseman M, Kloda LA, Saadat N, et al. Accuracy of depression
screening tools to detect major depression in children and
adolescents: a systematic review. Can J Psychiatry 2016;
61: 746–57.
141 Simmons M, Wilkinson P, Dubicka B. Measurement issues:
depression measures in children and adolescents.
Child Adolesc Ment Health 2015; 20: 230–41.
142 Thabrew H, Stasiak K, Bavin LM, Frampton C, Merry S.
Validation of the Mood and Feelings Questionnaire (MFQ) and
Short Mood and Feelings Questionnaire (SMFQ) in New Zealand
help-seeking adolescents. Int J Methods Psychiatr Res 2018;
27: e1610.
14 www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1
143 Daviss WB, Birmaher B, Melhem NA, Axelson DA, Michaels SM,
Brent DA. Criterion validity of the Mood and Feelings
Questionnaire for depressive episodes in clinic and non-clinic
subjects. J Child Psychol Psychiatry 2006; 47: 927–34.
144 Ambrosini PJ. Historical development and present status of the
Schedule for Affective Disorders and Schizophrenia for School-Age
Children (K-SADS). J Am Acad Child Adolesc Psychiatry 2000;
39: 49–58.
145 Goodman R, Ford T, Richards H, Gatward R, Meltzer H.
The Development and Well-Being Assessment: description and
initial validation of an integrated assessment of child and
adolescent psychopathology. J Child Psychol Psychiatry 2000;
41: 645–55.
146 Schleider J, Weisz J. A single-session growth mindset intervention
for adolescent anxiety and depression: 9-month outcomes
of a randomized trial. J Child Psychol Psychiatry 2018; 59: 160–70.
147 Schleider JL, Weisz JR. Little treatments, promising effects?
Meta-analysis of single-session interventions for youth
psychiatric problems. J Am Acad Child Adolesc Psychiatry 2017;
56: 107–15.
148 Michelson D, Malik K, Parikh R, et al. Effectiveness of a brief lay
counsellor-delivered, problem-solving intervention for adolescent
mental health problems in urban, low-income schools in India:
a randomised controlled trial. Lancet Child Adolesc Health 2020;
4: 571–82.
149 Uppendahl JR, Alozkan-Sever C, Cuijpers P, de Vries R,
Sijbrandij M. Psychological and psychosocial interventions for
PTSD, depression and anxiety among children and adolescents in
low- and middle-income countries: a meta-analysis. Front Psychiatry
2020; 10: 933.
150 Osborn TL, Venturo-Conerly KE, Arango G S, et al. Effect of
Shamiri layperson-provided intervention vs study skills control
intervention for depression and anxiety symptoms in adolescents
in Kenya: a randomized clinical trial. JAMA Psychiatry 2021;
78: 829–37.
151 Zhou X, Teng T, Zhang Y, et al. Comparative efficacy and
acceptability of antidepressants, psychotherapies, and their
combination for acute treatment of children and adolescents with
depressive disorder: a systematic review and network meta-
analysis. Lancet Psychiatry 2020; 7: 581–601.
152 Eckshtain D, Kuppens S, Ugueto A, et al. Meta-analysis: 13-year
follow-up of psychotherapy effects on youth depression.
J Am Acad Child Adolesc Psychiatry 2020; 59: 45–63.
153 Oud M, de Winter L, Vermeulen-Smit E, et al. Effectiveness of
CBT for children and adolescents with depression: a systematic
review and meta-regression analysis. Eur Psychiatry 2019;
57: 33–45.
154 Kunas SL, Lautenbacher LM, Lueken PU, Hilbert K. Psychological
predictors of cognitive-behavioral therapy outcomes for anxiety
and depressive disorders in children and adolescents: a systematic
review and meta-analysis. J Affect Disord 2021; 278: 614–26.
155 Garrido S, Millington C, Cheers D, et al. What works and what
doesn’t work? A systematic review of digital mental health
interventions for depression and anxiety in young people.
Front Psychiatry 2019; 10: 759.
156 Goodyer IM, Reynolds S, Barrett B, et al. Cognitive behavioural
therapy and short-term psychoanalytical psychotherapy versus
a brief psychosocial intervention in adolescents with unipolar
major depressive disorder (IMPACT): a multicentre, pragmatic,
observer-blind, randomised controlled superiority trial.
Lancet Psychiatry 2017; 4: 109–19.
157 Luby JL, Barch DM, Whalen D, Tillman R, Freedland KE.
A randomized controlled trial of parent-child psychotherapy
targeting emotion development for early childhood depression.
Am J Psychiatry 2018; 175: 1102–10.
158 Asarnow JR, Tompson MC, Klomhaus AM, Babeva K, Langer DA,
Sugar CA. Randomized controlled trial of family-focused treatment
for child depression compared to individual psychotherapy: one-
year outcomes. J Child Psychol Psychiatry 2020; 61: 662–71.
159 Jeppesen P, Wolf RT, Nielsen SM, et al. Effectiveness of
transdiagnostic cognitive-behavioral psychotherapy compared with
management as usual for youth with common mental health
problems: a randomized clinical trial. JAMA Psychiatry 2021;
78: 250–60.

160 Hetrick SE, McKenzie JE, Bailey AP, et al. New generation
antidepressants for depression in children and adolescents:
a network meta-analysis. Cochrane Database Syst Rev 2021;
5: CD013674.
161 Rink L, Braun C, Bschor T, Henssler J, Franklin J, Baethge C.
Dose increase versus unchanged continuation of antidepressants
after initial antidepressant treatment failure in patients with
major depressive disorder: a systematic review and meta-analysis
of randomized, double-blind trials. J Clin Psychiatry 2018;
79: 17r11693.
162 Eckshtain D, Marchette LK, Schleider J, Evans S, Weisz JR.
Parental depressive symptoms as a predictor of outcome in the
treatment of child internalizing and externalizing problems.
J Abnorm Child Psychol 2019; 47: 459–74.
163 Emslie GJ, Kennard BD, Mayes TL, et al. Fluoxetine versus
placebo in preventing relapse of major depression in children and
adolescents. Am J Psychiatry 2008; 165: 459–67.
164 Emslie GJ, Kennard BD, Mayes TL, et al. Continued effectiveness
of relapse prevention cognitive-behavioral therapy following
fluoxetine treatment in youth with major depressive disorder.
J Am Acad Child Adolesc Psychiatry 2015; 54: 991–98.
www.thelancet.com Published online August 5, 2022 https://doi.org/10.1016/S0140-6736(22)01012-1 15
Seminar
165 Brent D, Emslie G, Clarke G, et al. Switching to another SSRI
or to venlafaxine with or without cognitive behavioral therapy for
adolescents with SSRI-resistant depression: the TORDIA
randomized controlled trial. JAMA 2008; 299: 901–13.
166 Kim S, Rush BS, Rice TR. A systematic review of therapeutic
ketamine use in children and adolescents with treatment-resistant
mood disorders. Eur Child Adolesc Psychiatry 2021; 30: 1485–501.
167 Majumder P, Balan S, Gupta V, Wadhwa R, Perera TD. The safety
and efficacy of repetitive transcranial magnetic stimulation in the
treatment of major depression among children and adolescents:
a systematic review. Cureus 2021; 13: e14564.
168 McGorry PD, Mei C, Chanen A, Hodges C, Alvarez-Jimenez M,
Killackey E. Designing and scaling up integrated youth mental
health care. World Psychiatry 2022; 21: 61–76.
Copyright © 2022 Elsevier Ltd. All rights reserved.