Child Adolesc Psychiatric Clin N Am

15 (2006) 883–897

Depression in Infancy
Miri Keren, MDa,b,*, Sam Tyano, MDa,b,c
a
Tel-Aviv University Sackler School of Medicine, Lebanon Street, Tel-Aviv 69978, Israel
b
Infant Mental Health Unit, Geha Mental Health Center, Kupat Holim Clalit,
8 Orlanski Street, Petah Tiqva, Israel
c
Israeli National Project of Infant Psychiatry, Sacta-Rashi Foundation,
Kfar Hanoar Ben Shemen, Israel

The evolution of the concept of depression in infancy

The evolution of the concept of depression in infancy (0–3 years) and
toddlerhood (3–5 years) follows a path similar to the history of the diagnosis
of depression in adolescence and then in school-aged children. It starts with
the unexpected observation of similar symptoms in a specific age popula-
tion. In 1971, Cytryn [1] was the first to report depressive symptoms (sad-
ness, withdrawal, impairment in functioning, social isolation, helplessness
and hopelessness) in young adolescents with chronic medical illnesses.
This clinical presentation was first understood as a mimicry of adult depres-
sion; only later was it viewed as an entity in itself, with distinct features,
course, and response to medications [2,3]. The same happened for depres-
sion in children. In the 1960s and 1970s, depression in school-aged children
was thought as impossible because of the assumed lack of well-developed
sense of self. Puig-Antich and colleagues [4] published a pilot study that
was a major step in the validation process of the entity of depression in pre-
pubertal children. Kovacs [5,6] showed the existence of depression in chil-
dren as young as 6 years old as a significant illness with long-term impact.
Luby and colleagues [7,8] found empirical data that validated the existence
of preschool depression. In turn, it took many years until the notion that an
infant can be depressed was accepted and taught, despite the early report on
a depressive clinical syndrome, termed anaclitic depression, by Spitz [9].

* Corresponding author. Infant Mental Health Unit, Kupat Holim Clalit, 8 Orlanski
Street, Petah Tiqva, Israel.
E-mail address: addressofkeren@internet-zahav.net (M. Keren).

1056-4993/06/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved.
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884 KEREN & TYANO

Theoretical inferences about depression in infancy

Because children were assumed to be unable to develop depression
because of their lack of superego (the intrapsychic structure traditionally
linked to depression), it took many years to revise the assumption that in-
fants and toddlers cannot be depressed because of their limited emotional
incompetence and cognitive skills. Widlocher [10] defined three major com-
ponents in the diagnosis of depression: the psychic pain, the psychomotor
inhibition, and the loss of self-esteem. The capacity for psychic pain is a pre-
requisite for the existence of depression. The first person to infer the exis-
tence of psychic suffering in infants was Spitz [9], who observed that in
extreme cases, psychic pain ultimately can lead to an infant’s death, inde-
pendent of the availability of food and shelter. He described the existence
of a depressive syndrome in institutionalized infants. These infants had ex-
perienced separation from their parents and demonstrated apathy, sad facial
expression, and lack of responsiveness to alternative caregivers. Failure to
thrive and severe psychomotor delay were the rule. Spitz’s syndrome of an-
aclitic depression suggested that early and severe psychosocial deprivation
impinges on an infant’s developing affective system.
The fundamental significance of Spitz’s observations was missed for de-
cades, possibly because they came from children in extreme social situations,
such as orphanages and tragic loss of parents in war. Instead, greater atten-
tion was given in child psychiatry to neurobiologic conditions, such as infan-
tile autism and early-onset schizophrenia. In 1980, Bowlby [11] brought up
again the idea of depression in young children secondary to separation from
the infant’s caregiver. He described three stages: (1) anxiety, protest, crying,
sleep and feeding problems, (2) full depressive syndrome, with apathy, psy-
chomotor retardation, and loss of interest in surroundings, and (3) perma-
nent apathy despite the caregiver’s return. Bowlby and Spitz observed the
existence of depression in infants as secondary to separation (more or less
permanent) from their caregivers. In 1987, Kreisler [12] was one of the first
clinicians to link life-threatening feeding disorders with depression in in-
fancy. He described several cases of fatal psychogenic vomiting in infants
younger than 24 months and used the term ‘‘don’t want to live.’’ Kreisler
applied Freud’s [13] notions of ‘‘will to live’’ (the ‘‘eros’’ drive) versus the
lack of will to live (‘‘thanatos’’ drive) to infants. Lebovici [14] added the in-
tergenerational dimension to the infant’s development of self and demon-
strated through clinical observations an infant’s ability to perceive familial
painful and unconscious conflicts.

Developmental research data on the infant’s emotional competence

In parallel to these significant but somewhat anecdotal clinical observa-
tions, an important step was achieved by combining them with research
data coming from developmental studies on the development of emotions
and emotional competence in infancy. Izard and colleagues [15] demonstrated
 DEPRESSION IN INFANCY 885

an infant’s ability to produce discrete emotions, such as interest, contentment,

and distress, in 2-month-old infants and eight discrete emotions (joy, content-
ment, anger, disgust, surprise, interest, and sadness) at 8 months of age. The
next step was to show an infant’s ability to perceive and react to the emotional
expressions of others. Cohn and Tronick [16] developed a well-known proce-
dure, the still face paradigm, to study 3-month-olds babies’ reactions to a de-
pressive-like maternal affect. They found that the infants first reacted with
protest, then appeared weary, and finally avoided their mothers’ gaze. Affect
attunement between the baby and the parent has been described by Stern [17]
as a major step in the adaptive emotional regulation that is conceived as ‘‘the
ability to experience a broad range of emotions and to modulate the intensity
and duration of specific emotions’’ [18]. Recent neurobiologic research data
suggest the existence of a neurophysiologic mechanism termed the ‘‘mirror-
neuron mechanism’’ [19,20], which would play a major role in understanding
the actions and the emotions of others. Elaborate facial communication is ac-
companied by specializations in brain areas that control facial movement. The
evolution of emotional awareness (the premise of empathy) might have a neu-
ral basis in specialized cells in the neocortex, such as spindle cells that have
been associated with self-conscious emotions and mirror neurons that have
been shown to activate in response to communicative facial gestures [21]. Le-
slie and colleagues [22] suggest that there may be a right hemisphere mirroring
system that could provide a neural substrate for empathy. In parallel, we know
that the right hemisphere is dominant in infancy, and early attachment
experiences are dominant in an infant’s daily life. It is temptingdbut still
precariousdto create a link between this mirroring system and the mother-
infant interactive phenomena of mirroring described by Winnicott [23].
It is well established that as early as 3 years, children are able to identify
and name some of their discrete emotional states accurately [24], which
means that they are able to report sadness. They are also able to identify
emotional states from drawings of facial expressions and link them with ap-
propriate social situations, which reflects the development of a theory of
mind [25].

Developmental depressive states

One must distinguish developmental depressive states from the clinical
syndrome of depression. Melanie Klein introduced the psychoanalytical no-
tion of the 8-month-old infant’s depressive position [26,27]. Adopting
Freud’s ‘‘dual instinct theory,’’ she suggested that infants actively organize
their experiences of sexual and aggressive drives in specific and rich fanta-
sies, and she described two developmental phases: (1) the earliest phase of
the paranoid position, in which an infant feels persecuted by the maternal
object (as represented by the breast) and (2) the depressive position, a phase
of repair with the infant’s feelings of guilt for the aggressive impulses toward
the mother. Winnicott [28], unlike Klein, addressed the mother’s role: an
886 KEREN & TYANO

infant expects his or her needs to be satisfied immediately, and during the
normative postpartum 6- to 8-week period of the primary maternal preoccu-
pation, the mother usually does, which creates in the infant the omnipotent
illusion that the external reality corresponds to his or her own capacity to
create. A normal gradual disillusionment process follows, in which daily
small frustrations create some anxiety and sadness, which are alleviated
by the acquisition of a transitional object. Golse and Messerschmitt [29] de-
scribed three developmental depressive phases: stranger anxiety (at age 8
months), the oedipal period sadness, and the ‘‘sad thoughts’’ characteristic
of the adolescence period. They defined the phases as periods of vulnerabil-
ity linked to the developmental loss of a special status or a relational object.
An infant’s new understanding of the notion of unfamiliar signifies not only
a new cognitive ability of distinguishing between familiar and nonfamiliar
but also the emotional perception of the potential separation/loss of the pa-
rental object. This developmental phase bears a component of sadness and
anxiety. Arfouilloux [30] further developed the link between an infant’s nor-
mative depressive disposition and the phase of disillusionment over the ab-
solute power of the thoughts and desires, which embeds in it a loss of trust in
the human mind over the external reality and may lead to feelings of help-
lessness and despair. Healthy infants and, to a lesser but significant extent,
healthy adults must keep some of their belief in the power of the mind to
impact on the reality. Play or the capacity to create a transitional space is
the normative way an infant masters these moments of existential helpless-
ness, of potential clinical depression [31].
One must emphasize the theoretical nature of this concept of develop-
mental depressive states and the lack of empirical support. It is not sur-
prising that clinicians who work in the field of infancy and observe
symptoms in infants that evoke depression prefer to use the criteria for di-
agnosis of depression as defined in the Diagnostic Classification of Mental
Health and Developmental Disorders of Infancy and Early Childhood
(DC:0-3) [32] and in the newly revised edition (DC:0-3R) [33], as reviewed
later.

Etiology of depression in infancy

Primary versus secondary to the infant’s context
The inclusion of depression in the official diagnostic classification for in-
fants and toddlers was a significant step in the process of conceptualizing
the clinical cases that infant mental health clinicians face in various settings
around the world and designing research studies in this domain of disorders
of affect in infancy. Well-designed studies are greatly needed because of the nu-
merous questions that are still unanswered. In our view, a major question is
whether depression in infants can be endogenous, as in older children and ad-
olescents, or whether it is always reactive to environmental adverse factors.
 DEPRESSION IN INFANCY 887

This question is relevant to many of the disorders observed in infants be-

cause of their obvious basic dependence on primary caregivers. Some re-
searchers argue for understanding the symptoms of infants as a reflection of
a maladaptive relationship with their parents, which in turn leads to internal-
ized distortions and neurobiologic changes that are the basis of later disorders
that occur independent of the primary relationship, as early as preschool
age. Luby and colleagues [34] investigated whether a melancholic type of de-
pression, similar to that diagnosed in depressed adults, could be identified in
156 preschool children aged 3 to 5.6 years. The depressed group was divided
into depressed preschoolers with and without anhedonia (‘‘hedonic’’), com-
pared with a group of preschoolers with another psychiatric diagnosis, such
as attention deficit disorder or oppositional-defiant disorder, and a healthy
comparison group. Of the 54 identified depressed preschoolers, 57% were an-
hedonic, with greater depression severity, alterations in stress cortisol reactiv-
ity, increased family history of major depressive illness, psychomotor
retardation, and lack of brightening in response to joyful events. The authors
concluded that this subgroup of depression is similar to melancholic depres-
sion and adults and can manifest in children as young as 3 years old.
Although interesting, these findings still do not answer the fundamental
question of endogenous versus reactive etiology of depression in infancy, be-
cause one may argue that these children, already preschoolers, had experi-
enced in their first 3 years a familial transmission of depression through
parenting behaviors and not necessarily primarily genetic or biologic. To
the best of our knowledge, no similar study has been conducted in children
younger than age 3 years.

Infant depression contiguous to identifiable adverse conditions

Loss of parent and prolonged grief
This topic was described in a previous section under the term ‘‘anaclitic
depression.’’

Maternal major psychopathology

The impact of maternal depression on infants has been studied extensively
since Cohn and Tronick’s landmark study [16], in which they developed a par-
adigm that mimicked maternal depression (the still face procedure) and
showed that infants aged 3 months are sensitive and reactive to the expression
of negative affect in their caregivers. Field [35] compared infants of depressed
mothers with infants of healthy mothers in their reactions to the still face pro-
cedure. They found that the former did not show the normal reactions of anger
and protest and suggested that these infants of depressed mothers already had
acclimated to their caregiver’s flat or negative emotions. These findings sug-
gested a possible enduring effect of exposure to depressed caregivers, even be-
yond the immediate interactions with the infant, which has been strengthened
by a more recent study. Field and colleagues [36] found that infants of
888 KEREN & TYANO

depressed mothers, although they interacted better with other attachment fig-
ures (eg, fathers, daycare providers), seemed to have generalized their reac-
tions to interactions with unfamiliar adults.

Biologic findings in infants of depressed mothers

Decreased vagal tone (as measured by heart variability, a physiologic
measure of the parasympathetic nervous system function in stress regula-
tion) in infants of depressed mothers during face-to-face interactions led
to the question of whether biologic changes in infants of depressed mothers
may become trait related and ultimately independent of the quality of the
parent-infant relationship [37]. This issue has received even more attention
after reports on several electroencephalogram studies in depressed adults
and infants of depressed mothers. Greater right frontal activation (right
frontal asymmetry) and lower left frontal activation are characteristic of
healthy adults during normal negative emotional states, and with a reverse
pattern during positive emotional states. The same pattern of asymmetry
was recorded in 10-month-old infants in response to happy and sad video-
tapes [38]. Right frontal asymmetry in infants of depressed mothers at 3 and
6 months of age has been identified [39]. They have been shown as lacking
the control group infants’ greater right frontal activation during a stress-in-
ducing separation from their mothers [40]. Similar electroencephalogram
patterns have been reported in depressed adults [41]. To summarize, these
contingent findings on right frontal asymmetry may be associated with an
early acquired biologic vulnerability for later depression in infants who
have been exposed to depressive mothers in their first months of life. Possi-
bly linked to this assumption is Luby’s finding of alterations in stress corti-
sol activity in depressed preschoolers, which is consistent with findings
described in adults [42].
Maternal schizophrenia has been linked to infants’ abnormal patterns of
interactions with significant and social others, such as the lack of stranger
anxiety, insecure attachments [43,44], and lessened ability to attend to, reg-
ulate, and control their social surroundings [45,46]. To the best of our best
knowledge, no possible link between maternal schizophrenia and infant de-
pression has been reported, nor have infants of mothers who have severe ob-
sessive-compulsive disorder been studied. In our clinical experience, we had
several cases of infant depression secondary to severe maternal obsessive
compulsive disorder. Andre Green [47] introduced the concept of the
‘‘dead mother’’ to capture all the clinical conditions regardless of the
mother’s psychiatric diagnosis. In this concept the mother is psychologically
absent for the infant, and according to Green, the infant identifies with the
maternal emptiness to ultimately keep in touch with her. In Green’s clinical
perspective, such an early experience often leads to severe adult personality
psychopathology, in which emptiness is the most prominent symptom and
the patient resists its alleviation.
 DEPRESSION IN INFANCY 889

Clinical vignette
Patient A, a 2.5-year-old only child of a Jewish orthodox couple, was
referred to our unit because of severe delay in language, hyperactivity,
general lack of interest, and running away from the parents upon return
home from kindergarten. The child did not eat well sleep well, and he rarely
laughed. He was diagnosed with pervasive developmental disorder and at-
tention deficit disorder by a child neurologist. The parents asked for a second
opinion. They perceived their child as ‘‘dumb,’’ did not believe he would
ever talk, and had feelings of resentment and disappointment toward him.
On examination, he looked sad and poorly groomed and did not approach
his parents, but he did explore the room and the toys. The child hardly
spoke but said the words ‘‘my’’ and ‘‘I.’’ He did not ask for help when faced
with a difficulty but turned to a therapist. Along the next four sessions, a full
and gloomy picture of the context into which the child was born emerged.
The mother had suffered with severe obsessive compulsive disorder since
her teenage years and was never treated. Her family history was loaded
with psychopathology (own mother had severe anxiety disorder, a brother
had psychosis, a sister had trichotillomania). After A.’s birth, the mother be-
came overwhelmed with compulsive cleaning and increasing anger at the
baby, whose care interfered with her compulsions. She kept him in his
crib to prevent him from touching and messing things. The baby became ir-
ritable, but the parents attributed it to a bad temperament. He had severe
temper tantrums around bathing time and diaper changes, and the mother
washed him endlessly from fear of his stools. He was put in a daycare at
the age of 8 months, where he improved, but he did not improve at
home, and at the time of referral, he refused to go home until dawn. We di-
agnosed the child with depression reactive to maternal obsessive compulsive
disorder on the first DC:0-3R axis and mother-child relationship disorder on
the second axis. He did not meet any criteria for pervasive developmental
disorder. After 1.5 years of triadic psychotherapy, the child had improved
in all domains, was communicative, and had a good relationship with his fa-
ther but still was tense with his mother and had difficulties with peers.

Exposure to violence and early traumatic experiences

These events have been shown to impact on infants’ and toddlers’ quality
of interpersonal relationships (eg, aggressive and withdrawal behaviors to-
ward peers), affect regulation (eg, lack of pleasure and interest, together
with outbursts of crying and anger), and affect self-development (including
self-understanding, self-esteem, and self-efficacy) [48]. These infants, when
met early, look sad and meet criteria for depression; in toddlers, the aggres-
sive behaviors usually bring them to professional attention, but the underly-
ing depressive dynamics are the same. The treatment process is usually
complex when the perpetuators of the adverse attachment experiences are
the caregivers themselves.
890 KEREN & TYANO

Clinical vignette
Patient L, a 1.5-year-old boy, was referred to our infant mental health
clinic for irritability, head banging, biting, hitting himself and others, and
frequent awakenings at night with inconsolable crying. His father was
diagnosed with antisocial personality and was described as an impulsive,
violent man with unpredictable bouts of kindness and empathy. The mother
was diagnosed with borderline personality disorder and had a past history
of alcoholism and prostitution. L. was born at week 41 by caesarean section
because of fetal distress. He was perceived as a difficult baby, and his crying
made the father irritable. At the age of 2 months, his father lost patience and
hit him. The father was appalled by his own reaction and asked for psychi-
atric treatment. L. bit his mother at the age of 7 to 8 months, which elicited
no protest on her part. When L. was 10 months old, a second son was born
(unplanned). The Parents asked for help and seemed to understand the im-
pact of their poor parenting skills and their own histories on L. They fared
well with their second child, who was born with an easy temperament. Child
social welfare was involved, and the parents were given a chance to change.
At the evaluation, L.’s affect was sad, he showed no interest in play, he had
a disorganized attachment pattern to both parents, and he showed self-
injurious behaviors. He improved during the first year of outpatient
parent-infant psychotherapy and was referred to a therapeutic daycare,
where he spent 3 years. His parents were not consistently involved in the
therapeutic process and expressed strong rejection. After 4 years of treat-
ment, the parents asked to place L. in foster care. At that time, L. looked
sadder than ever and expressed feelings of hopelessness and lack of worth.
This case illustrates not only the severity of the reactive depression from
which this infant suffered but also the poor prognosis of such cases in which
biologic risk factors in an infant (eg, difficult temperament) and psycholog-
ical risk factors in the parents come together. In retrospect, we may have
needed to place the infant in foster care at the age of 1.5 years, when he
came to our attention, despite the impression the parents gave about their
readiness to change their emotional and behavioral attitudes toward the
child.

Life-threatening illness
Golse and Keren [49] reviewed the clinical phenomena linked to depres-
sion in young infants hospitalized for life-threatening illnesses. Besides the
impact of the hospitalization itself, which has become less detrimental
than in the past because of pediatricians’ awareness of the importance of
parents’ presence at a child’s bedside, the main issue the authors emphasize
is an infant’s ability to perceive the manifestations of giving up and the fre-
quent emotional abandonment by parents or staff while facing the menace
of the infant’s death (phenomenon of parental anticipated grief). The infant,
prematurely left with the loneliness of death, is then at real risk of
 DEPRESSION IN INFANCY 891

developing a depressive reaction, especially if it reactivates previous episodes

of parental withdrawal.

Chronic physical pain

Gauvain-Piquard and Meignier [50] collected clinical observations and
reports of young children’s reactions to pain and the medical pediatric
team’s lack of attention to it. The reactions manifested withdrawal and
muteness, which seemed like an autistic reaction.

Clinical vignette
Patient N was 21 months old at the time of referral to our unit because of
food refusal. He was diagnosed with a severe genetic skin disease, Netherton
syndrome, which is an autosomal-recessive disease characterized by massive
ichthyosis, recurrent skin infections, continuous itching, scars, hair defects,
and various degrees of failure to thrive and mental retardation. N.’s delivery
was difficult and traumatic. He spent his first 3 months of life in the neonatal
intensive care unit in total isolation because of fear of life-threatening infec-
tion. Nobody was allowed to touch him. To look at him was painful because
he appeared to be covered with third-degree burns. His mouth opening was
so small that he could be fed only through gastrostomy. Touching the mat-
ter of the infant’s illness was as painful for the parents (and the medical
team) as touching the infant. N. had a stern look in his eyes and sat motion-
less. Although there was no specific medical reason for the absence of crawl-
ing, L. looked as if imprisoned in his own body. He scratched himself in
complete silence, absorbed in his painful body. L’s parents also were ab-
sorbed in their own grief over the healthy baby who was not born. L’s still-
ness reminded us of Fraiberg’s [51] notion of ‘‘freezing’’ as one of the
pathologic defenses seen in infants. L’s mother also concealed her own de-
pression that had started at birth. Improvement in the infant’s condition
started with the process of approaching the issue of L.’s psychic pain with
the pediatrician, parents, and infant present together.
Developmental arrest, food refusal, extreme psychomotor retardation,
lack of vitality, and withdrawal from interactions were L.’s depressive symp-
toms that had been undiagnosed for months, mainly because the detrimental
impact of chronic severe pain and damaged skin envelope on the infant’s de-
velopment and the early parent-infant relationship was overlooked.

Diagnosis
Luby and colleagues [52] showed how DSM-IV criteria for depression
captured the most severely affected preschoolers and missed a substantial
number of children with potentially significant, although less severe, symp-
toms. These children, in turn, were captured by modified DSM-IV criteria,
in which the strict 2-week duration criteria were put aside and children with
892 KEREN & TYANO

core symptoms of sadness/irritability and anhedonia (even if they did not

have the five required symptoms) were included. Luby and colleagues [53]
recommended using the Preschool Feelings Checklist, because they have
found it to be a brief and sensitive measure for depression in young children.
The DC:0-3R diagnostic classification for infants and toddlers younger
than age 3 reflects a developmentally sensitive modification of the DSM-
IV-R criteria [33]. Empirical testing of these operational criteria is still
needed, however.
Type I: Major depression is defined as follows [33]: Five of the following
symptoms must be present most of the day, more days than not, for at least
2 weeks and must include one of the first two symptoms:
1. Depressed mood, as indicated by either the child’s direct expression
(such as ‘‘I’m sad’’) or observation by others (such as ‘‘the child appears
sad or is tearful’’)
2. Markedly diminished pleasure or interest in all, or almost all, activities
3. Significant weight loss or gain (a change of more than 5% of body
weight in a month, significant decrease or increase in appetite, or failure
to make expected weight gains)
4. Insomnia or hypersomnia
5. Psychomotor agitation or retardation
6. Fatigue or loss of energy
7. Evidence of feelings of worthlessness or inappropriate guilt in play (such
as self-punitive actions and play) or in the child’s direct expression
8. Diminished ability to think or concentrate or difficulty in solving prob-
lems, responding to caregivers, or sustaining attention
9. Recurrent allusions to or themes of death or suicide or attempts at self-
harm. The child may demonstrate these symptoms through thoughts,
activities, play, or potentially lethal behaviors
Type II: Depressive disorder not otherwise specified requires the presence
of three or four of the nine symptoms described for Type I, with at least one
of them being one of the first two symptoms, for at least 2 weeks.

Differential diagnosis
Organic diseases, such as space-occupying lesions, hypothyroidism, and
metabolic abnormalities, should be ruled out in every infant who has depres-
sive symptoms, especially in endogenous depression (ie, cases in which the
environmental trigger factor is not obvious). In the presence of severe psy-
chosocial deprivation, the diagnosis of deprivation/maltreatment disorder of
infancy should be considered. In the presence of significant trauma, post-
traumatic stress disorder of infancy should be considered as the primary di-
agnosis. Autism may be confused with the diagnosis of depression in young
preverbal and withdrawn children, as in the clinical vignette (A.’s case)
 DEPRESSION IN INFANCY 893

described previously. Adjustment reaction with depressive features should

be considered whenever depressive symptoms are not severe and appear in
the context of a clear stressful factor to which an infant is gradually
adjusting.

Prevalence of the diagnosis of depression in clinical settings for infants

Since the introduction of the DC:0-3, several infant mental health units
around the world have put forth special effort at diagnosing their referred
infants and parents. This common classification, despite its limitations,
has had the great advantage of enabling comparison of frequencies of diag-
noses among infant mental health clinicians. Reports on prevalence of the
diagnosis of depression range from 3% (n ¼ 343) in a Portugese unit [54],
to 1.2% (n ¼ 85) in a Parisian unit [55], and 0.5% (n ¼ 414) in an Israeli
unit [56]. As Emde and Wise [57] pointed out, the distribution of the various
diagnoses is influenced by the nature of the setting (outpatient clinic versus
general hospital). These figures are probably not absolute, but it is clear that
the diagnosis of depression was given in all the units. The DC:0-3R has de-
fined more precise guidelines that will help to improve the quality of the ep-
idemiologic data on depression in infancy.

Treatment
To the best of our best knowledge, there are no comparative data regard-
ing treatment modalities for depression in infancy. Parent-infant psycho-
therapy, setting up a support system, therapy and medications for ill
parents, and placement outside the home should be applied according to
the specific characteristics of the environmental trigger factors [58]. No
guidelines for antidepressant medications have been published to date.

Prognosis
An earlier pessimistic view about helping children who have suffered
early deprivation increasingly has been replaced by an optimistic one com-
ing from long-term follow-up observations, such as those of Harmon and
colleagues [59]. They followed from infancy to puberty a boy who had suf-
fered from anaclitic depression at the age of 8 months. He was in an orphan-
age, recovered after 7.5 months (in contrast to Spitz’s previous findings [9]
that anaclitic depression that lasts longer than 3 months cannot be expected
to recover), was adopted at 20 months, and experienced three major depres-
sive episodes during his preschool years, each triggered by separation from
a primary maternal figure (return to orphanage after the disruption of his
first adoptive family, new adoption at 3.5 years, new failure of the adoption,
return to orphanage). He started psychoanalytic psychotherapy at age 7.5,
894 KEREN & TYANO

which lasted for 3 years until he was again adopted, this time successfully.
Follow-up at adolescence revealed a 12-year-old boy who was doing well
at school and at home but seemed to want to cut off the therapy of his
past. They showed how therapy worked synergistically with the boy’s resil-
ience and buffered the potentially catastrophic impact of several failed
adoptions.
Still, to the best of our best knowledge, there is no study on the course of
depression from infancy to later childhood. Luby and Mrakotsky [60]
question whether some of the depressed preschoolersdchildren who have
bipolar family historydmay switch to mania later in development. Given
the biologic changes in the brain that have been associated with affective
symptoms in high-risk infants and preschoolers, the identification of
depressive symptoms in infancy and the preschool period seems to be signif-
icant. One also may want to elucidate the unanswered question of the exis-
tence of endogenous depression in infancy and compare its course and
prognosis with the reactive type.

Summary
In this article we reviewed the uniqueness of the clinical entity of depres-
sion in infancy and the evolution of the awareness that infants can be signif-
icantly depressed. Research in recent neurobiologic studies has found
biologic correlates of depression in high-risk infants, which, in turn, impacts
the brain development. Several clinical vignettes have been described to il-
lustrate the various clinical presentations of depression in infants who are
exposed to different types of depressogenic environmental situations. Issues
about diagnosis of depression in infancy and diagnostic criteria, based on
the diagnostic classification for mental health disorders in infancy, were
reviewed.
Many questions remain unanswered, such as whether depression can be
endogenous in infants or is always reactive to adverse environmental fac-
tors, such as maternal psychiatric illness, unresolved grief, severe psychoso-
cial deprivation, chronic pain, and life-threatening illness. The issue of
discontinuity versus continuity of depression from infancy to older ages
must be studied in well-designed longitudinal studies while comparing differ-
ent modalities of treatment.

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