Childhood Depression as Emerging Public Health Problem: a Systematic Review

As an important problem of public health, the childhood depression deserves special attention, in which the serious and long term consequences of the disease weigh to the childhood development. Taking this in consideration, the present study was based in the following research question: which practical contribution the actual scientific literature about childhood depression has to offer to clinicians and researchers? The aim of the present study was to evaluate the actual evidence concerning the different aspects (etiology/risk factors, diagnosis, treatment, prognostic and prevention) of childhood depression, with the purpose to systematize such evidences and to contribute with the knowledge about the problem. In way to reach this aim, it was performed a systematic review of articles about childhood depression, in the period from January first of 2010 to January 16 of 2014, in the databases PubMED, MEDLINE and SciELO. In the research, the following terms were used: “depression” (MeSH), “child” (MeSH) and “childhood depression” (Keyword). Of the 860 found studies, 76 met the eligibility criteria. The found studies covered a wide variety of aspects related to childhood depression, as diagnosis, treatment, prevention and prognostic. The actual scientific literature about the childhood depression converges to, directly or not, highlight the negative impacts of the depression disorders to the life quality of the children. Unfortunately, the found studies show that the childhood depression is a disorder that develops most commonly in a poverty and vulnerability scenery, where the individual and familiar necessities concerning the childhood depression are not always taken in consideration. In this context, this review demonstrates that the depression started in the childhood commonly leads to others psychiatric disturbs and comorbidities.Many of the found studies also confirmed the hypothesis that the human element involved in the care, especially the health professionals’ team, is still not adequately capacitated to deal with the childhood depression. In this way, additional researches focusing the development of programs destined to prepare health professionals to treat childhood depression are necessary, plus to complementary studies, with bigger and more homogeneous samples, centered in the prevention and in the treatment of childhood depression.


Introduction
The depression has been shown more evident from the 70's decade, when the interest in the clinic investigation field and in the academic mean increased. In this context, the depression theme in the children's scenery gained notoriety among the studiers and researchers. Since then, the identity of the childhood depression as a clinic form independent from that detected in adults has been discussed. Therefore, the medical notion of the disease has established itself, concomitantly to the consolidation of the child psychiatry as a specialization apart of the adult and pediatric psychiatry.
In the past three decades, public health recognition of depression in children and adolescents has increased significantly [1]. The depressive disorder in children and adolescents is a common condition that affects the physical, emotional and social development [2] and frequently persists until the adult age [3,4].
The depression prevalence is estimated at 0.3% to 7.8% in children under that 13 years [5][6][7][8]. In Brazil, the depression prevalence in childhood is 0.2% and 7.5% to those under 14 years, which varies mainly in accord with the used evaluation method [8][9][10][11]. With that being said, the incidence of depression among children and adolescents is of great concern because of the acute and lasting consequences associated with depressive disorders [2].
Risk factors include a family history of depression, parental conflict, poor peer relationships, deficits in coping skills, and negative thinking [2]. Besides these factors, several other problems in childhood and adolescence may present as depressive symptoms and should always be considered in the differential diagnosis: bereavement or adjustment disorders, oppositional defiant disorder, substance use disorders, hypothyroidism, anemia, infections, cancer, and autoimmune diseases [11].
Regarding the complications of the childhood depression, adverse effects on psychological development, elevated risk of suicide attempts and completion are included [12,13]. Besides, the depression in child interferes with school academic progress and with other adaptive functions. Children with depressive disorder have a significant risk of developing Bipolar Disorders, and added comorbid risks [14].
The present study was based in the following research question: which practical contribution the actual scientific literature about childhood depression has to offer to clinicians and researchers? Our hypothesis is that, notwithstanding the growing interest about the theme, the human element involved in the care, especially the health professionals' team, is not adequately capacitated to deal with childhood depression. Our aim was to ascertain evidences concerning to different aspects (etiology/risk factors, diagnosis, treatment, prognosis and prevention) of the childhood depression in scientific production, with the purpose to systematize such evidences and to contribute with the knowledge about the problem.

Method
It was performed a qualitative systematic review of the articles about the theme childhood depression, published in electronic databases previously selected. The qualitative approach was chosen once, regarding the use of quantitative methods, like metaanalysis: a) the necessary information in order to calculate the sample is not available, fact that can limit the analysis to a few quantity of study; the age interval adopted to definition of the term "child" varies a lot among the studies included in the sample, which difficult an adequate comparison from the statistical point of view among the diverse studies.
It was conducted a search in the literature through the online electronic databases PubMED, MEDLINE and SciELO, limiting it to published articles from January 1 of 2010 to January 16 of 2014. The reason to delimitate this time interval (2010)(2011)(2012)(2013)(2014) was that, in this period, the theme "depression" gained more space and notoriety in the scientific literature, through several researches posterior to the psychiatric reform. Also, gray literature was used to present important issues related to childhood depression in actuality [1,21,185,192,194,237].
In this perspective, it is important to show that from psychiatry to pediatric, new forms of interactions among knowledge gathered more detailed information in relation to social-demographic data, clinical information based in epidemiological data, assistance regime and proceedings. Empirically, it perceives that, since 2010, ethical concerns about public politics directed to mental health in children and adolescents became the focus of the investigations. In this sense, it is from 2010 to the actual moment that the information about the structure, composition and operation related to child mental health services were more clearly delineated, centering in the search of the definition of care in child mental health. The researches of interest about the child mental health, especially those related to childhood depression, are, therefore, centered in the period from 2010 to 2014.
Initially, the following descriptors were used to the search in MEDLINE database: 1. "depression" (Medical Subject Headings [MeSH] descriptor); 2. "child" (Medical Subject Headings [MeSH] descriptor); 3. "childhood depression" (Keyword) The performed researches were: 1 and 2, 3. Besides of the MeSH descriptors, it was decided to include the keyword "childhood depression" in the search strategy, although not part of the list of MeSH descriptors, it is frequently used to describe studies that approach the theme of this review. The search strategy and the articles obtained in the search were revised in two distinct occasions to ensure the adequate selection of the sample and its eligibility.
A similar search strategy was performed in the SciELO (using MeSH and DeCS) and PuMED (MeSH) databases, and equivalents in Portuguese language.
In order to establish a parameter to the limitation of the age group covered by this review, according to "MeSH", the term child refers to the age range from 6 to 12 years old and, consequently, the term "childhood" refers to the study or the time correspondent to this period.
The analysis of the results also followed the ensuing eligibility criteria previously determined. It was adopted the following inclusion criteria: (1) articles that had in title or in abstract at least one combination of the descripted terms in the search strategy (1 and 2, 3); (2) publications wrote in English or Portuguese languages; (3) studies that discussed the childhood depression theme;

Results
Initially, the search strategies previously mentioned resulted in 860 studies. After a title and an abstract analysis of the found articles for eligibility based in inclusion criteria, 784 were excluded and 76 were included in the final sample ( Figure 1). (Table 1) Figure 1: Flow Diagram summarizing the selection process of the included studies of this review.

Inclusion criteria -Manuscripts in English or
Portuguese; -Childhood Depression; -Original texts with full online access; -Prospective or retrospective observational studies (analytical or descriptive) and clinical essays.

Pediatrics
There are a number of effective interventions designed to prevent childhood/adolescent depression. Such interventions tend to comprise screening and the subsequent provision of psychological therapy.
The current study indicates that all depressive symptoms improve over the 12 weeks of acute antidepressant treatment, with the largest improvement occurring during the first 4 weeks of treatment. Two symptom factors, Morbid Thoughts and Observed Depressed Mood, were rated low at baseline, but did show improvement over the course of treatment.

BMC Psychiatry
The potential pitfalls of assuming that only translation and back-translation can capture cultural differences in performance of mental health instruments. While the specific process of transcultural translation and validation will vary based on objectives and local resources, a critical evaluation of the translation and validation process is indispensible.
The results of this study, therefore, suggest that co-rumination is not merely a correlate of ongoing depression. That is, current levels of co-rumination were related to children's past history of depressive diagnoses among children who were not currently depressed.

Archives of General Psychiatry
Voxel-based morphometry analyses indicated that individuals at high risk of depression had significantly less gray matter density in clusters in the bilateral hippocampus than low-risk participants. Tracing yielded a volumetric reduction in the left hippocampus in the high-risk participants.

Neuropsychopharmacology
The transmission of depression symptoms is due in part to environmental processes independent of inherited effects and is not accounted for by shared adversity measurements. Girls may be more sensitive to the negative effects of maternal depression symptoms than boys through environmental processes.

Swiss Medical Weekly
Pediatricians estimated that 15% percent of children in their pediatric setting reported psychological difficulties. Of these, childhood depression is one of the most frequent mental disorders among children, they have the important role in recognizing the early signs of mental problems.

Genes, Brain and Behavior
This longitudinal study in children and adults found no association of single nucleotide polymorphisms in the serotonergic system or core regulators of neurogenesis with Anxiety and Depression.

Psychopathology
The families with major depressive disorder children showed higher levels of conflict and lower levels of cohesion (p < 0.001), expressiveness and active-recreational orientation compared to the families without mentally ill children.

Psychiatry Research
This study found significantly lower levels of NAA (N-acetil-aspartase) in the right medial prefrontal cortex and significantly lower levels of NAA and GPC + PC (glycerolphosphocholine plus phosphocholine) in the right AC(anterior cingulate) of depressed children and adolescents compared with healthy control subjects.

Journal of Child Psychology and Psychiatry
Both the family environment as genetic factors are responsible for association between parental depression and onset of depressive symptoms in children. However, the environment factor was more significant.

European Child & Adolescent Psychiatry
The parenting stress was another risk factor for symptoms of depression in children both in the present, as a risk factor to onset of depressive symptoms on the future.

Social and Environmental Factors
Reflecting through ideas of Middeldorp et. al [15] the etiology of depression and anxiety has been extensively investigated in recent years. Given the accumulating evidence about the high prevalence and debilitating related to childhood depression, a better understanding of the etiology of depression in youth is needed [16,17] Several investigations have demonstrated a wide variation in the prevalence of depression in children and differences according to the criteria of diagnostic classification adopted, mainly due to the diverse mode of presentation of depression and the association of this disorder with other psychopathologies [18]. Prevalence estimates among different racial/ethnic groups vary widely too [19]: American Indian youths reported the highest prevalence of depressive symptoms (29%), followed by Hispanic (22%), non-Hispanic White (18%), Asian American (17%), and African American (15%) youths [19,20]. Thus, knowing the risk factors for depression during childhood is essential for a better understanding of the etiology of this disorder and for planning prevention strategies [18].
Major Depressive Disorder (Single or Recurrent) is twice as common in adolescent and adult females as in adolescent and adult males. In prepubertal children, boys and girls are equally affected [21]. Studies of Major Depressive Disorder have reported a wide range of values for the proportion of the adult population with the disorder. The lifetime risk for Major Depressive Disorder in community samples has varied from 10% to 25% for women and from 5% to 12% for men. The point prevalence of Major Depressive Disorder in adults in community samples has varied from 5% to 9% for women and from 2% to 3% for men [21].
In this context, studies addressing the etiology and risk factors of childhood depression emphasize some important points, among them are individual, environmental and family factors. Individual factors include age, gender, psychological and physical vulnerability [8,22], comorbidity with other disorders [8,23], emotional disturbance, impaired sociability, low self-esteem and social skill difficulties [8,24,25], according to Table 2 [8,22].
It´s well established that secondhand smoke (SHS) exposure causes adverse physical health conditions (eg, respiratory and cardiovascular) [35][36][37][38], and there is increasing evidence suggesting that it may also adversely affect mental health [35]. SHS may be a proxy for stressful living conditions, and stress has been associated with poor mental health [35,39,40]. In response to stress, the hypothalamicpituitary-adrenal axis and immune, metabolic, autonomic, and cardiovascular systems respond to keep the environment of the body in homeostasis [35,41]. Although chronic physical conditions usually manifest in adulthood, there is evidence that prolonged exposure to stress may have an effect on the response of the body to stress and result in poor health even among children [35,[42][43][44]. Other hypotheses suggest a link between smoking and poor mental health through nicotine and dopamine pathways [35,[45][46][47].
The study of Bandiera et. al. [35] was the first study to assess the association between biologically confirmed SHS exposure and mental disorder symptoms in a nationally representative sample of US children and adolescents. In this study, it was proved that SHS exposure was positively associated with symptoms of Major Depressive Disorder, Data in parenthesis reflect standard deviations or percentages. Different subscripts denote significant differences among groups.
1 Higher score is associated with higher socioeconomic status or higher level of functioning.
A Data in parentheses reflect standard deviations or percentages.
B Different subscripts denote significant differences among groups.
Generalized Anxiety Disorder, Attention Deficit and Hyperactivity Disorders, and conduct disorder.

Family and Hereditary Factors
A careful attitude is strengthened when considering the family environment may represent a critical early contribution to the risk for mood disorders [48][49][50]. Children exposed to chronic adversities early in life are more likely than other children to suffer a variety of mental health problems, as depression [51][52][53][54][55]. According to Van oort et. al. [56] the parenting stress was another risk factor to depressive symptoms in children. That said, children of parents with depressive disorders are a high risk group for developing depressive episodes [57][58][59][60][61]. They have two to three times more likely to show high levels of depression and symptoms of anxiety and depression than children of non-depressed parents [62,63]. It has been well established in recent studies that a family history of depression is an important predictor of emotional and behavioral problems in children [64][65][66][67][68][69] according SilBerg et. al. [69] despite the convincing evidence for transmission from parents to children, the mechanism by which parental depression increase the depression risk in children is not well understood.
WeitzMan et. al. [60] analyzing a representative sample of US children (N = 21 993) aged 5 to 17 years and their mothers and fathers have found the rates of such problem are lower among children with fathers who have mental health problems than among children with mothers with these problems. They have found too that the rates of emotional or behavioral problems are highest among children who have both mothers and fathers with mental health problems and depressive symptoms, with 25% of children living in such homes having behavioral or emotional problems.
Researches have shown consistently that children of depressed mothers are at elevated risk for developing a range of psychiatric disorders, as depression [70][71][72]. This risk persists beyond the duration of a given maternal depressive episode and can continue into adulthood [70,73]. Daughters may be especially vulnerable; investigators have found that daughters of depressed mothers are more likely to develop Psychopathology than are son [70,74,75].
leWiS et al. [62] yet seek to explain this transmission of depression from parents to the children. First, exposure to parent depression symptoms may have a direct environmental effect on children. Second, links between parent and child symptoms could arise through inherited factors. Researchers [76,77] explain that genes play an important role in explaining the appearance, behavior and personality characteristics of people. Therefore, genes involved in negative mood of the parents are involved in depression in adolescents and children. Also, shared exposure to adversities such as bereavement, divorce, or poverty may increase risk for depression in parents and children, accounting for observed transmission effects [62].
A consistent finding from twin research has been that genetic influences on depression symptoms are greater in adolescents, whereas shared environment is more influential in children [62,78]. This suggests that non-inherited factors could play a more prominent role in the intergenerational transmission of depression symptoms for younger children [62]. Also, there are findings suggesting that approximately 1/5 of the additive genetic influences on both Conduct Disorder and Major Depressive Disorder are shared between the two phenotypes in boys, but this is entirely accounted for by genetic influences on Negative Emotionality [79].
However, further research on the mechanisms underlying intergenerational transmission of depression is required. In addition to the role of shared adversity, such research should consider the effects of child gender and age, which have not been examined using genetically sensitive designs. As already mentioned, there is evidence that different factors may be involved in the etiology and intergenerational transmission of depression for boys and girls [70]. Some studies found that the association between maternal depression and offspring is stronger in daughters than sons [70,74,75]. However, other studies have not reported gender differences [62,80]. The etiology of depressed child can range according children's development stage too [62].
A better understanding of the pathways involved in the intergenerational transmission can help identify modifiable risk factors for the child/adolescent with depressive symptoms that could be the target of preventive and therapeutic interventions. The results of SilBerg et al. [69] still implicate a different etiologic role of parental depression depending upon the age of the child. Early in childhood, the effect of the parental depression is environmental. As children approach adulthood, the association between parental and child depression appears to be primarily genetic.
Sexual abuse experiences in childhood confer high risk for developing clinical depression and possible mechanisms by which they play their deleterious effect [81]. Studies point out that a history of childhood sexual abuse is associated with increased risk of major depressive disorder associated with suicidal thoughts and behavior, including suicidal thoughts, persistent suicidal thoughts, suicide plan and at-tempt. The researchers also reported risks associated to Psychopathology, include, but not limited to the major depressive disorder [82].
The study of Bennett et al. [83] demarcate the relation of the onset of depression in neglected children. Neglected children reported more likely to develop depressive symptoms than comparison children. Neglect often occurs in the presence of other psychosocial risk factors, such as low socioeconomic status (SES) and exposure to violence [83][84][85]. Low SES and exposure to violence have each been associated with increased depressive symptoms in childhood [83,86,87]. Specifically, children who experience neglect may be at increased risk of experiencing shame, which in turn increases their risk for depressive symptoms [83]. Shame is a highly negative and painful state in which the individual perceives the whole self as defective [83,88]. Heterogeneous groups of maltreated children, which have included neglected as well as physically and sexually abused children, exhibit elevated levels of shame [83,[89][90][91]. Similarly, children whose parents are negative and rejecting or who use an authoritarian style of parenting are at increased risk of exhibiting shame [83,89,[92][93][94].
There are several explanations as to how shame, which has been related to increased depressive symptoms in children among neglected children [83,[94][95][96]. When experiencing shame, individuals may try to suppress such an aversive feeling. Shame suppression, in turn, may lead to sadness and depression [83,97,98]. Alternatively, shame, which is characterized by a desire to hide the damaged self from others and to ''disappear,'' may be associated with social isolation [83,[98][99][100]. Shame also is associated with a depressogenic attributional style that may increase risk for developing depressive symptoms [83,[101][102][103]. Finally, shame has been related to increased pro-inflammatory cytokine activity and to cortisol changes, both of which may increase risk for depressive symptoms [83,104,105]. Although the precise mechanisms by which shame may lead to the development of depressive symptoms is currently unknown, the extent to which neglected children are prone to experience shame may also lead them to experience increased depressive symptoms [83].
Fear of abandonment has been found, associated with mental health problems for youth who have experienced a parent's death [106]. The parental death in childhood is associated with an increased risk for depression [106][107][108]. Disorganization and depression after bereavement are lessened only when an individual's regulatory system is able to adapt in another close relationship [106].
Children exposed to high levels of maternal repeated criticisms are subject to greater risk of developing depression. It is evident a potential modifiable risk factor for depression in childhood: repeated exposure to maternal criticism [17]. The societal pressure and social sanctions that result against even minor conduct problems may heighten girls' risk for subsequent depression [109,110]. In this context, family violence generally increases the risk of depression for children [111]. In older children, exposure to family violence has been linked to internalizing problems (eg, depression, suicide, anxiety, post-traumatic stress) [112][113][114].
The pathogenic influence of stressors in childhood, particularly maltreatment, increases risk for depression [115][116][117]. Indeed, severe stressors, such as childhood abuse and others already cited, have been postulated to lead to reduced hippocampal volume in adulthood and may represent a link between hippocampal volume and Psychopathology [118][119][120][121]. Results of Frodl et al., [122] indicate that subjects with both environmental and genetic risk factors are susceptible to stress-related hippocampal changes. In systemic inflammation, pro-inflammatory cytokines have been implicated in altering activity in brain regions known to affect emotion processing and emotion regulation in depression [123]. Structural brain changes due to stress represent part of the mechanism by which the illness risk and outcome might be genetically mediated [122].
It is noteworthy, however, not all individuals exposed to childhood adversity develop depression, and genotype may moderate the relationship between childhood adversity and mental health [115,124,125]. This fact shows that the etiology of depressive disorders is complex and multi-factorial, with an intricate interaction among environmental factors and genetic predisposition [126].
In the study of Mennella et al. [127], was revealed for the first time that in pediatric populations the co-occurrence of having a family history of alcoholism and self-reports of depressive symptomatology is associated significantly with preference for stronger sweet solutions. (Figure 2)

Neurochemical factors
The underlying neurobiology of depression is likely to represent an interaction between genetic susceptibility and environmental factors such as stress [122]. There are two major hypotheses regarding the etiology of anxiety and depression: the monoamine hypothesis and the hypothesis of an abnormal stress response acting partly via reduced neurogenesis. Forty-five SNPs were assessed in candidate genes that were involved in (1) the mono-aminergic system: serotonin receptors (HTR) 1A, 1D, 2A, catechol-O-methyltransferase (COMT), tryptophane hydroxylase type 2 (TPH2), (2) neurogenesis: brain derived neurotrophic factor (BDNF) and PlexinA2 and (3) cell signaling: regulators of G-protein signaling (RGS 2, 4, 16) [15].
For several reasons, researchers have focused on the role of the hippocampus in depression [118]. The hippocampus is involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis, which is responsible for production of stress-related glucocorticoids such as cortisol [118,128]. In this context, depressed individuals have consistently been found to report high levels of stress [118,129], which is reflected biologically in elevated rates of hypercortisolemia [118,130] and disturbed HPA-axis functioning [118,131].  Benko et al., [126] in a study with children aged between 9-12 years old have found a strong association between depressive symptoms and caffeine consumption. Previous studies have also suggested that the early consumption of caffeine can be an indication of later drug abuse [126]. The children with sleep problems were at risk for depression symptoms [132]. The question that remains unknown is whether high caffeine consumption may actually cause symptoms of depression or ease the symptoms of depression in children which already presented them, once studies have also shown that adults often use substances, as caffeine, to alleviate psychiatric symptoms [126,133].

Anatomopathological factors
With advances in neuroimaging techniques, investigators have been able to examine the function and structure of specific brain regions in this disorder [118]. Numerous magnetic resonance imaging (MRI) studies show volumetric reductions in the frontal cortex and its sub regions in adults with major depressive disorder (MDD) [134][135][136][137][138][139]. The few MRI studies done in children and adolescents with MDD, also suggest evidence of frontal lobe involvement [134]. Decreased frontal volume and increased ventricular size were seen in depressed children compared with psychiatric controls [134,140]. Another study found smaller left-sided prefrontal cortex (PFC) gray matter volumes in patients with familial MDD than in patients without a family history of MDD [133,141]. Furthermore, subjects without a family history of MDD had larger left sided total PFC volumes and PFC white matter volumes compared with patients with familial MDD [133,141].
Neuroimaging studies have shown that the hippocampus is about 4-5% smaller in patients with major depression than in healthy controls, and that reduced hippocampal volumes are consistently found in major depression [122, [142][143][144]. Pediatric patients with familial MDD showed decreased hippocampal volumes, indicating that reduced hippocampal volume may be present at very early stages and may be suggestive of a risk factor for developing MDD [122,145].
Moreover, depressed patients have also been found to be characterized by difficulties in hippocampal-dependent learning and memory [118,146]. These factors, in addition to the high degree of connectivity between the hippocampus and other brain regions critical for emotion and cognition make this structure a prime candidate for further investigation [118,147].
Researchers have found decreased hippocampal [122,145], prefrontal cortex, orbitofrontal cortex, gyrus cinguli, and the basal ganglia volumes in patients with MDD compared with healthy controls [122,143].
The study of gotliB et al. [148] has also documented a prominent role of the insula as an index of normal and disordered reward functioning; this structure may be a promising candidate for a biological marker of risk for the development of a depressive disorder.

Comorbidities
Both depression [149,150] and anxiety [149,151] have each been described as the most common psychiatric concern for children with autism spectrum disorder (ASD) [149]. The child's disability and the tension in the family are some factors that justify it [149]. Studies report prevalence rates in the range of 4% to 57% [149,150,152] and from 7% to 84% [149,151,152] for depression and anxiety disorders in children with ASD [149].
Several studies [153][154][155][156][157][158][159][160] in adults have shown that patients with syncope exhibit high levels of psychological distress, including anxiety and depression. HypHantiS et al. [153] reported an incidence of 35% in clinically significant depressive symptoms in children and adolescents with Neurocardiogenic Syncope, a 2.6-fold higher rate compared with healthy control subjects. Family functioning, as indicated by child-parent relationships and family cohesion, was associated with depressive symptomatology.
Children with cancer are also likely to develop some type of depressive disorder. Conflicts arising from cancer such as problems in daily life, increased frequency of visits to the hospital and poor quality of life in children were correlated to an increase in the child's tendency to suffer depression [162].
Depression is an important health problem in children and the onset of depression is occurring at a younger age than previously suggested [162]. The associations of being overweight and low socioeconomic status in childhood depression have been well documented [162]. Children in families of low socioeconomic status that experience family disruption or parental divorce, or that have a history of mental disorders may be at an increased risk of developing depression in later life [87,162,163].
Some studies reported the relationship between depression and obesity in boys and girls [164,165], whereas other studies reported the relationship in girls only [164,166,167]. Other studies found that boys with chronic obesity are more likely to be depressed [164,168].
According to the study of Wojnar et al., [169] sleep disturbances also increase the risk for developing depression across the life cycle [169][170][171][172]. High-weight depressed children would have worse sleep than both normal-weight depressed children and healthy control children [169]. Since poor sleep already poses a greater risk of relapse and recurrence of depression, then increasing body mass index (BMI) may further increase that risk [169].
The study of BanH et al., [19] have sought to analyze the ethnic influence in depression. Their findings suggested that the MFQ (Mood and Feelings Questionnaire) demonstrates sufficient measurement equivalence for 6 th or 8 th graders, males and females, youth with US-and non-US born parents. In general, their findings suggested that although there may be differences in symptom endorsements among depressed individuals across racial/ethnic groups, these differences do not impact overall scores MFQ in children with depressive symptoms.
Being a victim of negative peer experiences is significantly associated with depression [173,174], especially for girls [173,175]. Studies have consistently shown that depression is associated with exposure to bullying [176,177]. The study of Wang et al [176] examined associations between depression and four forms of bullying: three traditional (physical, verbal, and relational) and the fourth a relatively new form (cyber). For traditional bullying, the associations between depression and frequency of involvement within bullies, victims, and bully-victims were consistent with previous studies [176,178]. In contrast, for cyber bullying these associations were not found for bullies or bully-victims. Notably, cyber victims reported higher depression than bullies or bully-victims, which was not found in any other form of bullying. This may be explained by some distinct characteristics of cyber bullying [176,179]. For example, unlike traditional victims, cyber victims may experience an anonymous attacker who instantly disperses fabricated photos throughout a large social network; as such, cyber victims may be more likely to feel isolated, dehumanized, or helpless at the time of the attack [176,179].
The results of the UHer et al. [180] research affirm that statistical tests of gene-environment interactions showed positive results for persistent depression but not single-episode depression. Individuals with two short 5-HTTLPR alleles and childhood maltreatment had elevated risk of persistent but not single-episode depression.
The study of Uddin et al [181] highlights that in adolescent females, the 5-HTTLPR sl genotype confers protection against depressive symptoms independent of county-level social context, whereas in adolescent males, protection by the same genotype is conferred only within the context of county-level deprivation. Moreover, individuals carrying the 5HTTLPR short (risk) allele or BDNF Met allele had smaller hippocampal or amygdala volumes, or both, when they had a history of childhood maltreatment compared with those who had only one risk factor (environmental or genetic). Independent of genetic risk, childhood stress predicted additional hippocampal white matter alterations [1,122,181]. (Figure 3)

Diagnosis
Pediatricians estimated that 15% percent of children in their pediatric setting reported psychological difficulties. Of these, childhood depression is one of the most frequent mental disorders among children. Thus, the pediatricians, who are often in contact with children, have the important role in recognizing the early signs of mental problems in pediatric patients [183].
Depression in children younger than 12 years of age is less prevalent than among adolescents; however, it can be reliably diagnosed in children as young as 3 years of age [183,184]. The diagnostic criteria for major depressive disorder in adults can be applied to children, with the exception that children can express irritability rather than sad or depressed mood, and weight loss can be seen in terms of failure to achieve the proper weight for the age group. It is worth mentioning that several investigations have demonstrated a wide variation in the prevalence of depression in children and differences according to the criteria of diagnostic classification adopted, mainly due to the diverse mode of presentation of depression and the association of this disorder with other psychopathologies [18]. This happens because the current diagnostic criteria were developed for the adult population, neglecting many of the developmental differences between children/adolescents and adults [11]. The characteristics of symptoms in children vary widely than in adults [14]. So the difficulties in diagnosing depression in children and adolescents are higher than those found in older individuals [11].

22
Traditionally, self-report measures have been the dominant method for assessing internalizing disorders in youth [186][187][188] as they provide an efficient and cost-effective means of gathering information [188], nevertheless this method has some limitations.
The diagnostic assessment of depressive disorders can make use of formal procedures such as structured/semi-structured interviews or rating scales, in addition to general interviews to assess mental disorders in childhood and adolescence [11]. Neuroimaging data can be another tool in the diagnosis, because it provides a critical area of investigation to more rigorously test the validity of preschool depression [189].
The results of the study of cole et al. [190] have also shown that the use of IRT-based information (Item Response Theory) about symptom severity and discriminability in the measurement of depression severity may reduce measurement error and increase measurement fidelity. Some symptoms may be evident at relatively mild levels of the disorder, whereas other symptoms may only emerge at very severe levels. In other words, severe depression may be characterized by symptoms that are not often evident in mild depression. If the severity of depression is assessed simply by counting the number of symptoms, then all symptoms are treated as though they were of equal severity or importance and other valuable information that could be derived from the assessment process potentially is ignored. To avoid this error in the assessment of severity, the IRT gives for each symptom a certain level of severity of depression. (Figure 4) The importance of the work of these professionals is shown even greater due to the fact that many parents are late in recognizing depression in their children, in spite of obvious Science. These parents may not realize the magnitude of depression until their child's adaptive behavior at home and school has seriously deteriorated, until the child has expressed his desire in the form suicidal or other self-destructive behaviors, or until the child has fallen victim of a devastating drug abuse problem [14].
It is assumed that clinical depression starts as a response to some initiating stress event or process, which elicits sadness, distress, and dysphoria. From thereon, whether or not the dysphoric emotion develops into a disorder depends in large measure on the way in which the affected youngster responds to the emotion [191].
The common feature is the presence of sadness, emptiness, or irritability, accompanied by somatic and cognitive changes that significantly affect the individual's ability to function [192].
Depressive symptoms include cognitive and vegetative features in addition to affective features [193]. Patients with depression present with psychological symptoms of depressed mood, loss of interest in activities, impaired concentration, feelings of worthlessness or guilt, and suicidal ideation [194]. Children may have difficulty verbalizing their feelings or may even deny that they are depressed [11]. Thus, special attention should be given to observable manifestations, such as changes in sleep patterns, irritability, poor academic performance, and social withdrawal [11,195]. Excessive sleepiness during the day was also observed in children with depressive disorders [196]. It is recognized in some studies that depressive disorders increase the risk of suicidal behavior. They are often associated with morbidities, such as conduct disorder and substance abuse and anxiety disorders. Younger children are more likely to have somatic symptoms, restlessness, separation anxiety, phobias, and hallucinations [2,197]. However, little is known as to whether children with a history of very early occurring depression also show altered functional brain responses to negative affective stimuli [198]. It is known also that parents are more likely to indicate externalized symptoms such as irritability, whereas children are more likely to report internalized symptoms such as depressed mood [2,199].
Interpersonal dysfunction has also been linked to the course of depression, such that levels of social support and interpersonal impairment predict depression severity, rate of recovery from a depressive episode, and depression recurrence [200][201][202]. Regular observation of child development is a good basis for judgment of the problems presented the child: as normal, or as a state or behavior that may require treatment. At the same time, the identification and especially the treatment of mental disorders requires specific knowledge and strategies that are usually not included in pediatricians' training [183].
Thus, the clinician has to look for the cardinal symptoms of depression which include the presence of sadness or depression, anhedonia, crying, irritability, emotional withdrawal, hopelessness and associated guilt, sleep disturbances, failure to gain weight, decline in school performances, hyperactivity and associated restlessness, psychotic disturbances in the form of auditory or visual hallucinations [14]. Anhedonia, a core clinical feature of major depressive disorder [115,203], reflects loss of ability to experience pleasure or joy from activities normally considered pleasurable or, alternatively, lack of reactivity to pleasurable stimuli [115]. The anhedonia depression, sometimes referred to as melancholic subtype, has been identified as one of the more severe forms of major depressive disorder [115,204,205].
The study of allen et. al [206] examined depressive symptoms as a mediator of alexithymia and somatization in a sample of healthy children in order to better understand alexithymia-somatization link from a developmental perspective. Results indicated that depression significantly partially mediated this relationship, at least for two facets of alexithymia (difficulty identifying and describing feelings).
Each additional depressive symptom at ages 8-10 is associated with a 50-80% increase in risk for developing a depressive disorder by age 11-13 [207,208]. Sleep disturbances are common in depression; if they precede the onset of this disorder, they may be a biological marker of elevated risk for major depressive disorder [209].
The unremitting suicidal ideas or attempts are the important presentation in certain children. The clinician should also take the time to rule out anxiety or depression in the pediatric population with medically unexplained symptoms. Unexplained somatic symptoms can be often considered as an indicative of a neglected depressive disorder [14].
In this way, depressive symptoms can be understood as a continuum, a diagnostic decision is usually necessary to define the need for treatment  [11]. The identification of depression poses significant clinical challenges to the child psychiatrists. Child depression varies in the nature and intensity of its presenting symptoms. The psychiatrist should attempt to elicit as complete a picture of a child's depressive syndrome as possible by identifying a variety of symptoms associated with this disorder and by estimating their severity [14]. (Figure 5)

Treatment
The identification and treatment of mood disorders in children and adolescents has grown over the last decades. Major depression is one of the most common and debilitating disorders worldwide, imposing a massive burden to the youth population [11].
Every treatment plan for depression in children and adolescents should take into consideration developmental aspects, including psychoeducation, family support, assessment of comorbid conditions, and risk behaviors [11].
According to cHUa et al. [210] the referral of a child or adolescent with depression to a psychiatrist could be considered in any of the following situations: 1) failure to improve with psychosocial interventions or requiring specialized psychological interventions; 2) failure to improve after at least four weeks of medication treatment at maximum tolerated dose; 3) severe symptoms such as clear suicidal intention, disruptive psychotic symptoms.
According to koVacS et al. [191] the procedure for the treatment of childhood depression has to have at least four key features. First, the treatment's conceptual formulation (or explanatory framework) should include an explicit developmental component. In other words, the explanatory paradigm should specify which developmental parameters or skills are implicated in the unfolding of depression and how dysfunction in that regard paves the way to depression.
Second, a developmentally informed intervention should accommodate the fact that young patients will be at different stages of development of the targeted skills when they enter treatment, e. g., which will have ramifications for what the therapist can do [191]. The presentation of depressive symptoms can vary according to age groups. Regarding mood changes, younger children show more temporal variability, making harder to characterize a mood episode [11]. Moreover, even in a specific stage of development (children 7 years old), these children will not have the same skill levels and will also differ in the context where they are inserted, which can affect the treatment.
Psychosocial interventions are recommended in initial treatment of depression in children and adolescents based on the literature and local clinical experience [210]. Family-focused interventions also have the advantage of approaching critical issues of the child's context, emerging as a promising strategy in recent years, especially in young children [11,211,212]. Spending time with caring family members or peers could serve as a protective factor by supporting healthy affective experience and promoting response to treatment [193].
Parental involvement has long been considered indispensable in the treatment of conduct problems. From a psychological perspective, parents play critical roles in their children's emotional and social development and provide the crucible within which developmental skills unfold [191]. A close father-child relationship could provide a unique kind of support for improvement and response to treatment in young people [193]. Additionally, when parents (caregivers) themselves respond to a child's distress, they function as interpersonal regulatory agents [191].
Relationships with fathers and peers could provide a foundation for treatment outcome, albeit in opposite ways, suggesting that relationships could play a role in treatment response [192].
It is also known that paternal depressive symptoms and other mental health problems are also significantly associated with children's emotional or behavioral problems; this finding raises questions of great importance about how to educate the health care workforce about this, how to develop and implement strategies to facilitate identifying fathers with mental health problems [60].
Prolonged exposure therapy may work primarily by reducing posttraumatic stress, which in turn reduces depression [217].
Depressed children with poor sleep and high body mass index (BMI) may be particularly appro-priate for additional screening and intervention efforts targeted at improving sleep and reducing weight [168].
In relation to children who lost their parents, interventions that reduce the fear of abandonment of children can improve the quality of their social relationships and reduce symptoms of depression later in life. In this context, Wingo et al. [219] emphasized that protective factors such as resilience may be amenable to external manipulation and could present a potential focus for future treatments and interventions.
Affective characteristics such as high positive affect or low negative affect could have relevance for response to treatment in children and adolescents with depression, because these characteristics could indicate a more adaptive pattern of affective style that could promote improvement in response to treatment [193,220]. Therefore, according to ko-VacS et al. [191], the explanatory paradigm of a developmentally sensitive intervention should address how parents impact the skill that is being targeted or else, account for the role of the parents in those areas of the young patient's functioning that are relevant to treatment targets. Therefore, it is reinforced the importance and the need for research focusing on family interventions and family involvement in the treatment of children with depressive disorders [183].
Pharmacotherapy is recommended for patients with moderate or severe depression [2]. Antidepressants are commonly prescribed to children and adolescents for depression, anxiety, and a variety of other disorder [221,222]. The efficacy of pharmacologic treatment in pediatric depressive disorders remains unclear, as the majority of placebo-controlled randomized controlled trials (RCTs) of antidepressant medication do not show a significant benefit of medication over placebo [13,223]. This finding may at least partly explain the low efficacy of antidepressants. The questions about the safety and effectiveness of psychotropic drug use in the pediatric population are widely debated, in particular because of the lack of data concerning long term effects [224].
Few psychotropic drugs are licensed for use in children in Europe in general and only for some diseases. Selective serotonin reuptake inhibitors (SSRIs), first introduced in the late 1980s, were prescribed to children for depression on the basis of effectiveness data from trials on adult psychiatric disorders coupled with other trial data demonstrating the ineffectiveness of tricyclic antidepressants [222,[225][226][227][228].
Regarding the selective serotonin reuptake inhibitors (SSRIs), a link between its use and an increased risk of suicidal ideation has been documented in the pediatric population and in youth adults [224,229,230], a fact that ultimately makes the risk-benefit profile for SSRIs not very favorable. The emergence of suicidal thinking and behavior, or unusual changes in behavior should be monitored during the early phases (generally the first 1-2 months) of antidepressant treatment, especially in children, adolescents and young adults between 18 to 24 years old [210]. Fluoxetine is licensed for major depressive disorder in children over eight years [224] and is the only drug currently licensed to treat depression in children in the United Kingdom as its benefits were deemed greater than its risks [222]. Youth who are adherent to fluoxetine treatment have lower symptom severity over the course of treatment [231].
tao et al. [232] demonstrated in their study the benefits of therapy with fluoxetine. Their findings emphasize that all depressive symptoms improved, particularly during the first 4 weeks of acute treatment. Forty-seven percent of remitters reported at least one residual symptom following 12 weeks, with most common residual symptoms being impaired school performance, insomnia, and irritability. Residual symptoms are common, even among remitters, at the end of 12 weeks of acute treatment. There is a need for clinicians to monitor symptom improvement and potentially provide additional interventions for the more resistant symptoms, such as insomnia and school performance.
Other antidepressants such as venlafaxine may be considered as second line treatment of depression in children and adolescents [210].
Given that the behavioral effects of many antidepressant depend on neurogenesis in the hippocampus [118,233] and given that antidepressants treatment prevents stress-related hippocampal volume loss [118,234] and may reverse hippocampal volume reduction in depression [118,235], promoting neurogenesis through antidepressants or other interventions in individuals at high risk of depression may prevent or reverse neuronal or glial atrophy and ultimately delay or prevent onset of the disorder [118].
Today, several other classes of antidepressants are being used to treat depression in youths; these are modifications of the earlier antidepressants. Known as "third generation antidepressants", these medications include selective norepinephrine reuptake inhibitors, norepinephrine reuptake inhibitors, norepinephrine dopamine reuptake inhibitors, norepinephrine dopamine disinhibitors, and tetracyclic antidepressants [236,237]. To date, evidence does not clearly answer questions about the effectiveness and safety of these newer antidepressants [236,237]; clearly, further research is indicated [237].
In practice the response to treatment in child and adolescent affective disorder is variable, with limited ability of any one treatment to improve outcome across patients [193]. A combination of psychosocial interventions and selective serotonin reuptake inhibitors may be considered for moderate to severe depression in children and adolescents [210]. Unfortunately, we know little about the factors that explain this variability in treatment response. Individual differences in the social and affective dynamics of daily life could help to elucidate the characteristics of youth who respond to treatment [193].
In the pediatric population, evidence suggests the efficacy of pharmacological agents, cognitive behavioral therapy (CBT) or interpersonal therapy (IPT) -all these interventions, however, present only  [11]. There is increasing recognition of religious involvement as a protective influence that may prevent or assuage the development of depression [238][239][240][241].

InternatIonal archIves of MedIcIne
koHrt et al. [242] emphasize the problem of lack of culturally adapted and validated instruments for child mental health and psychosocial support in low and middle-income countries. This fact causes barriers to assess the prevalence of mental health problems in children from vulnerable populations and/or social risk, evaluating interventions effectively and in determining programs that ensure costeffectiveness.
The study of claVenna et al. [224] highlights that there is a need to define (and to comply with) appropriate diagnostic and therapeutic approaches for child and adolescent psychiatric disorders such as major depressive disorder. The findings showed that the majority of children were not treated in psychiatric services aimed at children and adolescents. In most instances, psychotropic drugs were prescribed by general practitioners without the advice of child psychiatrists. This fact is a cause for concern, because little is known about the side effects of the use of psychotropic drugs in children in the long term. The early accurate identification and treatment of mood disorders can have direct and indirect impact on subsequent ages, reducing disability, costs and even mortality across the lifecycle [11].
Considering that childhood depression is a disease that can present many different ways, every treatment plan for depression in children and adolescents should take into consideration developmental aspects, including psychoeducation, family support, assessment of comorbid conditions, and risk behaviors. Moreover, given the nature of chronic and recurrent depressive disorders, clear objectives should be established together with patients and their families not only for the acute treatment of the current episode, but also for phases of consolidation and maintenance, monitoring and preventing new episodes [11].
Thus, a developmentally informed intervention should be sufficiently flexible to accommodate multiple sources of variability across young patients and explicate how its implementation for chronologically and/or developmentally younger patients differs from that for older youths [191].

Prognosis
Early-onset depressive disorders can have serious consequences both in the aspects of development and functional. Recent studies suggest that depression in children may have negative impacts on their growth and development, school performance and family, relationships, and an important precursor to Psychopathology [162,243,244].
Besides the changes in social life, the emotional areas, and academics, as well as a wide range of psychiatric and health problems in adulthood [17,245], depression in childhood can substantially increase the risk of drug abuse and suicide [4,246]. Primary findings indicate that drug use initiation during early adolescence (e. g., ages 14-16) may not be tied to immediate proximal perturbations in risk factors, such as traumatic experiences and depressive symptoms. Rather, the effects of trauma on depression in this sample appear to be established earlier in childhood (ages 10-14 or younger) and persist in a relatively stable manner into middle adolescence when the risk for drug use may be heightened [247].
Anxiety and depression are not only associated with limitations in children's current functioning (e. g., poor social relations and academic performance, low self-esteem) [248,249], these disorders can also negatively affect children's emotional and social long term development [249].
Some studies reported the relationship between depression and obesity in boys and girls [164,165], whereas other studies reported the relationship in girls only [164,166,167].
Mental disorders emerge in childhood and adolescence and are important risk factors for mental disorders in adolescence and adulthood [183 ,250, 251]. Depression can have significant lasting effects when diagnosed in childhood and adolescence, and has been associated with later interpersonal difficulties, early parenthood, impaired school performance, unemployment, and other mental disorders and substance use disorders [185,[252][253][254].
Previous research demonstrating a longitudinal relationship between social withdrawal and negative social outcomes [99,202] as well as a prospective link between interpersonal difficulties and depression [202,255].
According to ogBUrn et al. [48] the families with major depressive disorder children showed higher levels of conflict and lower levels of cohesion, expressiveness and active-recreational orientation compared to the families without mentally ill children. In addition, families with major depressive disorder children show a lower degree of commitment, provide less support to one another, provide less encouragement to express feelings and have more conflicts compared to families with no mentally ill children or parents.
This situation may further complicate the situation of children with depression, for certain interpersonal characteristics such as high levels of "expressed emotion" (described as criticism, hostility or emotional over involvement of caregivers toward a family member suffering from a psychiatric illness) can negatively influence the treatment and prognosis of several psychiatric disorders, including unipolar depression and Bipolar Disorder [48,[256][257][258].

Prevention
Given the high prevalence of this disease and its widespread impact on youth, there is a critical need to identify the precursors of developing depressive disorders, as well as main indicators of time in development that create opportunities to prevent depression [162]. More specifically, the identification of contextual factors that contribute to the onset of childhood depression may help improve prevention and intervention efforts for this population [17].
Early prevention of these disorders is of utmost importance. This may not only have individual benefits with respect to children's current and future wellbeing, but may also serve society as a whole by reducing societal costs related to these problems (e. g., school drop-out, employment problems, health care use, medication) [248,249].
Research has established a strong link between environment stress and internalizing problems in children [56,259]. For children, their family is their closest environment. Not surprisingly, studies have shown that family stress is associated with anxiety and depression. In this context, important positive aspects of the family environment that contribute to the reduction and prevention of depressive disorder in children include supportive and facilitative interactions, and the absence of conflict [56].
Since schools offer the opportunity of reaching large groups of children, they are regarded as a suitable setting for the detection, prevention and early treatment of anxiety and depression [249,260,261]. In this sense, Gershon et. al. [70] suggest that schools may be a logical place to implement interventions aimed at reducing behavioral stress among children of depressed parents. The findings also suggest that there may be modifiable risk factors, such as the adolescent's coping skills, which can be targeted through early interventions to help identify and change the ways in which stress is self-generated. Having supportive friendships has traditionally been viewed as a protective factor that reduces risk for the development of depression during childhood and adolescence [262,263].
Still in the context of the school environment, köSterS et al. [249] emphasize the importance of using the program "FRIENDS for Life". This program can be used for the prevention and treatment of anxiety and depression in children [249,[264][265][266][267]. This cognitive-behavioral program teaches children skills to cope more effectively with feelings of anxiety and depression and builds emotional resilience, problem-solving abilities and self-confidence. In their study, köSterS et al. [249] provide information on the effectiveness of the implementation of "FRIENDS for Life" as a program indicated prevention in schools for children with early or mild signs of anxiety or depression.
Already cHen et al.
[118] point out the importance of identifying the factors that contribute to reduced hippocampal volume in individuals at high risk of major depressive disorder, because this will be critical in helping to understand the inheritance mechanisms of risk of this disorder.
Identifying early markers of vulnerability in the context of familial risk is of particular importance in understanding the developmental course of depression and potential mechanisms for its intergenerational transmission [57], thus being an important factor in the search for prevention of depression in children.
What is evident in the literature is that a family environment characterized by inadequate parenting behaviors [111 ,112], repetitive maternal criticism of the children [17], divorced parents [268] or the manifestation of the psychopathology of depression in a parent [57][58][59][60] appear to be closely linked to the onset of depressive disorders in children. So, the presence of the family dynamics difficulties would be a risk factor for the development of depressive symptoms in children, as well as their maintenance. In this sense, peer and family contexts could have relevance for treatment responses, as youth with depression exhibit differences from healthy youth in their social behavior in both family contexts [193,269] and peer contexts [193,270]. The family thus is revealed in a protective position, to prevent the children to develop depressive symptoms, and if they arise, are able to contribute to their recovery Therefore, understanding the relationship of multiple factors associated with childhood depression may lead to the identification of those at risk and the establishment of preventive protocols and early intervention [126]. However, despite all knowledge we have about the importance of early prevention, only a minority of children with anxiety and depression receive mental health care for their problems [249,[271][272][273]. Therefore, preventive strategies for high-risk individuals, as well as cost-effectiveness analyses for better definition of public policies should be considered priorities in future research [11].

Conclusion
Current scientific literature dealing with childhood depression converges to, directly or indirectly; highlight the negative impact of depressive disorders for the child's quality of life.
The presented studies show that childhood depression is a disorder that develops most commonly in poverty and vulnerability scenery where the individual and family needs concerning to child depression are not always taken into account. In this context, this review demonstrates that depression that starts in childhood often leads to other psychiatric disorders and comorbidities, failing to serve as a warning for families to seek appropriate treatment while it is still possible to quickly reverse the negative consequences for children's mental health.
Even though there are no longer any doubts about its occurrence [18,274], many gaps in knowledge still exist regarding childhood depression. There is no agreement about the criteria to be used to identify this condition in population-based studies. Prevalence varies depending on the age range studied. Factors associated with this disorder are also very different depending on the criterion used to identify depression, the setting and the age range of the studied population [18,20,275,276].
According to the studies selected, it can be concluded that depression in childhood is not simply a mood regulation disorder; it also involves alterations in the physiology and in the cognitive and social functions of children, and requires comprehension of developmental integration processes at multiple levels of biological, psychological, and social complexity in individuals [8,277].
In clinical cases, it was observed that emphasizes its relationship to depression negative emotional experiences and traumatic events during childhood. It is noteworthy, however, that not all individuals exposed to childhood adversity develop depression, and genotype may moderate the relationship between childhood adversity and mental health outcomes [115,124,125]. This fact indicates that the etiology of depressive disorders is complex and multi-factorial, with an intricate interaction among environmental factors and genetic predisposition [126].
According to current literature, the human being involved in care, in particular the team of health professionals is not adequately trained to deal with child depression [222]. Thus, further research is necessary focused on the development of programs designed to prepare health professionals to deal directly or indirectly with childhood depression in the family and clinical environment, enabling them to detect and properly treat this disease, minimizing its destructive effects. Lab (LABESCI) -Federal University of Cariri (UFCA), which always supported the work on this manuscript.

Role of Funding Source
We have no foundation source.