Children with depressed parents have structural differences in the brains


The largest brain imaging study of children ever conducted in the United States has revealed structural differences in the brains of those whose parents have depression.

Depression is a common and debilitating mental health condition that typically arises during adolescence.

While the causes of depression are complex, having a parent with depression is one of the biggest known risk factors.

Studies have consistently shown that adolescent children of parents with depression are two to three times more likely to develop depression than those with no parental history of depression.

However, the brain mechanisms that underlie this familial risk are unclear.

A new study, led by David Pagliaccio, PhD, assistant professor of clinical neurobiology in the Department of Psychiatry at Columbia University Vagelos College of Physicians and Surgeons, found structural differences in the brains of children at high risk for depression due to parental depressive history.

The study was published in the Journal of the American Academy of Child & Adolescent Psychiatry.

What the Study Found

The researchers analyzed brain images from over 7,000 children participating in the Adolescent Brain Cognitive development (ABCD) study, led by the NIH. About one-third of the children were in the high-risk group because they had a parent with depression.

In the high-risk children, the right putamen–a brain structure linked to reward, motivation, and the experience of pleasure–was smaller than in children with no parental history of depression.

In the high-risk children, the right putamen–a brain structure linked to reward, motivation, and the experience of pleasure–was smaller than in children with no parental history of depression.

What the Study Means

Randy P. Auerbach, PhD, associate professor of medical psychology at Columbia University Vagelos College of Physicians and Surgeons and senior author of the study, notes, “These findings highlight a potential risk factor that may lead to the development of depressive disorders during a peak period of onset. However, in our prior research, smaller putamen volumes also has been linked to anhedonia–a reduced ability to experience pleasure–which is implicated in depression, substance use, psychosis, and suicidal behaviors.

Thus, it may be that smaller putamen volume is a transdiagnostic risk factor that may confer vulnerability to broad-based mental disorders.”

Dr. Pagliaccio adds that “Understanding differences in the brains of children with familial risk factors for depression may help to improve early identification of those at greatest risk for developing depression themselves and lead to improved diagnosis and treatment.

As children will be followed for a 10-year period during one of the greatest periods of risk, we have a unique opportunity to determine whether reduced putamen volumes are associated with depression specifically or mental disorders more generally.”

Additional authors are Kira L. Alqueza, BA, Rachel Marsh, PhD.

Funding: The ABCD Study is supported by the National Institutes of Health (NIH) and additional federal partners under award numbers U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147.

Depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM–5) include diagnoses of different disorders, for example, major depressive disorder (MDD), disruptive mood dysregulation, persistent depressive disorder, and depression not otherwise specified. This article reviews major depressive disorder (MDD).

MDD is the first cause of disability among adolescents aged 10 to 19 years (WHO 2014). Suicide is the third cause of death in this age group, and adolescent depression is a major risk factor for suicide. Depressed adolescents experienced significantly more stressors during the year before onset when compared with a comparable 12-month period in normal controls.


The etiology of depression is multifactorial and complex resulting from interactions between biological vulnerabilities and environmental factors.

Genes and Heritability

A meta-analysis found that heritability is a main risk factor for mental health concerns, including depression, between ages 13 and 35.[1] In twin studies, heritability was found to be around 60% to 70%.

Offspring of depressed parents have an increased risk of 2 to 4 times compared with offspring of healthy parents. Genes-environmental interaction contributes to this risk, specifically by increasing by increasing susceptibility to environmental stress.[2] Also, different studies reported that the serotonin transporter gene variant (5-HTTLPR) might increase the risk of depression in the presence of adverse life events or early maltreatment.[3]

Puberty and Brain Development

Psychosocial Risk Factors

Stressful life events often precede the onset and recurrence of depressive symptoms and episodes in adolescents, especially with girls.[4] However, most children and adolescents who experience such events do not develop depression. Examples of life stressors include events involving loss, maltreatment, romantic break-up, being bullied by peers, and parent-child conflicts.

Cognitive Risk Factors

Depressed adolescents have an attentional bias and a memory bias. They recall more negative and fewer positive words than a non-depressed adolescent.[5] There is a bidirectional relationship between children’s low perceived competence and depression. Children’s underestimation of their competence predicts depressive symptoms and vice versa. Previous depression also predicts underestimation of competence.[6][7] Rumination, dwelling excessively, does also predict the onset and continuation of depression.[8]

Other Factors

  • Sleep problems such as shorter rapid eye movement (REM) latency, higher REM density, decreased sleep efficiency and higher frontal slow-wave activity were associated with the development of depression[9][10]
  • Co-morbid medical illness: Epilepsy, multiple sclerosis, diabetes, and others
  • Other mental illness: Anxiety disorders, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD)
  • Medications: Corticosteroids, interferons, mefloquine, progestin-releasing implanted contraceptives, and propranolol
  • Substance use: Alcohol


The pediatric depression annual incidence rate is 1% to 2% at age 13 and from 3% to 7% at age 15.[11] The ratio is equal between male and female during childhood (1:1) and 1:2 during adolescence. After puberty, the risk of depression increases by a factor of 2 to 4, particularly in females.[12] Different studies reported that lower or middle-income countries have higher rates of depression in adolescents compared to higher income countries (10% to 13% in boys and 12% to 18% for girls).[13][14]

History and Physical

DSM–5 criteria for diagnosing depression in the pediatric population:

  • The presence of at least 5 of the following items in the same 2-week period with having a change in the level of function. At least 1 of the items is either depressed mood or loss of interest or pleasure. It is important to note that other medical conditions can not explain symptoms.
    • Depressed or irritable mood most of the day, almost every day, as demonstrated by either subjective report, for example, the patient feels sad, empty, or hopeless, or observation made by others, for example, the patient appears sad. 
    • A significant decrease in interest or pleasure in activities most of the day, nearly every day as indicated by self-reporting or observation
    • Failure to make expected weight gain or remarkable weight loss when not dieting or a remarkable weight gain, or decrease or increase in daily appetite
    • Lack of sleep or excessive sleeping almost every day
    • Psychomotor unrest or retardation almost every day (observable by others, not merely subjective feelings of restlessness).
    • Lack of energy nearly every day
    • Feelings of worthlessness or inappropriate guilt (possibly delusional) nearly every day (not merely self-reported or guilt for being sick)
    • Decrease capacity to think or concentrate or indecisiveness, almost every day (either by self-report or as observed by others)
    • Repeated thoughts death (not just fear of dying), recurrent suicidal ideation without specific plans; suicide attempt; or a definite plan to commit suicide
  • The illness causes clinically remarkable distress or impairment in social, occupational, or other important areas of functioning.
  • The episode is not due to the physiological effects of a substance or another medical condition
  • The occurrence of the major depressive episode cannot be explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders
  •  Had no manic or hypomanic episodes


The USPSTF (US Preventive Services Task Force) recommends screening for a major depressive disorder (MDD) in adolescents aged 12 to 18 years.[15] Some screening questionaries are available to screen for depression in primary settings. Examples are:

  1. PHQ9: The 9-item Patient Health Questionnaire, scores each of the nine DSM criteria as “0” (not at all) to “3” (nearly every day), providing a 0 to 27 severity score
  2. The Zung Self-Rating Depression Scale: A 20-item self-report questionnaire.
  3. The Beck Depression Inventory-II (BDI-II): 21-item self-report inventory

There is no specific blood test or imaging that can be done to diagnose depression. However, the evaluation of depression needs to include some investigations to rule out some of the differential diagnosis. Examples are:

  • Complete blood count (CBC) and vitamin B-12 levels
  • Electrolytes including magnesium, calcium, and phosphate.
  • TSH, T3, free T4
  • Liver function tests, renal function test (blood urea nitrogen, creatinine)

Other investigations should be ordered whenever other medical illnesses are suspected, for example, urine toxicology screen, blood alcohol level, HIV test, dexamethasone suppression test, and ACTH stimulation test.

Treatment / Management

Treatment should aim for recovery, achieving full remission of symptoms, and returning to the premorbid level of functioning. Biopsychosocial treatment plans for children and adolescent is similar to adults’ plans. However, in children and adolescents, clinicians often start with psychosocial interventions.

Psychosocial Interventions Involving the Child and Parents

Psychosocial interventions are the first-line treatment in case of mild-to-moderate depression.

  1. Psycho-education including education about the illness, the importance of having a good sleep and good nutrition
  2. Exercising for at least 30 minutes a day
  3. Cognitive and behavioral therapy to help the depressed individual identify cognitive distortions and to learn cognitive restructuring skills, problem-solving skills and to use behavioral activation techniques
  4. Interpersonal therapy aimed to decrease interpersonal conflicts by helping depressed individual learning interpersonal problem-solving skills and changing dysfunctional communication and relational patterns
  5. Family therapy: Different family therapy modules could be of help to the depressed individual and family.


Different studies had shown that antidepressants efficacy is different between adults and children. The placebo effect is stronger among children and adolescents compared to adults, especially with mild-moderate depression.

It is important to discuss the effects and side-effects with the patient and parents. Typically, for the first month after prescribing an antidepressant follow-up should be weekly. This allows for close monitoring of side effects as well as supportive management.

Antidepressants that are most commonly used in this age group are fluoxetine, sertraline, citalopram, and escitalopram. Fluoxetine and escitalopram are approved by the FDA for adolescent depression. Venlafaxine, a serotonin-norepinephrine repute inhibitor (SNRI), is a second-line drug due to its side effects.

Side Effects

One of the major side effects of antidepressants is an increase in suicidal thoughts, but not suicidal attempts. Thus, monitoring suicidal risk is required. Other side effects include gastrointestinal problems, agitation, nightmares and sleep disturbance, weight gain, and sexual dysfunction.

Management of Comorbid Disorders

Clinicians should monitor comorbid disorders such as sleep disorders, anxiety disorders, and other underlying medical causes of depression.

Differential Diagnosis

Bipolar Depression

To diagnose a bipolar affective disorder, clinicians need to document one manic or hypomanic episode. The challenge with the pediatric population is that bipolar disorders often start with an episode of depression in childhood or adolescence.

Adjustment Disorder

The onset of symptoms in adjustment disorder occurs following a significant life event.

Substance Use Disorders

Either withdrawal from substances, for example, amphetamines or cocaine, or intoxication (alcohol) could present with a clinical picture similar to depression. Depression could be diagnosed as a concurrent disorder if depressive symptoms persist or precede the onset of substance use.

Medical Conditions

Different medical conditions could present with depression, for example, multiple sclerosis, stroke, or hypothyroidism.

Attention-Deficit Hyperactivity Disorder

Attention-deficit hyperactivity disorder (ADHD) could present with irritable mood, poor concentration, and these symptoms are similar in pediatric depression symptoms.


The most important factor in predicting the severity and improvement percentage of depression is the duration of untreated depression. Active treatment decreases the depressive episode duration.[16] 

Remission rate depends on different factors like disorder severity, with rates among people with severe disorders being 20% to 30% lower than mild-to-moderate depression.

Around, 60 % to 90% of mild-to-moderate depressive episodes in adolescents remit within a year. However, recurrence within 5 years occurs in around 50 % to 70%. Patients with major depression from specialist psychiatry settings have had long-term recurrence rates of between 50% and 64%.[17] 

Relapse rate is higher when the remission from depression is partial (67.6%) compared to when it is complete remission (15.18%).[18] Children and adolescents who develop a recurrent or chronic disorder extending into adulthood are more likely to suffer considerable disability and impairment.[19]

Columbia University
Media Contacts:
Eian Kantor – Columbia University
Image Source:
The image is in the public domain.

Original Research: Closed access
“Brain Volume Abnormalities in Youth at High Risk for Depression: Adolescent Brain and Cognitive Development Study”. David Pagliaccio et al.
Journal of the American Academy of Child & Adolescent Psychiatry doi:10.1016/j.jaac.2019.09.032.


Please enter your comment!
Please enter your name here

Questo sito usa Akismet per ridurre lo spam. Scopri come i tuoi dati vengono elaborati.