Clinical depression is a serious condition that negatively affects how a person thinks, feels, and behaves. In contrast to normal sadness, clinical depression is persistent, often interferes with a person’s ability to experience or anticipate pleasure, and significantly interferes with functioning in daily life. Untreated, symptoms can last for weeks, months, or years; and if inadequately treated, depression can lead to significant impairment, other health-related issues, and in rare cases, suicide.
(Sources: National Institute of Mental Health and National Women’s Health Center.)

What are some of the signs and symptoms of depression?
A person is diagnosed with a major depression when he or she experiences at least five of the symptoms listed below for two consecutive weeks. At least one of the five symptoms must be either (1) depressed mood or (2) loss of interest or pleasure.

Symptoms include:

Depressed mood most of the day, nearly every day
Markedly diminished interest or pleasure in activities most of the day, nearly every day
Changes in appetite that result in weight losses or gains unrelated to dieting
Changes in sleeping patterns
Loss of energy or increased fatigue
Restlessness or irritability
Feelings of anxiety
Feelings of worthlessness, helplessness, or hopelessness
Inappropriate guilt
Difficulty thinking, concentrating, or making decisions
Thoughts of death or attempts at suicide
(Sources: National Institute of Mental Health and National Women’s Health Center.)

How is depression diagnosed and treated?
The first step to being diagnosed is to visit a doctor for a medical evaluation. Certain medications, and some medical conditions such as thyroid disorder, can cause similar symptoms as depression. A doctor can rule out these possibilities by conducting a physical examination, interview and lab tests. If the doctor eliminates a medical condition as a cause, he or she can implement treatment or refer the patient to a mental health professional.

Once diagnosed, a person with depression can be treated by various methods. The mainstays of treatment for depression are any of a number of antidepressant medications and psychotherapy, which can also be used in combination.
(Sources: National Institute of Mental Health and National Women’s Health Center.)

Why is depression more prevalent in women than in men?
Depression is twice as common among women as among men. About 20 percent of women will experience at least one episode of depression across their lifetime. Scientists are examining many potential causes for and contributing factors to women’s increased risk for depression. Biological, life cycle, hormonal and psychosocial factors unique to women may be linked to women’s higher depression rates. Researchers have shown, for example, that hormones affect brain chemistry, impacting emotions and mood.

Before adolescence, girls and boys experience depression at about the same frequency. By adolescence, however, girls become more likely to experience depression than boys. Research points to several possible reasons for this imbalance. The biological and hormonal changes that occur during puberty likely contribute to the sharp increase in rates of depression among adolescent girls. In addition, research has suggested that girls are more likely than boys to continue feeling bad after experiencing difficult situations or events, suggesting they are more prone to depression.
(Sources: National Institute of Mental Health and National Women’s Health Center.)

What is Postpartum Depression (PPD)?
Women are particularly vulnerable to depression after giving birth, when hormonal and physical changes and the new responsibility of caring for a newborn can be overwhelming. Many new mothers experience a brief episode of mild mood changes known as the “baby blues.” These symptoms usually dissipate by the 10th day. PPD lasts much longer than 10 days, and can go on for months following child birth. Acute PPD is a much more serious condition that requires active treatment and emotional support for the new mother. Some studies suggest that women who experience PPD often have had prior depressive episodes.
(Sources: National Institute of Mental Health and National Women’s Health Center.)

What happens during menopause?
Menopause is defined as the state of an absence of menstrual periods for 12 months. Menopause is the point at which estrogen and progesterone production decreases permanently to very low levels. The ovaries stop producing eggs and a woman is no longer able to get pregnant naturally. During the transition into menopause, some women experience an increased risk for depression. Scientists are exploring how the cyclical rise and fall of estrogen and other hormones may affect the brain chemistry that is associated with depressive illness.
(Sources: National Institute of Mental Health and National Women’s Health Center.)

What about depression later in life?
For older adults who experience depression for the first time later in life, other factors, such as changes in the brain or body, may be at play. For example, older adults may suffer from restricted blood flow, a condition called ischemia. Over time, blood vessels become less flexible. They may harden and prevent blood from flowing normally to the body’s organs, including the brain. If this occurs, an older adult with no family or personal history of depression may develop what some doctors call “vascular depression.” Those with vascular depression also may be at risk for a coexisting cardiovascular illness, such as heart disease or a stroke.
(Sources: National Institute of Mental Health and National Women’s Health Center.)

What efforts are underway to improve treatment of depression?
Researchers are looking for ways to better understand, diagnose and treat depression among all groups of people. Studying strategies to personalize care for depression, such as identifying characteristics of the person that predict which treatments are more likely to work, is an important goal.
(Sources: National Institute of Mental Health and National Women’s Health Center.)

What is the most promising recent development to treat depression?
The biggest discovery for the treatment of depression is ketamine, a glutamate NMDA receptor antagonist that produces rapid (within hours) antidepressant actions in patients who have failed to respond to conventional antidepressants (i.e., are considered treatment- resistant). The ability of ketamine to produce a rapid and efficacious antidepressant response by a completely different mechanism represents the most important finding in the depression field in over 50 years. Studies aimed at characterizing the mechanisms by which ketamine works rapidly and effectively could lead to novel targets and agents that are safer and more long-lasting, and could revolutionize the treatment of depression. Numerous NARSAD Grants have supported this work. Recent research demonstrating that ketamine increases synaptic connections in brain regions that control mood and emotion also raises the possibility that behavioral therapies, as well as pharmacological agents, could reinforce and sustain these new connections and the antidepressant response to ketamine.
(Source: Dr. Ronald Duman, Brain & Behavior Research Foundation Scientific Council)

What is treatment-resistant depression?
Treatment-resistant depression (TRD) is a term used in clinical psychiatry to describe cases of major depressive disorder that do not respond to standard treatments (at least two courses of antidepressant treatments). For many people, antidepressant treatment and/or ‘talk’ therapy (such as Cognitive Behavioral Therapy) ease symptoms of depression, but with treatment-resistant depression, little to no relief is realized. Treatment-resistant depression symptoms can range from mild to severe and may require trying a number of approaches to identify what helps.
(Source: Biological Psychiatry)

How can treatment-resistant depression be treated?
Treatment of resistant depression has traditionally most commonly been treated with electroconvulsive therapy (ECT). ECT has been modified to avoid the pain previously associated with it and is the most effective and quick-acting treatment for resistant depression. The downside is that it works by inducing brain seizures and can impair memory. Its therapeutic benefits can also fade over time. New methods of brain stimulation also offer the possibility of relief. These technologies exploit the fact that the brain is an electrical organ: it responds to electrical and magnetic stimulation to modulate brain circuits and change brain activity. Repetitive transcranial magnetic stimulation (rTMS), pioneered by Dr. Mark George with the support of NARSAD Grants, was approved by the FDA in 2008 as a treatment for some otherwise untreatable depressions. rTMS is a noninvasive method that works through a coil held over the target area of the brain. A magnetic field passes through the skull to activate the appropriate brain circuit and no seizures are induced. Deep brain stimulation (DBS), a technique adapted for treating depression by Dr. Helen Mayberg with the support of NARSAD Grants, works through electrodes planted deep in the brain. Another method, vagus nerve stimulation (VNS), stimulates the vagus nerve in the neck to therapeutically activate brain function. Magnetic seizure therapy (MST) combines rTMS and ECT to achieve a safer form of seizure therapy. MST has been supported through NARSAD Grants to Dr. Sarah Lisanby.

What ideas are on the horizon for better, mor effective ways to treat depression?
The first attempts at defining depression as a biologically-based illness hinged on a theory of a ‘chemical imbalance’ in the brain. It was thought that too much or too little of essential signal-transmitting chemicals—neurotransmitters—were present in the brain. This idea has been useful—that the brain is a kind of chemical soup in which there may be too much dopamine or too little serotonin, but it is no longer adequate. All the current antidepressants are designed based on this theory, but many researchers are looking to understand in greater detail the brain biology that underlies depression’s symptoms so that novel therapies can be found.

One example in a recently published study (in Nature July 12, 2012) identifies a new molecular mechanism responsible for anhedonia, or the inability to experience pleasure, that is one of the most crippling symptoms of depression. The research team found that a hormone known to affect appetite, called melanocortin, turns off the brain’s ability to experience pleasure when an animal is stressed. This is the first study to implicate melanocortin in depression and could lead to an entirely new class of antidepressant medications.
(Source: Dr. Robert Malenka, Brain & Behavior Research Foundation Scientific Council)

Can brain scans guide treatment for depression?
A Psychiatric brain imaging has confirmed the biological nature of many psychiatric illnesses over the past twenty years. Yvette Sheline, M.D., in the mid 1990s, used functional magnetic resonance imaging (fMRI) to identify structural brain changes in depressed patients and established depressin as a brain disease.

Using positron emission tomography (PET) scan images, Dr. Helen Mayberg of Emory University identified, in 2013, specific brain activity that can potentially predict whether people with major depressive disorder will best respond to an antidepressant medication or psychotherapy. This important new work offers a first potential imaging biomarker for treatment selection. A team of researchers including NARSAD Grantee Stefan G. Hoffman, Ph.D., of Boston University and Frida E. Polli, Ph.D., of Massachusetts Institute of Technology have used brain imaging to predict the success of cognitive behavioral therapy, a specific type of talk therapy often used to help treat a wide range of mental illnesses including anxiety disorders, depression and schizophrenia.

J. John Mann, M.D., a 2008 NARSAD Distinguished Investigator Grantee, is using brain-imaging methods to study suicidal behavior. He and his team have found specific and consistent changes in the brains of people who died by suicide. They are testing depressed patients to see whether the same changes are visible in brain scans of living people.

Source: BBR Foundation