You Asked

Questions from Dr. Schatzberg's Lecture
"Depression and Anxiety: Similairites and Differences"
November 1, 2012

As I understand it, tricyclic [antidepressants] are more toxic and potentially dangerous in patients with kidney problems. Yet, for some patients they are the only effective molecules. What do you think of psychiatrists who believe one should no longer use tricyclics just because of toxicity?

Psychiatrists may be hesitant to use tricyclic antidepressants (TCAs) due to their

  • lethality in overdose
  • potential side effects (low blood pressure, urinary retention, sedation, dry mouth)
  • interactions with other medications.

That said, TCAs can be very effective for certain patients, and their use is within the scope of normal psychiatric practice. In general, TCAs are not known to be toxic to the kidneys; however, since they are metabolized in the liver, their use in patients with liver disease should be undertaken with caution. However, lithium, a medication that can be used in bipolar disorder or to augment treatment of depression, can be associated with kidney problems, and patients taking this medication need to have their kidney function periodically monitored.

With all of the drugs available, how do you best deal with patients who are simply noncompliant with taking their meds on a consistent basis?

When a patient reports noncompliance with prescribed medications, it may be helpful to inquire about the reasons the patient has been noncompliant. Oftentimes, patients may have experienced negative side effects, misunderstood how to take the medication, or simply not understood the end goal of treatment. Sexual dysfunction associated with antidepressant use, for example, is an issue that many patients may be hesitant to mention to their physician. However, it is important to remember that in some cases, including sexual dysfunction, there are treatments or ways to minimize bothersome side effects. Sometimes medications are dosed too frequently for patients to take.

Another factor that is associated with noncompliance is a poor therapeutic alliance between the patient and the physician. A possible fruitful avenue to explore is the quality of that relationship. Since patients may be hesitant to reveal noncompliance to their physicians, it is important for physicians to make such inquiries a routine part of their appointments. Psychiatrists can enlist the help of patients’ loved ones to improve medication compliance. Also, in certain conditions such as schizophrenia, there are long-acting injectable medications that can improve medication compliance.

How much of heredity is the source of psychosis?

Psychosis is a symptom that can occur in a variety of psychiatric illnesses including:

  • schizophrenia
  • bipolar disorder
  • major depressive disorder
  • schizoaffective disorder

Each of these has its own heritability pattern. One way of studying this question is to compare identical versus fraternal twins. For example, if a person with schizophrenia has an identical twin, that twin has a 45 percent chance of developing schizophrenia. If a person with schizophrenia has a fraternal twin, that twin has a lower chance, 15 percent, of developing schizophrenia. There is not one particular gene that confers increased risk of schizophrenia; rather, many genes are associated with increased risk. However, the risk conferred by any one gene is small; therefore, there is not a particular gene for schizophrenia. In addition, genes do not account entirely for the development of schizophrenia; environmental factors, including neonatal hypoxia and viral infections in the second trimester of pregnancy, are also known to be important in the development of this disorder.

Please be sure to attend the upcoming IDEAS lecture on February 7, 2013 at 6 pm. Dr. Matthew State – a psychiatric geneticist from Yale University School of Medicine’s Child Study Center – will discuss this topic in more depth.

Does behavior therapy result in corrections or changes on an MRI in patients with phobias?

There seems to be evidence that behavior therapy can indeed result in changes seen on MRIs in phobic patients. Three recent functional magnetic resonance imaging (fMRI) studies of spider-phobic patients exposed to pictures of spiders showed increased activation of the several areas of the brain including the

  • insula
  • dorsolateral cortex
  • medial orbitofrontal cortex
  • dorsal anterior cingulate cortex
  • amygdala
  • thalamus.

After completing either exposure therapy or cognitive-behavioral therapy, these regions of the brain showed decreased hyperactivity on repeat fMRI. Keep in mind that the brain is ‘active’ in normal everyday life, so these MRI findings are in comparison to normal controls.

Are there any studies using other neuroimaging techniques that show similar results (e.g. electroencephalogram)?

Studies of regional hemispheric asymmetries in depression have demonstrated decreased neuronal activity in left frontal and right posterior brain regions on electroencephalography (EEG), while patients with anxiety demonstrate increased activity in the right posterior brain regions. One recent study demonstrated that the theta band of the EEG (a type of brain wave) was significantly different between controls and patients with Post Traumatic Stress Disorder. These differences were apparent in the right temporal lobe and the right and left frontal lobes.

Another study of rapid eye movement (REM) during sleep determined that there is an association between early-life traumatic exposure and increased rapid eye movement fragmentation during sleep. Finally, a third study recently found that patients with Obsessive-Compulsive Disorder had impairment in smooth pursuit eye movements. Lastly, EEG study of patients with depression consistently shows that these patients have decreased amounts of slow wave sleep, increased amounts of REM sleep, decreased total sleep time, and decreased time to onset of the night’s first REM episode (called REM latency).

Can you explain more about anxiety disorders being more prevalent in young persons, i.e. can they grow out of anxiety – why and how?

Anxiety disorders commonly have their onset in childhood and childhood-onset anxiety disorders appear to be quite persistent. They are also associated with later onset of other mental illness including depression. However, when treated by cognitive behavioral therapy (CBT) and/or medications, childhood-onset anxiety disorders appear to respond as well as adult-onset anxiety disorders. It is difficult to say what percentage of children with anxiety disorders spontaneously recover, because more research efforts appear to have focused on outlining the importance of active treatment in order to prevent later psychiatric problems.

What Brodmann areas are affected by both anxiety and depressive disorders? Do all anxiety disorders affect the same Brodmann areas? What about the depressive disorders?

So many areas of the brain are involved with depressive disorders and anxiety disorders that a brief answer is difficult to formulate! Korbinian Brodmann was a German neurologist from the late 19th and early 20th century, who divided the outer layers of the brain into forty-seven distinct areas, according to how the cells in these areas looked under a microscope.

Areas of the brain involved in major depressive disorder include the

  • prefrontal cortex (Brodmann areas 6, 8, 9, 10, 11, 12, 32, 44, 45, 46, 47)
  • subgenual cingulate gyrus (Brodmann area 25)
  • hippocampus (Brodmann areas 27, 28, 34)
  • amygdala (Brodmann area 38)
  • basal ganglia (not labeled by Brodmann).

Anxiety disorders also affect a wide variety of brain areas, with specific areas depending on the disorder. For example, phobias appear also to involve the prefrontal cortex and amygdala, in addition to the insular cortex (Brodmann areas 13, 14, 15, 16), and dorsal anterior cingulate cortex (Brodmann area 24).

What developments have been made toward alternative treatments for depression and anxiety disorders? Do studies exist examining the effects of exercise, nutrition, alternative therapy techniques, etc., and what do results show?

Many studies have examined complementary and alternative treatments in major depression and anxiety disorders. Adequate nutrition certainly is required for normal functioning of mood and thinking; we know that various vitamin deficiencies and caloric insufficiency are associated with problems in mood, activity, cognition and well-being. However, this is not to say that high doses of vitamin supplements will alleviate depression or anxiety.

St. John’s wort, S-adenosyl methionine (SAM-E), EPA omega-3 fatty acids, light therapy, mindfulness meditation, and exercise appear to benefit some patients with depression. Kava kava, exercise, and mindfulness meditation appear to benefit some patients with anxiety disorders.

Caution is warranted especially with kava kava, as there have been reports of liver damage caused by this substance. Caution is also warranted with St. John’s Wort because it has the potential for causing harmful interactions with other medications.

Many alternative therapy techniques exist for treatment of general distress. In general, therapy is most successful when performed by a caring, interested, involved, and professionally trained and supervised therapist. It remains important, however, for any therapist to recognize the signs and symptoms of severe depression and anxiety, to screen for suicide risk, and to refer to a psychiatrist any patients needing evaluation for medication or hospitalization.

What role does the thyroid play in depression and anxiety?

This is an important question about the interaction between medical and psychiatric disorders. Disorders of thyroid function are clearly associated with mood and anxiety symptoms. For example, it is extremely common for patients with hypothyroidism to exhibit symptoms of clinical depression. In addition, patients with hyperthyroidism frequently demonstrate anxiety, restlessness, and agitated depression. Stemming from these clinical observations, researchers have long been interested in the endocrine system and its association with mood and anxiety disorders. In depressed patients without overt hypothyroidism, there still appears to be irregularities in thyroid function, such as reduced 24-hour thyroid stimulating hormone secretion. Interestingly, one augmentation strategy in treating depression is addition of thyroid hormone.

Do you see alcohol used to self-medicate for long-term depression/anxiety? Can this lead to dementia?

Problematic alcohol use is common in people with anxiety and/or depression. Conversely, anxiety and/or depression are common in people with problematic alcohol use. It is important to screen for problem drinking in any patient with anxiety and/or depression, and to screen for anxiety and depression in any patient with problem drinking. Treatment of alcohol problems is essential to successful treatment of anxiety and depression and treatment of anxiety and/or depression is essential to successful treatment of alcohol problems.

Long term problematic use of alcohol can lead to

  • cognitive problems, both from direct effects of alcohol, and secondary effects of alcohol-associated neglect of chronic medical problems
  • alcohol-associated nutritional deficiencies
  • alcohol-associated increased risk of traumatic brain injury.

However, consumption of alcohol in moderation may confer some protection from cardiovascular diseases and dementia, although this has not been tested in randomized controlled trials.