Dr. Grossi's Blog
In the last few days I have watched some of the TV coverage of hurricane Sandy and the devastation it caused. Many public figures referred repeatedly to the resilience of the suffering citizens and that they would overcome the adversity. In the office I often ask patients to assess their progress on a scale of one to ten. Yesterday I asked such a patient and he responded that he was about at six. I asked what needed to change to get him to the nine or ten range. He responded that he would need to feel more emotional resilience. By this he meant an increased ability to bounce back from trauma, adversity or hardship. We see this complex process played out on each fall weekend in football games we watch. Football is a game of overcoming adversity.
In humans the stress response to adversity is mediated by the sympathetic nervous system, the hypothalamic pituitary axis, neuropeptide Y, and the serotonin system. These in turn are influenced by the genes that encode variants of the components of those systems. An example I have previously blogged about (Not So Fast) is the long and short serotonin transporter resulting in differential serotonin uptake from the synapse and a differential risk of depression and response to stress. Repeated stress in childhood can result in learned helplessness and can cause exaggerated responsiveness to future stress. On the other hand, childhood stressors that are mastered help an individual become stress-adaptive and thus more resilient than normal.
Some psychological factors related to resilience are a history of mastery of problems and challenges, i.e., a history of success; loving caretakers; robust social support; cognitive flexibility, i.e., the ability to view issues from multiple positive and negative viewpoints; physical fitness; strong commitment to developing or enhancing skills; good and constant role models; quick recovery from stressful events; careful reflection and consideration of life's experiences and drawing conclusions from them; curiosity; espousing and adhering to important values.
To summarize, resilience in humans who face stress depends on genetic, cognitive, psychological, neurobiological, developmental, and protective factors.
In the last couple of years, Zarate et. al. have done depression research with an old drug that has been used as an anesthetic. This research may be the most important development in depression therapeutics in the past fifty years. Antidepressants currently available are derived from developments in the 1950s. At that time drugs used to treat tuberculosis were found to be monoamine oxidase inhibitors and this led to the monoamine theory of depression which was formally enunciated in the 1965 paper by Joseph Schilkraut. This led to research which eventuated in the SSRI drugs and other modern antidepressants. These drugs take weeks to produce a therapeutic response and are only moderately effective in about two thirds of patients. In contrast, ketamine, an N-methyl-o-aspartate antagonist, produces an antidepressant effect within hour and works in individuals who are resistant to typical antidepressants.
There are accumulating studies that show that depression is associated with reduced brain size in the prefrontal cortex and hippocampus and decreased neuronal synapses in those regions. Typical antidepressants can reverse these changes albeit slowly. Ketamine rapidly produces synaptogenesis and reverses synaptic deficits produced by stress and depression. This in turn suggests a new theory of depression, i.e., one of synaptogenic impairment and impoverishment. It also suggests that treatment of depression should be directed to correct these connections.
Typical antidepressants increase neuroplasticity as demonstrated by Rath et.al. with their electrophysiological studies showing enhanced synaptic transmission and long term potentiation. Other studies demonstrate antidepressant effects on BDNF, spine density, and blocking of spine atrophy by chronic stress. Yet these are slow-acting and work on modulatory neurotransmitters. A single dose of ketamine alleviates depressive symptoms within hours and the effects last about ten days. This drug increases the number and function of synaptic connections which has focused depression research on synaptogenesis as a central actor in mood control and regulation.
From a clinical standpoint, ketamine research has been done with infusions, i.e., I.V. drip done in a surgicenter. More recently four psychiatrists at the Harvard medical school have treated bipolar II patients with IM injections. They have reported positive results in a letter to the editor in the August 2012 American Journal of Psychiatry. It is likely that this treatment will be offered in my office in the next few months.
There are psychiatrists who have had a patient commit suicide and there are psychiatrists who will have a patient commit suicide. High-risk patients in clinical practice are not uncommon. Assessment of the risks have been complicated by a variety of factors in the past. Among them were flaws in the precision of definitions and measurements. For example, an overdose of medication might be called a gesture, an accident, a threat, a cry for help, an attempt, or a manipulation. This imprecision hindered a more organized study of this problem.
A number of years ago the FDA convened a task force to study this problem. It was largely driven by development and introduction of a large number of antidepressants in the 1990s and the desire to determine whether these newer agents were implicated in increasing suicidal behavior. This led to the "black box" warnings that are present in the antidepressant entries in the Physician's Desk Reference. It also led to a more precise measurement of suicidal risk. What follows is a description of factors to consider in a more modern risk assessment.
The assessment of suicide is divided into three areas. First is that of suicidal ideation. This includes wishes to be dead, thoughts of wanting to end one's life, thoughts of suicide with some consideration of means, thoughts of suicide with some intent to act, thoughts with a detailed plan that has been developed. The second area is designated intensity of ideation. This includes the number of times a person has suicidal thoughts per day or week, the amount of time engaged with those thoughts, whether the individual can control or stop thinking the thoughts, whether there are deterrents such as children, family, etc. that stop the individual from thinking about suicide. This area also includes the reasons for thinking about suicide such as attention, revenge, pain, etc. The third and final area is suicidal behavior. This includes whether an attempt was made, how many attempts, type of attempts, any non-suicidal self-injurious behavior, any interrupted or aborted attempts and any preparatory acts or behavior.
The weighing of the above factors as well as considering whether the patient has a substance abuse problem, is psychotic, has a history that includes the suicide of significant others as well as the quality and strength of the relationship to the psychiatrist or therapist make the final judgment about suicidality of a particular individual a complex and challenging decision. Taking all these issues into account does help to make a reasonably accurate but not perfectly accurate response to the individual's question, "To be or not to be."