Depression, Addiction, Suicide, and Robin Williams

The recent death of Robin Williams has brought up questions about the links between addiction and depression, or dual diagnosis. The Epidemiologic Catchment Area study conducted by the National Institute of Mental Health reported that nearly a third of individuals with depression also have a comorbid substance disorder at some point.¹ The daughter of former US Senator George McGovern, who was treated for depression, froze to death after having been drunk and passed out in the cold.²

With the DSM-5, we no longer make the distinction between substance abuse and substance dependency but place them together under the diagnosis of substance use disorder. It is interesting that alcohol and the various drugs of abuse all seem to cause activation of the brain’s reward circuits, especially the dopamine neurons located in the ventral tegmental area (VTA) with projections to the nucleus accumbens.³ Repeated activation leads to euphoria and an alteration in the reward mechanism, which is defined by the addict as “craving” when the drug is not present. This process is often referred to as sensitization. Eventually, with increased tolerance, the individual feels sick most of the time and will use the drug to feel “normal.” Given sufficient consequences for alcohol or drug use, the person with an addiction will seek help through rehab and/or a 12-Step program and may achieve a period of sobriety. Unfortunately, even one drink can again sensitize the neural circuits to want more and more. Last September, in an interview with Jon Stewart, Williams described the loss of 20 years of sobriety: “The moment I had the first sip…it was like…rahh…all of a sudden it was like, welcome back a**hole.”

Depression is one of the most common forms of mental illness, affecting about 15% of the population.⁴ A number of different brain areas are affected, which create different symptoms. The frontal cortex may be involved with disturbances of cognition,⁵ the hippocampus with feelings of suicidality,⁶ and the VTA and nucleus accumbens may mediate anhedonia and decreased motivation.⁷ The fact is that addiction and depression seem to share common neural substrates.⁸

An additional factor in Robin Williams’ death is the news from Mrs Williams that her husband had early Parkinson’s disease. Each illness—depression and Parkinson’s—can worsen the other, with increases in problems with concentration as well as movement problems and anxiety.⁹ In Parkinson’s disease, the dopamine-producing brain cells die, which we know are linked to reward and pleasure. In the 1990 movie Awakenings, Robin Williams portrayed a physician at a hospital in the Bronx caring for patients suffering from catatonia caused by an encephalitis epidemic. After attending a lecture, Dr Sayer (Robin Williams) believes the Parkinson’s drug L-Dopa may help, and he gives it to patient Leonard Lowe (Robert DeNiro). Leonard “awakens,” falls in love, and desires freedom, but then he develops facial and body tics. The tics grow more prominent, Leonard starts to shuffle, spasms, and then cannot move. Leonard returns to catatonia.

In a 2010 interview with comedian Marc Maron, Williams spoke about contemplating suicide but said the big picture was far more positive than any of the troubles of the present. It is possible that, following the diagnosis of Parkinson’s, the big picture changed for Mr Williams. He may have made the decision to end his life now rather than face a living death of depression, dementia, and the catatonic-like rigidity of Parkinson’s disease.

Financial disclosure:Dr King had no relevant personal financial relationships to report.

References

1. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990;264(19):2511–2518. PubMed

2. McGovern G. Terry: My Daughter’s Life-and-Death Struggle With Alcoholism. New York, NY: Plume; 1997.

3. Gardner EL. Addiction and brain reward and antireward pathways. Adv Psychosom Med. 2011;30:22–60. PubMed

4. Bromet E, Andrade LH, Hwang I, et al. Cross-national epidemiology of DSM-IV major depressive episode. BMC Med. 2011;9:90. PubMed

5. Clark L, Chamberlain SR, Sahakian BJ. Neurocognitive mechanisms in depression: implications for treatment. Annu Rev Neurosci. 2009;32:57–74. PubMed

6. Labonté B, Suderman M, Maussion G, et al. Genome-wide methylation changes in the brains of suicide completers. Am J Psychiatry. 2013;170(5):511–520. PubMed

7. Kroemer NB, Guevara A, Teodorescu IC, et al. Balancing reward and work: anticipatory brain activation in NAcc and VTA predict effort differentially [published online ahead of print August 6, 2014]. Neuroimage. PubMed

8. Peña CJ, Bagot RC, Labonté B, et al. Epigenetic signaling in psychiatric disorders [published online ahead of print April 5, 2014]. J Mol Biol. PubMed

9. Raskind MA. Diagnosis and treatment of depression comorbid with neurologic disorders. Am J Med. 2008;121(11 suppl 2):S28–S37. PubMed