Mood Disorder, or Mad Disorder?

The leap from depression to psychosis may be shorter than you think.


June 15, 2007 — -- The elderly woman with depression is convinced God is punishing her for having sinned in her youth through sexual improprieties. The middle-aged depressed man believes he deserves to die because he (inaccurately) thinks he has mismanaged his family's finances and will leave them destitute. The young woman with depression hears voices telling her she is no good and should kill herself.

Depression is officially classified as a mood disorder, and, indeed, people with depression typically experience major changes in their mood, often feeling sad, down, numb, empty or hopeless.

But sometimes people with depression go mad, as in crazy, or to use the technical lingo, psychotic.

At one level, this underscores that clinical depression is not the same thing as merely feeling down in response to having had a bad day or a bad week. Rather than merely being the blues that we all have from time to time, depression can involve a break with reality, as when someone experiences hallucinations, such as hearing voices when no one is around or seeing things when nothing is there, or delusions, irrational beliefs of the kind noted above.

These symptoms of madness, these psychotic symptoms, are common in the mood state we call mania, which is the high pole of bipolar disorder, occurring in more than half of this type of disordered mood. But they also occur in a smaller proportion of depressive mood episodes: Most studies say about 15 percent of them.

How are these psychotic depressions different from other depressions? As you may guess, adding psychosis to the picture means even more difficulties for people who are already battling depression; as confirmed by William Coryell, at the University of Iowa, and his colleagues when they studied people with psychotic depression over a period of 10 years.

In a study here at John Hopkins that will soon be published in the journal Bipolar Disorders, my colleagues and I studied 4,724 people with mood disorders to see whether psychotic depression was more common in people with bipolar disorder than in those with depression only.

The depression-only group never had the mild highs or hypomanias characteristic of bipolar disorder, type 2, or the severe highs characteristic of bipolar disorder, type 1.

We observed that people with bipolar disorder, type 1 had about a five times higher rate of psychotic symptoms in their depressions than did the other two groups; more than 25 percent of their depressions were psychotic compared with 6 percent for bipolar disorder type 2 and for depression only.

What this means is that the more severe form of depression is strongly associated with the most severe type of mood disorder.

What about the implications for treatment?

Psychotic depression is often treated with both an antidepressant medication and also an antipsychotic medication. The research to date shows that this combination is more effective than using an antipsychotic medication alone -- and although it is probably more effective than an antidepressant alone, this has not been conclusively proved.

Electroconvulsive treatment, sometimes called "shock therapy," is often an effective alternative to medication for these very ill patients. Consideration should also be given to whether the patient has bipolar disorder and might need mood stabilizer medication.

Psychotherapy, or talk therapy, tends to have little impact in helping to treat madness, or psychosis, as these patients typically do not have the reasoning power with which to unlock the doors to the prison of false belief in which they are locked up. Directly altering the chemistry of the brain provides the key to releasing them from the throes of illness.

When treatment takes hold, patients' moods improve; the depression lifts. And the delusional beliefs disappear.

How and why these symptoms of madness arise remains a mystery. It has long been known that genetic predisposition plays a role. The Swiss physician Paracelsus wrote in his 1520 treatise, "Diseases Which Lead to a Loss of Reason," that "the truly insane are those who have been suffering from it since birth and have brought it from the womb as a family heritage"

Yet we cannot explain why the transient psychotic symptoms that emerge in some depressions occur and then disappear. Our best clue at the moment centers on the neurotransmitter dopamine, which transmits signals from one brain cell to the next. We know that antipsychotic medications work primarily by blocking this transmission, suggesting that there is an excess of dopamine signaling in the midst of psychotic illness.

We anticipate that ongoing research into the genetics and neurobiology of depression will allow us to follow this clue and flesh out the rest of what is likely to be a complex story of disordered chemistry in the brain.

Dr. James Potash is an Associate Professor of Psychiatry and Co-Directorof the Mood Disorders Program ( at theJohns Hopkins School of Medicine in Baltimore, Maryland. If you havequestions or comments, please email at To participate in ourstudies, call 1-877-MOODS-JH.

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