James Holmes, the suspect responsible for the worst mass shooting in U.S. history, has begun a legal journey that will include an extensive psychiatric evaluation and may include a plea that he is not criminally responsible for his acts--an "insanity" plea. As a forensic psychiatrist, I have participated in many such evaluations and then rendered expert testimony about killers in court.

Here's how they work:

First, given the extraordinary change in Holmes' mental status--from brilliant neuroscience Ph.D candidate to a mass killer--all organic (i.e. physical) causes for psychiatric symptoms must be excluded via an extensive medical work-up, including an MRI (to rule out a brain tumor or slow bleed), an EEG (to rule out seizures), a lumbar puncture (to obtain cerebrospinal fluid to rule out a central nervous system infection) and blood work (to rule out toxicity from heavy metals, other physiological abnormalities and any use by Holmes of illicit drugs). Any medication with which Holmes has recently been treated will be considered for its possible psychiatric side effects.

Second, a detailed series of psychiatric interviews will be conducted to create a timeline of Holmes' life story--from birth right through any recent stressors--and to attempt to determine how Holmes thinks, feels and communicates. This will include an analysis of Holmes' personality, as well as a determination of whether he harbors any fixed and false beliefs (delusions)--like being under the control of aliens, being specially selected to save the world, being pursued by the CIA or having thoughts implanted into his head by devices in the walls of his apartment. Pains will be taken to observe whether he acts as though he is hallucinating--hearing voices or seeing visions or experiencing odd bodily sensations (of, for example, his skin peeling away) in the absence of any stimulus to account for them.

Long, written psychological tests--like the Minnesota Multiphasic Personality Inventory--will likely be used, as well, in order to support or refute data gleaned from the clinical interviews, to gain further insight into Holmes' ways of thinking and feeling and to determine whether he is faking or exaggerating symptoms or, conversely, attempting to cover up symptoms. The tests and the way they are analyzed have built-in mechanisms to identify those who are trying to seem crazy when they are not--or trying to seem normal when they are not.

The medical work-up, psychiatric interviews and psychological testing will probably both be used first to determine whether Mr. Holmes is competent to stand trial or too burdened by mental illness. The bar is pretty low. The issue is whether Holmes knows how a courtroom works (that a judge administrates the proceedings and a jury determines guilt or innocence, that his defense attorney will attempt to establish his innocence and a prosecutor will attempt to establish guilt, that he is the one accused of a crime) and that Holmes can assist his attorney in defending him (rather than being too confused to follow along or too distracted by voices or refusing to speak with his attorney, whom he considers, for example, to be an alien or one of the people sent by the devil to make him renounce God).

The medical and psychiatric evaluation(s) will also form the basis of any "insanity" plea Holmes may put forward. The questions at the heart of that matter will be whether a major mental illness so impaired Mr. Holmes as to render him unable to tell right from wrong, or if he still knew right from wrong, and whether an illness so impaired him as to render him unable to conform his behavior to the requirements of the law.

While forensic psychiatrists hired by the state and those hired by the accused often disagree whether a defendant suffers from a mental illness that qualifies him or her as not criminally responsible, sometimes they do agree--and, sometimes, the fact that they are in complete agreement even before trial leads to a trial never taking place. After all, the district attorney in Colorado will need to decide whether to take this case to court or, after receiving information from psychiatrists, whether to agree Holmes should simply have his plea of insanity (if offered) automatically accepted, leading to his hospitalization on a locked psychiatry unit.

It is important to note that while planning a killing is part of the data used to evaluate the mental state of a killer, some people who are psychotic and who kill based on incredibly powerful, unavoidable delusions, do so with a great deal of planning. If, for example, one were to believe that aliens had invaded the Earth and taken the form of one's family, one might plan for a long time how to do away with them and save the universe. Yet, the foundation of one's motivation would be a product of mental illness.

Contrary to popular belief, defendants who are found not criminally responsible by virtue of a mental illness generally remain on locked psychiatry units for several decades--or for life. This has been the case, for example, for John Hinckley, Jr., the man who, in 1981, shot Ronald Reagan to impress actress Jodi Foster. He has remained an inpatient--with some passes to his family home--at St. Elizabeth's Hospital in Washington, D.C. for more than 30 years.

Holmes' journey through the system is just beginning. Insanity pleas are notoriously unsuccessful. The vast, vast majority fail, probably because juries simply don't want to worry over whether a person capable of horrific acts will ever hit the streets. So, if Holmes should offer such a plea and prevail, it will be because he isn't even close to sane and because the culprit who stole 12 lives and shattered dozens more was mental illness, camouflaged by those accomplices who saw it hobbling a man and did nothing--or too little.