Criminal Justice Section  


Criminal Justice Magazine
Spring 2002
Volume 17 Issue 1

The Biology of Violence: Serotonin, Alcoholism, Hypoglycemia

By Paul Rossby

An increasing body of scientific evidence, collected over the last 20 years, suggests a link between low levels of the brain chemical serotonin, type-2 alcoholism, and hypoglycemia and deficient impulse control leading to intermittent explosive disorder, pyromania, suicide, and severe unrestrained aggression (rage). This article will examine whether a defendant suffering from these disorders is biologically capable of controlling his violent behavior. (Note: Scientific studies to date have not included women.)

Serotonin is a naturally occurring brain chemical that regulates, among other behaviors, impulse control. Type-2 alcoholism is an exclusively male disorder that is frequently passed on from fathers to sons and is characterized by the early onset of alcohol consumption and aggressive/violent behavior. Finally, a tendency towards hypoglycemia (low blood sugar) is commonly found in impulsively violent offenders.

The connection between these disorders and criminal behavior has come to be known as the "serotonin defense" as illustrated in the 1998 case of State v. Sanders, 2000 WL 1006574 (Ohio App. 2d (2000).)

S tate v. Sanders

On December 31, 1997, Dion Wayne Sanders was indicted by a grand jury in Montgomery County, Ohio, on 10 counts arising from the shotgun slayings of his maternal grandparents. The indictment included four counts of aggravated murder, each with death penalty specifications. With respect to each grandparent, Sanders was charged with one count of felony murder and one count of purposely causing the death with prior calculation and design. Sanders’s elderly grandfather had been severely beaten and shot at close range through his thighs with a 12-gauge shotgun. He bled to death. The grandmother was shot in the back of the head at close range with the same single-shot shotgun.

Sanders was residing with his grandparents during the week preceding the homicides. When they found out that he had lied about applying to a junior college and moving into an apartment with a fellow student, the grandfather ordered him out of the house. It was the dead of winter and Sanders had no place to go, no money, and no one to fall back on. He was estranged from the rest of his family because he stole from them to support his drug addictions (mostly cocaine). While his grandparents were at the grocery store, Sanders broke into the house to look for money or other valuables so that he could rent a motel room (the temperature outside was 17 degrees Fahrenheit). Finding nothing except his grandmother’s jewelry (which he didn’t take) he decided to plead with his grandparents when they returned. The grandparents, however, became irate with him for breaking into the house and an argument ensued that rapidly escalated from pushing and shoving to a fistfight. Sanders struck both grandparents with a flower vase and an iron skillet. He then killed them with the grandfather’s single-shot, 12-gauge shotgun.

According to the state’s theory of the case, Sanders shot his grandfather in the legs, reloaded, and shot his grandmother in the back of the head. Leaving his bloody jacket behind, he took his grandparents’ car and led the police in a high-speed chase through the streets of Dayton. Police found him sitting on a railroad track with his head in his hands. As they approached he raised his hands and said, "Shoot me."

Defense attorney Victor A. Hodge and cocounsel Dennis Lieberman reasoned that it was unlikely that a person would kill his or her grandparents without serious provocation and/or mental breakdown. The lawyers developed a theory that the double murder was an aberrant act of uncontrollable rage—despite the fact that supporting medical evidence was lacking. In fact, the absence of any disease or defect upon which to base an insanity case was confirmed independently by a psychologist and a psychiatrist. It was at this time that Hodge attended a death penalty seminar sponsored by the Tennessee Association of Criminal Defense Lawyers and became acquainted with the serotonin defense. It would play a pivotal role in the Sanders case, as explained below.

First, though, it will be helpful to the reader to understand how the serotonin defense came to be.

History of serotonin defense

In 1982, Gerald L. Brown, of the Biological Psychiatry Branch and Laboratory of Clinical Psychobiology, National Institute of Mental Health in Bethesda, Maryland, reported that results from 13 peer-reviewed journals showed an increase in aggressive/impulsive and suicidal behaviors was associated with abnormally low serotonin activity in the brain. The most productive research on serotonin and impulsive violence was conducted over a 20-year period by Dr. Markku Linnoila, of the Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, and by Dr. Matti Virkkunen, Department of Psychiatry, Helsinki University Central Hospital in Finland. During the period of their collaboration only two forensic psychiatric units in the world performed serotonin measurements on violent criminal offenders: the Department of Forensic Psychiatry in Helsinki and the Department of Social and Forensic Psychiatry, Karolinska Institute, in Sweden.

Conducting large-scale studies utilizing hundreds of violent offenders (Finnish prison inmates) Linnoila and Virkkunen consistently found strong connections between low serotonin activity, type-2 alcoholism, and a tendency towards hypoglycemia (low blood sugar) leading to impulsive violence, suicide, and fire setting. In one such study that involved 101 alcoholic violent offenders, 33 fire setters, and 27 healthy volunteers who were followed for a period of 12 years, the authors reported that among alcoholic criminal offenders, impulsive violent behavior and fire setting were associated with low serotonin activity in the brain. Equally violent alcoholic offenders, who premeditated their crimes, had normal to high serotonin activity.

Serotonin and impulsivity

In order to understand how low serotonin activity in the brain is linked to impulsivity and violence it is necessary to consider some basic principles of brain function. The brain is essentially comprised of nerve cells (neurons) that are chemically induced to fire "electrical" impulses. Naturally occurring brain chemicals known as neurotransmitters are classified as "excitatory," i.e., those chemicals that cause nerve cells to fire, and "inhibitory," i.e., those that inhibit nerve cell firing. The functioning of the "normal" brain involves constant interplay between excitatory and inhibitory chemicals. This constant interplay produces consciousness, emotions, and memory.

Serotonin is a naturally occurring brain chemical. Its effects on nerve cell firing are predominantly inhibitory, and considerable research indicates that serotonin orchestrates other inhibitory systems in the brain to control pain, fear, and impulsive behaviors. In fact, the preponderance of scientific evidence both from human and animal studies supports the conclusion that serotonin is essential for self-control.

Serotonin and alcohol

The assertion that type-2 alcoholics are prone to violence during intoxication is supported by many studies, including a 1994 Finnish report that found that among all perpetrators of recidivist homicides in Finland 85 percent were type-2 alcoholics. (J. Tihonen, P. Hakola, Psychiatric Disorders and Homicide Recidivism, 151 Am. J. Psychiatry 436–38 (1994).) In addition, two large-scale Swedish studies were conducted in 1981 and 1996 involving more than 3,000 adopted subjects who were defined as type-1 and type-2 alcoholics. (C. Robert Cloninger, Neurogenetic Adaptive Mechanisms in Alcoholism, 236 Sci. 410–16 (1987).) Type-1 alcoholics are unable to terminate drinking binges, but can abstain for long periods. They are cautious, inhibited, and shy, and they suffer from guilt, depression, and medical complications. Children of type-1 alcoholics have a threefold increased risk for alcoholism compared to the general population. All of the female alcoholics and 75 percent of the male alcoholics studied were type-1. The onset of the disease is in late adulthood and it is not related to serotonin.

Type-2 alcoholism affects only males—sons inherit it from their fathers. In fact, the sons of type-2 alcoholics were shown to have a risk of becoming type-2 alcoholics that is nine times greater than sons of nonalcoholic fathers—even when reared in a non-alcoholic (adoptive) environment. The type-2 alcoholic is often termed a "mean drunk" who is transformed by a few drinks. The disease is typified by early onset of drinking (prior to age 25), disruptive behavior in school, multiple arrests for driving while intoxicated, recklessness (thrill-seeking, low harm avoidance), and aggressive/violent behavior while intoxicated. Most type-2 alcoholics have abnormally low serotonin function. Although the relationship between type-2 alcoholism and low serotonin is not completely understood, there is evidence that alcohol causes the release of serotonin stores in the brain producing a transient feeling of euphoria (serotonin inhibits pain and fear). However, soon after the serotonin has been released it is degraded (metabolized) and this further depletion results in sudden extreme irritability and a loss of impulse control. It should be noted that researchers emphasized that the type-1/type-2 subgroups should not be considered discrete disease entities because many alcohol abusers have some features of each type.

Unconscious or conscious control?

The control of impulsive behavior occurs primarily in two regions of the brain, the limbic system, which is a very primitive region associated with instincts, emotions, and memory formation, and the prefrontal association cortex, which is the seat of higher decision making. Within the limbic system, a subregion known as the amygdala regulates instinctual behaviors—arousal, fear, predatory attack and defense, sexuality, eating, sleeping, and dreaming—based on past experiences, or memories. For example, it’s apparently in the amygdala of a Vietnam veteran suffering from post-traumatic stress disorder that the smell of frying pork is linked to the massacre of an entire village so that every time the man smells frying pork he relives the massacre in hallucinatory detail. Essentially, the amygdala is the region of the brain in which ongoing experience is linked with past experiences (memories) on a nonverbal, instinctual/emotional level. The "declarative" component of memories—information that can be verbalized—is recorded in another subregion of the limbic system known as the hippocampus. Accordingly, because the declarative and non-declarative (emotional) components of memories are formed in different subregions of the limbic system, it is possible to react emotionally (even violently) to external triggers without remembering the past traumas with which they are associated.

Within the limbic system there is a hierarchy of inhibitory mechanisms that have evolved to provide us with unconscious control over our impulsive, instinctual behaviors. These mechanisms involve serotonin, GABA (the most ubiquitous inhibitory chemical in the brain), and the brain’s natural opioids (endorphins, enkephalins, dynorphins). The opioids are released when worst comes to worst, i.e., in the face of inescapable excruciating pain and/or one’s own death. They inhibit pain by a mechanism that is similar to morphine and produce dissociative, surreal, dream-like states of consciousness. The opioids represent the bottom-line mechanism of self-preservation.

In the context of a legal defense, what’s important is the evidence that these unconscious (neurochemical) mechanisms of impulse control may be genetically impaired and/or overwhelmed and permanently damaged as a consequence of pre- and postnatal trauma and physical/sexual abuse in early childhood.

The second brain region involved in impulse control is the prefrontal association cortex, known among neuroscientists as the executive/cognitive region. This is where humans think and imagine, make informed decisions based on facts, and engage in an almost continuous internal dialogue. The prefrontal association cortex also enables us to consciously and intentionally control our emotions, drives, and impulses via its reciprocal connections with the limbic system (primarily with the amygdala and hypothalamus). In other words, there is a communications loop between the prefrontal association cortex and the limbic system that is facilitated by neurochemicals, serotonin among them.

In addition, it has been shown that low blood sugar (hypoglycemia) in the frontal cortex can cause confusion, the release of adrenaline (a fight-or-flight neurotransmitter), a sense of impending doom, heart palpations, anxiety, and panic. Consequently, a tendency towards hypoglycemia can significantly impair one’s capacity to form intent.

Forensic analyses

Measuring serotonin. Serotonin activity in the brain is measured by lumbar puncture (spinal tap) followed by high-pressure liquid chromatography (HPLC), electrochemical detection, and a computer-based data analysis system. The spinal tap is performed by an anesthesiologist (usually in the infirmary of a correction facility) in the morning after overnight bed rest and fasting. Samples of cerebrospinal fluid (CSF) are drawn from the lumbar subarachnoid region of the spine (to avoid nerve damage), immediately frozen on dry ice, and subsequently stored at minus 70 degrees Celsius. HPLC analysis separates the components of the CSF so that the concentration of 5-HIAA (the major serotonin metabolite) can be measured by electrochemical detection. These data are automatically fed into a computer-based analysis program to eliminate human error. The mean (average) concentration of 5-HIAA in the defendant’s CSF samples is then compared statistically with the mean concentration of 5-HIAA in CSF obtained from a group of male control subjects diagnosed as normal at the time of testing. Although there are alternative methods for measuring serotonin activity in the brain, the method described here is utilized by the majority of neurobiologists in the field. If the samples are analyzed in triplicate and the analysis is repeated three times, the potential for error is negligible.

Diagnosing alcoholism. Type-2 alcoholism is routinely diagnosed by a clinical psychologist, psychiatrist, or addictionologist based on early onset of alcohol abuse, the father’s drinking history as well as that of maternal uncles, and diagnostic behavioral and psychological criteria set forth in a study conducted by the Department of Psychiatry at the Washington University School of Medicine in St. Louis, Missouri. ( See C. Robert Cloninger, Neurogenetic Adaptive Mechanisms in Alcoholism, 236 Sci. 410–16).

Determining hypoglycemia. A tendency toward hypoglycemia (non-diabetic) is determined by a five-hour glucose tolerance test (GTT). This is a routine test performed in hospitals and diagnostic labs.


Interpreting the results of the serotonin analysis, a diagnosis of type-2 alcoholism, and a tendency towards hypoglycemia in the context of a defendant’s family and social history and the events leading up to the crime requires the expertise of a forensic neurobiologist as well as that of a clinical psychologist, psychiatrist, or both. The role of the forensic neurobiologist is (1) to conduct tests to determine the presence if any of genetic factors and/or disorders in brain chemistry that may offer a plausible biological explanation for the defendant’s behavior leading up to and including the crime, and (2) to support and substantiate all opinions regarding the defendant’s test results with scientific evidence published in peer-reviewed professional journals.

The verdict in State v. Sanders

In State v. Sanders, the jury appeared to accept the theory that the grandfather was shot in an unplanned fit of rage because it returned a verdict of not guilty to the charge of premeditated murder. However, it returned guilty verdicts on the charge of felony murder of the grandfather and the capital murder counts with regard to the grandmother. The defense then proceeded to the sentencing phase with a focus on utilizing the serotonin/type-2 alcoholism evidence to counter assertions that the killings were cold, considered acts.


According to the HPLC analysis, Sanders’s serotonin activity in his brain was extremely low—lower than nearly 88 percent of males in the total population. This finding indicated that the defendant’s biological capacity to control his impulses was severely impaired.

The defense argued that Sanders inherited his tendency for low serotonin brain activity and, thus, a genetic vulnerability for impaired impulse control. They presented family testimony that tracked violence and alcoholism from the great-grandfather to the defendant. Sanders’s great-grandfather was an alcoholic—probably type-2—with an explosively violent temper. Family members recalled that he once threw a hammer at his five-year-old son for failing to immediately answer a question. Sanders’s grandfather, in turn, abused the drug marijuana and was eventually diagnosed with depression and treated with Prozac, a drug that increases serotonin activity. Sanders’s father, a drug abuser, suffered from bipolar disorder and was also placed on Prozac and other antidepressants. He, too, was known to have an explosive temper. His family offered examples: He attacked a Little League umpire and spectators had to pull him off. He shot at a neighbor kid’s stereo after the boy refused to turn down the volume. He claimed his actions "just occurred automatically."

According to his lawyers, Dion Sanders’s behavior was similarly explosive. A former girlfriend said he would "go off" and act like a "madman." Another ex-girlfriend said that when she tried to get him to quit using cocaine he became enraged, slammed her head against the car window, and tried to choke her.

Sanders reported that he began using alcohol and marijuana at the age of 14. By age 18 he was drinking one to two cases of malt liquor per day and his drug abuse had progressed to cocaine, LSD, Darvocets, Percodans, and anything else that was available. He complained of nervousness, depression, tension, headaches, nausea, insomnia, and suicidal ideation. In 1997, he—like his father—was diagnosed with bipolar disorder and placed on lithium. At that time, he told the doctors that he suffered from blackouts that he believed were caused by his extensive alcohol abuse. Based on the early onset of his alcohol abuse and other factors, he was diagnosed with type-2 alcoholism.

In order to explain the rapid escalation from aggressiveness to rage, the defense noted that Sanders and his girlfriend had been using cocaine every day for two weeks prior to the murders. The defense described a form of pharmacological violence that has been associated in both forensic and clinical literature with chronic cocaine abuse that "kindles" a limbic dyscontrol syndrome. Cocaine produces an exaggerated level of excitatory transmitters (including adrenaline) in the brain, making it a "speedy" drug. Cocaine also reduces overall serotonin synthesis (and release), thus leaving its excitatory effects relatively unopposed. With chronic use of cocaine, the limbic system (especially the amygdala) becomes increasingly hyperexcitable. Eventually, with even minor provocation, a massive electrical discharge (dyscontrol) may ensue spreading throughout the limbic system like a forest fire out of control—thus the term "kindling." Cocaine kindling of limbic dyscontrol has been associated with rage attack and panic disorder.

The state presented no evidence to rebut the serotonin evidence. After less than four hours of deliberation, the jury returned verdicts of life without parole as to all three of the capital offenses. Though the jury refused to speak with anyone following the verdict, the defense lawyer, Victor Hodge, said the serotonin theory was the only mitigating evidence presented.

Finally it should be noted that low serotonin/type-2 alcoholism is not affected by punishment, so future dangerousness is an issue. However, in structured environments (correctional facilities and hospitals) selective serotonin re-uptake inhibitors (SSRIs) such as Prozac have been shown to reduce incidents of aggression and violence. Intervention at an early age, when the central nervous system is still developing, may hold the keys. By late adolescence, the brain is mostly hard-wired.

Does your case fit?

The following criteria indicate that an analysis of serotonin function is warranted in order to assess a defendant’s biological capacity to control his impulses:

1. The defendant began drinking alcohol on a regular basis and demonstrated persistent alcohol-seeking behavior prior to age 25.

2. The defendant’s father, uncle(s), or maternal male relatives abused alcohol and were generally regarded as "mean drunks."

3. The defendant has a history of drug abuse (other than alcohol) associated with personality changes, erratic behavior, and violent outbursts.

4. The defendant’s behavior in adolescence and early adulthood is/was associated with impulsivity, risk-taking (thrill-seeking), low harm avoidance, and a tendency toward antisocial behavior such as fighting and arrests for reckless driving while intoxicated.

5. The defendant or family member(s) has been treated with antidepressant drugs, i.e., Prozac (fluoxetine), Paxil (paroxetine), Desyrel (trazodone), Celexa (citalopram), Zoloft (sertraline), Effexor (venlafaxine), or other selective serotonin re-uptake inhibitors (SSRIs).

6. The defendant has a history of suicide attempts.

7. The defendant has a history of setting fires.

8. The facts of the case suggest that the defendant’s acts of violence may have been the consequence of a sudden, rapid loss of control "triggered" by some known or unknown factor.

In any case that warrants an analysis of serotonin function, a diagnosis for type-2 alcoholism and a glucose tolerance test (GTT) are recommended.


S. Paul Rossby holds a Ph.D. in molecular biology from the University of Arkansas for Medical Sciences. He is director of Rossby & Associates in El Paso, Texas. To view his website go to


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