Lithium Antisocial Behavior

LITHIUM AS A NEUROSCIENCE/PUBLIC HEALTH APPROACH 1

Lithium as a Neuroscience/Public Health Approach to Reducing Antisocial Behaviors

James M. DeCarli, MPH, MPA, CHES

University of Southern California


Abstract

Despite interventions to help eliminate maladaptive aggression and antisocial behaviors,

victimization of violence remains a public health problem in the United States. While not all

those who are genetically predisposed to antisocial behaviors become violent, those with the

MAO-A gene, when exposed to appropriate environmental stimuli, are influenced to exhibiting

antisocial behaviors. Environmental stimuli might be observed as the problem among both the

antisocial parent and the child, but this becomes a barrier and those are not likely to seek

treatment. A public health approach to reach this difficult to reach anosognosic group, confirm a

nutritional lithium supplementation as an effective mechanism to help close this gap among those with

antisocial behaviors who choose not to seek or accept treatment, because of their denial and lack

of conscious self-awareness of illness and help meet the Health People 2010 leading health

objective to reduce youth violence. Lithium is found to reverse neurochemical and

neurostructural effects of antisocial behaviors through a protective effect among

neurotransmitters.


Lithium as a Neuroscience/Public Health Approach to Reducing Antisocial Behaviors

Maladaptive aggression and antisocial behaviors among both children and adolescents in

the United States have remained high over the past decade. The consequences of youth violence

have resulted in public health officials to establish youth violence as one of the leading health

objectives of the Healthy People 2010 to help address this public health problem. However,

despite public health interventions to help eliminate aggression and antisocial behaviors still 20%

of the United States population becomes victims of violent and nonviolent illegal behavior each

year (U.S. Bureau of Justice Statistics, 2002). To add to the problem, many more cases go

unreported. While public health officials promote some of the best programs found to prevent

antisocial behaviors, only 12% have been shown to reduce juvenile offender’s recidivism (Lipsey

& Wilson, 1998). While programs have not shown to be effective, this review takes a

neuroscience approach to answer if lithium supplementation can become a potential public health

strategy to reduce and control violence.

Background

Antisocial behaviors & violence. Antisocial behaviors include a complicated group of behaviors

exhibited early in adolescence and continue through adulthood. While these behaviors show a

lack of consideration for others and disregard for their rights with common problematic

characteristics in emotional regulation, impulsivity, attentional deficits, and poor judgment, the

DSM-IV identifies these behaviors not only among Antisocial personality disorder, but also

among impulse control disorders and substance use disorders. Intervention research may have


tried to demonstrated evidence to prevent antisocial behaviors in some programs, but outcome

evaluation has demonstrated that even the best of these programs have not shown evidence to

reduce antisocial behaviors (Weissbeerg, Kumpfer, & Seligman, 2003). Authors suggest this is

due to behavioral science not fully understanding causality of antisocial behaviors. While

causality remains in remains in question, personality traits and disorders are also common among

antisocial behaviors. Attention Deficit Hyperactivity Disorder (ADHD), Oppositional Defiance

Disorder (ODD), and Conduct Disorder (CD), and are three disorders observed in childhood that

have a predisposing link to adult antisocial behaviors, specifically Antisocial personality disorder

(Holmes, Slaughter, & Kashani, 2001). Whereas children diagnosed with ADHD are at risk for

developing ODD and CD. And presence of ODD and CD in childhood is a predictor of antisocial

behaviors later in adulthood (Kaplan, 2004). In an effort to understand causality, prevention

research has moved toward genetic interventions. Whereas studies have demonstrated 10% of

individuals perpetrate more than 50% of crimes in the general population (Wolfgang, Figlio, &

Sellin, 1972). This confirms a familial concentration of crime in the general population, in that

less than 10% of families account for more than half of that community’s criminal offenses.

Moffitt (2005) illustrates that causation however is not fully understood because while these

studies show that the family concentration of antisocial behaviors might seem to be influenced by

genetics, but could also be explained by non-genetic social transmission of antisocial behaviors

within families. However as further suggested by Moffitt, few studies have demonstrated the

causal status of most risk factors. As observed in intervention research on antisocial behavior,

this results in costly interventions that not only lead to failure but also other consequences. Tax

dollars and other resources have been wasted because intervention programs have been

implemented on the basis of risk factors without sufficient research to understand causal


processes (Moffitt, 2005). These include mentoring programs, family preservation programs, and

peer-group programs, more specifically programs such as Drug Abuse Resistance Education

(DARE) or boot camps, for example have not shown to reduce antisocial behaviors. For

programs to be effective in changing behaviors, while causality has not yet determined, authors

suggest better understanding genetic predisposition and the role neurotransmitters play in

antisocial behaviors.

Genes, Neurotransmitters & Violence. Genetic predisposition to violent behaviors is becoming

more prevalent in the prevention literature. Authors have suggested that genes may have existed

as protective mechanisms and evolved through “mutation” or “polymorphisms” that when

exposed to specific environmental stimuli one can exhibit antisocial behaviors (Moosajee, 2003).

In 1993, Brunner et al. confirmed a relationship between a point mutation in the structural gene

for monoamine oxidase (MOA). Neurochemicals are responsible for activating behavioral

patterns in the brain (Elliot, 2000). MOA, an enzyme that acts as a catalyst to oxidize

monoamines, has been shown to be associated with antisocial behaviors and aggression

(Brunner, et al, 1993). MAO-A is necessary for the catabolism of monoamines ingested in food.

These enzymes provide inactivation of monoaminergic neurotransmitters that are highly

associated with antisocial behaviors. Serotonin, norepinephrine (noradrenaline) and epinephrine

(adrenaline) is broken down by MAO-A. Phenethylamine is broken down by MAO-B, but both

break down dopamine.

Serotonin. Serotonin is a neurochemical, responsible for personality traits of anxiety,

depression, and bipolar disorder (Larsen & Buss, 2005). It is also involved with brain

development and is known as a primary neurotransmitter that modulates impulsive aggression


(Leownstein, 2003). Dysfunction of serotonin results in an observed increase of impulsivity and

aggressiveness (Morley & Hall, 2003). Other studies have shown that low level of serotonin is

also associated with emotional aggression (Elliot, 2000). Low levels of serotonin among children

are associated with increased risk of conduct disorder (Elliot, 2000). Low levels of serotonin in

cerebral spinal fluid are associated with large effect size of impulsivity and violence (Linnoila, et

al, 1983).

Norepinephrine. Norepinephrine (epinephrine), a catecholamine and phenethylamine, is a

neurotransmitter in the nervous system that acts as a stress hormone in the brain affecting

attention and impulsivity. Upon exhibiting excessive levels of norepinephrine, irritability,

anxiety, fear, and panic is observed, often leading to aggression, agitation, and psychosis

(Herrmann, 2004). Low levels however are associated with a poor memory, loss of alertness, and

depression.

Dopamine. Dopamine, a neurotransmitter in the brain, associated with pleasure but most

importantly highly associated with aggression. Dopamine is responsible for emotional and

predatory aggression (Elliot, 2000). Genes within this neural pathway is associated with

Attention Deficit Hyperactivity Disorder (ADHD) (Morley & Hall, 2003).

MOA dysfunction. Heritability is found to be a significant factor among neurotransmitters

and violence. Dysfunction of MOA is influenced from maltreatment during childhood, which

predisposes children to antisocial behaviors (Caspi, 2002). This is due to the MAO having too

low or too high of activity. Having too low or too high activity is further associated with

depression, social phobias, aggression, attention deficit, substance abuse and criminality. While

maltreated children are found to exhibit low-activity of MOA-A, these children were likely to

develop antisocial conduct disorders compared to children with high-activity MOA-A. Children


with low-activity exhibit decreased ability to degrade norepinephrine, which is involved in

sympathetic arousal and rage (Caspi, et al, 2002).

Gene-Environment Interplay: While genetic heritability is shown to be a predisposing factor to

antisocial behaviors, twin studies have demonstrated that not all children who exhibit these

neural dysfunctions exhibit antisocial behaviors in adulthood. This is due to the gene-

environment interplay that can influence the behavior. Similarly among those with MOA

dysfunctions, the primary barrier to influencing association is the environmental stimuli.

Behavioral-genetic studies have documented that environmental stimuli have mediated effects on

antisocial behaviors, whereas these risk factors interact with genetic vulnerability that influences

antisocial behaviors (Caspi, 2006).

Lithium. Lithium, a monovalent ion, is an alkali element that has been approved by the Food and

Drug Administration (FDA) for short-term prophylactic treatment of aggressive and agitation

behaviors among patients with bipolar I disorder (Dinan, 2002). It is also a common therapeutic

indicator for treating mood stability for children with conduct disorder (Malone, 2001) and for

treating aggressive behaviors among those with schizophrenia (Sachs, et al, 2000). Lithium

(Eskalith, Lithonate, Lithobid) has shown to be 80% effective in treating both manic and

depressive episodes of bipolar I disorder. It also has predictive responses to treat borderline

characteristics, neuroticism, rapid cycling, substance abuse, and manic/depressive symptoms

(Kaplan, 1998)


Pharmacokenetics. After ingestion, lithium is absorbed by the gastrointestional tract and

almost completely eliminated by the kidneys. It is also excreted in breast milk and insignificant

amount in perspiration and feces. Lithium has a half-life of 20-hours with equilibrium after 5-7

hours of medicinal oral ingestion. Lithium affects the thyroid, hematopoietic system, kidneys,

and heart.

Pharmacodynamics. The mechanism of action of lithium involves various

neurotransmitter systems that block inositol phosphatases within the neurons. This inhibition

results in decreased cellular responses to neurotransmitters. The biochemical mechanisms of

action of lithium appear to be multifactorial and intercorrelated among several enzymes,

hormones and vitamins (Schrauzer, 2002). The two major neurotransmitters in the pathogenesis

of affective disorders that are modulated by lithium are serotonin (5HT) and norepinephrine.

Lithium increases serotonin and norepinephrine, and shown to increase grey matter (Sassi, 2002).

Discussion

Gene-Environment Interplay Revisited. While not all those who are genetically predisposed to

antisocial behaviors become violent, those with the gene, when exposed to appropriate

environmental stimuli, are at increased risk of exhibiting antisocial behaviors. This is similar to

alcoholics, while they may have an addictive gene, only when exposed to the appropriate

environmental stimuli (bar, club, etc.), can influence the addictive behavior. Similarly among

those with antisocial and aggressive genes, studies have shown that the environment influences

the genetic predisposition. While the environmental stimuli might be observed as the problem to

an antisocial parent and even the child, this becomes a barrier to seeking treatment. While the


problem of the antisocial child may be seen as a result of the environmental stimuli, throughout

the developmental and learning processes, plasticity of neural network is altered through

environmental pathogens (i.e. bad parenting) that result in antisocial behavioral outcomes (i.e.

hitting, fighting, etc.) of childhood aggression and continues the cycle.

Nonadherence to treatment: As observed with many mood disorders and antisocial behaviors

nonadherence to treatment are common, leading to a barrier to being treated as well. Some

common themes of nonadherance include fear of dependency, side effects, discomfort of

psychiatric diagnosis and most importantly denial of illness (Byrne, 2006) or anosognosia. Before

one is capable of seeking or accepting treatment they first need conscious self-awareness of their

illness.

Self-Awareness deficit. The frontal lobes are critical for understanding and processing of

conscious self-awareness, deception, and to monitor perceptions of reality (Stuss, 2001). Those with

brain lesions to the frontal lobe, similarly among those with antisocial behaviors, often experience life in

the moment or present. These patients generally experience no regard for the past or anticipation of the

future, as defined by characteristics of antisocial and personality disorders. No connection with past, it is

difficult to project into the future (Stuss, 2001). The frontal lobes are also necessary for learning new

activity. When this region is damaged, patients often exhibit disturbed self-awareness that also results in

impaired judgment of objective facts with reference to their self and their own personal lives. i Research

suggests that human beings are interactive entities who base their future on their past experiences. This

behavior can be attributed to the frontal lobes that provide executive functions that “selects, explores,

monitors, modified, and judges nervous system activities. The purpose of this function is to effectively

carry out and plan new activity. However after repeated stress often exhibited form antisocial

behavior, often referred to as restraint stress, which is also common among bipolar disorder,


schizophrenia and PTSD. Further, with chronic stress where the victim adapts to this stimuli as a

method of survival that has been shown to cause structural changes in the hippocampus and

amygdale (Magarinos, 1997). Studies have shown that under restraint stress, structural plasticity

of the hippocampus has been observed, with neurogenesis of the dentate gyrus and dendritic

remodeling (resulting from hypoglucocorticoids in CA3 region (McEwen, 2001). This results in a

patient becoming anosognosic, or not consciously perceiving the difference between what is expected

and what is. They do not recognize the deficits that are clear to others who observe them. Prigatano

(1989) confirmed this further, in that anaosognosics perceive themselves to be normal, similarly to

antisocial and personality behaviors.

The Conscious Awareness System. The Conscious Awareness System (CAS) approach to

understanding the genesis of anosognosia is responsible to experience, remembering, and perceiving

awareness (McGlynn and Schacter, 1989). The CAS is suggested to also be within the parietal lobes.

Lesions to this region affect the executive system causing interruption of the flow of information between

the executive system and the CAS. Damage to this region will result in unawareness leading to problems

in problem-solving, social, behavioral and personality changes, as observed in bipolar disorder and

antisocial behavior. The lack of impaired illness has also been further shown among individuals with

bipolar disorder and schizophrenia via clinicians. Whereas it is common for these patients to not take

their medications because they do not believe they are sick (Lin, 1979). Without conscious awareness

and acceptance of illness, those with antisocial behaviors and personality disorders that lead to

aggressive and violent behaviors are less likely to seek help on their own. Children of antisocial parents

are at particular risk because if the parent exhibits denial of illness, they are likely not to see their

children of having a problem, rather someone or something else is the problem. As a result, this is a

barrier to seek treatment.


Lithium-low level-supplementation. Lithium has been shown to be an effective prophylactic for

the short-term treatment of aggressive and agitation behaviors among patients with bipolar I

disorder and common therapeutic indicator for treating mood stability for children with conduct

disorder, aggressive behaviors, manic and depressive episodes, neuroticism, rapid cycling,

substance abuse, and manic/depressive symptoms. While those with antisocial and violence

behaviors exhibit reduced gray matter, specifically among the amygdala in emotional

dysregulation, low level of serotonin is also common, resulting in an increased risk of conduct

disorder among children. Lithium however has been shown to reverse neurochemical and

neurostructural effects of antisocial behaviors. Whereas lithium is shown to increase gray matter

and increase serotonin, thus improving emotional stability and reducing aggression. Studies have

shown that the incidence of rape, homicide, and suicide were significantly higher in areas where the

drinking water contained little or no lithium. This has confirmed that low level dose of lithium has a

beneficial effect on human behavior (Schrauzer, 1990). Additionally, lithium supplementation has an

effective mood stabilizer and mood improving effect among former drug users, intimate partner violence

perpetrators, and other violent offenders.

Summary/Conclusion

Therapeutic indications of nutritional lithium for controlling aggression and violence behavior.

In summary, this review has accomplished its objective in answering the research question:

lithium supplementation can be a potential public health strategy to reduce and control violence.

While not all those who are genetically predisposed to antisocial behaviors become violent, when

exposed to appropriate environmental stimuli, are at increased risk of exhibiting antisocial


behaviors. While the environmental stimuli might be observed as the problem to an antisocial

parent and even the child, this becomes a barrier to seeking treatment. In addition as observed

with many mood disorders and antisocial behaviors nonadherence to treatment are also common,

leading to a barrier of denying the illness.

Public Health Approach. As a public health approach to reaching this difficult to reach

this anosognosic group, studies suggest that a nutritional lithium supplement may be effective in both

public health suicide and violence prevention programs (Schrauer, 1994). As a result, nutritional

lithium supplement could help close this gap among those with antisocial behaviors who choose

not to seek or accept treatment because of their denial and lack of conscious self-awareness of

illness and help meet the Health People 2010 leading health objective to reduce youth violence.

Dose-Response: Further study however is needed to estimate a lithium dose response. It

would however be appropriate to begin by applying a similar estimate as defined in drinking

water as established by Schrauzer (1990).

Application: Nutritional lithium can be supplemented in established low-level doses in

water or other food sources. These can best be applied among those at most risk in communities

that exhibit high levels of community and youth violence. These sources can be supplemented in

food or water sources in schools as an example.


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