SUICIDE ETIOLOGY AND RISK FACTORS

Suicide etiology and risk are complex and include family history, genetics, epigenetics, neurobiology, medication use, gender, mental health disorders, psycho-sociocultural factors, age, life experiences, and other considerations.

Family History and Genetics

One of the most prevalent risk factors for suicide is a family history that includes first- and second-degree biological relatives with histories of suicidal behaviors, as well as relatives with histories of neuropsychiatric conditions (Pollak, 2021).

In the largest genetic study of suicide attempts, a region of the genome on chromosome 7 containing four genes identified as heightening the risk of suicidal thoughts and actions. The study also found an overlap in the genetic basis of suicide attempts and related psychiatric disorders, especially major depression (Mount Sinai, 2021).

The gene with the strongest association with self-harm ideation is DCC, a protein coding gene involved in prefrontal cortex innervation and development. DCC has been linked to suicidal severity, and there is evidence of elevated DCC expression in the prefrontal cortex of post-mortem brains of those who died by suicide.

The estrogen receptor ESR1 has been identified as a causal genetic driver gene of posttraumatic stress disorder (PTSD) and depression, both of which increase the risk for suicide. Estrogen is suspected as a cause of gender differences in depression rates, and loss of ESR1 has been found to produce effects on brain tissue in men.

The dopamine receptor DRD2 has been found to be associated with suicide attempts, schizophrenia, mood disorders, ADHD, risky behaviors, and alcohol use disorder, all of which increase the risk for suicide.

Antisocial behavior, substance use, and ADHD are associated with TRAF3, a protein-coding gene, all of which increase the risk for suicidal behavior (Avery, 2022).

Epigenetics

Epigenetics refers to the impact of environmental influences on gene activity and expression. Epigenetic regulation of brain-derived neutrophic factor (BDNF), HPA axis components, and GABA-A receptors have all been found to be associated with the development of major depressive disorder and suicidal behavior. Also, in those who have died by suicide, researchers have found increased expression of DNA methyltransferase (DNMT)—the enzyme that methylates DNA in the frontal cortex—and total DNA hypermethylation in the Wernicke cortex and prefrontal cortex (Wislowska-Stanek et al., 2021).

Neurobiology

The core element of suicide etiopathogenesis is believed to be neuroinflammation. Inflammatory mediators play a critical role in the pathophysiology of suicide, and patients with suicidal ideation display elevated markers of inflammation in the central nervous system and peripheral tissues, irrespective of their primary diagnosis, age, and gender.

These mediators subsequently stimulate the kynurenine pathway, causing subsequent serotonin and melatonin depletion. Serotonin deficits are implicated in the pathogenesis of depression and also in aggression, impulsivity, suicidal ideations, and suicide attempts. Mood spectrum disorders, including major depressive disorder, are observed in those with dysregulation in secretion of melatonin (Conte Center Suicide Prevention, 2021; Offord, 2020).

Suicidal behaviors also are associated with hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, which controls the release of the stress hormone cortisol and is known to be upregulated in clinical depression. Increased cortisol levels may cause disturbance in the control of stress, impaired function of the hippocampus, and significant defects. Adrenal gland cortical hypertrophy has been found in patients who died by suicide.

Imbalances in the level of the neurotransmitters glutamate and gamma-aminobutyric acid (GABA) in the central nervous system have been implicated in different neurological and psychiatric disorders, including major depressive disorder. Existing data demonstrate that glutamate may play an important role in suicide-related personality traits, including impulsivity and aggression. Gamma-aminobutyric acid (GABA) plays an important role in behavior, cognition, and the body’s response to stress.

The frontal and prefrontal cortex play an essential role in suicidal behavior through its involvement in cognition, stress response, and suppression of impulsiveness. Patients with a history of suicide attempts have altered prefrontal area activation, patterns that are associated with impaired decision-making, risk-reward, and social assessment. The anterior cingulate cortex, responsible for negative self-thinking and processing emotional stimuli, is strongly implicated in suicidality (Wislowska-Stanek et al., 2021).

Medications

Antidepressants have an important role in the treatment of mood disorders. In rare cases, they can induce or exacerbate suicidal tendencies during the first weeks of treatment, especially in children and adolescents. Some of the selective serotonin reuptake inhibitors (SSRIs) may increase suicidal behavior by stimulating depressed patients to act on preexisting suicidal thoughts. That is, as depression starts to lift, patients may feel less helpless but still depressed enough to decide that suicide is a way out. Before they were too immobilized, but now they are capable of making and carrying out a suicide plan.

Patients taking anticonvulsant drugs, such as gabapentin, tiagabine, and oxcarbazepine, have been found to have approximately double the risk of suicidal behavior or ideation as compared with patients receiving a placebo (Moutier, 2022; Levin et al., 2023).

Gender

The rate of completed suicide in men is higher than in women. However, attempted suicide is more common among women than men. Studies have found that the reason women are not as suicidal is that they often have more psychological support, they more easily decide to seek help, and they find it harder to fall into a state of social isolation. Explanations for this include biological gender changes, different ways of expressing aggression, and diversity in learning social and gender roles.

Marriage and children have been found to be protective factors for women, but not for men. But studies have also found that divorced and widowed women have a four to five times higher risk of suicide and that women without children are more likely to commit suicide than those with children (Samaritans, 2021).

Over the past decade, nearly 9% of females of childbearing age (15–44) who died by suicide were pregnant or recently postpartum. Mental health conditions and substance use disorders were common preceding circumstances. Among those with co-occurring behavioral health issues, such as anxiety, depression, bipolar disorder, or substance use disorders, the increase in rates of suicidality was significantly higher (Akkas, 2022).

Men react more strongly to changes in socioeconomic conditions, so that employment stress, income, and wealth have a greater impact on them. Higher mortality in men can also be explained partly by a greater propensity for violent behavior and a more frequent choice of the most effective means of death by suicide (Maloku & Maloku, 2020; Samaritans, 2021).

Mental Health Disorders and Suicide Risk

Three clinical groups have been identified to be at significant risk for suicidal behavior. These groups include patients with:

• Neurodevelopment disorders: Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, and specific learning disorders, all of which are highly associated with elevated rates of cognitive/neuropsychological impairment
• Neuropsychiatric disorders: Including, but not limited to, major depression, bipolar disorder, schizophrenia and related psychotic disorders, obsessive-compulsive disorder, posttraumatic stress disorder, and borderline personality disorder
• Acquired cognitive/neuropsychological impairment: Including impairment that results from a multiplicity of medical conditions, such as brain injury, brain neoplasm, central nervous system infection, cerebrovascular disease, seizure disorder, multiple sclerosis, neurodegenerative brain disease, and exposure to neurotoxins and an assortment of medications and substances

The patients who are among these three clinical groups experience challenges that negatively impact their psychosocial development, executive functioning, and quality of life. Additional difficulties can result from one or more components of negative affectivity, including irritability, lability, anxiety, and depression. In addition, a large number of patients who fall into one or more of these groups have a reduced ability to profit from experience, which can increase the risk for suicidal behaviors (Pollak, 2021).

Psycho-Sociocultural Factors

Psycho-sociocultural factors refer to a person’s ability to consciously or unconsciously interact with the social and cultural environment. They involve past experiences; the environment in which a person lives; relationships with and support from others; cultural norms; and cognitive abilities, intellect, personality, and other psychological factors that cause individuals to respond to their environment in a unique way. Such factors may be:

• Personality characteristics: May include, but are not limited to, paranoid personality features, histrionic and/or borderline personality features, obsessive-compulsive and dependent personality features, and impulsive or aggressive traits
• Developmental factors: May include substance use, cognitive deficits, behavioral disinhibition, and negative effects, which refer to the subjective experience of a group of negative emotional states such as anxiety, depression, stress, worry, guilt, shame, anger, and envy
• Interpsychic conflicts: A range of longstanding internalized psychological conflicts that contribute to a patient feeling emotionally trapped in response to certain stressors or triggers
• Psychological markers: Feelings of hopelessness, rage, anxiety, loneliness, and desperation
• Life experiences: Early-life adversity, history of trauma or abuse, and previous suicide attempt
• Environmental factors: May include job or financial loss, relational or social loss, stigma associated with help-seeking behavior, certain cultural and religious beliefs, barriers to accessing mental health care and substance abuse treatment, and exposure to the influence of others who have died by suicide, including media exposure
  (Nevada DPBH, 2021; Garcia, et al. 2021)

SOCIOCULTURAL FACTORS

The degree to which a person’s surroundings exert a positive or negative influence on suicidal behavior depends on factors such as demographic characteristics, life stressors, coping skills, biological factors as well as whether an individual’s family, community, and country are supportive or stressful. Research has shown that social support can help prevent someone moving from suicidal ideation to suicide attempts.

Identity is inherently social, and a social network of relationships is an important part of and foundation for many people’s sense of self-esteem and self-efficacy. People with close relationships with others cope better with stressors and have better overall psychological and physical health. This can include a great array of relationships, such as spouses or life partners, parent-child, friend-friend, relative-relative, and fellow group members.

Social networks provide opportunities for emotional release and feeling a connection to others. Isolation, on the other hand, can lead to feelings of alienation and depression that may ultimately lead to suicidal thoughts and behaviors.

Social and cultural groups can be supportive and create feelings of belonging, love, and comfort, thereby serving as a “safety net” to catch those who are experiencing problems or stressors. Being a member of a highly integrated group often serves as a suicide deterrent.

Group membership, however, can sometimes require stress-inducing obligations and high levels of commitment, which can then lead to the adoption of behavioral and attitudinal norms, rather than thinking for oneself. These types of groups can feel repressive and stifling and may actually contribute to suicidal thoughts and feelings. In some instances, groups can even demand that someone die by suicide as an offering for the “greater good.”

A norm is a rule that is socially enforced, and a group, community, or nation promotes what is the norm regarding attitudes and behaviors. Social norms regarding suicide can influence whether or not it is stigmatized as well as its frequency. Many societies and religious traditions ban suicide and view it as sinful or taboo behavior. Others portray suicide as a legitimate behavior in certain circumstances.

Societies that are experiencing upheaval and unrest have higher rates of suicide. Social change that results in the breakdown of a culture’s traditional values can accompany a rise in suicide rates (Mental Help, 2023).

ADVERSE LIFE EVENTS

The experience of negative life events is associated with poor mental health and well-being. Some specific types of events that increase the risk of suicide are described in the table below.

EVENTS THAT INCREASE SUICIDE RISK

Category	Events
(Carstensen et al., 2020)
Bereavement	Death of a family member or other loved one
Illness or injury	Physical illness Serious injury Chronic physical pain Illness or injury of a loved one
Relationship Stress	Interpersonal conflicts (family or relationships with third parties) Separation/divorce Rejection Humiliation
Social/environmental stress	Unemployment Problems at work Financial problems Problems with the law
Violence	Serious physical attack Sexual or physical abuse Rape Domestic violence Witnessing violence between parents as a child Witnessing a family member or other person being injured or killed
Disaster	Major fire, flood, earthquake, or any natural disaster Tragedy or disaster (e.g., shooting, bombing) caused by people in the community

Systematic reviews of data have found a strong and consistent association between intimate partner abuse and both suicidal ideation and attempts. They also found that women who experienced childhood maltreatment, particularly sexual abuse, were more at risk of engaging in self-injurious thoughts and behaviors (Maloku & Maloku, 2020; Samaritans, 2021).

Suicide Risk According to Age

Suicide occurs throughout the lifespan, affecting individuals in various age groups differently, and some have higher suicide rates than others.

CHILDREN AND ADOLESCENTS

Suicide is the third leading cause of death among U.S. children and adolescents ages 5–19 years. The number of children ages 5–11 who have died by suicide has increased significantly between 1999 and 2020, most of these being children between 10–11 years old and 75% being male. Younger children who die by suicide are more likely to be of above-average intelligence, which possibly exposes them to the developmental level of stress experienced by older children.

Puberty may have a negative impact, especially for girls. Girls who mature early have been found to be more likely to have a lifetime history of disruptive behavior disorder and suicide attempts than their peers.

During adolescence, abstract and complex thinking begin to develop, and these youth become more capable of contemplating life circumstances, envisioning a hopeless future, generating suicide as a possible solution, and planning and executing a suicide attempt.

During adolescence, the prevalence of depression increases and becomes twice as high among girls than boys, which explains some differences in rates of suicide between boys and girls. As puberty progresses, most boys develop a positive self-image, but girls, particularly White girls, have a diminished sense of self-worth.

After puberty, the rate of suicide increases with increasing age. Potential reasons for this include an increased access to firearms and potentially lethal drugs; increased rates of psychiatric illness, substance abuse, and other comorbidities; or a history of aggressive, impulsive conduct with a tendency to act out emotions in damaging ways.

The risk of suicide among children and adolescents is increased due to:

• Family tensions
• Emotional and physical abuse
• Violence
• Lack of family connectivity
• Parental mental health problems
• Death of a loved one
• Family homelessness
• History of foster care and adoption
• Bullying
• Sexual orientation
• Substance abuse
  (Kennebeck & Bonin, 2021; Sruthi, 2022; Nationwide Children’s Hospital, 2021)

YOUNG ADULTS

Young adults experience mental health challenges at higher rates than any other age group. Close to half of those ages 18–24 struggle with mental health issues, and in 2021, 25.5% of young adults seriously considered suicide, including 10% of college students, and over 1,000 college students died by suicide. For specific ethnic and cultural groups, rates of suicide are even higher. Among American Indian and Alaska Native young adults, the rate of suicide is 2.5 times higher than that of their peers.

Many young adults continue to deal with the consequences of the COVID-19 pandemic, which has resulted in high levels of depression, loneliness, anxiety, and trauma.

The top reasons for suicide among young adults include the following:

1. Depression, anxiety, and other mental health disorders
2. History of substance abuse
3. Exposure to violence, abuse, or other trauma, either chronic or acute
4. Social isolation and loneliness
5. Losing a family member through death or divorce
6. Financial or job loss
7. Conflict within relationships
8. Starting or changing psychotropic medications
9. Feeling stigmatized
10. Lack of a support system
    (Newport Institute, 2022)

MIDDLE-AGED ADULTS

Middle age (35–64 years) is a time of maximum risk, with suicide rates increasing in both middle-aged men and women, although men are much more likely than women to die by suicide. Middle-aged adults account for 47.2% of all suicides in the United States, and suicide is the ninth leading cause of death for this age group (CDC, 2022d).

Middle age is a period characterized by high familial and social expectations, increased self-confidence, leadership, and community contribution, making midlife a time of well-being and peak functioning as well as a time of high stress. Well-being during this phase of life can vary considerably, from being confident and resilient when meeting changes and difficulties, to being nervous or overanxious in response to stressful events and conflicts.

Suicide rates for middle-aged women have increased more quickly compared to rates for men in recent years. Many of these women are in the “sandwich” generation, those who take care of their children as well as older parents. They are more likely to be very stressed as a result of the responsibilities they carry, increasing their risk for suicide.

Unemployment has been found to be present in 43.2% of those who die by suicide in midlife and is associated with an almost fourfold increased risk of suicide. Separation and divorce increase suicide risk by more than three times. People in this age group, especially men, consider work position, employment, and marital relationship as indicators of their social identity, and problems in these areas can be deeply distressing (AACI, 2020; Qin et al., 2022).

OLDER ADULTS

Adults ages 65 and older comprise just 12% of the population but make up approximately 18% of suicides. Men 65 and older face the highest overall rate of suicide. Older adults tend to plan suicide more carefully and are also more likely to use more lethal methods. Among people who attempt suicide, 1 in 4 older adults will succeed, compared to 1 in 200 youths. Even if an older adult survives a suicide attempt, they are less likely to recover from the effects.

Loneliness has been found to top the list of reasons for suicide among this age group. Many of them are homebound, live on their own, and may lack the social connections needed to thrive. Other reasons may include:

• Grief over the loss of family members and friends, and anxiety about their own death
• Loss of self-sufficiency and independence
• Greater likelihood of illnesses and chronic and/or debilitating diseases such as arthritis, cardiac problems, stroke, or diabetes, which compromise quality of life
• Loss of vision and hearing make it harder to do the things they’ve always enjoyed doing
• Cognitive impairment and dementia, which can affect a person’s decision-making abilities and increase impulsivity
• Financial stress, such as living on a fixed income and/or struggling to pay bills or afford food
• Clinical depression brought on by physical, emotional, and cognitive struggles
  (NCOA, 2021)

Terminally Ill and Disabled Individuals

Individuals who are terminally ill or disabled may elect to end their life by assisted suicide or euthanasia. There are different terms applied to the practice of helping a terminally ill or disabled person die by suicide. These can include medical aid in dying, physician-assisted suicide, death with dignity, right to die, or assisted suicide.

The term euthanasia means “good death.” It is an umbrella term for taking measures to end the life of someone with unbearable suffering associated with terminal illness. When a physician provides the means to die by suicide but does not administer it, it is known as passive voluntary euthanasia in the form of physician-assisted suicide. When a second party fulfills a dying person’s request to be put to death, it is referred to as active voluntary euthanasia.

In the United States, Oregon was the first state to legalize physician-assisted suicide in 1994. Since then, it has become legal in California, Colorado, Hawaii, Maine, New Jersey, New Mexico, Vermont, Washington, and the District of Columbia. Montana has legal physician-assisted suicide via a Supreme Court ruling, as there is nothing in state law prohibiting a physician from honoring a terminally ill, mentally competent patient’s request. Other states consider assisted suicide illegal (Triage Cancer, 2023; Johnson, 2022).

Suicide Risk among Specific Populations

Although suicide affects all groups of the population, the risk and protective factors for suicide may differ. The following summarizes risk and protective factors among specific populations.

PERSONS WITH DEMENTIA

Overall, people with dementia have no higher risk of dying by suicide than the general population, but the risk is significantly increased in three groups of people with dementia: those diagnosed before the age of 65, those in the first three months following diagnosis, and those with dementia and psychiatric comorbidity. In people younger than 65 years and within three months of diagnosis, suicide risk was seven times higher than in those without dementia.

Patients with early dementia may have greater cognition, giving them more insight into their disease and better enabling them to carry out a suicide plan. Severe dementia, however, could protect against suicide by decreasing a person’s capacity to implement a suicide plan. Also, impairment in cognition and personal activities of daily living are associated with greater risk of nursing home admission, which in itself is a risk factor for suicide (Alothman et al., 2022; Joshaghani et al., 2022).

CAREGIVERS

More than 21% of the U.S. population serves as caregivers to someone with an illness or disability. They are usually spouses, older children, parents, and family friends. Men and women equally share in the responsibility, which is fulfilled mostly by those ages 38–64. In 2020, 24% of caregivers were looking after more than one person. As a result of their significant social, economic, and personal contributions, caregivers experience high rates of physical and mental illness, social isolation, and financial distress. They are also at high risk for suicide.

In a U.S. study asking hospice and palliative social workers to identify patients and caregivers at risk for suicide in the previous year, 55.4% reported one or more caregivers who exhibited warning signs of suicide, 6.8% reported one caregiver who had attempted suicide, and 4.1% reported one caregiver who died by suicide (Herman & Parmar, 2022; O’Dwyer et al., 2021).

MILITARY SERVICE PERSONNEL

Suicides among military service personnel have been steadily rising during the past 10 years, and suicide is now the second-leading cause of death among this group. Greater than 90% of military suicides are by male personnel who are most often younger than 35 years of age. The most common method used for military personnel to die by suicide is a firearm.

In a study asking a group of active-duty soldiers why they tried to kill themselves, all of the soldiers indicated a desire to end intense emotional distress. Other common reasons included the urge to end chronic sadness, a means of escaping people, or a way to express desperation. In addition, rates of mental health problems have risen 65% in the military since 2000, with nearly one million troops diagnosed with at least one mental health issue. Risk for suicide increases when military personnel experience both depression and posttraumatic stress together (MSRC, 2022; ABCT, 2022).

Experiencing child abuse, being sexually victimized, and exhibiting suicidal behavior before enlistment are significant risk factors for service members and veterans, making them more vulnerable to suicidal behavior when coping with combat and multiple deployments. Military personnel reporting abuse as children have been found to be three to eight times more likely to report suicidal behavior. Sexual trauma of any type increases the risk for suicidal behavior. Men who have experienced sexual trauma are less likely than females to seek mental health care, which they may see as a threat to their masculinity. This is a strong predictor of suicide attempts in military personnel. Service members who attempted suicide before joining the military are six times more likely to attempt suicide post enlistment (APA, 2023).

Suicide among women in the military has increased at twice the rate of male service members. When compared to civilian women, those in the service are two to five times more likely to die by suicide. The primary reason is sexual trauma, particularly incidences of harassment and rape while stationed overseas, resulting from a pervading military culture that is antagonistic toward women in the military (Gorn, 2023).

There is strong evidence that among veterans who experienced combat trauma, the highest suicide risk has been observed in those who were wounded multiple times and/or were hospitalized as a result of being wounded.

Studies that looked specifically at combat-related posttraumatic stress disorder (PTSD) found that the most significant predictor of both suicide attempts and the preoccupation with thoughts of suicide is combat-related guilt about acts committed during times of war. Those with only some PTSD symptoms have been found to report hopelessness or suicidal ideation three times more often than those without PTSD (VA, 2022a).

OCCUPATION-RELATED SUICIDE

Professions that are associated with high suicide rates include law enforcement, public safety officers, physicians, and firefighters. These professionals often work long, irregular hours; witness all types of injuries; and have exposure to guns, all of which places them at high risk for suicide. Many of these professionals use alcohol, and often the trigger is divorce. Physicians have a particularly high rate of divorce because of job-related stress and the reluctance to seek help (O’Rouke & Siddiqui, 2022).

Among female nurses, the risk of death by suicide is nearly twice the risk observed in the general population. The COVID-19 pandemic has placed nurses at substantially higher risk for poorer mental health relative to other health professions (Lee & Friese, 2021).

Suicide Protective Factors

Although there are many risk factors for suicide, there are also factors that protect people from making an attempt or dying by suicide. These protective factors are both personal and environmental.

Personal protective factors include:

• Values, attitudes, and norms that prohibit suicide, such as strong beliefs about the meaning and value of life
• Strong problem-solving skills
• Social skills, including conflict resolution and nonviolent ways of handling disputes
• Good health and access to mental and physical healthcare
• Strong connections to friends and family as well as supportive significant others
• Strong sense of cultural identity
• A healthy fear of risky behaviors and pain
• Optimism about the future and reasons for living
• Sobriety
• Medical compliance and a sense of the importance of health and wellness
• Good impulse control
• A strong sense of self-esteem or self-worth
• A sense of personal control or determination
• Strong coping skills and resiliency
• Being married or a parent

External/environmental protective factors include:

• Opportunities to participate in and contribute to school or community projects and activities
• Strong relationships, particularly with family members
• A reasonably safe and stable environment
• Availability of consistent and high-quality physical and behavioral healthcare
• Financial security
• Responsibilities and duties to others
• Cultural, religious, or moral objections to suicide
• Owning a pet
• Restricted access to lethal means
  (WMU, 2023; CDC, 2022e)