Social isolation, lack of mental-health treatment, drug and alcohol abuse and gun ownership are among the factors that contribute to suicide.

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Suicide rates rose steadily in nearly every state from 1999 to 2016, increasing 25 percent nationally, the Centers for Disease Control and Prevention (CDC) reported Thursday. In 2016, there were more than twice as many suicides as homicides.

The figures were released two days after the death by suicide of celebrity designer Kate Spade and a day before the death by suicide of chef, author and TV personality Anthony Bourdain.

She had struggled with depression and anxiety for years, according to a statement released by her husband, Andrew Spade. “She was actively seeking help and working closely with her doctors to treat her disease,” he wrote.

Warning signs of suicide

If you are experiencing suicidal thoughts or have concerns about someone who may be, call the National Suicide Prevention Lifeline at 1-800-273-TALK (8255). You will be routed to a local crisis center where professionals can talk you through a risk assessment and provide resources in your community. The more of the signs below that a person shows, the greater the risk of suicide:

•Talking about wanting to die

•Looking for a way to kill oneself

•Talking about feeling hopeless or having no purpose

•Talking about feeling trapped or in unbearable pain

•Talking about being a burden to others

•Increasing the use of alcohol or drugs

•Acting anxious, agitated or recklessly

•Sleeping too little or too much

•Withdrawing or feeling isolated

•Showing rage or talking about seeking revenge

•Displaying extreme mood swings

Source: National Suicide Prevention Lifeline

CDC officials, however, said the national increase in suicide rates cannot be linked to a particular mental-health diagnosis.

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The new analysis found that nearly 45,000 Americans ages 10 or older died by their own hand in 2016.

The 1999 to 2016 suicide-rate increase varied widely by state, from a low of 6 percent in Delaware to more than 57 percent in North Dakota; in Washington state, it was 18.8 percent. The rate fell in just one state, Nevada, where it has historically been higher than average.

Social isolation, lack of mental-health treatment, drug and alcohol abuse and gun ownership are among the factors that contribute to suicide.

Suicide is the tenth leading cause of death in the United States, and one of three that are increasing. The other two are Alzheimer’s disease and drug overdose, in part because of the spike in opioid deaths, said Dr. Anne Schuchat, principal deputy director of the CDC.

Firearms were by far the leading method, accounting for about half the suicides. That number has remained steady over recent decades, she said.

Suicide rates varied from 6.9 per 100,000 residents a year in the District of Columbia to 29.2 per 100,000 in Montana.

The analysis found that slightly more than half the people who had killed themselves did not have any known mental-health condition. But other problems — such as the loss of a relationship, financial setbacks, substance abuse and eviction — were common precursors, both among those who had a mental-health diagnosis and those who did not.

Other studies have found much higher rates of mental-health disorders among people at high risk of suicide, experts noted.

“The reason most suicide decedents don’t have a known mental disorder is that they were never diagnosed, not that they didn’t have one,” said Dr. David Brent, a professor of psychiatry at the University of Pittsburgh.

Access to guns can make it more likely that an impulsive or intoxicated person will attempt suicide even if he or she has no clear mental-health problem, Brent added.

“We have worked really hard to explain to the public that suicide is not simply a matter of too much stress, but that it involves the identification and treatment of mental disorders as one important component,” he said.

In a conference call with reporters Thursday, Schuchat and Deborah Stone, lead author of the CDC analysis, stressed that other factors were also critical to preventing suicide.

Effective strategies, she said, included teaching coping and problem-solving skills to those at risk, establishing more social “connectedness,” and safe storage of pills and guns.

The CDC found that men accounted for three-quarters of all suicides, and women one-quarter. The numbers were highest among non-Hispanic whites, and among those ages 45 to 65 years old.

Previous CDC reports have found rate increases of 80 percent among white, middle-age women since 1999, and of 89 percent among Native Americans. The rates declined slightly among black men and people older than 75 during that time.

Suicide rates have waxed and waned over the country’s history and tend to reach highs in hard times. In 1932, during the Great Depression, the rate was 22 per 100,000, among the highest in modern history. The rate in the new CDC data was 15.4 per 100,000.

The past three decades have presented a morbid puzzle. Rates have risen steadily in most age and ethnic groups, even as rates of psychiatric treatment and diagnosis have also greatly increased.

The reasons are many, experts said. The biggest increases have been in states like Oklahoma, Montana and Wyoming, where gun ownership, drug use and economic hardship are common. Among middle-age people across the country, marriage rates have declined, and social isolation has increased.

Prevention has been elusive, in part because doctors have not had programs that reliably reduce suicide rates. Crisis hotlines can save lives; so can psychiatric treatment. But suicide is such an unpredictable, often impulsive act that no single intervention has proved sufficient.

“A big problem that has not yet been addressed in practice is that we continue to rely almost entirely on people themselves to proactively tell us if they are suicidal,” said Matthew Nock, a professor of psychology at Harvard University.

Yet research has shown that nearly 80 percent of people who die by suicide explicitly deny suicidal thoughts or intentions in their last communications, he added.

Researchers have only recently begun to understand the elements of suicidal thinking that actually predict an attempt.

The key risk factors include engaging in extremely risky behavior and refusing to answer questions about suicidal thinking, or its severity, Nock said. “Using these factors, we can predict attempts with greater than 90 percent accuracy.”

In 2015, most of the people who died by their own hands had alcohol or some sort drug in their blood, including tranquilizers like Valium or Xanax, and opioids.

“Our data show that suicide is more than a mental-health issue,” Schuchat said. “We want improved access to care and better diagnostics, but we think that a comprehensive approach to suicide is what is needed.”