Recently published survey results provide insight into why some young Hispanic males think about, attempt, and commit suicide, while also identifying social and psychological factors that appear to be protective.

Dr. Thomas Locke of the University of California-Los Angeles and Dr. Michael Newcomb of the University of Southern California recruited 349 Hispanic males from communities in Los Angeles County whose average age was 19. An analysis of the participants' responses to questionnaires revealed several risk factors for suicidality and three significant protective factors.

Emotional abuse was the strongest predictor for suicidality, followed by the individual's abuse of cocaine, heroin, and other drugs, sexual abuse, and having a mother with alcohol-related problems. Factors considered protective against the idea and action of suicide were confidence in one's own problem-solving abilities, feeling connected to and valued by one's parents, and being law-abiding.

What it means: Hispanic youth are at great risk for attempting suicide and are at increased risk for nonfatal suicidal behavior. Adverse and abusive childhood experiences are early familial risk factors that contribute to suicidality and drug use in this population. Treatment and prevention efforts aimed at young Hispanic males should screen for suicidal thoughts and behaviors, particularly among those who abuse drugs like cocaine and heroin. Screening by healthcare providers also is suggested when a young Hispanic male reports maternal alcohol-related problems.

The study, which was partly supported by NIDA, was published in the August 2005 issue of the Hispanic Journal of Behavioral Sciences.

NIDA NewsScan, October 28, 2005

Teens who engage in sexual intercourse and/or drug abuse (including abuse of alcohol and tobacco) are significantly more likely than youth who abstain from such activities to become depressed, have suicidal thoughts, and attempt suicide.

NIDA-funded scientists at the Pacific Institute for Research and Evaluation and the University of North Carolina at Chapel Hill analyzed sex and drug behavior patterns among 18,924 teens from 132 U.S. schools. The data were gathered from September 1994 to December 1995 as part of the National Longitudinal Study of Adolescent Health.

The researchers found that teens who had not initiated sex or drug abuse had the lowest levels of depression, suicidal thoughts, and suicide attempts. The highest levels were seen in youth with patterns that included illegal drug abuse and risky sexual behavior. The scientists also observed that although girls were less likely than boys to pursue high-risk behaviors, girls who did were more vulnerable to depression and suicidal behaviors.

What it means: Healthcare professionals should consider screening youth for depression and suicidal tendencies if they suspect the youth are engaging in risky behaviors. Further research is warranted to understand whether causal links exist between such behaviors and mental health status.

Dr. Denise Hallfors and her colleagues published this study in the October 2004 issue of the American Journal of Preventive Medicine.

NIDA NewsScan, March 9, 2005

Research has shown that adolescents with substance use disorders are most likely to attempt suicide when they also have a co-occurring mood disorder. NIDA-funded scientists at the University of Pittsburgh have extended this research and found that generally, both male and female substance abusers who attempt suicide begin taking drugs at an early age and have more symptoms of psychiatric and substance use disorders than adolescents who do not attempt suicide.

Dr. Thomas Kelly and colleagues collected data from 188 females and 315 males, aged 12 to 19 years, who were diagnosed with an alcohol or substance use disorder and who participated in studies between 1991 and 2000 at the Pittsburgh Adolescent Alcohol Research Center. The adolescents completed standardized assessments of substanceand nonsubstance-related psychiatric disorders. Both the adolescents and their parents answered standardized questions about age of onset for all diagnosed psychiatric disorders. Adolescents who attempted suicide and their parents estimated the age(s) at which the adolescent attempted suicide.

Overall, 29 males and 56 females made one or more suicide attempts during their lifetimes. Males with hallucinogen use disorders, inhalant use disorders, sedative-hypnotic use disorders, and attention-deficit hyperactivity disorder were more likely to have attempted suicide than males who were not diagnosed with these disorders. Male suicide attempters had more symptoms of mood, alcohol, and disruptive behavior disorders compared with male nonattempters. There existed an earlier age of onset for alcohol use disorders and conduct disorders among male suicide attempters compared with the age of onset among males with these disorders who did not attempt suicide.

Females with conduct disorders and substance use disorders (other than cannabis use disorders) were at higher risk for attempting suicide than females who were not diagnosed with conduct disorders or noncannabis substance use disorders. Female suicide attempters had more symptoms of substance use disorders (other than cannabis use disorders) and mood disorders compared with female nonattempters. Female suicide attempters with mood disorders had an earlier age of onset of mood disorders compared with the age of onset for mood disorders among female nonattempters.

The researchers also found that risk of attempting suicide generally begins to increase at age 11 for females and about 12.5 for males with substance use disorders. Co-occurring mood disorders place both males and females with substance use disorders at highest risk for attempting suicide.

What it means: These findings indicate that clinicians should closely monitor adolescents with substance use disorders for suicide risk. Clinicians should also be aware of gender differences in suicidal behavior based on the course and severity of a co-occurring psychiatric disorder in this population.

Dr. Kelly and colleagues published these findings in the January 2004 issue of Drug and Alcohol Dependence.

NIDA NewsScan, April 30, 2004

Scientists from the Stanford University School of Medicine and the University of California, San Francisco, have found that drugs of abuse and stress may trigger similar changes in brain circuitry. The scientists demonstrated that in mice, five drugs of abuse (each with different mechanisms of action) and stress enhanced the transmission of electrochemical signals in dopamine neurons, which previous research suggests may be involved in addiction.

In the study, the scientists administered cocaine, amphetamine, morphine, nicotine, ethanol, or the nonaddictive psychoactive medications, fluoxetine and carbamazepine, to groups of mice. The addictive substances caused an increase in the signaling to dopamine neurons while the nonaddictive drugs did not.

What it means: Certain drugs of addiction and stress appear to produce similar changes on dopamine signaling, which may play a role in addiction. This also may contribute to the effects of stress on drug seeking and relapse. Understanding the effects of drugs of abuse and stress on brain circuitry may aid in developing therapeutic medications to treat addiction.

This study was published by lead investigator Dr. Robert Malenka in the February 2003 issue of Neuron. It was funded, in part, by the National Institute on Drug Abuse.

NIDA NewsScan, July 30, 2003

Evidence from animal studies suggests that specific types of stressful experiences in early life may increase vulnerability to drug abuse. For example, animals that are isolated or separated from their mothers in early life increase self-administration of morphine and cocaine.Several human studies have reported a link between adverse life events, chronic stress, and increased drug abuse. Individuals with a history of physical or sexual abuse at a young age have an increased risk of abusing substances.

One proposed explanation for this link between stress and increased drug abuse has been that the use of addictive substances serves to both alleviate emotional distress and enhance mood, thereby reinforcing drug taking as an effective, but maladaptive, coping strategy. However, more recent animal studies suggest that stress may enhance the reinforcing effects of drugs that are commonly abused.

With those studies, scientists have sought to elucidate the neurological events in the brain that underlie the relationship between stress and substance abuse. The two main components of the brain’s stress circuitry are corticotropin releasing factor, which originates in the hypothalamus and amygdala, and the noradrenergic activation initiated in the brain stem. Activation of the stress

circuits also increases dopaminergic neuro- transmission in the mesolimbic regions of the brain.

The mesocorticolimbic dopaminergic system is generally considered to be the brain’s reward pathway, and increased transmission in this pathway has been shown to be critical for the reinforcing properties of drug abuse. Thus, it seems that exposure to stress stimulates some still-to-be-identified neural activity which in turn simultaneously activates both the stress circuitry and the reward pathway and, by doing so, enhances the likelihood of taking drugs and the pleasure obtained from taking drugs.

What it means: Research shows that stress, in addition to the drug itself, plays a key role in perpetuating drug abuse and relapse.

The paper, “How does stress increase the risk of drug abuse and relapse?” was published by Dr. Rajita Sinha in Volume 158, 343-359, 2001 of the journal Psychopharmacology.

NIDA NewsScan, April 8, 2002

The preface of the Stress and Drug Abuse issue of the journal Psychoneuroendocrinology includes a brief synopsis of the relationship between stress and the risk of substance abuse. Understanding the cascade of hormonal and neurobiological events that are set off by experiencing trauma helps to explain the linkage between stress andsubstance abuse. Both clinical experience and research have shown that posttraumatic stress disorder (PTSD) is a risk factor for substance abuse.

Traumatic stress may have negative effects on the neurotransmitter systems and neuroendocrine axes that are activated during acute stress. Although stress affects practically all aspects of physiology, the most important physiological stress responses include activation of the central nervous system, the autonomic nervous system, and the limbic-hypothalamic-pituitary-adrenal (LHPA) axis.

Animal studies examining catecholamine function show that traumatic stress activates the locus coeruleus, the major catecholamine-containing nucleus in the brain, leading to the biologic changes of the “fight-or-flight” reaction.

Increases in catecholamine turnover in the brain lead to increases in heart rate, blood pressure, metabolic rate, alertness, and in the circulating catecholamines epinephrine and dopamine. During severe stress, the HPA axis is stimulated, setting off a neurochemical cascade that results in anxiety and hypervigilance, core behavioral symptoms of PTSD.

Glucocorticoids released during chronic stress alter gene expression and influence functions of

practically all tissues. Research has shown that chronic exposure to glucocorticoids can result in many deleterious health effects, including acceleration of heart disease and diabetes, reduced volume of the hippocampus and cerebral cortex, cognitive impairments and psychiatric disorders.

The link between stress and drug abuse is supported by studies that show that administration of cocaine to humans evokes similar physiological reactions, such as secretion of adrenaline and corticosteroids, and psychological arousal that are evoked by stress. Discontinuation of cocaine in long-time addicts is associated with lasting disturbances of HPA axis functions, somewhat similar to those observed after chronic stress. And animals that maintain low levels of arousal and manifest relatively low concentrations of plasma glucocorticoids in response to a stressor are more likely to develop drug-seeking behaviors than are those with a normally functional HPA axis.

What it means: Stress is clearly interwoven with increased predisposition to psychiatric disorders and drug abuse.

The study was published in a special issue on stress and drug abuse by the journal Psychoneuroendocrinology (Volume 27, Number 1/2, Jan/Feb 2002).

NIDA NewsScan, April 8, 2002

This review paper by Michael D. DeBellis from the University of Pittsburgh Medical Center discusses studies thatlook at the developmental effects of traumatic events in early childhood. The evidence points to the conclusion thatmaltreatment or other stresses during childhood disrupt the major biological stress response systems, resulting inadverse effects on brain development.

Dysregulation of biological stress response systems may lead to an increased vulnerability to psychopathology,particularly posttraumatic stress disorder (PTSD) and depression. These disorders, in turn, may put a child at increased risk for

adolescent-onset or young-adult-onset alcohol or substance abuse disorders.

What it means: Changes in biological stress response systems in childhood can increase vulnerability to“self-medicating” with alcohol and various illicit substances.

The study was published in a special issue on stress and drug abuse by the journal Psychoneuroendocrinology (Volume 27, Number 1/2, Jan/Feb 2002).

NIDA NewsScan, April 8, 2002

Researchers from the Harvard Medical School and McLean Hospital found that repeated sexual abuse during childhood causes physical changes in the brain, changes that can explain why abused children often develop substance abuse problems later in life.

The investigators found that young adults who had been sexually abused as children had changes in the blood flow and function of a brain region called the cerebellar vermis, a portion of the brain that may play a role in modulating response to addictive drugs.

Testing revealed that the young adults with a history of childhood sexual abuse had substantially higher

scores in some psychiatric symptoms associated with substance abuse.

What it means: The findings suggest that early trauma may interfere with the development of the vermis and produce neuropsychiatric symptoms associated with drug use.

Dr. Carl M. Anderson of McLean Hospital led the study, which was published in a special issue on stress and drug abuse by the journal Psychoneuroendocrinology (Volume 27, Number 1/2, Jan/Feb 2002).

NIDA NewsScan, April 8, 2002

Researchers at the Louisiana State University Health Sciences Center used rats to study the role of the HPA axis in the acquisition, maintenance, and relapse of cocaine use. They found that corticosterone, a stress hormone produced by the HPA axis, is necessary for the acquisition of drug-taking behavior, and that the animals did not self-administer cocaine unless the level of corticosterone was increased above a threshold critical for reward.

It was also found that corticosterone is involved in the stress- and cue-induced relapse of cocaine abuse.

What it means: Stress reduction, either alone or in combination with medication targeting the HPA axis, may help promote abstinence in individuals seeking treatment for cocaine addiction.

The Louisiana research team was led by Dr. Nick E. Goeders. The study was published in a special issue on stress and drug abuse by the journal Psychoneuroendocrinology (Volume 27, Number 1/2, Jan/Feb 2002).

NIDA NewsScan, April 8, 2002

Investigators led by Dr. Michael J. Meaney of the Douglas Hospital Research Center in Montreal, Canada, found that, in rodents, maternal separation during early postnatal life alters the development of the ascending mesocorticolimbic dopamine system.

As adults, animals raised under conditions of prolonged maternal separation showed decreased dopamine transporter binding in one part of the brain, increased dopamine release in response to acute stress, and enhanced behavioral sensitivity to cocaine.

What it means: These findings suggest that parental care in early life could alter the development of the mesocorticolimbic dopamine system and thus form the basis for a vulnerability to certain forms of drug abuse in later life.

The study was published in a special issue on stress and drug abuse by the journal Psychoneuroendocrinology (Volume 27, Number 1/2, Jan/Feb 2002).

NIDA NewsScan, April 8, 2002

Researchers led by Dr. Mary L. Schneider from the University of Wisconsin present evidence from studies using monkeys that prenatal stress and exposure to alcohol result in offspring with reduced attention span and delayed motor development in infancy.

The researchers also addressed the issue of whether prenatal alcohol exposure or stress contributes to increased risk for alcohol or substance abuse later in life. In some of the monkeys, increased alcohol consumption during adolescence was associated with prenatal stress.

What it means: The effects of stress during pregnancy (alone or in combination with fetal alcohol exposure) need to be better understood in humans.

The study was published in a special issue on stress and drug abuse by the journal Psychoneuroendocrinology (Volume 27, Number 1/2, Jan/Feb 2002).

NIDA NewsScan, April 8, 2002

The investigators used a rat model to study the impact of chronic injection of the tricyclic antidepressant desipramine and 24-hour material deprivation on the developing rat brain.

At 80 days of age, the animals that received desipramine during the newborn period consumed more alcohol than did those that were not injected. History of maternal deprivation had no impact on alcohol consumption. The investigators noted 5-HT1B receptor down-regulation in the animals subjected to chronic injection treatment.Low 5-HT1B receptor levels have been associated with cocaine self-administration.

What it means: The investigators conclude that

5-HT1B receptor down-regulation may be one of the biological mechanisms whereby early life stress increases vulnerability to substance abuse later in life.

Dr. Delia M. Vazquez led the research team from the University of Michigan. The study was published in a special issue on stress and drug abuse by the journal Psychoneuroendocrinology (Volume 27, Number 1/2, Jan/Feb 2002).

NIDA NewsScan, April 8, 2002