Heidi Moawad, MD

Shift work sleep disorder is characterized by insomnia and excessive sleepiness lasting for at least 3 months in association with fluctuating work schedules. Patients who have this disorder experience an overall decreased amount of sleep. As defined by the 

International Classification of Sleep Disorders

, the condition also known as circadian rhythm sleep-wake disorder, shift work type or circadian rhythm sleep disorder (in DSM-5) is estimated to affect 

Because the inherent circadian rhythm is largely regulated by the 24-hour light/dark cycle, people who work overnight generally feel sleepier at night than during the day, even when they are at work or have slept during the day. Patients who work schedules with some or all shifts during the night when they would otherwise be sleeping may consequently experience disruptions in their circadian rhythm. These disruptions affect one’s ability to get adequate sleep, even when they have enough time to sleep. Most people who have shift work sleep disorder have 

Sleep disruption is also associated with behavioral manifestations of mood changes, such as irritability and social withdrawal. In addition to fatigue as a contributing factor, when mood changes like depression and anxiety are associated with shift work sleep disorder, they are thought to be caused by molecular alterations linked to circadian rhythm disruption. Research 

that the circadian clock is likely to regulate monoaminergic signaling, which mediates changes in dopamine, serotonin, and noradrenaline levels throughout the day.

 A disturbance in the circadian rhythm causes deregulation of these hormones at the level of molecular transcription, and this may result in symptomatic mood alterations.

Many shift workers are unable to adjust their circadian rhythm to their altered sleep wake schedules. This is evidenced by samples of salivary melatonin concentration, which normally 

 The diagnosis of shift work sleep disorder is a clinical diagnosis based on a patient’s medical history. The combination of insomnia, excessive sleepiness during waking hours, lack of sleep, and chronic shift work that is inconsistent with a regular day/night wake/sleep schedule leads to the diagnosis. Research 

that between 10% to 30% of shift workers fit the criteria for shift work sleep disorder, and it unclear why some shift workers are more prone to the condition than others.

Many pharmacological treatment strategies have been used to treat this acquired sleep disorder, including melatonin, zopiclone, lormetazepam, and modafinil. For example, one 

that was fairly representative of the effects of medications on the condition showed that pharmacological therapies increased sleepiness in some patients but did not improve overall sleep for the majority of patients.

 Non-pharmacological interventions include sleep education, use of bright light, napping, and physical exercise. These 

also have not been consistently effective.

A 47-year-old man has trouble falling asleep and reports not getting enough sleep throughout the night. He says he has no energy to do anything other than work and sit around at home.

His wife and daughter have accompanied him to the office visit. They explain that his moodiness has gotten worse over the past year. They say that he is irritable and sometimes seems down and uninterested in talking with them at home.

The patient works rotating shifts in a factory and has had the same job and schedule for about 5 years. He works 10-hour shifts with a schedule that varies weekly. He is scheduled to work from 10 PM to 8 AM on any 4 days of 1 week, followed by a week of working any 4 days from 10 AM to 8 PM. When an extra shift opens up with bonus pay, he takes it. He has often come home and gone back to work within 6 hours for an additional 10-hour shift when he can fit it in, which happens approximately 3 times per month.

The patient often tosses and turns in bed for hours before falling asleep, and sometimes he only gets a few hours of sleep before his next shift. He has not established a consistent sleeping pattern. He and his wife have installed heavy curtains with full window coverage to made sure their bedroom is completely dark during the daytime.

He agrees with his wife and daughter that he is quiet sometimes and irritable at others, but his family says these issues are getting progressively worse and he is very difficult to be around. The patient says he isn’t sad or anxious; instead, he is just tired and “zoned out.”

He gets enough to eat, and his wife is very attentive to planning healthy meals at home and packs healthy meals for him on his works days. He drinks 2 cans of caffeinated cold beverages at the beginning of every shift, and he doesn’t consume caffeine at any other time.

The patient smoked 1 pack of cigarettes per day since his 20s, but he quit about 5 years ago when a friend was diagnosed with lung cancer. He does not have any medical problems, and he isn't stressed at work or home. His physical examination is completely normal.

This patient was preliminarily diagnosed with shift work sleep disorder on his first visit. He and his wife agreed to keep a sleep diary over the course of 1 month. When they returned, they discussed the diary, which showed he had a very inconsistent sleeping schedule. He often came home and went to bed right away after a day or night shift, and sometimes he delayed going to bed for 3 to 7 hours after a day or an evening shift.

While shift work sleep disorder can cause diminished attention and increase the risk of accidents,

 this did not seem to be a problem for him. However, because he did not directly deal with equipment and rarely drove anywhere except work, he had limited opportunities to get into an inattention-induced accident.

The patient said that he did not want to look for a different job, as his pay rate and benefits were the best he had ever had in his life. He was advised to try to regulate his sleep schedule by going to bed at the same time every day during his week of night work and at the same time every day during his week of daytime work. He also wanted to try melatonin.

After several months, he was able to regulate his sleep on the weeks of his daytime shifts, but he still had an inconsistent sleep schedule on his week of nighttime work because he did not want to sleep during the day on his 3 days off. He continued to accept extra shifts whenever possible. He believed the melatonin helped him fall asleep and he felt that he was getting more rest on the days when he took it.

Overall, he did not have more energy, but he tried to be less irritable. His wife and daughter agreed he was more pleasant, yet still not very interactive. The family felt satisfied that learning about the disorder helped all of them cope with its clinical effects. They also all agreed the patient would aim eventually to get a job with a more regular schedule if he could find one without having to take a pay cut.

• Some people are more susceptible to shift work sleep disorder than others, and the reasons for this predisposition are unclear.

• Shift work sleep disorder is extremely difficult to overcome with medication. Because some patients’ symptoms improve with medication, it may be worth trying for those who can’t change their work schedule.

• Alternative therapies have shown limited success in the management of shift work sleep disorder. Nevertheless, sleep education can help patients and families cope and may serve as a motivation to eventually change circumstances when possible.

is Adjunct Professor at John Carroll University, and Instructor, Case Western Reserve University in Cleveland, OH. She is the Editor in Chief Emeritus of 

1. Boivin DB, Boudreau P. Impacts of shift work on sleep and circadian rhythms. 

https://pubmed.ncbi.nlm.nih.gov/25246026/

2. Gumenyuk V, Roth T, Drake CL. Circadian phase, sleepiness, and light exposure assessment in night workers with and without shift work disorder. 

https://pubmed.ncbi.nlm.nih.gov/22823876/

3. Albrecht U. Molecular Mechanisms in Mood Regulation Involving the Circadian Clock. 

https://pubmed.ncbi.nlm.nih.gov/28223962/

4. Liira J, Verbeek JS, Costa G, et al. Pharmacological interventions for sleepiness and sleep disturbances caused by shift work. 

https://pubmed.ncbi.nlm.nih.gov/25113164/

5. Slanger TE, Gross JV, Pinger A, et al. Person-directed, non-pharmacological interventions for sleepiness at work and sleep disturbances caused by shift work. 

https://pubmed.ncbi.nlm.nih.gov/27549931/

Articles

A case of a patient with difficult-to-treat insomnia highlights the pervasive daytime effects of this condition.

Insomnia Associated With Shift Work Sleep Disorder

Insomnia is characterized by difficulty falling asleep, trouble staying asleep, and/or early waking. The result is usually inadequate sleep, with daytime effects associated with sleep deprivation. Up to 50% of adults 

they have experienced insomnia at some point in their life.

While not as common as insomnia, anxiety and depression are also fairly prevalent among adults. 

 surveyed a random sample of 3406 participants ranging from aged 18 to 79 years. Of the participants, 13.9% (10.0% men, 17.0% women) reported they had received a diagnosis of anxiety; 6.4% (5.5% of men, 7.1% of women) had received a diagnosis of depression; 28.6% (23.5% of men, 32.7% of women) reported a diagnosis of insomnia; and 14% reported self-perceived stress.

Anxiety and stress are closely linked, and they are among the chief causes of insomnia. The exact prevalence of stress and/or anxiety among persons with insomnia is unknown, but stress and anxiety have an 

 because of a variety of emotional and physical factors.

 As with insomnia due caused by other factors, sleep deprivation due to anxiety-associated insomnia can bring about a variety of distressing symptoms during the day. Fatigue, irritability, anxiety, and depression are common consequences of sleep deprivation of any cause. Health problems like weight gain, hyperglycemia, and elevated lipid levels are associated with chronic sleep deprivation as well.

A 61-year-old man complains of insomnia, with difficulty falling asleep, frequent waking throughout the night, and early morning awakening. He estimates this has been going on for at least 6 months to a year, but he reports it is getting worse. He has been having trouble sleeping every night for the past few months and he naps during the weekend and in the evenings after work. He notes that he feels tired throughout the day and drinks cold caffeinated beverages “all the time,” to stay awake, totaling about 6 standard 8 oz cans per day.

He has gained 35 pounds in the past year. He used to regularly ride his bike for about 20 miles 3 or 4 times per week, but he stopped because of a stressful situation at work that has been distracting him. 

For the past 2 years, he has been embroiled in a lawsuit related to an accidental injury of an employee at his place of business, where he is a manager. The lawsuit is related to what is described as inadequate safety equipment, and he explains that he is part of the group of people who are responsible for implementing safety at his workplace. The patient says the employee’s injury and disability have been upsetting for him. He also says the lawsuit has been stressful. He was disturbed when he heard about the injury, but he was able to manage the stress because he thought the employee would have a quick recovery and the legal proceedings would be resolved within a month or so.

As he began to realize the issue would not be resolved quickly, he became more and more anxious about it. He explains the work environment is anxiety-provoking because there are meetings about the lawsuit approximately once per month, often with just a few hours’ notice. It should be noted that the business and his own salary have not been impacted and he says he is not stressed about the financial implications of the situation.

He lives with his wife and he says he has maintained a calm demeanor at home. He has 2 sons in their late 20s who live on their own and he says there is no strain in his relationships with his family. Over the past years, he has been going to fewer social outings and often leaves gatherings early because he feels bored. He explains his loss of interest in social gatherings began around the same time as the lawsuit.

He reports he has felt anxious and worried for as long as he can remember, but he doesn’t remember ever complaining of insomnia, and he has never felt the need to talk to a doctor about it. The patient mentions he experienced anxiety for a year after his father died because he had to manage his mother’s home and finances when she didn’t know what to do.

Past medical history consists of allergic asthma diagnosed in his 30s for which he takes nasal steroids as needed. He also is sensitive to many foods, which give him a stomach upset and heartburn.

Stress and anxiety are linked with each other. Stress is typically a response to a situation, while anxiety is a lingering feeling of disturbance or unease. Stress can cause anxiety, which is the case in this patient’s situation. The patient’s history strongly suggests a correlation between his difficult experience at work, his anxiety, and his insomnia.

During a clinical workup, it is important to keep in mind that underlying medical issues can contribute to insomnia and anxiety. Thyroid disease and heart disease, in particular, can exacerbate patients’ symptoms. When other causes are not found, it is helpful for patients to understand symptoms such as weight fluctuation, indigestion, stomach upset, sweating, appetite changes, and sexual dysfunction can all be symptoms of anxiety.1 This patient has noted some of these effects.

, especially without a precipitating factor that is out of the ordinary, it is often described as generalized anxiety disorder (GAD).

 The patient suggests he might have GAD, but based on his detailed history, it appear he is not excessively prone to anxiety out of proportion to the circumstances of his life.

The patient described in the vignette also has signs of depression. He has lost interest in socializing and exercise, which he used to enjoy. A depression screening would be beneficial as well. Major depression occurs in almost two thirds of patients with anxiety.

Treatment of comorbid anxiety, depression, and insomnia requires a treatment strategy that is designed to avoid exacerbating any of the 3 issues. Serotonin reuptake inhibitors (SSRIs) are among the 

 Additionally, SSRIs can help reduce symptoms of insomnia for some patients.

Treatment of comorbid anxiety, depression, and insomnia requires a treatment strategy that is designed to avoid exacerbating any of the 3 issues. Serotonin reuptake inhibitors are among the first-line treatments for depression with comorbid anxiety. Additionally, SSRIs can help reduce symptoms of insomnia for some patients.

This patient started taking paroxetine (Paxil) but became very tired. He was unable to tolerate the fatigue, so the medication was discontinued. He wanted to try another medical treatment, however. He was prescribed amitriptyline (Elavil), a tricyclic antidepressant. He was more satisfied with the treatment and wanted to continue to take it. He also agreed he might benefit from counseling, as he did not see a clear light at the end of the tunnel regarding his situation at work, and he didn’t anticipate an improvement of his symptoms until the issue resolved.

• Anxiety and GAD are not the same conditions, even though people with anxiety may be prone to recurrent episodes.

• Insomnia is caused by and can cause anxiety and depression.

• Treatment of insomnia with anxiety and depression entails a strategy that is mindful of all 3 conditions.

The above case is for illustrative purposes only. Identifying factors have been changed. -Ed

1. Pharmacological Treatment of Mental Disorders in Primary Health Care. In: World Health Organization. 

Pharmacological Treatment of Mental Disorders in Primary Health Care.

https://www.ncbi.nlm.nih.gov/books/NBK143206/

2. Höglund P, Hakelind C, Nordin S. Severity and prevalence of various types of mental ill-health in a general adult population: age and sex differences. 

. 2020;20:209. doi: 10.1186/s12888-020-02557-5 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212684/

3. Kalmbach DA, Anderson JR, Drake CL. The impact of stress on sleep: Pathogenic sleep reactivity as a vulnerability to insomnia and circadian disorders. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045300/

4. Munir S, Takov V. Generalized Anxiety Disorder (GAD). 

Treasure Island (FL): StatPearls Publishing; 2020 Jan-. 

https://www.ncbi.nlm.nih.gov/books/NBK441870/

5. Coplan JD, AaronsonCJ, Panthangi V, Kim Y. Treating Comorbid Anxiety and Depression: Psychosocial and Pharmacological Approaches. 

2015;5(4):366-378. doi: 10.5498/wjp.v5.i4.366. 

https://pubmed.ncbi.nlm.nih.gov/26740928/

Anxiety and stress are closely linked, and they are among the chief causes of insomnia. Watch for a variety of emotional and physical factors that may play a role in worsening depression. More in this case report.

Anxiety-Associated Insomnia With a Twist of Depression

During these uncertain times, it is easy to fall into a hole of negativity. There are so many unknowns, restrictions have been imposed on normal daily rituals, and the fear of the COVID-19 virus and potential death loom.

Yet, for years we have heard about the power of positive thinking and using laughter and happiness as a coping mechanism. Norman Cousins popularized the idea that 

. Since then, research continues to explore the role of positive and negative thinking. In fact, 

 links negative thinking with cognitive decline and markers of Alzheimer disease.

So what can you do? Here, Heidi Moawad, MD, discusses the pitfalls of negative thinking and shares specific tips to avoid falling into the trap of negative thinking.

Dr Moawad is Adjunct Professor at John Carroll University; Instructor, Case Western Reserve University in Cleveland, OH; and Editor in Chief Emeritus of Neurology Times (2017-2019).

Videos

Heidi Moawad, MD, discusses the pitfalls of negative thinking and shares specific tips for heatlh professionals and the public to avoid it.

Tools for Avoiding Negativity in the Face of Uncertainty

Nightmares are among the causes of secondary insomnia. Scary dreams are often associated with sleep disturbances. Waking up from a bad dream interferes with the restorative benefits of sleep. Insomnia, which is different than disturbed sleep, can also occur when bad dreams are recurrent to the point of anticipatory dread.

Dreaming occurs during the rapid eye movement (REM) stage of sleep. Most people remember only a small fraction of their dreams, and many people don’t remember their dreams at all. It is unclear whether people are more inclined to remember bad dreams than dreams with neutral content, but 

 that disturbing dreams are more likely to be recalled, at least in the first few minutes right after waking up from a dream.

Because dream stages (including REM) cycle several times throughout a normal night’s sleep, bad dreams can occur in one of the earlier REM stages of the night. When they cause a person to wake up, these waking episodes can interrupt sleep in the middle of the night and may make it hard to fall back asleep. Abruptly waking up can disrupt some of the restorative effects of a night of sleep.

Insomnia associated with bad dreams is distinct from primary insomnia. Patients may recognize the difference and may seek professional help in pursuit of restful sleep. It isn’t unusual for a patient to request pharmacological therapy to try to fall asleep and sleep through the night-even when insomnia is recognized as secondary to a cause.

The patient described in the vignette below had insight into the source of her insomnia and wanted to get professional help because her resulting sleep deprivation started to affect her overall well-being during the day.

A 28-year-old female seeks medical attention because she has been irritable and having trouble concentrating. Although she has had these symptoms for a year, they are getting worse and starting to interfere with her life. Over the past several months, she has also had intermittent shoulder pain and frequently notices she has dry eyes. She thinks these symptoms are all related to her lack of sleep.

She works full time in a retail store and is enrolled part time in graduate school. Her job is not stressful, and she is doing well in school and getting good grades. She often stays up until about 3 AM to get her assignments done, but she never pulls all-nighters. She has friends and a pleasant social life and gets along with her roommate. She doesn’t smoke and she drinks alcohol every other weekend with friends, typically about one beer or glass of wine.

She says that she doesn’t sleep well in general, even when she has time to sleep. She has been having bad dreams for about a year, and they have become so upsetting that she stays up until she falls asleep from extreme fatigue. The dreams generally involve a vague fear that someone is breaking into her parents’ home or the entrance of the apartment building where she lives, but never entering her childhood bedroom or her apartment unit. During the dreams, she thinks the intruder wanders with bad intentions around her home or in the building, and this presence is frightening to her. She wakes up frequently throughout the night, whether she has had this dream or not. It often takes her some time to get back to sleep, and she doesn’t know how long it takes because she deliberately avoids looking at a clock. She wakes up early in the morning for classes four days a week. She doesn’t like to take naps due to the brightness in her apartment and the sound of her roommate coming in and out throughout the day. She usually sleeps in until about noon on Friday, Saturday, and Sunday and her roommate makes a point of being quiet during these times.

The patient explains that she had a summer job at a local restaurant when she was in college, and the restaurant was robbed while she was working. She says the thieves walked in and pointed a gun at her coworker who was working at the register while customers were present. The coworker handed the thieves a pile of cash, and they left. The patient did not witness the event because she was working in another area of the restaurant. The offenders were caught in what she understands was an uneventful arrest. The patient says she thinks her nightmares could be related to the event, but she doesn’t understand why they just started a year ago and why her sleep wasn’t affected for several years after the robbery.

The only other precipitating factor she can think of is that she and her roommate shared a dog until a year ago when they moved to a building that did not allow pets. Due to the pet restriction, the dog was sent to live with her roommate’s parents. A few months before that, her own childhood dog, who had been with her parents, died. She says she was attached to both dogs and that each one typically slept on a dog bed in her bedroom.

She has no past medical history and her parents and only sibling are healthy. Her physical examination is completely normal. The patient denies symptoms of depression or anxiety, and she has not experienced any delusions or hallucinations. She was administered depression screening, and she did not have any signs of depression.

The patient agreed that her insomnia was likely caused by her reluctance to fall asleep due to her fear of bad dreams. While the patient initially requested medication to help her fall asleep at the urging of her mother, she agreed to first try behavioral therapy and counseling to learn how to reduce both the negativity of her dreams and her apprehension about the dreams.

She and her doctor decided together that she needed to talk through her fears about the robbery and the lack of nighttime comfort she had been getting from her dog. She also felt that she needed some encouragement so she could try to change the course of the fearful feelings during her dreams. She acknowledged that she would also benefit by accepting the fact that she might still occasionally have unpleasant dreams, and that she didn’t want to be so scared of the dreams themselves.

Nightmares that cause sleep disturbances are associated with an 

 This patient does not have signs of mental illness at this point and treating her symptoms could help avert further complications from developing. According to the American Academy of Sleep Medicine, behavioral therapy and pharmacological therapy are both 

 for treating nightmare disorders in adults.

 Physicians are encouraged to decide on the treatment approach based on the individual situation of the patient, and with input from the patient. The statement includes several medication recommendations, including olanzapine and tricyclic antidepressants, and recommends against using certain medications, including clonazepam and venlafaxine.

• Patients do not usually seek help for treatment of insomnia until it begins to affect daytime quality of life.

• Patients who experience insomnia often provide a thorough background regarding the factors that interfere with their sleep. 

• Pharmacological therapy can help improve sleep quality for people who have secondary insomnia, but when there is a clear reason besides primary insomnia, it can be beneficial to address the underlying cause.

The above case is a composite and not meant to identify any one person. -Ed

s Adjunct Professor at John Carroll University, and Instructor, Case Western Reserve University in Cleveland, OH. She is the Editor in Chief Emeritus of 

1. Cipolli C, Ferrara M, De Gennaro L, Plazzi G. 

Beyond the Neuropsychology of Dreaming: Insights Into the Neural Basis of Dreaming With New Techniques of Sleep Recording and Analysis

2. Sheaves B, Porcheret K, Tsanas A, et al. 

Insomnia, Nightmares, and Chronotype as Markers of Risk for Severe Mental Illness: Results from a Student Population

3. Morgenthaler TI, Auerbach S, Casey KR, et al. 

Position Paper for the Treatment of Nightmare Disorder in Adults: An American Academy of Sleep Medicine Position Paper

A patient's sleep deprivation started to affect her overall well-being and compromised her ability to enjoy life.

Insomnia Triggered by Nightmares: Evaluation and Treatment Options

It is commonly believed-and well supported by evidence and anecdotal reports-that substances and substance abuse are a strategy for coping and mediating the feelings that result from both recent and remote stress. Due to their cellular and biochemical features, the structural changes associated with stress may increase an individual’s post-stress susceptibility to substance abuse.

Stress impacts the brain causing anatomical changes at the cellular level. While not visible with imaging studies, other investigational modalities, such as biochemical testing and microscopic examination, can verify the presence of post-stress brain tissue alterations.

There are similarities between some of the cellular changes associated with stress and those cellular changes that result from drug abuse. Several common features include neural plasticity and microglial changes. Researchers have suggested that these overlapping features could be clues to a causative association between exposure to stress and a predisposition to drug abuse.

Of course, many people who experience severe stress do not use or abuse drugs, and extremely difficult experiences are not always a part of the life history of those who abuse drugs. So, while there is a relationship between stress and subsequent drug abuse, other variables (eg, genetic predisposition) are involved.

 researchers at Temple University, have examined synaptic plasticity, which is believed to be altered in association with both stress and substance abuse. The authors suggest that increased microglial alterations result from substance abuse and stress, both of which could cause the observed changes in synaptic plasticity.

This possible causative link is relevant in the study of the impact of stress on the predisposition to drug abuse for a number of reasons. Clinicians treating stress and substance use disorder (SUD) must take into consideration the fact that patients may have experienced cellular changes in brain tissue. If altered glial activity can be targeted in the treatment of stress or in the treatment or prevention of an SUD, it may prevent or correct alterations in synaptic plasticity.

Nevertheless, patients who experience stress-related neurobehavioral effects (including drug abuse) may benefit from a variety of therapeutic approaches. These include non-pharmacological therapies, such as counseling and mindfulness. In fact, if stress can induce cellular changes (eg, altered synaptic plasticity, microglial activation) in the brain, interventions like behavioral modification may also induce positive structural changes at a cellular level.

Genetic predisposition is one of the factors that links stress with subsequent drug abuse. Genes may shed some light on the question of whether stress undeniably and consistently induces cellular changes in the brain, which currently remains unanswered. The same gene variations that mediate how strongly a person feels stress in response to life events may also be linked with a patient’s ability to abstain from drugs after a period of substance abuse.

Specific genetic changes are linked both to stress responses and an ability to abstain from addictive substances. A multi-center 

 examined over 1000 participants who were recovering from heroin addiction.

 Participants who had specific genetic variations were better able to avoid relapse than participants who did not have this variation. Interestingly, the gene variations identified-CRHBP rs1500, NPY1R/NPY5R rs4234955, and NR3C1 rs10482672-are associated with variations in individual stress response. The researchers suggested that these results could point to a possible link between abnormal stress regulation and a vulnerability to relapse.

 examined the effects of gene variations in OPRM1, NPYR1/NPYR5, NR3C1, and CRHBP on cocaine use. Findings revealed that “reduction in cocaine abuse may be mediated by a genetic effect in a stress-related gene.” These results suggest that the effects of the stress genes on drug use are correlated with several drugs, not only with one drug of abuse.

It appears that stress can increase predisposition to SUD through changes in neuronal activity that occur at the cellular level. Genetic factors that increase susceptibility to drug abuse also appear to increase the chances of being highly impacted by stress.

It is possible that patients who have these genetic variations could also be more susceptible to the cellular changes associated with stress and SUDs, but a definitive link with a genetic predisposition to the noted structural changes has not been established.

• Stress can change the microstructure of the brain in a way that predisposes a person to drug abuse.

• There are individual differences in stress response, and these differences are sometimes linked to an individual’s ability to abstain from addictive substances.

• Treatment approaches to reduce the effects of anatomical changes in the brain can include behavioral approaches and non-pharmacological interventions (eg, counseling).

Dr Moawad is Adjunct Professor at John Carroll University, and Instructor, Case Western Reserve University in Cleveland, OH. She is the Editor in Chief Emeritus of 

Researchers provide clues to whether there is a causative association between exposure to stress and a predisposition to drug abuse.

Stress and Drug Abuse: A Structural and Genetic Link

Processed foods, also described as “junk-food,” are often reported to be highly addictive in humans-leading to behavioral effects such as overeating, eating compulsions, and loss of control. These foods have been associated with physiological stimulation of the same neurobiological reward response in the brain as that of drug addiction. It is often believed that the addictive quality of processed foods could be related to their preparation method, but the specific biochemical components of processed foods that induce addiction have not yet been identified.

There is a wide variation in the types of foods that stimulate an addictive response-these items include sweets (eg, chocolate and ice cream); salty carbohydrates (eg, potato chips); and prepared products that contain more than one distinctly discernible element (eg, pizza).

Despite a desire to avoid eating addictive foods, many people find themselves unable to restrain from their consumption. In fact, some people experience addictive intake of junk food despite describing them as unhealthy, and even unappetizing.

The term abuse liability is often used to describe the addictive potential of drugs. Because foods also generate abuse potential, studies that assess food addiction attempt to measure and quantify the abuse liability of various foods. Identifying the addictive components of certain foods could potentially help guide patients to recognize them and to guard against consuming products that may lead to unhealthy food addiction.

Food addiction is not necessarily the same as liking a particular type of food or wanting to seek it out. An 

describes a research study from the University of Michigan that examined characteristics of highly processed food that lead to food addiction.

 The investigators reported that processed foods were rated as having a high abuse liability when compared with foods that were not highly processed. However, it is worth mentioning that the study participants did not report enjoying these addictive foods.

This divergence between food enjoyment and food addiction is not consistent, however. Another research study, performed by the same investigators at the University of Michigan, examined the association of different foods with abuse liability. 

 concluded that highly processed foods were associated with an indicator of addictive eating defined as loss of control. These same processed foods were also rated high on scales of liking, pleasure, and craving.

This inconsistency in finding a correlation between subjective enjoyment of processed foods and their addiction liability (even when the same researchers carried out different studies) suggests that positive experiences associated with these foods may only be partially responsible for their addictive qualities. There may be another mechanism to food addiction than traditional definitions of food enjoyment.

Some of the physiological routes that meditate food addiction are similar to the biochemical pathways that mediate drug addiction. 

 used a mouse model to simulate human junk food addiction. Junk food consumption increased activation of the nucleus accumbens (NAc) AMPA receptor (AMPAR). Motivational responses are mediated in part by NAcAMPAR transmission. The NAc is part of the mesolimbic pathway. It is located anterior to the caudate head, and posterior to the prefrontal cortex. This structure has a role in regulating dopaminergic reward activity.

Based on the mouse models and their responses to junk food, the study authors concluded, “alterations in NAc function similar to those that are known to underlie drug addiction might also contribute to junk food addiction.

The specific components of processed food that may trigger addictive behaviors are still not defined. It has been suggested that the taste, texture, and/or convenience of these foods could be responsible for their behavioral effects.

 suggest that “added fats and/or refined carbohydrates, clustered together are associated with greater loss of control, liking, pleasure, and craving.” In a multicenter research article examining the human behavioral response to ultra-processed food, 

 state that strategies utilized in the preparation of these foods could be responsible for their addictive effects. The authors reported that processed foods contain “enhanced amounts of salt, added sugar, and fat, as well as the use of additives in an attempt to make this food category highly palatable.”

However, experts do not know whether the abuse liability of processed foods is mediated by a conscious experience (such as taste) or by a subconscious effect that directly stimulates the brain while bypassing recognizable experiences such as enjoyment. To date, it remains unclear whether a specific food ingredient activates metabolic responses that stimulate the nucleus accumbens (NAc) AMPA receptor (AMPAR)-leading to an addictive nature of highly processed foods-or whether it is a more apparent feature of the foods that ultimately leads to addiction.

• Junk food and highly processed foods have high abuse liability 

• It is unclear which features or components of processed foods trigger abuse and addiction

• Processed foods increase abuse potential through a series of biochemical actions that affect nucleus accumbens (NAc) AMPA receptor (AMPAR) transmission

1. Schulte EM, Sonneville KR, Gearhardt AN. 

Subjective experiences of highly processed food consumption in individuals with food addiction

Foods are differentially associated with subjective effect report questions of abuse liability

3. Oginsky MF, Goforth PB, Nobile CW, et al. 

Eating ‘Junk-Food’ Produces Rapid and Long-Lasting Increases in NAc CP-AMPA Receptors: Implications for Enhanced Cue-Induced Motivation and Food Addiction

4. Gibney MJ, Forde CG, Mullally D, Gibney ER. 

Ultra-processed foods in human health: a critical appraisal

Processed foods, also described as “junk-food,” are often reported to be highly addictive in humans-leading to behavioral effects such as overeating, eating compulsions, and loss of control.

Underlying Mechanisms of Highly Processed Food Addiction

In 2019, a number of serious health effects and even deaths were reported in association with e-cigarette use. The US government also created new restrictions on e-cigarettes. In addition to the health effects already known about e-cigarettes, adults and young people who obtain them through "black market" routes may experience health effects that have not yet been observed or described, especially if these products contain materials that were not present in products that had been previously legal.

E-cigarettes have become commonplace and are used by people of all ages. Some proponents suggest that they could be safer than traditional cigarettes and that they may be used as a means to prevent or replace the smoking of combustible (regular) cigarettes. Some of the current 

 shows that use of e-cigarettes is associated with a lower incidence of substance abuse disorder (SUD) and tobacco use disorder (TUD).

Yet, the use of e-cigarettes may precede cigarette smoking as well as the use of other substances, especially among young people. It is therefore not clear whether e-cigarettes protect against SUD, lead to it, or are a sign of an inherent predisposition to the condition.

The concept of gateway drugs is well established in the area of illegal recreational drugs of abuse. An inherent disposition to SUD could precede or be exacerbated by the use of drugs that are typically considered gateway drugs, such as combustible cigarettes, alcohol, and marijuana. E-cigarettes are also gaining recognition as a potential gateway to smoking cigarettes and using other drugs.

E-cigarettes vary in their nicotine content. Not only does the experience of smoking nicotine e-cigarettes differ from the experience of smoking non-nicotine e-cigarettes, the subsequent tendency to smoke regular cigarettes may differ depending on whether a person smokes nicotine e-cigarettes or non-nicotine e-cigarettes.

 followed a group of 3474 students beginning when they were 15 and 16 years old, and again when the same students were ages 17 and 18. Students who had smoked nicotine e-cigarettes when they were 15 and 16 years old were more likely to smoke regular cigarettes at age 17 and 18 than the students who had smoked non-nicotine e-cigarettes.

 The researchers found that students who smoked non-nicotine e-cigarettes at aged 15 and 16 years were no more likely to smoke regular cigarettes than students who did not smoke e-cigarettes at all when they were ages 15 and 16.

The researchers concluded that nicotine addiction started with the early use of nicotine e-cigarettes and could have predisposed the students to cigarette addiction as well. There are several other possible reasons for the outcome, however. For example, it is possible that students who smoked non-nicotine e-cigarettes deliberately chose that type of e-cigarette to avoid nicotine exposure or that they did not enjoy nicotine.

While conclusions remain uncertain, marijuana is often thought of as a gateway drug because its use frequently precedes use of illegal drugs. Among some people, smoking E-cigarettes may predispose marijuana use.

 examined the relationship between e-cigarettes and subsequent use of marijuana. The researchers found that “odds of marijuana use were higher in youth who had an e-cigarette use history in comparison to those who did not.” They did not distinguish between study participants who used nicotine e-cigarettes and study participants who used non-nicotine e-cigarettes. Given that the study was a large retrospective meta-analysis that included 128,227 participants, it is not easy to draw a conclusion regarding the cause of this link or whether the students were addicted to either substance.

Marijuana is one of the substances commonly used by individuals who suffer from SUD. The role of e-cigarettes prior to the use of marijuana could be related to an inherent tendency to use substances, or it could increase the chances of trying marijuana.

E-cigarette use is also associated with the use of several substances that are commonly abused among people who suffer from SUD. In a longitudinal multi-center study, 

 surveyed the drug use habits of 662 participants in an ethnically diverse sample to examine a possible association between e-cigarettes and abuse of other substances.

The researchers found that e-cigarette use was closely linked with use of “combustible cigarettes, alcohol, marijuana, cocaine, amphetamines, inhalants, hallucinogens, ecstasy, and misuse of over-the-counter and prescription medications.” They also noted that users of e-cigarettes reported that their taste was their primary appealing feature. This suggests a very different motive for using e-cigarettes than the motives that are typically associated with some of the other drugs-most of which are not typically associated with a taste. Alcohol, marijuana, and regular combustible cigarettes, all of which have been described as gateway drugs, are, however associated with a distinctive taste, which may also be an appealing factor for some users.

The link between e-cigarettes and numerous drugs that are commonly abused in people who have SUD suggests that e-cigarettes have a stronger effect on users than satisfying their need for the taste, and that they could predispose to use of other drugs.

• E-cigarettes are often the first substance that young people use, and they have been associated with a future risk of multi-substance use.

• Adults or youth who are trying to curb their use of regular combustible cigarettes may begin to use e-cigarettes as a strategy to help reduce smoking.

• Adults and youth who use e-cigarettes along with combustible cigarettes are at a higher risk of SUD than those who use e-cigarettes but do not smoke combustible cigarettes.

• It is worthwhile to discuss warning signs of addiction with patients who use e-cigarettes. At an early stage, patients may be receptive to recognizing, admitting, and addressing the signs of substance abuse disorder before the condition begins.

The use of e-cigarettes may precede cigarette smoking as well as the use of other substances, especially among young people.

Author | Heidi Moawad, MD