1. Context
Drug abuse is a pervasive worldwide problem. According to 2016 statistics, six percent of the world’s population between the ages of 15 and 64 probably smoked once in their lifetime (1). The U.S. Food and Drug Administration (FDA) defines drug abuse as “the intentional, non-therapeutic use of a drug product or substance, even once, to achieve a desired psychological or physiological effect” (2). Global statistics show that 35 million people are drug addicts, 11.8 million people inject drugs, and the prevalence of AIDS is 13.1%. One hundred forty-eight countries reported injecting drugs, while 120 countries reported HIV infections among this population (3). Given the adverse physical, mental, psychological, and social consequences of drug abuse for countries, identifying the causes and evidence-based policymaking by governments can be effective in preventing the occurrence of drug abuse (4).
Numerous studies have been conducted on the factors that predict the risk of substance abuse (5, 6). One of the factors evaluated in these studies concerns the initial 1000 days of life (7). The first 1000 days of life begin from pregnancy to when a child is two years old. This unique stage is fundamental for optimum health, nerve growth, and development throughout life (8). Various studies referred to the relationship between the first 1000 days of life and the harmful consequences in adulthood. For example, maternal stress during pregnancy affects long-term health outcomes in children, including stress and low self-esteem (9). However, no investigation has mentioned any aspects of the first 1000 days of life and the future drug abuse. The main objective of this narrative review is to present scientific evidence to demonstrate the effect of the unpleasant events on the first 1000 days of life, such as maternal separation (MS), maternal-infant bonding, adverse childhood experiences (ACEs), substance use during pregnancy, prenatal stress, and one’s future drug abuse. Therefore the present study aimed to indicate the relevance of the first 1000 days of life and the risk of future drug abuse.
2. Evidence Acquisition
This article is a narrative review that identifies the role of the first 1000 days of life on vulnerability to addiction later in life. The articles were extracted from valid databases, including PubMed, Scopus, Science Direct, Web of Science, and Embase. Due to the nature of the study, no sampling was performed, and studies involving the first 1000 days of life and drug use were reviewed. Keywords included: First 1000 days, drug abuse, adverse childhood experiences, maternal bonding, maternal separation, and other similar keywords.
Conventional content analysis was used in the analysis of the data. The related sections of the articles were studied separately by two team researchers, and the content was extracted. Disputes were discussed in a meeting with the research team.
3. Results
3.1. The Effect of Prenatal Stress
For the first time, Baker have referred to the fetal origins of adult disease (10). When the fetus in the womb is exposed to unpleasant events, one may expect an increase in disease risk in adulthood (11). One of those unpleasant events is maternal anxiety and stress during pregnancy (12).
Many studies have examined the harmful impact of a mother’s anxiety and stress during pregnancy and its adverse effect on children over the long term (13). It is, to some extent, related to maternal stress hormones like cortisol, which are fundamental to the neural development of the fetus; nevertheless, high exposure to these stress hormones can harm the fetal hypothalamus-pituitary-adrenal axis (HPA) (14). The HPA axis has a ubiquitous influence on vital regulatory systems such as the immune system, microbiome, and autonomic nervous system (15).
Exposure to stress during pregnancy and childbirth through embryonic planning affects animal behavior in three fields: learning disabilities, increased anxiety and depressive behaviors, and increased sensitivity to drug abuse (16).
When exposed to stress, rodent offsprings showed higher sensitivity to a broader range of drugs like amphetamines, methamphetamines, ethanol, morphine, and cocaine (17).
Most studies focus on the relationship between stress during pregnancy and the HPA axis in children with fatal anxiety (18). Epigenetic changes such as DNA methylation influence gene expression and suppression. It can last for generations and even reach generations of grandchildren (19). Also, DNA methylation is found in children whose grandmothers have experienced violence during pregnancy (20).
3.2. The Effect of Microbiota
The microbiota composition of the digestive system in adulthood is shaped in the early years of life. They are sensitive to environmental factors like childbirth, breastfeeding or bottle-feeding, diet, medicine like antibiotics, and exposure to viral, bacterial infections, and stress (21). The relationship between the intestine and brain was first introduced at the beginning of the twentieth century when terms like autointoxication and intestinal toxemia described how toxins derived from the intestine affected mental health (22). Studies have referred to the change of intestinal microbiota in patients suffering from mental illnesses like depression. Clinical evidence implies a change in the diversity of microbiota and its complexity in patients with autism, schizophrenia, and attention deficit disorder, as well as mood disorders including bipolar disorder, anxiety, stress, and depression, and disorders associated with neuroinflammation, including Alzheimer’s and Parkinson’s (23, 24).
Scientific research has shown the mutual effect of the intestinal tract through microbiota and the brain. Some researchers even consider the intestine as the second brain. Moreover, microbiota usage has effectively cured psychiatric disorders (25).
Another study demonstrated that psychosocial stress in pregnancy might adversely influence children through microbiota (26). There was also a relationship between a mother’s stress and anxiety during the pregnancy and a less varied meconium microbiota community with fewer Enterococcaceae in the offspring (27).
Many studies investigated the relationship between intestinal microbiota and CNS through the intestinal-brain axis and have introduced a mechanism by which these microbes affect the host (26). Mostly, drug consumption is accompanied by dysbiosis intestinal microbiota (an imbalance in bacterial colonies of the gastrointestinal system) (28), and these changes may influence the creation and maintenance of addiction by changing the signals between the intestine and the brain (26). In this case, probiotic intervention is introduced as a new type of substance use disorder treatment (29). Recent evidence showed that probiotics significantly cure other mental disorders like anxiety and depression (26).
3.3. The Effect of Substance Use During Pregnancy
Several animal studies have paid enough attention to the danger of increasing the risk of drug abuse in children whose mothers consumed drugs during pregnancy. For instance, being exposed to morphine before birth is accompanied by increased cocaine and heroin in adult rats (30).
Considerable evidence has been found in human beings that can indicate that if a fetus is exposed to drug abuse by its mother, the risk of the child, at last, becoming an addict is high (31). The onset of drug abuse in children is highly related to exposure to a mother’s consumption of nicotine and alcohol during pregnancy (32).
Moreover, several studies have focused on the response of cortisol in children being exposed to drug consumption (33-35). As a neural biological mechanism, chronic stress and dysfunction of the HPA axis have been stimuli to drug consumption and addiction disorders. Pieces of evidence have proved that the malfunction of the parasympathetic nervous system and the basic cortisol level at the age of eleven are all indicators of the period of exposure of fetuses to drug use (36).
Many investigations on animal and human beings identified drug-addicted children exposed to prenatal drug use. Additionally, clinical studies showed that pre-birth drug consumption would predict higher cortisol levels in later life (37).
Overall, numerous studies have presented enough evidence that being exposed to drug consumption before birth is a significant risk factor that would predict changes in the HPA axis and susceptibility to drug abuse in adulthood (38).
3.4. The Effect of Adverse Childhood Experiences
Adverse childhood experiences (ACEs) describe traumatic events that some people suffer during childhood (39). Adverse childhood experiences include physical, emotional, and sexual abuse or neglect. Their life may be filled with parenting problems, domestic violence, parental divorce, and drug and alcohol abuse by a household member (40). Frequent activation of the stress response system during childhood and the lack of interaction with sympathetic adults can strongly influence the regulation of the neuroendocrine system, immune system and metabolism, and social and emotional development, leading to poor health conditions (41).
Results showed that there exists a substantial and concurrent relationship between being exposed to psychological, physical, or sexual abuse as a child and family dysfunction as a child and also the occurrence of high-risk behaviors in adulthood, such as suicide attempts, alcoholism, drug abuse, and multiple sexual partners (42, 43). Studying the relationship between ACEs and illicit drug abuse showed that ACEs would increase the likelihood of drug abuse by two to four times, and those who have experienced more than five ACEs will have five to seven times more likely to the illicit drug abuse (44).
3.5. The Effect of Maternal-Infant Bonding
According to Bowlby’s attachment theory, whenever the child feels in danger, it will seek to be close to its primary caregiver. In an ideal situation, parents will calm children down and give them a sense of safety (47). This feeling of safety or the “basis of safety” will assist the children’s primary attachment experience. They will adjust their feelings and take an essential step toward appropriate strategies in the event of fear or anxiety (48).
Evidence showed that a child’s secure attachment to a mother significantly prevents drug abuse. On the other hand, insecure attachment is a risk factor for substance abuse in later life (49). While many studies have referred to insecure attachment and drug abuse among children, few studies have focused on how children’s attachment to parents affects substance abuse (44). One study noted the mediation role of emotional dysregulation in insecure attachment and addiction. Emotional dysregulation refers to deficits in awareness, perception, and acceptance of emotions and the ability to manage emotional experiences (50). Emotional regulation may occur through adaptive tools such as social support, but it may also happen through maladaptive tools such as engaging in addictive behaviors. One of the theories in the field of addiction considered coping with negative emotions as a motivational factor in drug use initiation, and various studies emphasized this relationship in the way that those who have an unsafe attachment style have less ability to regulate emotions relative to others with secure attachment style (51). Consequently, those with an insecure attachment style use addictive behaviors as a pathologic strategy to regulate emotions and attachment needs (50). MacLean noted that drug abuse replaces a secure attachment style and helps addicts modify self-regulatory responses (52). Addiction can be considered a transition where "emotional bonds" are replaced by "addictive bonds" to self-regulate. Hence, considering addiction as a sign of relationship trauma during the early years of life, drug abuse can be viewed as an attempt to self-regulate, adapt, self-care, and create a feeling similar to secure attachment through drug abuse (53).
Negative self-perceptions failed relationships with others, and distorted worldviews through distorted perception lenses can lead to attachment problems (41). Attachment behaviors resulting from the failed bond and intimacy of the child and caregivers in early childhood (insecure attachment style) may ultimately lead to addiction while representing past traumas as a defense strategy (53). Despite the persistent effects of insecure attachments throughout life, many highlighted that attachment styles are not permanent and can evolve for a lifetime (53). The protective role of the child's caregivers is vital. Furthermore, parent-child attachment appeared to be a significant factor in protecting adolescents from addiction (41). Therefore, it seems that insecure attachments, especially attachment anxiety and emotion dysregulation, are essential psychological characteristics that increase the risk of drug abuse (38).
3.6. The Effect of Maternal Separation
Most mammals spend their childhood in close contact with their mothers. Maternal separation (MS) is a stress factor during childhood, and it is defined as the termination of the continuity of the mother-child relationship once the relationship is established (54).
Experimental studies regarding MS mainly use animal samples, while human samples are retrospectively studied. Evidence implied that rats with MS had the self-administration of morphine, cocaine, ethanol, and amphetamine (55).
Increasing the length of MS has also increased the use of drugs and alcohol in rats (54). Treating rats with selective serotonin reuptake inhibitors decreased drug consumption in rats with a more extended MS (56). Another study showed that MS rats were more prone to alcohol consumption (57). However, those rates with MS but enough handling had less consumption of cocaine (56). It is implied that a baby’s reaction to MS and its level of care is critical and can cause changes in neuroanatomy and neurochemistry (58). MS is mainly caused by changes in a mother’s caring levels and not necessarily her total separation (56). Analyzing the effect of MS on the children’s spiritual, physical, and social aspects, one should be aware that living in a calm environment without the stress and having a kind and compassionate caregiver can alleviate the harmful effect of MS (59). In addition, the consequences of MS were related to age, duration of separation, type of separation, and gender of the child (60). For example, studies have shown that males are more vulnerable to alcohol abuse due to the experience of MS in childhood than females (61). On the other hand, having a mother is not enough, and the fact that the baby is the victim of maternal harassment is also very detrimental (54, 62).
4. Conclusions
In conclusion, this can be inferred that adverse events in the first 1000 days of one’s life can lead to neurobehavioral problems later in life. If this vulnerable period of human development is tainted with unpleasant incidents, it may diminish a person’s resiliency to drug consumption in later life. Thus, while developing social prescriptions to prevent drug abuse in society, we should take these stages seriously. Health policymakers can reduce the potential for drug abuse by designing appropriate interventions during pregnancy and early childhood.
