Reactive Attachment Disorder:

Etiology, Symptoms, Affected Brain Areas and Treatment

Reactive Attachment Disorder (RAD) is characterized by considerably disturbed and inappropriate social interaction, across situations, that is manifested before the age of five (DSM-IV-R). Evidence for the disorder is usually seen in continuous failure to respond appropriately in social situations (being hypervigilant, inhibited, or ambivalent) and/or inability to develop and exhibit selective attachment to primary caregiver(s) (DSM-IV-R). The causes for the disturbed behavior in Reactive Attachment are associated with the developmental stages of Infancy and Early childhood, when pathogenic care can have profound and lasting effects. DSM-IV outlines three aspects of pathogenic care that explain the disturbance in normal development and behavior: persistent disregard for the child’s physical and emotional needs, as well as repeated changes of primary caregiver and/or surroundings. The connection between pathogenic care and disrupted behavior is compelling and reminds of the critical importance of nurture and effective parenting. Many psychologists have studied in depth child development during the first years of life and reveal that this is an extremely sensitive period for both physical and emotional development and maturation. It is a critical time for cultivating attachment, social skills, developing empathy and understanding basic values.

Maltreatment, no matter whether it is abuse, neglect, abandonment, or witnessing violence, can lead to enduring negative changes in the still developing brain of a child. Each time there is some sort of traumatic experience, the brain suffers a particular change. Many of the brain abnormalities that have been studied in abused and neglected children are located in the left hemisphere. Very often, in children, victims of abuse, there were fewer dendritic connections between different areas in the left hemisphere (Gunnar & Vazquez, 2001). Children that had showed such abnormal results demonstrated self-destructive or aggressive behavior, as well as certain disturbances in behavior, thinking and physiology (higher blood pressure, heart rates temperature, hyper vigilance) (Gunnar & Vazquez, 2001). Studies of neglected children found that their cortex was about 20 percent smaller than that of a control group of subjects (children) who have not suffered neglect (Gunnar & Vazquez, 2001). The data is compelling and reveals that providing stable environment of nurture is of utmost importance. About 1% of children who have developed insecure-ambivalent attachment develop RAD (Lehman and Jegtvig, 2004) and without intervention, support and help, many of these children might grow up to develop Antisocial Personality Disorder and live a disruptive life. Eventually, many of these individuals end up in correctional facilities. This compels helping professionals to promote and teach effective parenting and explain the implications of early childhood stress. In addition, the issue has to be considered within the context of adoption and foster care where, very often, children would be moved often and are being exposed to very different/inconsistent treatment and living conditions.

The non-pharmaceutical treatment of RAD appears to be more successful and beneficial than the behavioral medical model (Lehman and Jegtvig, 2004). It utilizes the attachment model as described by Dr. Daniel Hughes in his book “Building the Bonds of Attachment: Awakening Love in Deeply Troubled Children.” The emphasis is on effective parenting - nurturing holding, eye-contact, providing opportunities for enjoyment, encouragement, unconditional love and being a model for self-regulation abilities (Daniel Hughes). Parents and caregivers are to love, nurture, accept and respect the child, so that he/she can grow healthy and happy. Also, professionals in the helping field need to unite their efforts in attempt to educate people and advocate affective parenting and children’s well-being.

Prozak (fluoxetine) is among the Selective Serotonin Reuptake Inhibitors (SSRIs), aka. second-generation antidepressants. As all SSRIs, Prozak blocks the reuptake transporter for serotonin, preventing it from being taken back to the axon terminal. Since this transporter is blocked, serotonin remains in the synaptic cleft for long periods, continuing to have its effect on the postsynaptic neuron. Although this effect takes place very quickly, depression symptoms take long periods to be alleviated. This phenomenon is not fully understood, but it’s interesting to note that Prozak increases the production of new neurons in the hippocampus – a limbic structure that is very vulnerable to stress-induced damage. Therefore, it is suspected that this renewal in the hippocampus is exactly the reason behind this antidepressant’s effect.

The danger is found in drugs’ effect on GABA receptors.

Drugs like alcohol, barbiturates, and benzodiazepines all seems to affect the same target – the major inhibitory neurotransmitter GABA. Neurons containing GABA receptors are very common in the nervous system and their function is to inhibit other neurons. One such receptor that is affected by GABA is the GABAa receptor that contains chloride channels. When the receptor is excited, an influx of Cl ions takes place, increasing the negative charge on the inside – hyperpolarization – making initiation, or propagation of an action potential much more difficult. However, this GABAa receptor has not only a binding site for GABA, but two other binding sites as well. One is the sedative-hypnotic site, the other is the anxiety site. That’s why it is possible that both sedative-hypnotic drugs (alcohol and barbiturates) and antianxiety drugs (benzodiazepines) can bind to the same receptor, amplifying their effects. Sedative-hypnotic drugs (alcohol or barbiturates) have precisely this effect -making it hard for action potential to take place and, therefore, sedating the body and affecting bodily functions. Antianxiety drugs (benzodiazepines) enhance binding effects of GABA and so alcohol, or barbiturates will have an even stronger sedative effect, possibly leading to coma, or even death.

The threat of mixing drugs and alcohol is not just a myth, it is a deadly cocktail that you don’t want to be experimenting with.

Position Emission Tomography (PET) and Functional Magnetic Resonance Imaging (fMRI) have allowed us to distinguish sexually dimorphic areas in the human brain. This can possibly explain certain differences in traits and behavioral tendencies between men and women.

· The temporal lobe of the brain is quite different for males and females. In general, among females, there is greater density of the neurons in that area (associated with language development and processing).

· The corpus collosum is larger in female brains. This brain structure facilitates the communication between the hemispheres of the brain. (This may be considered supportive argument for the idea that females easily blend emotions and logic. Many will argue this is advantage, while others consider it a weakness.)

· The overall size of the cerebral cortex, however, is larger in males. It has more neurons and is, somewhat, more complex. In fact, both female and male babies have the same number/amount of neurons, but the process of programmed cell death (apoptosis) continues longer in females. The bigger size of the cerebral cortex in males is only natural, considering males are generally bigger, compared to females. Within the animal kingdom, larger brain size infers more complex cognitive functioning and behavior. Within the same species, however, this general law does not apply. Bigger brain by no means implies being more intelligent.

· There is a sexually dimorphic nucleus in the anterior hypothalamus that is larger (more neurons) and denser in males. This area is believed to contribute to the control of sexual behavior, but the correlation is not quite well explained yet. The  female hypothalamus has developed to generate menstrual cycle, which, itself, helps explain many of the differences between males and females.

Symptoms of Major Depression

Feelings of helplessness and hopelessness; sadness; loss of interest and pleasure (from food and/ or sex) – anhedonia; may be accompanied by significant weight loss or gain (sometimes hyperphagia); insomnia or hypersomnia (middle of the night awakening, early morning awakening); fatigue, general loss of energy; having hard time concentrating. People with depressive symptoms are indecisive, have low self-esteem; pessimism; disturbance of body rhythms; suicidal tendencies are common.

Evidence for genetic predisposition for Depression

Although the impact of genes varies, depending on the type of depression, there is a correlation. Depression tends to run in families. That is why adopted children, resembling their real parents’ genes may have depression in spite of living in a cheerful, lively atmosphere. One is at risk of depression if one has close relatives who have had severe early-onset depression, especially if that relative is a female. However, no single gene has been identified to have a strong link with that mood disorder. So, obviously, depression depends on a combination of genes and environmental factors.

Are males or females more vulnerable to depression? What is the role of hormones?

Depression is much more common in women, in all cultures. For sure, hormonal changes can trigger an episode of depression, but this correlation does not necessarily imply causation, as some women are more vulnerable than others. Still, the reason why women suffer depression more often is not clearly identified.

What is the role of traumatic experiences for episodes of depression?

Stress is a typical trigger for an episode of depression, as it causes the release of cortisol that prepares the body for action and, in the long run, exhausts the body. A lot of women experience postpartum depression, after giving birth and some of them enter a more serious, long lasting depressed condition. However, giving birth itself does not cause depression as many of the women have already suffered previous onsets. Thus, traumatic experiences may trigger an episode of major depression, but do not cause the disorder.

What are the patterns of hemispheric dominance with happy moods in normal people? How do they differ from patterns in depressed people?

Happy mood is generally related with increased activity in the left prefrontal cortex. Depressed people, however, have decreased activity in that area, whereas it is increased in the right prefrontal cortex. Also, many people who have had damage to the left hemisphere become seriously depressed. Fewer become depressed after damage to the right hemisphere. And sometimes, people with right hemisphere damage become manic.

What is Borna disease? What evidence links it to depression?

Borna disease was first noticed in European farm animals. It affects behavior, causing frantic activity or inactivity. In severe cases, the disease can be fatal. As many other viruses, Borna disease can be passed between humans and other species. However, the effect is different in humans. In an experiment/ survey, in all 12 cases of people with Borna disease, those same people had either major depression or bipolar disorder.

What are 3 groups of antidepressants? How does each of them exerts its effects?

Tricyclics prevent the presynaptic neuron from reabsorbing catecholamines or serotonin after they have been released. Thus, the neurotransmitters remain in the synaptic cleft longer, continuing to stimulate the postsynaptic cell. They inhibit the reuptake of NE and dopamine. However, tricyclic also block certain receptor which may lead to side effect.

Selective serotonin reuptake inhibitor (SSRIs) block the reuptake of serotonin by the presynaptic terminal (in a way, those are similar to tricyclics). SSRIs have little and only mild side effects. Still, sometimes, they may cause nervousness and, thus, are not recommended for people suffering anxiety.

Monoamine oxidase inhibitors (MAOIs) block the enzyme monoamine oxidase, which has the function to metabolize catacholamines and serotonin into an inactive form. O, when this enzyme I blocked, the amount of those neurotransmitters in the presynaptic terminal and the cleft increases. However, MAOIs tend to affect blood pressure, which can be very dangerous and, in general, are very dangerous in the long run, although they tend to work within a few days.

Why does Prozac/ fluoxetine preferred over tricyclics and the monoamine oxidase inhibitors?

It almost no side effects (sometimes mild nausea, headache, or nervousness, very rarely people react with having Serotonin fever). Also, there is almost no risk of over dosage. In addition, it takes only within 2 – 4 weeks to work and, in the short term, causes loss of weight, which is, generally desired by people.

What are atypical antidepressants? For whom are they used?

This is a miscallaneous group of drugs that have the antidepressant effect, but very little side effects. They are being prescribed to people who did not respond to the other drugs. Some atypical antidepressants are bupropion (inhibiting the reuptake of DA and sometime NE, but not 5HT), venlafaxin (mostly inhibit the reuptake of serotonin, and lightly of DA and NE).

How effective is St. John’s wort? Which class of antidepressants produces similar effect? What is one potential problem?

St. John’ wort is an herb that works like the selective serotonin reuptake inhibitors. However, it efficacy I not yet accurately determined, a different studies how different results (some suggest it is more effective that SSRIs, some claim it is equal to them, others that it is not effective at all). One potential dangerous side effect is that St. John’s wort increases the production of the liver enzyme that breaks don toxins, also medicines. Thus, it decreases the effectiveness of many medicines that may be vital. Another problem is, that it is cheaper that drugs and can be taken without prescription, which hides risk of inappropriate use and dosage.

Explain the problem of time course effects on neurotransmitters and depressive symptoms. What are some delayed effects of antidepressants?

Antidepressant drugs, in general, have delayed effects that limit the excitation of the postsynaptic cell, decreasing the sensitivity or the receptors on the postsynaptic cell. They also affect autoreceptors (the negative feedback receptors on the presynaptic terminals). Also, Prozac, for example, causes gain of weight hen used for a long time.

What neurotrophin is produced as a result of repeated use of antidepressants? In which brain areas is it produced?

Brain-derived neurotrophic factor is produced that aid the growth, survival and connections between the neurons. The cerebral cortex and the hippocampus.

How is electroconvulsive therapy (ECT) applied today? How is this an improvement over practices in the 1950s?

In the 1950, ECT was widely used without patients’ consent, being tried on many people in mental hospitals. Today, however, ECT is used only with informed consent for patients who do not respond to other antidepressant drugs. During ECT, the patient is under general anesthesia, with muscles being blocked. Thus, the process is not painful and the risk of injury is minimized. A common side effect is that the patient has a loss of memory for that particular time hen ECT has taken place.

For which two groups of patient is ECT most often used?

ECT is used with people ho do not respond to other antidepressant drugs and with people ho have severe depression and suicidal tendencies, who need fast results and betterments (may be the difference between life and death).

What are the advantages and disadvantages of ECT?

Advantage is that it is the most effective treatment available nowadays and gives very fast results. Some disadvantages are that it may cause prolonged convulsion that can be fatal. Also, ECT should be applied over long periods of time and, as people lose memory of that time, it may, eventually, cause amnesia. Often, the case is that, after ECT treatment, patients enter another episode of depression within 6 months.

What are the effects of ECT on neurotransmitter receptors? What newer treatment is similar to ECT?

ECT stimulates the production of additional dopamine (types D1 and D2 receptors) and decreases the number of norepinephrine receptors.

How does the onset of REM sleep differ in depressed people, compared in non-depressed? How may this be related to body temperature cycles?

People with mood disorders also suffer some disorder of the biological rhythms. Depressed people have troubles sleeping and people who have sleep problems are more likely to get depressed, so it is a two way street. After going to sleep, most non-depressed people enter REM sleep after about 80-90 minutes and the amount of REM sleep is increased in the second half of the night. Depressed people, however, enter REM phase of sleep after about 45 minutes after going to bed. Also, the have trouble staying asleep and feel drowsy the next day.

What change in sleeping schedules has been found to alleviate depression? How long do the benefits last?

Surprisingly, sleep deprivation improves the condition of depressed people, relieving the symptoms of the disorder. Yet, this is not a solution as sleep deprivation is dangerous in the long run. Both antidepressant drugs and sleep deprivation decrease the amount of REM sleep. So, there is something about that stage of sleep that may be a hidden cure for depression, but researchers are not certain yet.

Many studies have focused on investigating the physiological characteristics and the neurobiology of borderline patients in attempt to relate these symptoms with the purely psychological characteristics.

A study with 30 young women with Borderline personality disorder that used structural magnetic resonance imaging (3D-MRI) showed that the borderline patients had significantly smaller hippocampus (-17%) and a smaller right parietal cortex (-11%) than the control group. This significantly leftward asymmetry in borderline patients was associated with stronger psychotic symptoms and some signs of schizoid personality traits while the smaller hippocampal size was related to trauma-related clinical symptoms and neuropsychological deficits (Irlea E, 2005).

Another study of 21 female borderline patients and a similar group of healthy control subjects took magnetic resonance imaging volumetric measurements of subjects’ hippocampus, amygdala, temporal lobes and prosencephalon. The results showed that patients with BPD had approximately 16% smaller hippocampus and about 8% smaller volumes of the amygdala (Driessen M, 2000).

Studies show that suicide victims, that are often borderline personality patients, have certain neurobiological abnormalities and hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA-axis) (Lopez JF, 1997). Also, it has been discussed that severe anxiety associated with elevated corticotrophin-releasing factor is related to suicidal tendencies and depression (Fawcett J, 1997) that are traits of Borderline personality disorder.

The effect of child abuse on the brain and the impact of stress hormones on emotional and cognitive development

Maltreatment, no matter whether it is abuse, neglect, abandonment or witnessing violent acts, can lead to enduring negative changes in the still developing brain of a child. Each time there is some sort of trauma, the brain suffers a particular change. So far, research have noted changes in the prefrontal cortex, the cerebellum and the limbic system (Wheeler T, 2006) It is important to point out that infancy and early childhood are times for rapid brain development and formation of dendritic connections. Of course, they continue to develop throughout adolescence an early adulthood, but are even more vulnerable earlier in life (Kalat J, 2003).

The prefrontal cortex is the most anterior part of the frontal lobe of the brain that is involved in critical thinking and judgment as well as any behavior that, in one way or another, depends on the context. Therefore, people with damaged prefrontal cortex often cannot modify their behavior and become inflexible in changing situations, which can make their reactions and behavior too impulsive and socially unacceptable (Kalat J, 2003). Damage to the prefrontal cortex can eventually result in many deficits such as not being able to regulate motivation and efforts as well as impaired short-term and long-term goal-directed behavior. In addition, damage and disruption of prefrontal cortex functions due to any type of abuse may lead to not being able to integrate positive emotions. Thus, the person is stuck in a negative stance of fear and anger, and cannot engage in experiencing positive emotions. Needless to say, this may lead to developing depression, antisocial or borderline personality disorders (Wheeler T, 2006).

The cerebellum is a large structure in the hindbrain that is mainly known for controlling movement, achieving balance and coordination (Kalat J, 2003). However, it also plays a role in attention and emotions, as well as in regulating the limbic system (Wheeler T, 2006). It is important to note that many people with psychiatric disturbances have certain abnormalities in the cerebellum (Wheeler T, 2006). This is probably so, because in cases of childhood abuse the cerebellum is extremely vulnerable to the stress hormones that are present in large amounts during stress, trauma or abuse. The changes that occur then can result in depression or hyperactivity, and inattention. Also, the cerebellum is considered to play a role in suppressing irritability. Therefore, abnormalities or damage to the cerebellum may cause chronic irritability and make the person seek external means, such as drugs, to deal with that (Wheeler T, 2006).

The limbic system is the forebrain area next to the brainstem that includes a number of interdependent structures under the cerebral cortex that deal with motivation and is critical for regulating emotions, sexual activity, eating, drinking, anxiety, and aggression (Kalat J, 2003). The hippocampus and the amygdala are essential parts of the limbic system, and are crucially important for controlling the emotional response to a particular situation. They also take part in memory formation and learning (Wheeler T, 2006). Prolonged and continuous exposure to stress hormones can cause serious damage to these parts of the limbic system and, thus, disrupt mood regulation, memory, and one’s way of interpreting the environment. Besides, damage to the limbic system can lead to epileptic seizures and abnormal EEGs that usually affect the temporal lobe of the left hemisphere. Usually, damage to the left hemisphere is associated with poor verbal development, but, more importantly, with aggression, self-destructive behavior and suicide (Wheeler T, 2006).

What is stress? Many things can be considered stressful for an individual, including insufficient nutrition, lack of rest, overstimulation, especially of the fear-related response system, not to mention abuse, neglect or witnessing violence or death (Gunnar & Vazquez, 2001). The prolonged exposure to stress and, therefore, the produced stress hormones in the body, can be very serious and especially harmful to the infants and young children (Gunnar & Vazquez, 2001). In fact, exposure to stress activates two body systems: the autonomic nervous system that prepares the body to react quickly to whatever stimuli in the environment; and the HPA-axis – the hypothalamus, pituitary and adrenal cortex.

The HPA-axis reacts more slowly, but is critically important in prolonged exposure to stressors (Kalat J, 2003). The activation of the hypothalamus stimulates the ‘master gland’ (the pituitary gland) to secrete adrenocorticotropic hormone (ACTH) that, in turn, stimulates the secretion of cortisol. Cortisol is generally regarded as ‘The’ stress hormone. It helps the body mobilize energy and respond to stress quickly, but has negative effects in the long run, since it enhances metabolism and elevates blood sugar levels (Kalat J, 2003). Other stress-related hormones are corticosteroids, corticotrophin release hormone (CRH), epinephrine, norepinephrine and others (Gunnar & Vazquez, 2001). Serotonin is also very important for the adequate coping with stress. Therefore, abnormal function of serotonin is associated with some depression and anxiety-related disorder, such as BPD.

Research has proven that elevated stress hormone levels can cause malfunctions in the amygdala and hippocampus (Gunnar & Vazquez, 2001). Severe or merely constant exposure to stress may lead to the shriveling of certain dendrites in the hippocampus, which can cause its degeneration and malfunction (memory loss and inability to control the release of other stress hormones) (Gunnar & Vazquez, 2001). As a matter of fact, shrunken hippocampus was found in autopsies of children who have experienced repeated abuse or in people who were suffering posttraumatic stress disorder. In addition, disruption of the HPA-axis that is also related to exposure to stress in early age is associated with depression, inattention, and poor memory (Gunnar & Vazquez, 2001). The hippocampus is a particularly vulnerable brain structure, especially during infancy and childhood, when it is still developing (Gunnar & Vazquez, 2001).

If too many stress hormones are being produced in the early stages of development, the developing brain may be permanently damaged, becoming incapable of initiating a normal stress response. It may either overproduce stress hormones, so that the person becomes hyper-vigilant, fearful and always on the alert, or it may underproduce stress hormones so that the person becomes “emotionally flat”, sad and angry (Berger, 2005). A study of Cicchetti & Rogosch (2001) identified a lot of “atypical cortisol regulation patterns” that are obvious among children that have been maltreated (Gunnar & Vazquez, 2001). Studies like this are evidence for the correlation between child maltreatment and the disrupted function of certain brain structures that cause inflexibility in behavior, such as depression, chronic stress, anxiety, aggression and many others that can often be associated with a number of illnesses and disorders, Borderline Personality Disorder among them.

Many of the brain abnormalities that have been studied in abused and neglected children are located in the left hemisphere. Very often, in children, victims of abuse, there were fewer dendritic connections between different areas in the left hemisphere (Gunnar & Vazquez, 2001). Children that had showed such abnormal results demonstrated self-destructive or aggressive behavior, as well as certain disturbances in behavior, thinking and physiology (higher blood pressure, heart rates temperature, hypervigilance) (Gunnar & Vazquez, 2001). Since these could all be characteristics of a borderline personality patient, the results give food for thought as to the relation between abuse in childhood and the development of the disorder.

Studies of neglected children found that their cortex was about 20 percent smaller than that of a control group of subjects (children) who have not suffered neglect (Gunnar & Vazquez, 2001).