Biology of Mental Disorders
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Biology of Mental Disorders

Updated: Nov 8, 2021




The brain is the most complex organ in the human body and is responsible for hearing, seeing, learning, memory, and thinking, as well as many other bodily functions (Urbas, 2019). It is part of the human body’s nervous system and consists of many services and processes that create an elaborate network for electrical and chemical signals to flow through (Episode 2: Diagnosis and Chemistry, 1999). These chemicals and brain functions control many processes like emotions, pain perception, sleep, appetite, fear, memory, energy, alertness, and concentration (Chara, 2019). An imbalance or physical deformity in the brain can cause an array of health problems, including many mental disorders.


The surgeon general reports that some form of mental illness touches almost every American family, and statistically, one in five adults are diagnosed with a mental disorder in their lifetime (NIH, 2007). The causes of mental illness are a popular, yet tenuous, field of research for scientists today and have been for centuries. While a variety of foundations have been established through the sociological and psychological perspectives, most, if not all, disorders, have some element of biology. In fact, psychological and sociological causes usually act as triggers for the underlying biological roots already established in that person.



Anxiety Disorders

Anxiety, the body’s natural response to stress, is a reasonable and realistic feeling for every person to experience. Occasional fear or worry is part of life, but when these symptoms become persistent, chronic, intense, or excessive, a disorder may exist. Physical symptoms might include increased heart rate, muscle tension, fidgeting, and trembling (Barlow & Durand, 2018). The negative mood state created by anxiety is a result of fearing a future threat and feeling a sense of apprehension, which initiates an escapist reaction and physiological rush in the sympathetic nervous system (Barlow & Durand, 2018). The six main types of disorders related to anxiety are generalized anxiety disorder, panic disorder, phobia-related disorders, trauma disorders, and obsessive-compulsive disorder (NIMH, 2018).


Generalized Anxiety Disorder (GAD)

GAD is characterized as chronic, excessive, and uncontrollable worry that causes distress and constant restlessness (Goossen, van der Starre, & van der Heiden, 2019). GAD affects 4-6% of the general population and is more prevalent in older adults, even more so than depression (Wu et al., 2019). Diagnosis is based on symptoms existing for at least six months, where patients worry about lifestyle issues such as health, social life, occupation, school, and every-day tasks of life (NIMH, 2018). It is ubiquitous for patients with GAD to also possess another separate condition, such as chronic pain, sleep disorders, and depression (Goossen, van der Starre, & van der Heiden, 2019). To explore the neurobiological implications specific to GAD, doctors study MRI results obtained during various psychological tests aimed at GAD analysis. Findings showed that GAD patients were prone to early amygdala disengagement during stress (Goossen, van der Starre, & van der Heiden, 2019). It is also suggested that GAD is a consequence of an underactive prefrontal cortex (PFC) which is used in emotion regulation; this is important because reappraisal, the emotional and mental process of “getting over” bad and stressful things in life, is controlled by the PFC and is an element of concern with GAD patients (Goossen, van der Starre, & van der Heiden, 2019).


Panic Disorders

Panic disorders bring on sudden, unexpected panic attacks (PAs) in those that suffer from it, causing constant worry of having another attack, which in turn can cause additional phobias (NIMH, 2018). During attacks, a person experiences acute, intense fear or discomfort that many times, is accompanied by physical symptoms of shortness of breath, heart palpitations, chest pain, and dizziness (Barlow & Durand, 2018). PAs are categorized into two classes, expected and unexpected. Expected PAs are cued by situations or phobias that are known to cause fear in that person, such as being afraid of heights or enclosed spaces. Unexpected attacks are spontaneous and unplanned and can be an indication of a more serious psychological disorder (Barlow & Durand, 2018).

Panic disorders are usually prescribed by medication that is similar to what is naturally released in the brain during long-term exercise (Machado, 2019). Noradrenaline and monoamine, essential neurotransmitters in the brain that help emotional and physical regulation during panic, are expressed during exercise. These chemicals are now being used to control panic attacks.


Phobia Disorders

Fear is induced when a person feels a potential risk of safety for themselves or others. A phobia-related disease occurs when a person exhibits an intense, unrealistic fear of something. Many phobias exist, but the most common are specific phobias or fears of specific things like social interaction, public places, separation, flying, heights, particular animals or insects, blood, and needles (NIMH, 2018). These very specific fears can be a result of a disrupted complex web of circuits and neurological functions. The biology of phobias centers on what is called “fear circuits,” specific defensive responses in the brain (amygdala) that result from a flight or fight response (Garcia, 2017). Researchers suggest that these fear circuits can only be exposed to so many stimuli, and when they are overactivated regularly, specific phobias are created (Garcia, 2017). For example, a child who is a victim of a dog attack at a young age may continue to experience stress, worry, and fear every time they see a dog, causing overactivation of this specific fear circuit, creating, over time, a specific phobia to dogs.

Another prevalent phobia-related disorder is social-phobia disorder, also known as social anxiety disorder. ****Social anxiety disorder involves having an intense fear of social situations, interactions, and performance (NIMH, 2018). These powerful feelings are associated with fear and worry of embarrassment around or in front of others (NIMH, 2018). To explore the biological causes of social anxiety, researchers have based much of their research on rodent experimentation, specifically the metabotropic glutamate receptor (mGluR) (Zoicas & Kornhuber, 2019). MGluRs exist synaptically, regulating the release of the brain’s neurotransmitters. Studies intimate that mGluRs benefit abnormal social behavior, particularly social memory deficit, impaired social interaction, and intensified hostility (Zoicas & Kornhuber, 2019).


Post-Traumatic Stress Disorder

One of the newer categories in anxiety disorders established by the DSM-5 is the trauma-induced anxiety category, typically associated with post-traumatic stress disorder (PTSD). PTSD is a common anxiety disorder where a person has experienced, either first-hand or witnessed, a traumatic event that has caused recurring fear and anxiety that results in an extreme emotional reaction (Sherin & Nemeroff, 2011). PTSD activates a similar response in the brain to phobia-related fear circuits. Likewise, an experience that occurs due to a traumatic event can repetitively affect the amygdala, causing an oversensitivity (Sherin & Nemeroff, 2011). Other than the overactive traumatic stimuli sensitizing individual sections of the brain, there are a few other biological components to PTSD. First, the psychological shock that induces PTSD is a result of dysregulation of stress-controlling processes in the brain. Second, it is found that some people have a genetic predisposition to PTSD, and finally, some interesting research studies have shown that if the cortisol levels are low at the time of trauma, then PTSD is more likely to instill as a result (Sherin & Nemeroff, 2011).


Obsessive-Compulsive Disorder (OCD)

Biological and genetic causes have led the forefront in the understanding and treating of OCD (Kelly, 2019). OCD works off neural circuits in the brain that transfer information from one side to the other and impact most regions of the brain first-hand; these are the same circuits that regulate sexuality, aggression, and bodily excretions (Kelly, 2019). When these circuits are activated, the body reacts through impulse. For example, a reasonable person understands that after they wash their hands, they are clean, and they can go about their typical day. A person with OCD is unable to realize that their hands were clean after being washed and so the impulse to wash their hands continues throughout their day. People with OCD have an overactive circuit that continues to reactivate in the brain, causing their OCD behavior.

Additionally, patients with OCD have shown beneficial reactions to drugs containing serotonin; this suggests that OCD is associated with serotonin dysregulation as well (Kelly, 2019). Finally, researchers have developed a theory that OCD has a significant genetic component, finding that people who have a close family member with OCD are 25% more likely to develop OCD themselves. Even more so, twin studies conducted on the subject have shown that genetics contribute 45-60% in getting OCD (Kelly, 2019).



Mood Disorders

Historical evidence of mood disorders dates back to ancient times, being referenced in the Bible and written about by ancient philosophers (Nelson, 2019). They are characterized as any disturbance in mood and grouped into two main categories, depression and bipolar disorders (Nelson, 2019). Everyone experiences some degree of depression in their lives and mood swings now and then, but the clinical diagnosis of a mood disorder occurs when a person exhibits signs of major depression, manic episodes, or hypomanic episodes (Nelson, 2019).


Depression

For major depression, a person must experience at least four of the following symptoms for more than two weeks: changes in weight, appetite, sleep, or energy level, feelings of worthlessness or guilt, problems concentrating, and thoughts of suicide (Nelson, 2019). Many times, symptoms affect a person’s occupation and personal life. The cause of depression is somewhat of a mystery, but scientists have found great weight in the biological implications. A recent study at Cornell University examined the biologically-determined sex differences found in the chromosomal matter and compared these differences to the levels of depression in its subjects (Altemus, Sarvaiya, & Epperson, 2014). While they did find vital genetic factors that affect the way the sexes acquire and handle mood, they found that these factors were highly influenced by age, specifically during adolescence and menopause in women (Altemus, Sarvaiya, & Epperson, 2014).


Recently, micro-RNA (miRNA) studies have given promising results in considering the biological causes of depression. miRNA is a genetic component that encourages neuroplasticity and neurodevelopment, and doctors have found it to be directly and indirectly related to depression (Gruzdev, Yakovlev, Druzhkova, Guekht, & Gulyaeva, 2019). Interestingly, those same miRNAs are associated with bipolar disorder as well.


Bipolar Disorder

The second type of mood disorder is bipolar disorder (BD). The American Psychiatry Association’s Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) divides BD into three groups, bipolar I, bipolar II, and cyclothymic disorder. Bipolar I is characterized by one or more manic episodes as well as one or more depressive episodes; bipolar II is characterized by one or more depressive episodes and one or more hypomanic episodes and cyclothymic disorders are defined as chronic, fluctuating, periods of depressive and hypomanic episodes (Nelson, 2019). BD is treated with psychotherapy and medications called mood stabilizers.

Biological causes of BD are rooted in neurotransmitter dysfunction, hormonal imbalance, and triggering of environmental factors. Just like many mental disorders, BP is associated explicitly with amine neurotransmitter dysfunction, as well as dopamine and serotonin deficiencies (Manji et al. 2003). Also, many illnesses, like Wolfram disease, Darier’s disease, and Mendelian disease, can cause neurological effects that influence bipolar disorder (Kato, 2019). These diseases disrupt mitochondrial makeup, stress responses, and serotonin and dopamine levels, which regulate healthy psychological function (Kato, 2019).



Sleep Disorders

Sleep is an essential function of the body and allows for the restoration of many bodily functions. Insomnia, restless leg syndrome, sleep apnea, and narcolepsy are the most common sleep disorders (Mayo Clinic, 2019). The body relies on the circadian rhythm, which is regulated by the amount of adequate sleep a person gets every night. Also, the sleep-wake cycle is closely connected to the melatonin hormone in the brain, the body’s temperature, blood pressure, immunities, and internal order (Zisapel, 2007). Insomnia exists when a person has trouble falling asleep or staying asleep. The biological causes of insomnia manifest in several other pathological health problems such as chronic pain, breathing problems, heart problems, dementia, depression, and anxiety (Zisapel, 2007). In addition to these causes, multiple types of medications, as well as alcohol, drugs, and caffeine, can biologically influence insomnia.

Sleep apnea affects 6 million U.S. adults and can cause serious health concerns like heart attack and death. Reduced breathing abilities characterize it during sleep caused by compromised airways, irregular muscle movement, and dysfunctional motor muscle neurons (Dempsey, Veasey, Morgan, & O'Donnell, 2010). These neurotransmitters and neuromodulators directly affect the upper airway motor nuclei of the pharyngeal, and advancements in pharmacology have adopted this theory in upper airway dilators as a treatment for sleep apnea (Dempsey, Veasey, Morgan, & O'Donnell, 2010).



Eating Disorders

Eating disorders are mental disorders and affect a large portion of the population. They are usually diagnosed into three main categories: anorexia nervosa, bulimia nervosa, and binge eating disorder, all having the ability to cause medical, social, and cognitive problems, and affecting approximately 13% of all adolescents (Culbert, Racine, & Klump, 2015). Recent studies show that eating disorders run in families and that genes influence the risk by 56%; so much so, that if a close relative, like a sister or mother, has an eating disorder, then the risk of acquiring anorexia increases by twelve times and bulimia four times (Engel & Patricelli, n.d.).


Neurotransmitters are also involved in eating disorders. Neurotransmitters control many different bodily functions, including mood, appetite, energy, etc. Binging behavior, specifically the binging associated with bulimia, has been linked to serotonin. Researchers at the University of Pittsburgh found that patients with bulimia had low serotonin levels but normal dopamine and norepinephrine levels (Engel & Patricelli, n.d.). Accordingly, bulimia has been successfully treated with serotonin-boosting anti-depressant medications (Engel & Patricelli, n.d.).


Binge eating, which affects 5% of U.S. adults and is often associated with numerous other medical problems like obesity, diabetes, and depression, has its own particular biological foundation. Binge eating is characterized by excessive and unnecessary food consumption that associated with a variety of emotional problems like feeling a loss of control or psychological distress (Mathes, Brownley, Mo, & Bulik, 2009). Scientists claim that the neurobiology behind binge eating is very similar to the neurobiology of substance abuse. The area of the brain that controls learning and memory also regulates the body’s reaction to food and drugs (Mathes, Brownley, Mo, & Bulik, 2009). Food creates a dopamine reaction, and people who are depressed or stressed tend to create repeated stimulation in these reward centers in the brain through binge eating (Mathes, Brownley, Mo, & Bulik, 2009).



Substance Use Disorders

Addiction is defined as the inability to stop consuming a substance or chemical. Substance use disorders, characterized by the DMS-5, are addictions to one or more of these ten substances: alcohol, tobacco, caffeine, marijuana, hallucinogens, inhalants, opioids, sedatives, hypnotics, and stimulants (Ranes, 2016). Many people believe addiction to be an issue of character, not biology. However, substance use disorder is considered a mental health issue and is biologically quite difficult for the brain to overcome (NIH, 2015).

Initially, genetics play a significant role in the risk of getting a substance use disorder, accounting for 50% of the likelihood of getting the disease. The biological makeup of the brain also contributes to the act of substance abuse, such as changes to the cerebral cortex. Substance use and addiction disorders are biologically similar to eating disorders as well. The same neurotransmitters that react to food Addictive agents cause a dopamine rush in the brain, which creates a dependency (Ranes, 2016). Specific dopamine receptors in the striatum region of the brain are responsible for a person’s motivation to overcome obstacles such as addiction. Those who find it more difficult to overcome addictions have lower levels of this specific dopamine, while those with higher levels find it easier to conquer addiction through behavioral changes (Ranes, 2016).



Personality Disorders

Personality disorders (PDs) are a class of mental disorders that restrict the patient’s patterns of thought, feelings, and behaviors (Marsh, 2016). PDs are a result of genetic traits or temperaments passed down by relatives, which make a person more vulnerable to getting a PD (Mayo Clinic, n.d.). Genes account for about half of a person’s personality variance, including PDs, but no specific allele has been associated, yet it is observed that a biologically, weak, or vulnerable temperament may influence the development of PD (Paris, 2015). Even though PDs have a neurobiological component, research does not associate PDs with chemical imbalances (Paris, 2015). Alternatively, studies show a connection between PD and impulse control, emotion regulation, and decreased activity in the prefrontal cortex (Paris, 2015). These findings have been very apparent in suicide or attempted suicide patients (Paris, 2015). Even though prescription drugs are currently a popular method of biological treatment by doctors, some researchers believe that the natural pathogenesis of PD is too unknown to allow medications for treatment, as no specific chemical or neurotransmitter imbalance is seen or wholly understood; and consequently, antidepressants, mood stabilizers, and antipsychotics have not proven to be successful in treating PD (Paris, 2015). There are approximately ten PDs: cluster A consists of paranoid, schizoid, and schizotypal; Cluster B is antisocial, borderline, histrionic, and narcissistic; and cluster C is avoidant/anxious, dependent, and obsessive-compulsive (Marsh, 2016; Kour, Wani, & Dar, 2019).


Cluster A Disorders

Paranoid PD (PPD) is an unusually high disability in the U.S. and is linked to depression, violence, aggression, stalking, and suicide (Lee, 2017). Scientists have found that PPD patients exhibit physiological hypervigilance to the environment around them. This is represented neurobiologically by elevated neuropeptide hormone levels. In one particular study, all PPD patients had high hormone levels while borderline PD had normal levels (Lee, 2017).

Schizoid PD (SPD) has been neurologically associated through CT and MRI with reduced gray matter, brain asymmetry, and other abnormalities of shape and size. Other scientists debate that SPD is caused by differing nuclei within the thalamus, the region of the brain that relays sensory and motor signals (Dickey, 2002)

Schizotypal PD (StPD) also has a specific biological marker. StPD patients have decreased plasma activity as well as impaired smooth pursuit eye movement (the eye’s natural ability to follow a moving object) (Siever, 1985). Many of the biological markers that arise for StPD are synonymous with schizophrenia and have promoted psychiatrists to examine this relationship further.


Cluster B Disorders

Recent neuroimaging studies have focused explicitly on borderline PD (BPD), finding that those with BPD have significantly smaller regions of the brain like the hippocampus and amygdala (Pier, Marin, Wilsnack, & Goodman, 2016). Also observed through MRI, is that patients with BPD experience intensified brain reactions and heightened activation during negative stimuli (Pier, Marin, Wilsnack, & Goodman, 2016).

The cognitive neuroscience behind narcissism is quite unique as well. Narcissistic PD (NPD) exists when a person possesses an exaggerated feeling of self-importance, self-admiration, and a lack of acknowledgment of the importance of others (George & Short, 2018). Most research has been on the cognitive level, but biological testing shows that people with NPD have issues with the insular cortex of the brain, which controls the feeling of empathy (George & Short, 2018).


Cluster C Disorders

Avoidant PD (APD) is typical and affects everyone equally, plaguing the person who has it with a constant feeling of anxiety and fear. People with this disorder have low self-esteem, are prone to a sense of rejection, and typically avoids social and other interpersonal interactions. (Cleveland Clinic, 2017a). Genetics, in combination with environmental factors, are to blame for the manifestation of APD.

Dependency PD (DPD), another cluster C disorder, describes a person who experiences an intense need to be with other people, not be alone, or continually needing reassurance from others (Cleveland Clinic, 2017b). The biological causes of this illness are linked to people who have chronic diseases or separation anxiety during childhood (Cleveland Clinic, 2017b).

Obsessive-compulsive PD (OCPD), not to be confused with OCD, is said to be highly heritable and follow a slow life history strategy, which is the opposite projection of psychopathy (Hertler, 2016). It biologically and physiologically slowly evolves over time.


Schizophrenia

While schizophrenia (SCZ) is not a super common illness, it is severe, producing disabling symptoms that commonly cause the patient to lose their sense of reality (Tandon & Jibson, 2002). It can affect every aspect of their life negatively. The symptoms of SCZ are grouped into two categories: positive symptoms which include hallucinations, delusions, uncontrollable physical movements; and negative traits which include apathy, lack of speech or thought, reduced social drive, loss of feeling of pleasure, and inattention to social or cognitive input (Tandon & Jibson, 2002).

Research actively and consistently shows that genetically inherited traits cause SCZ, but no one gene alone is solely responsible: a recent study shows 18 commonly affected genes in SCZ patients (Haghighatfard, 2018). The closer you are in relation to the genetic marker, the higher the risk one has of inheriting SCZ (Tamminga & Medoff, 2000). Much attention has recently been given to prenatal exposures and behaviors that lead to mental illness in the offspring. Specific pre- & perinatal biological events like toxemia, hypoxia, and winter birth are linked to SCZ (Tamminga & Medoff, 2000). In addition, stress hormone induction and the mother’s immune responses during pregnancy are key risk factors (Meli, Ottl, Paladini, & Cataldi, 2012). Some have noticed a link between mothers who get toxoplasmosis, a parasite carried in cats, and SCZ (Torrey & Yolken, 2018).


CATs & MRIs show various neurological differences and brain abnormalities of people with SCZ, including enlarged cerebral ventricles, smaller temporal gyrus, and hippocampal regions, reduced prefrontal metabolism and blood flow, increased dopamine release, and altered neural systems (Tamminga & Medoff, 2000). A vitamin D deficiency that directly and negatively affects the hippocampus region has also been seen in causing SCZ (Shivakumar et al., 2015). While other perspectives attempt to explain the various causes of SCZ, all rely on an underlying biological susceptibility (McFarlane, 2011). Antipsychotic medications called neuroleptics are commonly used as a natural/neurological approach to treatment. They work by reducing or increasing specific neurotransmitters in the brain, most often, dopamine (Kapur, Agid, Mizrahi, & Li, 2006). Adequate prenatal and perinatal health helps in preventing SCZ as well.



Dementia

Dementia is a syndrome that affects many operations of the brain, including cognition, memory, attention, language, spatial orientation, and executive function (Ellison, 2019a). While the exact causes of dementia are still being investigated, research shows that it is directly related to the biological makeup of the brain and genetics and can manifest in any person of any background at any time (Ellison, 2019a).

Dementia can take form in many different illnesses and diseases. The most common type of dementia is Alzheimer’s disease (AD). In 2017, 5.5 million Americans had AD, making it the most common and costly form of dementia in the United States (Martone & Piotrowski, 2019). While AD affects people of all ages, symptoms gradually begin in older adults over the age of 65. They include apraxia, the misunderstanding of shared meanings and movements, dysphasia, the inability to arrange language appropriately, and agnosia, the loss of sensory perception interpretation (Martone & Piotrowski, 2019). Additionally, patients with AD exhibit several neurological abnormalities in the brain: AD patients form plaque, or protein deposits, in the brain; they test positive for amyloid (abnormal bone marrow protein.) disease; and show signs of tangled nerve fibers in the brain (Martone & Piotrowski, 2019).


Recently, studies have shown that genes play a significant role in the predisposition and body’s immune response to AD. Specific genes can fight off these harmful forming plaques and proteins in the brain, which many scientists and researchers are currently using to advance in AD pathology (Martone & Piotrowski, 2019). In addition to the idea of gene therapy, research is actively experimenting with many other possible treatment and therapy options for dementia. A November 2019 phase 3 study published in the Journal of Alzheimer’s Disease examined the effects of protein blockers on the brain. The tau protein, in particular, creates fibrous tangles that cause dementia. Brain cells use microtubules to transfer nutrients to one another, and the tau protein is used to stabilize these microtubules (Ellison, 2019b). Tau dysfunction is commonly associated with AD. This biological association has become a meaningful discovery in the clinical research of dementia.


Conclusion

Mental illness is a pervasive phenomenon in society. Understanding and treating psychopathology is an ever-evolving concentration for doctors and scientists. Many different factors and perspectives contribute to the origin of mental illness. Environmental, sociological, and psychological influences are all represented in some way in the foundation of mental illness. However, it is the genetic, bio-neurological underpinnings that many believe to be most important, yet also the most nebulous. Specific hereditary traits, mainly physical deformities or chemical imbalances in the brain, make a person predisposed to certain mental illnesses. People with mental illness are born with these individualities. It is later in life that the supplemental environmental, sociological, or psychological dynamics then trigger the biological penchant that ultimately results in mental illness — because of this, understanding the biological foundations is crucial for furthering research and narrowing the scope of future research in the field.


-Elizabeth Hertweck, MS, HN, HWC, FS


 

References


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