Suicide and suicidal behaviors are very rare in animals and seem to be more of defensive nature unlike in humans that is not so, but intentional and against life. (1-2) Suicide in humans is a global issue that has resulted in 842,000 deaths globally in 2013, up from 712,000 deaths in 1990. (3) This makes it the 10th leading cause of death worldwide. (4) 75% of suicides globally occur in the developing world. Rates of completed suicides are generally higher in men than in women, ranging from 1.5 times as much in the developing world to 3.5 times in the developed world. (5) There are an estimated 10 to 20 million non-fatal attempted suicides every year. (6) Non-fatal suicide attempts may lead to injury and long-term disabilities. In the Western world, attempts are more common in young people and females, and suicide is the second cause of death among adolescents after accidents. (7-8)

 

Factors that affect the risk of suicide include mental disorders, drug misuse, psychological states, cultural, family and social situations, and genetics. (8) Mental disorders and substance misuse frequently co-exist. (9) Other risk factors include having previously attempted suicide, the ready availability of a means to take one’s life, a family history of suicide. (7) For example, suicide rates have been found to be greater in households with firearms than those without them. (10) Socio-economic problems such as unemployment, poverty, Homelessness, and discrimination may trigger suicidal thoughts. (11) About 15–40% of people leave a suicide note. (12) Genetics appears to account for between 38% and 55% of suicidal behaviors. (13) War veterans have a higher risk of suicide due in part to higher rates of mental illness such as post traumatic stress disorder (PTSD) and physical health problems related to war. (14)

 

Half of all people who die by suicide may have major depressive disorder; and having a mood disorder such as depression or bipolar disorder increases the risk of suicide 20-fold. (6) Other mental disorders’ risk of suicide are Schizophrenia (14%) that leads about 5% of such patients die from suicide, borderline personality disorder, PTSD, eating disorder, and substance use disorders. (6-7, 15) Approximately 20% of suicides have had a previous attempt, and of those who have attempted suicide, 1% complete suicide within a year, and more than 5% die by suicide within 10 years. (7) Acts of self-harm are not usually suicide attempts and most who self-harm are not at high risk of suicide. Some who self-harm, however, do still end their life by suicide, and risk for self-harm and suicide may overlap. (16) 

Substance use is the second most common risk factor for suicide after mood disorders, with both chronic substance use and acute intoxication are associated. This risk further increased when combined with personal grief due to losses. (9) Most people are under the influence of sedative-hypnotic drugs such as alcohol or benzodiazepines when they die by suicide, with alcoholism present in between 15% and 61% of cases. (9, 17) Alcoholics who attempt suicide are usually male, older, and have tried to take their own lives in the past. (9) Between 3 and 35% of deaths among those who use heroin are due to suicide (approximately 14 fold greater than those who do not use). (18) The abuse of cocaine and methamphetamine has a high correlation with suicide, with the greatest risk during the withdrawal phase. Abuse of inhalants are also associated with about 20% attempting suicide risk and more than 65% suicidal thoughts. (9, 19) Gambling addiction is also between 12-24% associated with suicide attempts. (20) Medical and physical conditions such as chronic pain, HIV, other chronic diseases and cancers are associated with the increased risk of suicide, even after controlling for depression. (7,21)    

 

Inside the suicidal brain (mind):

Many researchers as briefed above have associated suicide to mood disorders, specifically depression. Many also argue that suicides in other states of minds and diseases occur when the person is depressed at the time. In the core of depression, many researchers believe that “hopelessness” is the underlying reason leading to suicide. But there are many people with depression, even chronic one, or in acute state of depression and at the stage of hopelessness do not kill themselves. There are many people with suicidal thoughts who do not proceed to intention and plan to take their own lives. Traditionally and theoretically there are stages to completed suicide, that is first suicidal thoughts, then intention, plan and attempt. But there are many suicide attempts that do not end up in death, either for not being serious and using lethal methods or changing mind, seeking help or being rescued. There are many self-harm behaviors that do not end even in suicide attempt, lest final suicide, and are done for relief of emotional pains. So what is going on inside a suicidal brain or mind who contemplate suicide successfully and takes life?! Answer to this vital question could save many otherwise healthy lives around the globe.

There has been a Cartesian argument if suicide is a matter of the human brain or human emotions (22). However, recent advances in neuroscience are providing a unified theory that connect both sides of this old arguments and map the human emotions underlying suicide with well-defined brain regions (23-24). Underlying the suicide triggered by a life event or a mental/emotional condition, lies a predisposing diathesis. (25) The diathesis begins with the individual’s genetic risk and develops further as the accumulation of traumatic events, mental and physical illnesses, and losses leads to neurobiological changes in the organism. The key component of the underlying diathesis is an altered stress response, within the Hypothalamic-Pituitary-Adrenal Axis (HPA), and Corticotropin-Releasing hormone (CRH) and the Locus Ceruleus-Norepinephrine (LC-NE) systems. 

 

As it is seen in the diagram below, stress activates the Hypothalamus (that secrets vasopressin and CRH, then in turn cortisol) and Locus Ceruleus (that secrets Norepinephrine). (26) Studies comparing depressed individuals who have died by suicide to non-psychiatric comparison subjects report elevated CRH and vasopressin levels in the forebrain, raphe, and locus ceruleus of their brain. (27-28) Studies have also showed adrenal cortex hypertrophy in violent suicides, supportive of an overactive HPA axis. (29) Stress in acute, repeated and chronic manner impacts on the above axes, causing inflammation of these regions of the brain. But the suicide brain, that is a sensitive and emotional mind, is already inflamed and upon further stress is inflamed and damaged more until giving up by suicide. This intentional behavior is a short cut to the natural process of inflammation in the above brain axes that will cause naturally apoptosis or cellular deaths. (30-33)

 

As it is seen in the above diagram, the opioid system plays a key role in stress response and interacts with both the HPA axis and the LC-NE system. Stress causes pituitary release of POMC, the precursor of ACTH and β-endorphin and a major endogenous opioid. Endogenous opioids reduce the emotional component of pain, but not pain perception per se. As such, these peptides may attenuate stress effects, and their alteration may contribute to suicide risk. (34) Serotonin that is the main chemical or neurotransmitter in depression, is linked also to suicide, but in a different manner than in non-suicidal depression. For example, the deficit in the serotonin transporter binding has been shown to differ from that seen in major depression, where it extends over most of the prefrontal cortex, whereas in suicide it is restricted to the ventromedial prefrontal cortex and anterior cingulate regions, which are implicated in decision making and willed action. (35) Also low CSF and brain stem levels of 5-HIAA, an index of serotonin turnover have been a predictor of suicide. Conversely there has been increased 5-HIAA levels in the hippocampus and amygdala, with no differences in the cortex. But one study of drug-free nonviolent suicide victims has shown significantly lower 5-HIAA level in the hippocampus than the violent suicide victims. (36-38)

 

As it is depicted in the above diagram, neuroplasticity of the brain has a major role in the suicide. Structural and functional adaptation to environmental demands is possible through synaptic plasticity and neurogenesis, processes regulated by neurotrophins, that brain-derived neurotrophic factor (BDNF) is the most important. (39) In suicide brains, the neuroplasticity and neurogenesis is defective or reduced and instead accelerated neuron loss due to apoptosis, or loss of neuropil are observed in different regions of the brain, specifically those related to mood regulation such as dorsolateral prefrontal cortex neurons, dentate gyrus, hippocampus and parahippocampus. (40) Also teenage and adult suicide victims with diverse diagnoses have been reported to have lower BDNF protein expression in the prefrontal cortex, and hippocampus. (41-42) Of note, BDNF levels were similar between antidepressant-treated suicide victims and nonpsychiatric comparison subjects, suggesting normalization of neurotrophin levels with antidepressants. (43)

 

Lastly there is a neuro-psychosocial cognitive model of suicidal behavior, explaining the sensitivity of such individuals in their perception of reality of self and others in time of past and future. Based on such sensitivity, particular life events may reflect signals of defeat in the suicidal mind due to their negative cognitive biases, such as feeling at loss, trapped, helpless and hopeless, with insufficient capacity to solve problems in different domains such as interpersonal or social. (44-46) The social cognitive component or appraisal of a life event, stress or interpersonal issue is modulated by the frontal and temporal cortices in conjunction with the hippocampus, and chemically mediated by the (5-HT)1A receptor of serotonin and noradrenalin neurotransmission. Then the behavioural reaction to such negative appraisal that could be behavioral disinhibition and impulsivity to act on the feelings of hopelessness and helplessness by the act of suicide is modulated through the lower systems of limbic system, particularly amygdala and chemically through the 5-HT2A receptors of serotonin and dopaminergic neurotransmission. (44, 47-50) Animal studies have shown that a balance between the lower and upper parts of the brain (limbic and amygdala vs. hippocampal and cortical specifically frontal and prefrontal) anatomically and the 5-HT1A and 5-HT2 receptors of serotonin and noradrenergic and dopaminergic neurotransmission is essential for an adequate and healthy response to social stress.(50) 

Conclusion:

The human’s brain while it is the source and cause of his achievements and prospects, it is the root of his misery and unhappiness, and can lead him to take his own life, unlike other species who lack such sophisticated brain. Despair and depression that could be acute, fleeting, situational or momentary would not lead to suicide and ending life. The suicide mind or brain has been wired for a while with perhaps a genetic or inherent sensitivity, that upon repeated stress or negative appraisals of the environment (that is not containing and protective) would lead to a state of hopelessness and helplessness. Still a suicide mind or brain will not act on taking his life, until the impulsivity or behavioral disinhibition kick in to act on the long-standing suicidal thoughts. The impulsivity or behavioral disinhibition that is illogical and against life, and in the eyes of caring others also selfish, is only possible by blocking the higher cortical logical part of the brain, and act on the impulses of the lower limbic part of the brain. This could happen in those who inherently own impulsivity and behavioral disinhibition, or is created by others through nihilistic justification of life, or by the use of substances to knock down the higher cortical logical part of the brain by some.     

 

Therefore to curb the suicidal mind or brain, the caring others need to realize from the start, the sensitive mind to contain and protect it, to lower stress upon it, treat its depression when occurs. For those with inherent impulsivity or behavioral disinhibition, for example in the cases of ADHD persons, the caring others need to have it treated, as there is nothing to curb it, contain, protect or translate it! 

 

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