Chapter 1: Opening—90% of Those Who Die by Suicide Have Psychiatric Comorbidities

Positioning of the Four-Layer Interaction Framework: This chapter serves as the introduction to the book, establishing the core argument that "only by understanding psychiatric disorders can we prevent suicide," and introducing the four-layer interaction cognitive framework (genetic mutation → development → metabolism → social environment) that runs throughout the book. Subsequent chapters will expand on these four levels one by one.

1.1 The Statistical Reality of the Suicide Crisis

Suicide is a global public health crisis. The World Health Organization estimates that more than 800,000 people die by suicide worldwide each year—one person every 40 seconds. Suicide is the tenth leading cause of death across all age groups, but it jumps to the second leading cause among adolescents and young adults aged 15–29. Approximately 80% of suicide cases occur in low- and middle-income countries, suggesting that poverty and social inequality are significant structural factors.

The numbers for suicide attempts are even more staggering: for every completed suicide, there are at least 20 or more attempts. Each year, approximately 16 million people worldwide attempt suicide but do not die, behind which lie extreme suffering and ongoing risk.

In terms of demographic characteristics, suicide shows clear patterns: the male suicide mortality rate is 3 to 4 times that of females, and men tend to use more lethal methods; conversely, the rate of suicidal ideation and attempts in females is 3 to 4 times that of males. The group with the highest suicide rate is elderly people over the age of 70, with the risk increasing as age advances.

1.2 The Relationship Between Psychiatric Disorders and Suicide

Core Fact: Approximately 90% of individuals who die by suicide met the criteria for one or more diagnosable psychiatric disorders prior to their death. More than half of suicide decedents suffered from major depressive disorder or bipolar disorder. This dataset directly rescues suicide from social prejudices such as "being unable to think straight" or "impulsive acts," pulling it back to the realistic battlefield of psychiatry and neuroscience.

Suicide risk varies dramatically across different psychiatric disorders, summarized briefly below (for a detailed analysis, see Chapter 8):

1.3 Overview of Suicide Risk in Major Psychiatric Disorders

Table 1. Overview of Quantitative Suicide Risk Indicators in Common Psychiatric Disorders

Psychiatric Disorder	Quantitative Indicator Type	Core Value	Data Source	Risk Level
Anorexia Nervosa	SMR	18–31 times	11	Extremely High Risk
Borderline Personality Disorder	SMR	45.1	15	Extremely High Risk
Schizophrenia	SMR	13.03	20	High Risk
Bipolar Disorder	SMR	10.26	20	High Risk
Substance Use Disorder	SMR/Risk Ratio	10–14 times	29	High Risk
Alcohol Use Disorder	SMR	6.78	20	High Risk
Major Depressive Disorder	Incidence Rate	534.3 / 100,000 person-years	20	Moderate Risk
Post-Traumatic Stress Disorder	HR	3.96–6.74	20	Moderate Risk
Generalized Anxiety Disorder	OR (Comorbidity Amplification)	3-fold amplification	20	Auxiliary Risk
Insomnia Disorder	OR	1.71	20	Auxiliary Risk
Unspecified Eating Disorder	Risk Ratio	4 times	11	Auxiliary Risk

Extremely High Risk Group:

• Anorexia Nervosa: Do not assume this is merely "eating less." Its suicide risk ranks highest among all psychiatric disorders, standing 18 to 31 times higher than that of the general population. Approximately one in five individuals with anorexia nervosa ultimately dies by suicide. This pathological bodily control may abnormally enhance their tolerance to pain, while paradoxically weakening their fear of death.
• Borderline Personality Disorder (BPD): This condition carries a terrifyingly high suicide risk: up to 70% of patients have attempted suicide, and approximately 10% eventually die by suicide. Its Standardized Mortality Ratio (SMR) can soar to 45.1, higher than any other psychiatric disorder.

High Risk Group:

• Schizophrenia: SMR is 13.03, and the adjusted Hazard Ratio (aHR) is 5.91. The period of highest risk often concentrates in the early stages of the disease, following the first psychotic episode, and when symptoms have alleviated but the patient begins to develop "insight" into their own illness.
• Bipolar Disorder: Up to 15–20% of patients eventually die by suicide. The SMR is 10.26, and the aHR is 6.05. Its unique "mixed episode" or "rapid cycling" states dangerously combine manic impulsivity with depressive hopelessness.
• Substance Use Disorders (SUDs) and Alcohol Use Disorder (AUD): Overall, the risk of suicide mortality in individuals with SUDs is 10 to 14 times higher than in the general population. The SMR for Alcohol Use Disorder is 6.78, and the Odds Ratio (OR) for acute alcohol use (AUA) can be as high as 6.97.

Moderate Risk Group:

• Major Depressive Disorder (MDD): Widely recognized as the most prevalent risk factor for suicide, with a suicide rate of 534.3 per 100,000 person-years and an aHR of 2.98. Although its SMR is not as extreme as that of BPD or anorexia nervosa, it remains the most common known diagnosis among all suicide decedents (accounting for approximately 46%).
• Post-Traumatic Stress Disorder (PTSD): The suicide risk for patients is significantly higher than that of the general population; the suicide Hazard Ratio (HR) is 6.74 for female patients with PTSD and 3.96 for males.

Comorbidity and Auxiliary Risk Group:

• Generalized Anxiety Disorder (GAD): Its role as an isolated lethal risk factor is limited, but as a comorbidity, it significantly amplifies the suicide risk of other disorders (for instance, patients suffering from both GAD and depression have a three-fold increase in suicide risk compared to those with depression alone).
• Insomnia Disorder: Identified as an independent, modifiable suicide risk factor, it can increase the suicide risk of patients with major depressive disorder by 1.71 times.
• Unspecified Eating Disorder: The suicide risk is four times that of the general population.

1.4 Comorbidity: The Superposition and Amplification of Risk

Diagnoses of psychiatric disorders rarely exist in isolation. In clinical practice, a single patient is frequently diagnosed with more than one psychiatric disorder, a phenomenon known as "comorbidity." The existence of comorbidity is by no means accidental; it often shares a common genetic foundation. For instance, recent genomic research has revealed that many genes associated with bipolar disorder overlap with risk genes for other psychiatric disorders, such as schizophrenia and depression.

Prevalence of Comorbidity

The rate of comorbidity among psychiatric disorders is far higher than what would occur by random chance. For example, a study targeting military recruits demonstrated that with each additional psychiatric diagnosis, the Odds Ratio (OR) for suicidal ideation increased geometrically: from 3.1 times for a single diagnosis to 11.7 times for seven or more diagnoses. This strongly indicates that comorbidity does not merely add risks together but instead generates an exponential amplification effect.

Common Comorbid Combinations:

• Comorbidity of Substance Use Disorders and Depression/Personality Disorders: For male patients suffering from both SUD and MDD, the long-term suicide risk can reach as high as 16.2%. Among patients with borderline personality disorder, comorbid substance abuse significantly increases the frequency and severity of suicidal behavior.
• Comorbidity of Depression and Personality Disorders: For MDD patients with comorbid personality disorders, the suicide risk is a staggering 16 times (for males) to 20 times (for females) higher than that of patients with MDD alone.

Cases: Sia and Van Gogh—When Diagnoses Multiply

• Sia: The famous Australian singer Sia Furler was not only diagnosed with bipolar disorder but also struggled with multiple psychiatric challenges, including autism spectrum disorder (ASD) and alcohol dependence. Multiple diagnoses entail intertwined symptoms, making treatment exceptionally complex.
• Van Gogh: Modern medical research and re-evaluations of his medical history suggest that Van Gogh likely suffered not only from bipolar disorder but also experienced psychotic symptoms, substance use disorder, and possible temporal lobe epilepsy, constructing a complex picture of comorbidity.

How Comorbidity Increases Treatment Difficulty and Suicide Risk:

• Diagnostic Difficulty: The overlap and mutual masking of symptoms make it hard for clinicians to accurately identify all comorbidities.
• Complexity in Treatment Selection: Requires more refined drug choices and dosage adjustments.
• Decreased Treatment Adherence: Patients may need to take multiple medications.
• Poor Prognosis: Patients with comorbidities often present with more severe symptoms, a longer course of illness, and higher recurrence rates.
• Exponential Increase in Suicide Risk: Comorbidity acts as one of the most critical amplifiers of suicide risk.

1.5 The Book's Psychiatric Disorder Inventory and Cognitive Framework

Based on the suicide risk data above, this book will focus on analyzing the following eight psychiatric disorders, understanding their essence through the four-layer interaction of "genetic mutation → development → metabolism → social environment":

1. Bipolar Disorder — SMR 10.26, high risk; mixed episodes and rapid cycling states are the most lethal.
2. Major Depressive Disorder — The most prevalent diagnosis in suicide (accounting for 46%), moderate risk but with a massive baseline population.
3. Schizophrenia — SMR 13.03, high risk; the early stages of onset and the period of insight recovery are the most dangerous.
4. Anorexia Nervosa — SMR 18–31, extremely high risk; abnormally enhanced tolerance to pain.
5. Substance Use Disorders (including Alcohol Use Disorder) — 10–14 times the risk; impairs judgment and impulse control.
6. Borderline Personality Disorder — SMR 45.1, extremely high risk; 70% have attempted suicide.
7. Post-Traumatic Stress Disorder — HR 3.96–6.74, moderate risk; the shadow of trauma is profound.
8. Comorbidity — Risk is exponentially amplified; with each additional diagnosis, the suicide risk increases geometrically.

Four-Layer Interaction Cognitive Framework:

Genetic Mutation Layer → Developmental Layer → Metabolic Layer → Social-Environmental Layer
         ↓                       ↓                   ↓                     ↓
 Genetic Variation       Neurodevelopment    Neurotransmitters       Family/Society
Genetic Susceptibility     Time Points          Endocrine            Culture/Economy
    Epigenetics         Brain Connectivity  Pharmaco Evidence       Policy/Resources

Chapters 2 through 7 of this book will sequentially analyze the aforementioned psychiatric disorders from these four levels, constructing a scientific "cognitive framework and knowledge paradigm for psychiatric disorders"—replacing those non-empirical philosophical speculations and psychological theories lacking verifiability.

1.6 Clinical Overview of Each Disorder: What Exactly Are They?

Before diving deep into the four-layer framework, we must first understand "what these psychiatric disorders look like"—their clinical manifestations, diagnostic criteria, and core characteristics. This is not a simple "listing of symptoms," but rather the foundation for understanding how the four-layer interaction manifests differently across various illnesses.

1.6.1 Bipolar Disorder: The Emotional "Roller Coaster"

The core feature of bipolar disorder is the extreme fluctuation of mood—the recurrent, alternating episodes of mania (or hypomania) and depression. It is not merely "being in a bad mood," but rather emotional dysregulation rooted in a physiological foundation.

Manic/Hypomanic Episode: Patients experience extreme happiness, elation, or intense irritability and agitation. Activity and energy levels rise significantly, the need for sleep decreases drastically, speech becomes unusually rapid and pressured, thoughts race, and attention is easily distracted. Judgment is severely impaired, frequently leading to impulsive and reckless behaviors—such as shopping sprees, sexual indiscretions, or foolish investments. In severe cases, psychotic symptoms like grandiose or persecutory delusions may emerge.

Depressive Episode: A profound low mood, characterized by a loss of interest or pleasure in nearly all activities. Significant changes in appetite and weight, sleep disturbances, and extreme fatigue occur. Patients experience self-deprecation, intense feelings of worthlessness or guilt, slowed thinking, and recurrent thoughts of death.

Mixed Episode: The most complex and painful state, where manic/hypomanic and depressive symptoms occur simultaneously. While feeling deeply depressed and hopeless, patients concurrently experience racing thoughts, anxiety, and restlessness. This contradictory state causes suicide risk to escalate sharply.

Challenges to Personality: The core issue of bipolar disorder lies in this: when emotions, attitudes, and behaviors change drastically and cyclically due to the illness, can the patient still possess a "stable personality"? Patients often say, "I would never do that normally," and onlookers frequently remark, "She is not herself right now." This sense of subjective and objective discontinuity indicates that the disease directly and profoundly disrupts the manifestation of personality. Recurrent mood episodes can also produce a "scar effect," leading to enduring changes in certain personality traits—where high neuroticism and low agreeableness may persist even during remission (Quilty et al., 2009, Journal of Affective Disorders).

1.6.2 Major Depressive Disorder (MDD): The Silent Epidemic

Depression is not simply "feeling blue" or "being unable to let things go"; rather, it is a complex disorder involving disruptions in brain function, neurotransmitters, and physiological metabolism. Its diagnosis requires meeting the DSM-5 criteria: at least five or more of the following symptoms persisting for at least two weeks (must include at least depressed mood or loss of interest/pleasure):

1. Depressed mood: Feeling sad, empty, or hopeless most of the day, nearly every day.
2. Loss of interest or pleasure (anhedonia): Markedly diminished interest or pleasure in all, or almost all, activities.
3. Significant weight or appetite change: A weight change of more than 5% within a month.
4. Sleep disturbances: Insomnia or hypersomnia.
5. Psychomotor agitation or retardation: Restlessness or being slowed down, observable by others.
6. Fatigue or loss of energy: Persisting even with rest.
7. Feelings of worthlessness or guilt: Excessive self-blame over minor issues, sometimes reaching delusional proportions.
8. Diminished ability to think or concentrate, or indecisiveness.
9. Recurrent thoughts of death or suicidal ideation.

The clinical presentation of depression exhibits high heterogeneity—different patients can present with entirely different combinations of symptoms. Anhedonia is considered one of the most core symptoms of depression, closely linked to functional deficits in the reward system (ventral striatum, nucleus accumbens) (Der-Avakian & Markou, 2012, Neuropsychopharmacology).

1.6.3 Schizophrenia: The Rupture Between Thought and Reality

Schizophrenia is a severe chronic psychiatric disorder whose clinical manifestations can be divided into four major categories:

Positive Symptoms (abnormal experiences present in patients but absent in healthy individuals):

• Delusions: Persecutory delusions (believing someone is out to harm them), delusions of reference (believing surrounding events are specifically related to them), and delusions of control.
• Hallucinations: Most commonly auditory hallucinations—hearing voices that do not exist, such as commentary, arguments, or commands.
• Thought Disorder: Loose associations, incoherent speech, and disorganized logic.
• Bizarre Behavior: Disorganized behavior and catatonia (immobility, rigid posture).

Negative Symptoms (functions present in healthy individuals but lacking in patients):

• Flat Affect: Lack of facial expression and a monotonous voice.
• Alogia (Poverty of Speech): Reduced speech output and empty content.
• Avolition: Lack of motivation for goal-directed activities.
• Anhedonia: Loss of interest in activities that typically bring pleasure.
• Social Withdrawal: Avoiding interpersonal interactions.

Cognitive Symptoms: Impairments in attention, working memory, information processing speed, and executive function—these symptoms often appear early in the course of the disease and exert a severe impact on social and occupational functioning.

Affective Symptoms: Frequently accompanied by depression, anxiety, and irritability, which increase distress and suicide risk.

Diagnosis requires symptoms to persist for at least 6 months, including at least 1 month of active-phase symptoms. The suicide risk in schizophrenia is concentrated at two key time points: the early stage of onset (following the first psychotic episode) and the period of insight recovery (when the patient begins to realize they have "gone mad").

1.6.4 Anorexia Nervosa: The Most Lethal Psychiatric Disorder

The core feature of anorexia nervosa is the deliberate restriction of energy intake leading to a significantly low body weight, accompanied by an intense fear of gaining weight and a disturbance in the perception of one's own body shape. Its suicide risk ranks first among all psychiatric disorders—standing 18 to 31 times higher than the general population, with approximately one-fifth of deaths in anorexia resulting from suicide.

Clinical Manifestations:

• Significantly Low Body Weight: BMI is typically below 17.5 kg/m².
• Intense Fear of Gaining Weight: Even when weight is already extremely low.
• Distorted Body Image: Viewing oneself as "too fat" despite being emaciated.
• Restricting Type vs. Binge-Eating/Purging Type: The former controls weight through strict restriction of food intake; the latter involves periodic binge eating followed by purging behaviors (self-induced vomiting, abuse of laxatives).
• Physical Complications: Bradycardia, hypotension, amenorrhea, osteoporosis, and electrolyte imbalances—which can be life-threatening in severe cases.

Suicidal behavior in patients with anorexia nervosa exhibits unique characteristics: chronic malnutrition may abnormally enhance their tolerance to pain and consequently diminish their fear of death—a concept known as "Acquired Capability for Suicide," which occupies a core position in Joiner's interpersonal theory of suicide (Joiner, 2005, Why People Die by Suicide).

1.6.5 Substance Use Disorders and Alcohol Use Disorder: Hijacking the Reward System

The core feature of substance use disorders is the uncontrollable, persistent use of a substance despite knowing its harmful consequences. Clinical manifestations include:

• Increased Tolerance: Requiring larger doses of the substance to achieve the same effect.
• Withdrawal Symptoms: Experiencing physiological and psychological distress upon stopping or reducing substance use.
• Loss of Control: Attempting to cut down or stop use but failing.
• Intense Craving: An ongoing, powerful urge to use the substance.
• Functional Impairment: Impairment in social, occupational, or academic functioning due to substance use.

Particularity of Alcohol Use Disorder: Alcohol is the most widely used addictive substance globally, and its harms are often masked by social culture. Chronic heavy drinking leads to adaptive changes in the GABAergic system—to counteract the inhibitory effects of alcohol, the brain reduces GABA receptor sensitivity and increases glutamatergic activity. Once alcohol use stops, inhibition is lifted and overexcitation ensues, resulting in withdrawal symptoms: tremors, anxiety, and sweating, which in severe cases can progress to Delirium Tremens and seizures.

Mechanism of Suicide Risk: Substance use disorders impair judgment and impulse control while frequently co-occurring with depression and personality disorders, forming a vicious cycle of suicide risk. Acute alcohol use can increase suicide risk nearly seven-fold (Borges et al., 2017, Addiction).

1.6.6 Borderline Personality Disorder: The Emotional "Storm"

The core feature of borderline personality disorder (BPD) is a pervasive instability of interpersonal relationships, self-image, and affects, alongside marked impulsivity. Its suicide risk is extremely high—with an SMR of 45.1 and approximately 70% of patients attempting suicide.

Clinical Manifestations:

• Fear of Abandonment: Frantic efforts to avoid real or imagined abandonment.
• Unstable Interpersonal Relationships: A pattern of unstable and intense relationships alternating between extremes of idealization and devaluation.
• Identity Disturbance: Markedly and persistently unstable self-image or sense of self.
• Impulsivity: In areas such as spending, sex, substance abuse, reckless driving, and binge eating.
• Recurrent Suicidal Behavior or Self-Mutilation: Suicidal threats or self-harming behavior are hallmark features of BPD.
• Affective Instability: Intense emotional reactivity, usually lasting a few hours.
• Chronic Feelings of Emptiness.
• Inappropriate, Intense Anger.
• Transient, Stress-Related Paranoid Ideation or Severe Dissociative Symptoms.

The reason BPD carries such an extremely high suicide risk is partly because its core symptoms—fear of abandonment and affective instability—themselves constitute persistent triggers for suicide, while repeated self-harm may lower the fear of death through the mechanism of "acquired capability."

1.6.7 Post-Traumatic Stress Disorder (PTSD): The Shadow of the Past

The core feature of PTSD is the development of the following symptom clusters persisting for over a month after experiencing or witnessing a life-threatening traumatic event:

• Intrusive Symptoms: Recurrent, involuntary, and intrusive distressing memories of the trauma, nightmares, or flashbacks.
• Avoidance: Avoidance of trauma-related thoughts, feelings, places, or people.
• Negative Alterations in Cognition and Mood: Persistent negative beliefs (e.g., "the world is completely dangerous"), persistent negative emotional states (fear, anger, guilt), diminished interest in significant activities, or feelings of detachment from others.
• Alterations in Arousal and Reactivity: Irritability, hypervigilance, exaggerated startle response, difficulty concentrating, or sleep disturbances.

The suicide risk in PTSD is closely related to the severity and duration of the trauma, as well as comorbidities (especially depression and substance use disorders). It is noteworthy that the neurobiological core of PTSD involves abnormalities in the HPA axis and the amygdala-prefrontal cortex circuitry—which overlaps with the dysregulation of the stress system seen in depression, explaining the high rate of comorbidity between the two.