18.7 Biopsychosocial Etiology, Schizophrenia, Mood & Anxiety Disorders

18.7 Biopsychosocial Etiology, Schizophrenia, Mood & Anxiety Disorders

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Etiological Models: Biopsychosocial & Diathesis-Stress

• The Biopsychosocial Model: Posits that mental illness arises from the complex, non-linear interaction of three interdependent domains:
  1. Biological: Genetic vulnerabilities, monoamine imbalances, structural neuroanatomy, and neuroendocrine dysregulation.
  2. Psychological: Maladaptive cognitive schemas, appraisal styles, perceived self-efficacy, and learned behaviors.
  3. Sociocultural: Socioeconomic adversity, systemic prejudice, interpersonal trauma, cultural expectations, and social support.
• The Diathesis-Stress Model: Asserts that psychological disorders manifest when an underlying constitutional vulnerability (diathesis)—which may be genetic (e.g., 5-HTTLPR short allele), neurodevelopmental, or cognitive—is triggered by an environmental or psychological stressor. An individual with a high genetic diathesis requires only modest environmental stress to develop a disorder, whereas an individual with a low diathesis requires severe, chronic stress.

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Schizophrenia & Psychotic Disorders

Schizophrenia is a severe neurodevelopmental psychotic disorder affecting approximately 1% of the global population. Diagnosis requires continuous signs of disturbance for at least 6 months, including at least 1 month of active-phase symptoms with at least two of the following five criteria (and at least one must be 1, 2, or 3):

1. Delusions
2. Hallucinations
3. Disorganized speech
4. Grossly disorganized or catatonic behavior
5. Negative symptoms

Symptom Typology

• Positive Symptoms (Pathological Excesses): Behaviors, perceptions, or thoughts added to normal functioning:
  • Delusions: Fixed, false beliefs resistant to contradictory evidence. Includes delusions of persecution (believing one is targeted by enemies), reference (believing mundane environmental events have personal significance), grandeur (believing one possesses divine powers), and control (thought insertion, thought broadcasting).
  • Hallucinations: Sensory perceptions occurring without an external physical stimulus. Auditory hallucinations (hearing derogatory or commanding voices) are by far the most prevalent.
  • Disorganized Speech & Thought: Derailment (loose associations), tangentiality, and neologisms (invented words), culminating in extreme cases in "word salad".
  • Disorganized / Catatonic Behavior: Bizarre posturing, purposeless motor agitation, or waxy flexibility (maintaining limbs in positions placed by an examiner).
• Negative Symptoms (Pathological Deficits): Normal functions subtracted from healthy mental life:
  • Affective Flattening (Blunted Affect): Reduced range and intensity of emotional expression.
  • Avolition: Profound lack of motivation and inability to initiate or persist in goal-directed activities.
  • Alogia: Poverty of speech in fluency and productivity.
  • Anhedonia: Inability to experience pleasure from previously rewarding activities.
  • Asociality: Profound lack of interest in social interactions.

Neurobiological Pathophysiology

• The Dual Dopamine Hypothesis:
  • Mesolimbic Hyperactivity: Excessive dopaminergic transmission from the ventral tegmental area (VTA) to the nucleus accumbens mediates positive symptoms. First-generation (typical) neuroleptics (e.g., haloperidol) antagonize D2 receptors, alleviating positive symptoms but carrying high risk of extrapyramidal motor side effects and tardive dyskinesia.
  • Mesocortical Hypoactivity: Deficient dopaminergic transmission from the VTA to the prefrontal cortex mediates negative and cognitive symptoms. Second-generation (atypical) antipsychotics (e.g., risperidone, clozapine) antagonize serotonin 5-HT2A and D2 receptors to modulate both circuits.
• Neuroanatomical Hallmarks: Marked enlargement of the lateral and third cerebral ventricles (ventriculomegaly), reflecting widespread loss of cortical gray matter in the prefrontal cortex and temporal lobes.

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Mood Disorders: Depressive & Bipolar Disorders

1. Major Depressive Disorder (MDD)

Requires at least two weeks of persistent depressed mood or loss of interest/pleasure (anhedonia), accompanied by at least five of the nine symptoms summarized by the clinical mnemonic SIGECAPS:

• Sleep disturbances (insomnia or hypersomnia)
• Interest loss (pervasive anhedonia; mandatory core symptom)
• Guilt or feelings of worthlessness (inappropriate or delusional)
• Energy deficiency (chronic fatigue, psychomotor anergia)
• Concentration impairment (indecisiveness, cognitive slowness)
• Appetite or weight alterations (significant change of $\ge 5\%$ in a month)
• Psychomotor agitation or retardation (observable by others)
• Suicidal ideation, intent, or recurrent thoughts of death
• Neurobiology: Grounded in the Monoamine Hypothesis—deficiencies in synaptic transmission of serotonin (5-HT), norepinephrine (NE), and dopamine (DA) in limbic-cortical networks. Supported by the efficacy of Selective Serotonin Reuptake Inhibitors (SSRIs). Patients frequently exhibit sustained HPA axis hyperactivity (hypercortisolemia) and hippocampal volumetric reductions.

2. Bipolar Disorders & The Manic Episode

• Bipolar I Disorder: Requires the occurrence of at least one full manic episode. Major depressive episodes are common but not required for diagnosis.
• Bipolar II Disorder: Requires at least one hypomanic episode AND at least one major depressive episode. A full manic episode precludes a Bipolar II diagnosis (immediately converting it to Bipolar I).
• Cyclothymic Disorder: At least 2 years of alternating hypomanic symptoms and depressive symptoms that do not meet full criteria for an episode.
• Diagnostic Criteria for Mania: At least one week of abnormally elevated, expansive, or irritable mood with increased goal-directed energy, presenting with at least three (or four if mood is irritable) symptoms from the mnemonic DIG FAST:
  • Distractibility (attention easily drawn to trivial external stimuli)
  • Indiscretion (hedonistic, high-risk activities: unrestrained spending, reckless driving)
  • Grandiosity (inflated self-esteem, delusions of omnipotence)
  • Flight of ideas (subjective experience that thoughts are racing)
  • Activity increase (hyperactivity, psychomotor agitation)
  • Sleep deficit (decreased need for sleep, feeling rested after only 2–3 hours)
  • Talkativeness (pressured, rapid, loud, uninterrupted speech)
• Hypomania vs. Mania: Hypomania lasts at least 4 consecutive days, does not cause marked social or occupational impairment, does not involve psychotic symptoms, and does not require psychiatric hospitalization.

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Anxiety Disorders, OCD & Trauma-Related Conditions

• Generalized Anxiety Disorder (GAD): Pervasive, excessive, uncontrollable worry regarding multiple daily domains for at least 6 months, accompanied by motor tension, restlessness, fatigue, and sleep disturbances.
• Panic Disorder: Characterized by recurrent, unexpected panic attacks—abrupt surges of intense autonomic terror accompanied by palpitations, dyspnea, chest pain, tremors, and fear of impending death or losing control. Requires at least 1 month of persistent concern regarding future attacks or maladaptive behavioral modifications (frequently progressing to agoraphobia—fear of open, enclosed, or crowded spaces from which escape might be difficult).
• Phobias: Specific phobias (animals, natural environments, blood-injection-injury) vs. Social Anxiety Disorder (severe, persistent fear of social or performance situations involving scrutiny or humiliation).
• Obsessive-Compulsive Disorder (OCD):
  • Obsessions: Recurrent, persistent, intrusive thoughts, urges, or images that cause marked anxiety. Crucially, obsessions are ego-dystonic (the patient recognizes them as irrational, intrusive, and contrary to their core self).
  • Compulsions: Repetitive behaviors (hand-washing, checking, ordering) or mental acts (counting, silent prayer) that the individual feels driven to perform to neutralize the anxiety generated by obsessions.
  • Neurobiology: Hyperactivity within the cortico-striato-thalamo-cortical (CSTC) circuit, linking the orbitofrontal cortex, anterior cingulate, and caudate nucleus.
• Post-Traumatic Stress Disorder (PTSD): Emerges following direct exposure to actual or threatened death, serious injury, or sexual violence. Symptoms must persist for greater than 1 month (distinguishing it from Acute Stress Disorder, which spans 3 days to 1 month) across four symptom clusters: (1) Intrusion (nightmares, flashbacks), (2) Avoidance (evading trauma reminders), (3) Negative alterations in mood/cognition (dissociative amnesia, blame, anhedonia), and (4) Hyperarousal (hypervigilance, exaggerated startle reflex).

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Schizophrenia: Symptom Domains and Duration Criteria

Positive and negative symptoms map to opposite dopaminergic abnormalities in different tracts, which is why one domain responds far better to antipsychotics than the other.

Duration separates the psychotic disorders: symptoms lasting less than one month indicate brief psychotic disorder, one to six months schizophreniform disorder, and six months or more schizophrenia.