const pptxgen = require("pptxgenjs");

const pres = new pptxgen();
pres.layout = "LAYOUT_16x9";
pres.title = "Bipolar Disorder";
pres.subject = "Kaplan & Sadock's Comprehensive Textbook of Psychiatry";
pres.author = "Orris Medical Education";

// ── Color Palette ──────────────────────────────────────────────────────────
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};

// ── Reusable helpers ─────────────────────────────────────────────────────
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}

// ══════════════════════════════════════════════════════════════════
// SLIDE 1 — Title
// ══════════════════════════════════════════════════════════════════
{
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  s.addText("A Comprehensive Clinical Overview", {
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  s.addText("Based on Kaplan & Sadock's Comprehensive Textbook of Psychiatry", {
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}

// ══════════════════════════════════════════════════════════════════
// SLIDE 2 — Outline
// ══════════════════════════════════════════════════════════════════
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  const topics = [
    "Historical Perspective",
    "Classification & Types",
    "Epidemiology",
    "Clinical Features – Mania & Hypomania",
    "Clinical Features – Depression & Mixed States",
    "Etiology & Pathophysiology",
    "Genetics of Bipolar Disorder",
    "Diagnosis (DSM-5-TR Criteria)",
    "Treatment: Acute Mania",
    "Treatment: Bipolar Depression",
    "Maintenance & Prophylaxis",
    "Psychosocial Interventions",
    "Comorbidities & Special Populations",
    "Prognosis & Course",
  ];

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}

// ══════════════════════════════════════════════════════════════════
// SLIDE 3 — Historical Perspective
// ══════════════════════════════════════════════════════════════════
{
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  addSlideHeader(s, "Historical Perspective", "From Ancient Greece to Modern Psychiatry");

  const timeline = [
    { era: "~150 CE", text: "Aretaeus of Cappadocia – first clear description of mania; recognized link with melancholia: \"Melancholy is the commencement and a part of mania\"" },
    { era: "Medieval", text: "Arabic scholars (Ishaq Ibn Imran, Ibn Sina) transmitted and expanded classical Greek concepts of mood disorders" },
    { era: "1899", text: "Emil Kraepelin unified the disorder as 'Manic-Depressive Insanity' — distinguishing it from dementia praecox (schizophrenia)" },
    { era: "1957", text: "Karl Leonhard coined the bipolar/unipolar distinction, later validated by Angst and Perris (1966)" },
    { era: "1980", text: "DSM-III formally introduced 'Bipolar Disorder' as a diagnostic category" },
    { era: "2013", text: "DSM-5 separated Bipolar and Related Disorders into its own chapter, recognizing the 'bridge' between psychosis and depression" },
  ];

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}

// ══════════════════════════════════════════════════════════════════
// SLIDE 4 — Classification & Types
// ══════════════════════════════════════════════════════════════════
{
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  addSlideHeader(s, "Classification & Types", "DSM-5-TR Bipolar Spectrum");

  const types = [
    { label: "Bipolar I", color: C.navy, items: ["≥1 manic episode (≥7 days or hospitalized)", "Depressive episodes common but not required", "May include psychotic features", "Most severe form of bipolar spectrum"] },
    { label: "Bipolar II", color: C.teal, items: ["≥1 hypomanic episode (≥4 days) + ≥1 MDE", "Never a full manic episode", "More prevalent than BP I in outpatient settings", "High burden of depression and suicide risk"] },
    { label: "Cyclothymia", color: C.indigo, items: ["≥2 years of hypomanic & depressive symptoms", "Never meets full criteria for MDE or mania", "Subthreshold cycling mood instability", "Prevalence ~0.4–1% in general population"] },
  ];

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// ══════════════════════════════════════════════════════════════════
// SLIDE 5 — Epidemiology
// ══════════════════════════════════════════════════════════════════
{
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  addSlideHeader(s, "Epidemiology", "WHO World Mental Health Surveys & NESARC Data");

  // Stat boxes row
  const stats = [
    { val: "~1%", label: "Lifetime Prevalence\nBipolar I (classic)" },
    { val: "3.3%", label: "NESARC Lifetime\nBipolar I (updated)" },
    { val: "2.4%", label: "Bipolar Spectrum\n(cross-national WMH)" },
    { val: "1.8%", label: "Pediatric/Adolescent\nBipolar (meta-analysis)" },
  ];
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    "Bipolar II prevalence is ~1.1% lifetime (NESARC), though often underdiagnosed",
    "12-month prevalence rates: BP I ~2.0%, BP II ~0.8%",
    "BP disorder is enduring — longitudinal estimates converge at 1.4–2.1%",
    "Equal prevalence in men and women; men more often have mania, women have more depressive episodes",
    "Mean age of onset: late teens to mid-20s; often delayed 6–10 years before correct diagnosis",
    "High comorbidity: anxiety disorders (~75%), substance use disorders (~60%), ADHD (~20%)",
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  addSource(s);
}

// ══════════════════════════════════════════════════════════════════
// SLIDE 6 — Clinical Features: Mania
// ══════════════════════════════════════════════════════════════════
{
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  addSlideHeader(s, "Clinical Features: Mania & Hypomania", "Psychopathology of the Manic Syndrome");

  // Left column — Mood
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    "Psychomotor acceleration; pressured speech",
    "Flight of ideas; clang associations",
    "Decreased need for sleep",
    "Heightened sensory acuity",
    "Grandiose beliefs; inflated self-esteem",
    "Racing thoughts",
  ], { fontSize: 12 }), { x: 3.6, y: 1.65, w: 3.0, h: 2.0 });

  // Right column — Behavior
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  s.addText("BEHAVIOR", { x: 6.9, y: 1.25, w: 2.6, h: 0.38, fontSize: 12, bold: true, color: C.navy, align: "center", valign: "middle", fontFace: "Calibri" });
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    "Pathologic overfamiliarity with strangers",
    "Hypersexuality",
    "Reckless spending",
    "Poor judgment",
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    { text: "Hypomania is a distinct period of at least a few days of mild mood elevation with sharpened thinking and increased energy — without the marked impairment or psychosis of mania. It is not merely a milder form of mania. Insight is relatively preserved. Antidepressants can sometimes mobilize hypomania.", options: { fontSize: 12, color: C.dark, fontFace: "Calibri" } },
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}

// ══════════════════════════════════════════════════════════════════
// SLIDE 7 — Clinical Features: Depression & Mixed States
// ══════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: "100%", h: "100%", fill: { color: C.light } });
  addSlideHeader(s, "Clinical Features: Depression & Mixed States");

  // Depression box
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  s.addText("BIPOLAR DEPRESSION", { x: 0.4, y: 1.25, w: 4.3, h: 0.42, fontSize: 14, bold: true, color: C.white, align: "center", valign: "middle", fontFace: "Calibri" });
  s.addText(bulletItems([
    "Depressed mood; anhedonia; fatigue",
    "Psychomotor retardation (more common than agitation)",
    "Hypersomnia (vs insomnia in unipolar depression)",
    "Increased appetite / weight gain",
    "Leaden paralysis (heavy limb sensation)",
    "Atypical features more common",
    "Depressive mixed states: depressed mood + manic features (flight of ideas, increased drives, impulsivity) — present in ~60% of BP II",
    "High suicide risk — especially in BP II with cyclothymia",
  ], { fontSize: 12 }), { x: 0.4, y: 1.7, w: 4.3, h: 3.3 });

  // Mixed states box
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  s.addText("MIXED FEATURES / STATES", { x: 5.1, y: 1.25, w: 4.4, h: 0.42, fontSize: 14, bold: true, color: C.navy, align: "center", valign: "middle", fontFace: "Calibri" });
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    "Coexistence of manic and depressive features simultaneously",
    "Soranus described mixed episodes as early as 1st century CE",
    "DSM-5 introduced the 'with mixed features' specifier for both manic and depressive episodes",
    "Escalating irritability, anger, agitation, insomnia",
    "Dysphoric mania: Kraepelinian 'anxious-depressive mania'",
    "Often refractory to antidepressants; mood stabilizers preferred",
    "Increased suicide risk; careful monitoring required",
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  addSource(s);
}

// ══════════════════════════════════════════════════════════════════
// SLIDE 8 — Etiology & Pathophysiology
// ══════════════════════════════════════════════════════════════════
{
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  addSlideHeader(s, "Etiology & Pathophysiology", "Immune, Neurobiological & Neuroprogressive Mechanisms");

  const boxes = [
    {
      title: "Immune & Inflammatory", color: C.navy,
      items: [
        "Elevated circulating CRP, TNF, IL-6, IL-1RA, sIL-2R",
        "Increased inflammatory Th1 / decreased anti-inflammatory Th2 responses",
        "KYN (kynurenine) pathway activation — disrupts glutamate and dopamine signaling",
        "Inflammatory gene expression precedes clinical relapse in BD",
      ],
    },
    {
      title: "Neuroprogressive (Kindling)", color: C.teal,
      items: [
        "Each relapse increases risk and severity of subsequent episodes",
        "Increasing cognitive/neurologic dysfunction over time",
        "Allostatic load — chronic immune activation from recurrent stress",
        "Innate immune factors central to neuroprogression",
      ],
    },
    {
      title: "Neurotransmitter Systems", color: C.indigo,
      items: [
        "Dopamine excess in mania (dopamine hypothesis)",
        "Serotonin dysregulation — related to depression phase",
        "Glutamate & GABA imbalance — inflammation-linked",
        "HPA axis dysregulation; cortisol hypersecretion",
      ],
    },
  ];

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    const x = 0.25 + i * 3.25;
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    s.addText(bulletItems(b.items, { fontSize: 12 }), { x: x + 0.1, y: 1.75, w: 2.8, h: 2.5 });
  });

  // NAC / therapeutic note
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    { text: "Immunotherapy Research: ", options: { bold: true, fontSize: 12, color: C.navy, fontFace: "Calibri" } },
    { text: "N-acetylcysteine (NAC) has shown positive results across all phases of BD by targeting oxidative stress. NAC + aspirin combination demonstrates better response than monotherapy. Infliximab showed subgroup effects in patients with early life stress and elevated CRP (>5 mg/L).", options: { fontSize: 12, color: C.dark, fontFace: "Calibri" } },
  ], { x: 0.6, y: 4.5, w: 8.8, h: 0.75 });

  addSource(s);
}

// ══════════════════════════════════════════════════════════════════
// SLIDE 9 — Genetics
// ══════════════════════════════════════════════════════════════════
{
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  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: "100%", h: "100%", fill: { color: C.light } });
  addSlideHeader(s, "Genetics of Bipolar Disorder", "Heritability, Twin Studies & Molecular Findings");

  // Heritability stat boxes
  const hstats = [
    { val: "65–100%", label: "MZ Twin\nConcordance" },
    { val: "10–30%", label: "DZ Twin\nConcordance" },
    { val: "60–80%", label: "Overall\nHeritability" },
    { val: "30–40%", label: "Unipolar MDD\nHeritability (compare)" },
  ];
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    const x = 0.3 + i * 2.35;
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    s.addText(h.val, { x, y: 1.25, w: 2.1, h: 0.7, fontSize: 24, bold: true, color: C.gold, align: "center", valign: "middle", fontFace: "Calibri" });
    s.addText(h.label, { x, y: 1.9, w: 2.1, h: 0.55, fontSize: 11, color: C.white, align: "center", valign: "top", fontFace: "Calibri" });
  });

  s.addText(bulletItems([
    "BD is substantially more heritable than unipolar major depression",
    "Early single-gene linkage studies (chromosomes X and 11) produced false-positive findings — not replicated",
    "Genome-wide association studies (GWAS) support polygenic model with multiple interacting loci",
    "Suggestive linkage regions: chromosomes 18, 4p, 21q, 8q, 12q, 16p — but none unequivocally confirmed",
    "Rapid decrease in recurrence risk from MZ twins to first-degree relatives argues against single-gene inheritance",
    "Gene expression studies: inflammatory gene upregulation precedes relapse and normalizes during remission",
    "Shared genetic risk between BD and schizophrenia: CACNA1C, ANK3, TENM4, TRANK1 among top candidates",
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  addSource(s);
}

// ══════════════════════════════════════════════════════════════════
// SLIDE 10 — DSM-5-TR Diagnostic Criteria
// ══════════════════════════════════════════════════════════════════
{
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  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: "100%", h: "100%", fill: { color: C.light } });
  addSlideHeader(s, "Diagnosis: DSM-5-TR Criteria", "Bipolar I & Bipolar II Disorder");

  // BP I column
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  s.addText("BIPOLAR I DISORDER", { x: 0.4, y: 1.25, w: 4.2, h: 0.42, fontSize: 14, bold: true, color: C.white, align: "center", valign: "middle", fontFace: "Calibri" });
  s.addText(bulletItems([
    "Criterion A: Distinct period of abnormally elevated, expansive, or irritable mood + increased goal-directed activity/energy",
    "Duration: ≥7 days (or any duration if hospitalization required)",
    "Criterion B (≥3 of 7, or ≥4 if only irritable mood):",
    "    • Inflated self-esteem or grandiosity",
    "    • Decreased need for sleep (≥3 hrs less)",
    "    • More talkative / pressured speech",
    "    • Flight of ideas or racing thoughts",
    "    • Distractibility",
    "    • Increased goal-directed activity / psychomotor agitation",
    "    • Risky behavior (spending sprees, sexual indiscretion)",
    "Criterion C: Marked impairment / hospitalization / psychotic features",
    "Not due to substances or medical conditions",
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    "Criterion A: ≥1 hypomanic episode + ≥1 major depressive episode",
    "Never a full manic episode",
    "Hypomania criteria:",
    "    • Same symptoms as mania",
    "    • Duration ≥4 consecutive days",
    "    • Observable change in behavior by others",
    "    • NOT severe enough for hospitalization",
    "    • No psychotic features",
    "MDE criteria (≥5 of 9 symptoms ≥2 weeks):",
    "    • Depressed mood, anhedonia, weight changes, insomnia/hypersomnia, psychomotor changes, fatigue, worthlessness, poor concentration, suicidal ideation",
    "Clinically significant distress or impairment",
    "Not better explained by cyclothymia, schizoaffective, etc.",
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// ══════════════════════════════════════════════════════════════════
// SLIDE 11 — Treatment: Acute Mania
// ══════════════════════════════════════════════════════════════════
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        "First-line; ~50% response rate in 3-week trials",
        "Onset: 7 days; target serum level 0.8–1.2 mEq/L",
        "Starting dose: 900 mg/day (lower in elderly: 0.4–0.8 mEq/L)",
        "Toxicity >1.5 mEq/L: GI, neuro, cardiac — medical emergency",
      ],
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    {
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      points: [
        "Efficacy equivalent to lithium in adult mania",
        "Oral loading (20–30 mg/kg/day) → effect by day 5",
        "Target serum level: 50–125 mcg/mL",
        "Effective regardless of prior episodes, rapid cycling, psychosis",
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        "As effective as lithium and typical antipsychotics",
        "Extended-release (Equetro): FDA-approved for acute mania",
        "Response rates 40–60%; onset 7–10 days",
        "Starting dose: 100–200 mg bid; target 400–800 mg/day",
      ],
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    {
      name: "Atypical Antipsychotics", color: "4A4A8A",
      points: [
        "Olanzapine, risperidone, quetiapine, aripiprazole, asenapine",
        "Asenapine: FDA-approved as mono- and adjunctive therapy",
        "Faster onset than mood stabilizers in first 3 days",
        "Useful for psychotic mania; combination with mood stabilizers",
      ],
    },
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// ══════════════════════════════════════════════════════════════════
// SLIDE 12 — Treatment: Bipolar Depression & Maintenance
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    "Quetiapine (monotherapy): FDA-approved for BP I & II depression",
    "Olanzapine-fluoxetine combination (Symbyax): FDA-approved for BP I depression",
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    "Lurasidone (mono or adjunctive with Li/VPA): FDA-approved",
    "Lithium: antidepressant effects documented, especially with Li levels ≥0.8",
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    "Valproate: effective maintenance, particularly for rapid cycling",
    "Lamotrigine: superior maintenance for depressive relapses",
    "Aripiprazole, quetiapine, olanzapine: adjunctive maintenance",
    "Serum level monitoring (lithium, valproate, carbamazepine) essential",
    "Address medication adherence — key predictor of relapse",
    "Monitor for metabolic side effects (weight, glucose, lipids) with SGAs",
    "ECT: reserved for severe, refractory, or pregnant patients",
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// ══════════════════════════════════════════════════════════════════
// SLIDE 13 — Psychosocial Interventions
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    { name: "Psychoeducation", color: C.navy, text: "Group format (up to 50 participants + families). Focuses on risk factors, warning signs, coping strategies. Cost-effective; reduces relapse rates and improves medication adherence. Colom et al., Barcelona model." },
    { name: "CBT\n(Cognitive-Behavioral)", color: C.teal, text: "Identifies and modifies maladaptive thought patterns. Shown to increase 'well time' and reduce recurrence as adjunct to pharmacotherapy. Effect size comparable to divalproex or lamotrigine prophylaxis." },
    { name: "IPSRT\n(Interpersonal & Social Rhythm)", color: C.indigo, text: "Stabilizes social rhythms and sleep-wake cycles. Addresses interpersonal triggers of mood episodes. Effective for both depressive symptoms and social functioning in STEP-BD trial." },
    { name: "FFT\n(Family-Focused)", color: "2E6B3E", text: "Involves patient and family. Addresses communication, problem-solving, and psychoeducation for caregivers. Significant effects on depressive symptoms and functioning in STEP-BD." },
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// ══════════════════════════════════════════════════════════════════
// SLIDE 14 — Comorbidities & Special Populations
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    "Anxiety disorders: ~75% (most common comorbidity)",
    "Substance use disorders: ~60% — bidirectional relationship",
    "ADHD: ~20%; especially in BP II",
    "Personality disorders: borderline PD often confused with BP II + cyclothymia",
    "Metabolic syndrome: increased risk with SGAs and weight gain",
    "Cardiovascular disease: higher prevalence and mortality",
    "Migraine: ~35% of BD patients",
    "Thyroid dysfunction: especially with lithium use (hypothyroidism)",
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    "Pediatric: Prevalence 1.8% (meta-analysis); often presents with mixed/irritable features rather than euphoria",
    "Elderly: Lower lithium doses (level 0.4–0.8 mEq/L); more sensitive to side effects",
    "Pregnancy: Valproate teratogenic; lithium — cardiac defects (Ebstein); lamotrigine relatively safer",
    "HIV/AIDS: Lithium problematic; rapid level fluctuations; valproate preferred; low-dose SGAs",
    "Rapid Cycling (≥4 episodes/year): Valproate, lamotrigine; avoid antidepressants",
    "Elderly-onset mania: Suspect organic cause — vascular, pharmacologic",
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// ══════════════════════════════════════════════════════════════════
// SLIDE 15 — Prognosis & Course
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    "Bipolar disorder is a chronic, episodic illness — most patients experience multiple recurrences across a lifetime",
    "Neuroprogressive model (kindling): each episode increases risk and severity of the next, with greater cognitive dysfunction",
    "Mean age of first episode: late teens–20s; often 6–10 years before correct diagnosis",
    "Functional impairment is common even between episodes — subsyndromal symptoms, cognitive deficits",
    "Suicide risk: BD carries one of the highest suicide rates among psychiatric conditions (~15–20× general population); BP II especially high due to cycling depression",
    "Rapid cycling (≥4 episodes/year): associated with poorer prognosis, often triggered by antidepressants or thyroid disease",
    "Better prognosis associated with: later age of onset, shorter episode duration, good medication adherence, strong social support",
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// ══════════════════════════════════════════════════════════════════
// SLIDE 16 — Summary / Key Takeaways
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    "Bipolar disorder is highly heritable (60–80%) with a polygenic basis; environmental factors (childhood adversity, stress) modulate expression",
    "BP I requires ≥1 manic episode; BP II requires hypomanic + depressive episodes — never full mania",
    "Lifetime prevalence: BP I ~1–3.3%; BP Spectrum ~2.4%; median onset late teens–20s",
    "Mania triad: elevated/irritable mood + psychomotor acceleration + decreased sleep — recognize early to prevent disaster",
    "Mixed features are common and underappreciated — associated with highest suicide risk",
    "First-line acute mania: lithium, divalproex, carbamazepine, or atypical antipsychotics",
    "Bipolar depression: quetiapine, lamotrigine, OFC (Symbyax); avoid antidepressant monotherapy",
    "Psychosocial interventions (CBT, IPSRT, FFT, psychoeducation) significantly reduce relapse when added to mood stabilizers",
    "Neuroprogression — treat early, maintain adherence, prevent recurrence",
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