• Kaplan & Sadock's Comprehensive Textbook of Psychiatry (CTP)
• Maudsley Prescribing Guidelines
• Stahl's Essential Psychopharmacology
• ICD-10 / ICD-11 diagnostic criteria
• DSM-5 / DSM-5-TR

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Classification of Obsessive-Compulsive and Related Disorders (OCRDs)

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1. Historical Context & Rationale for a Separate Chapter

• Phenomenology (repetitive, intrusive thoughts + repetitive behaviors)
• Psychobiology (cortico-striato-thalamo-cortical [CSTC] circuit dysfunction)
• Genetics (familial clustering)
• Treatment response (SRIs + ERP)

"OCRDs constitute a new chapter in both the DSM-5 and the ICD-11... given the evidence that these share some phenomenologic and psychobiological features, and to improve the recognition and management of these underdiagnosed and undertreated conditions."

• Kaplan & Sadock's CTP, p. 5482

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2. DSM-5 / DSM-5-TR Classification

• Other specified OCRD
• Unspecified OCRD

• Insight specifier: Good/fair insight | Poor insight | Absent insight/delusional beliefs
• With tic-related disorder (important - tic specifier unique to DSM-5)

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3. ICD-11 Classification (6B2x codes)

• Kaplan & Sadock's CTP, p. 3715 (ICD-11 codes 6B20-6B2Y)

• Fair to good insight
• Poor to absent insight (Note: ICD-11 did NOT include a tic specifier, unlike DSM-5)

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4. ICD-10 Classification

• F45.2 - Hypochondriacal disorder (under somatoform)
• F63.3 - Trichotillomania (under habit and impulse disorders)
• F45.22 - BDD (under somatoform disorders)

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5. Comparative Summary Table (Exam-Ready)

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6. Key Points from Stahl's (Psychopharmacology Basis)

• OCD was removed from the anxiety disorder chapter in DSM-5 because compulsions are better understood as habit-driven behaviors (conditioned responses from the environment) rather than purely anxiety-driven acts - Stahl's, p. 592
• The underlying circuit is the CSTC loop (cortico-striato-thalamo-cortical), which is hyperactive in OCD
• Stahl conceptualizes compulsions similarly to addictive behaviors - both involve loss of cognitive flexibility and inability to inhibit habits via the orbitofrontal cortex
• First-line pharmacotherapy: SSRIs (though efficacy is modest; ~50% show poor response)
• ERP (Exposure and Response Prevention) often shows greater efficacy than pharmacotherapy alone

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7. Clinically Important Nuances (MCQ + Viva Points)

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Tic Disorders - Complete PG-Level Review

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1. CLASSIFICATION

DSM-5 / DSM-5-TR Classification

ICD-11 Classification (under OCRDs)

Key ICD-11 change: Tourette syndrome is placed under the OCRDs chapter (alongside OCD, BDD etc.), unlike DSM-5 which places it under Neurodevelopmental Disorders.

ICD-10 Classification

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2. EPIDEMIOLOGY

"The exact relationship between childhood tics and Gilles de la Tourette syndrome remains uncertain." - Goldman-Cecil Medicine, p. 3975

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3. PHENOMENOLOGY

Definition

"A tic is a sudden, rapid, recurrent, nonrhythmic motor movement or vocalization." - Kaplan & Sadock's CTP, p. 9742

Types of Tics

Phenomenological Features

• Premonitory urge: A sensory discomfort or tension that precedes the tic - distinguishes tics from other involuntary movements. Patients describe it as an urge, itch, or pressure that is temporarily relieved by performing the tic. This is called the "just right phenomenon."
• Suppressibility: Tics can be partially suppressed voluntarily (unlike chorea/myoclonus), but suppression leads to increased urge and a "rebound" in tics - this is why tics often worsen at home after school
• Waxing and waning: Fluctuation in severity over weeks/months is characteristic; new tics replace old ones
• Stress-sensitive: Emotional conflict, anxiety, fatigue, and excitement increase tic frequency
• Sleep: Tics persist during sleep (unlike psychogenic movements which do not)
• Coprolalia: Highly publicized but present in <10% of TS patients - not required for diagnosis
• Voluntary vs. involuntary: Some patients describe tics as "partially volitional" - triggered by and leading to relief from premonitory urge (functionally parallel to obsession-compulsion cycle)

Key Distinction: Tics vs. Compulsions

Course and Prognosis

• Onset of motor tics typically in early childhood; vocal tics follow 1-2 years later
• Peak severity at ~10-12 years; majority show improvement after mid-adolescence
• Tics involving limbs/trunk remit less promptly than facial tics
• Chronic motor tics last 4-6 years and often remit in early adolescence
• For TS: 43-68% continue to meet criteria up to 14 years after initial diagnosis (in OCD literature context)

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4. NEUROBIOLOGY

Genetic Basis

• Highly heritable: Twin studies show high concordance in MZ twins for either TD or chronic motor tics - supports hereditary transmission
• Bilineal transmission (inherited from both parents) may explain genetic heterogeneity
• HDC gene mutation: Functional mutation in HDC (encoding L-histidine decarboxylase) - implicates histaminergic neurotransmission
• Copy number variants: NRXN1 and CNTN6 increase risk for TS
• No single causative gene identified; genome-wide association studies have found multiple susceptibility loci
• First-degree relatives of TD probands have higher frequencies of both TD and OCD - supports shared genetic diathesis

Neurobiological Models

• Robust response to dopamine receptor-blocking medications strongly implicates dopaminergic dysfunction
• However, PET studies have NOT demonstrated consistent dopaminergic hyperactivity in TS - the picture is more complex
• The leading model is dysregulation of the cortico-striato-thalamo-cortical (CSTC) circuit - same circuit implicated in OCD

• PET with [11C]-flumazenil shows decreased GABA-A receptor binding in:
  • Ventral striatum, globus pallidus, thalamus, amygdala, right insula (bilaterally)
• Increased GABA-A binding in:
  • Bilateral substantia nigra, periaqueductal gray, posterior cingulate cortex, cerebellum
• This suggests TS is fundamentally a "disinhibition" disorder - failure of inhibitory GABAergic control over corticostriatal circuits allows tics to "break through"

• HDC gene mutation (histidine decarboxylase) - implicated in rare familial TS
• Histamine modulates dopamine and GABA in the striatum

• Implicated in comorbid OCD component; SRIs effective for OCD-TS overlap

• CSTC circuit uses glutamate as the primary excitatory neurotransmitter
• Riluzole (glutamate modulator) has been studied

• Structural MRI: Reduced volume of caudate nucleus bilaterally in TS
• fMRI: Abnormal activation in prefrontal cortex, striatum, thalamus, motor cortex
• The core circuit dysfunction: Prefrontal cortex → Striatum → Globus pallidus → Thalamus → Cortex (CSTC loop)

• PANDAS = Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections
• Post-streptococcal autoantibodies targeting basal ganglia neurons proposed as a trigger
• Remains controversial but clinically relevant for acute-onset tic exacerbations in children

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5. PHARMACOLOGICAL MANAGEMENT

"The goal of treatment is not to eliminate tics but to relieve tic-related discomfort or distress and to achieve a degree of control of tics that allows the patient to function as normally as possible." - Kaplan & Sadock's CTP, p. 11457

First-Line: Alpha-2 Adrenergic Agonists

Second-Line: Antipsychotics (Dopamine Receptor Blockers)

Third-Line / Specialized Options

For Comorbidities

Deep Brain Stimulation (DBS)

• For severely disabling, treatment-refractory tics
• Targets: Thalamus (centromedian nucleus) or Globus Pallidus Internus (GPi)
• Recommended by American Academy of Neurology practice guidelines for refractory cases

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6. NON-PHARMACOLOGICAL MANAGEMENT

"Nonpharmacologic treatments have been developed that are as successful as pharmacotherapy. In fact, the first-line treatment for mild to moderate tics is cognitive-behavioral intervention." - Kaplan & Sadock's CTP, p. 11457

A. Psychoeducation (Essential First Step)

• Education of patient, parents, teachers, and school personnel
• Clarify that tics are not intentional - relieves enormous psychological burden
• Families should know tics can be partially suppressed but suppression causes rebound
• Referral to Tourette Association of America and local support groups for all newly diagnosed patients
• Practical goal: personal management of symptoms, not elimination

B. Comprehensive Behavioral Intervention for Tics (CBIT)

1. Habit Reversal Training (HRT) - the core component:
   • Awareness training: Patient learns to detect the premonitory urge before tic onset
   • Competing response training: Patient performs a physically incompatible movement when the urge is felt (e.g., for a head-jerk tic, isometric neck tensioning)
   • Social support: Family members reinforce implementation
2. Function-based assessment and intervention:
   • Identify antecedents that worsen tics (stress, social situations, screen time)
   • Modify environment to reduce tic-triggering contexts
3. Relaxation training:
   • Deep breathing, guided imagery, progressive muscle relaxation, mindfulness
   • Particularly useful for the anxious TS patient

C. Exposure and Response Prevention (ERP)

• Exposure to the premonitory urge without performing the tic
• Based on habituation learning - urge intensity decreases with repeated non-performance
• Large RCT evidence supporting ERP as efficacious

D. Relaxation and Stress Management

• Yoga, mindfulness, biofeedback
• Caffeine and excess sugar should be minimized (may exacerbate tics in some patients)
• Balanced diet and exercise regimen contribute to stress reduction

E. "Tic Room" / Containment Strategy

• A designated space where the patient can release suppressed tics
• Allows private "de-stimulation" after periods of voluntary suppression at school/work
• Prevents the buildup and explosive rebound

F. School Accommodations

• Individualized education plan (IEP) or 504 plan
• Extended time for exams; preferential seating; breaks during testing
• Educating peers and teachers reduces stigma and bullying

G. Psychotherapy

• Supportive psychotherapy for emotional adjustment
• CBT for comorbid anxiety, OCD, depression
• Family therapy to address the secondary social difficulties
• Social skills training for peer rejection due to tics

H. Transcranial Magnetic Stimulation (TMS)

• Investigational; some evidence in refractory cases
• Convergent with DBS in providing neuromodulatory benefit

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7. TREATMENT ALGORITHM SUMMARY

STEP 1: Diagnosis + Psychoeducation + School/Work Advocacy
         ↓
STEP 2: Mild-Moderate Tics → CBIT (first line)
         ↓ (if insufficient)
STEP 3: Add Alpha-2 Agonist (Clonidine or Guanfacine)
         ↓ (if still insufficient)
STEP 4: Atypical Antipsychotic (Aripiprazole or Risperidone)
         ↓ (if still insufficient)
STEP 5: Typical Antipsychotic (Haloperidol, Pimozide, Fluphenazine)
         ↓ (refractory, disabling)
STEP 6: VMAT2 inhibitors / Botulinum toxin / DBS

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8. EXAM POINTS / VIVA PEARLS

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Epidemiology and Neurocircuitry of Stimulant Use Disorder

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1. DEFINITION & CLASSIFICATION

• Cocaine (crack cocaine, powder cocaine)
• Amphetamine-type stimulants (ATS): amphetamine, methamphetamine, MDMA (ecstasy), methylphenidate (when misused)
• Other stimulants: synthetic cathinones ("bath salts" - MDPV, mephedrone, methylone), khat, phenylpropanolamine

• 6C44 - Cocaine dependence
• 6C43 - Stimulant including amphetamines, methamphetamine, or methcathinone use disorders

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2. EPIDEMIOLOGY

• Amphetamine-type stimulants increasingly detected in India
• Ephedrine diverted for methamphetamine synthesis
• Surveys show rising amphetamine use in urban youth
• NDPS Act covers amphetamines, cocaine, and precursor chemicals

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3. NEUROCIRCUITRY OF STIMULANT USE DISORDER

3A. The Mesolimbic Dopamine Pathway - Final Common Reward Pathway

"A leading theory of addiction for over 40 years has been the dopamine theory, proposing that the final common pathway of reinforcement and reward in the brain for anything pleasurable is the mesolimbic dopamine pathway." - Stahl's, p. 557

• VTA (Ventral Tegmental Area): Origin of mesolimbic dopamine neurons
• Nucleus Accumbens (NAc) / Ventral Striatum: Primary reward terminal; site of acute drug-induced dopamine flooding
• Prefrontal Cortex (PFC): Executive control, decision-making, impulse inhibition - progressively loses control as addiction advances
• Amygdala: Encodes drug-related emotional memories and conditioned cues
• Hippocampus: Contextual memory of drug-associated environments

3B. Neurotransmitter Regulation of the Reward Circuit

"The inputs to the mesolimbic pathway that mediate these natural highs include... the brain's own morphine/heroin (endorphins), the brain's own marijuana (anandamide), the brain's own nicotine (acetylcholine), to the brain's own cocaine and amphetamine (dopamine itself)." - Stahl's, p. 558

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3C. How Stimulants Specifically Hijack the Circuit

Mechanism of Action

• Cocaine = reuptake inhibitor (blocks DAT, stops DA clearance)
• Amphetamine/methamphetamine = releasing agents (forces DA out of vesicles and neurons into synapse via reverse transport) - hence more powerful and more neurotoxic

"The reinforcing effects and abuse of stimulants occur when DATs in the mesolimbic reward circuit are suddenly blasted and massively blocked." - Stahl's, p. 559

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3D. Pharmacokinetics and the "High" - Why Route of Administration Matters

"The speed with which a stimulant enters the brain dictates the degree of the subjective 'high'... stimulants when abused are often not ingested orally but instead are smoked, inhaled, snorted, or injected." - Stahl's, p. 559-560

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3E. Tonic vs. Phasic Dopamine Firing - The Core Neurobiological Concept

• Therapeutic stimulant use (ADHD dose): Amplifies tonic DA → pro-cognitive PFC effects
• Stimulant abuse: Explosive phasic DA release in NAc → intense euphoria, high addiction potential
• The "therapeutic window": Moderate DAT/NET occupancy = therapeutic; >80% DAT occupancy = addictive

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3F. Progression of Stimulant Abuse - The Ventral-to-Dorsal Striatal Shift

"Dopamine neurons terminating in the ventral striatum actually stop responding to the primary reinforcer (taking the drug) and instead dopamine neurons terminating in the dorsal striatum begin to respond to the conditioned stimuli (handling the crack pipe) before the drug is even taken!" - Stahl's, p. 561

• Why addicts are motivated and aroused when seeking drugs
• Why they are withdrawn and apathetic to non-drug rewards
• Why craving is triggered by cues (people, places, paraphernalia) not just the drug itself

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3G. Neuroadaptation and "Burn-Out"

• Oxidative stress from massive DA release
• Damage to DAT-expressing axons in striatum and PFC
• Serotonergic axon degeneration
• Neuroimaging shows reduced striatal DAT density and grey matter loss in PFC, hippocampus, cingulate cortex

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3H. The Three-Stage Addiction Cycle (Koob & Volkow Model)

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3I. Dopaminergic Pathways Involved

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4. ADDITIONAL NEUROTRANSMITTERS BEYOND DOPAMINE

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5. EXAM SUMMARY TABLE

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