Cognitive & Biological Perspectives on Depression & Schizophrenia

Introduction & Lecturer Context

  • Lecturer: Dr. Andrew Martin, Senior Lecturer in Cognitive Neuropsychology, University of Kent.

  • Dual appointment across Medicine & Psychology; open‐door policy for email/office meetings.

  • Lecture Goals:

    • Re-cap Year-1 diagnostic concepts.

    • Explore biological & cognitive explanations for Depression and Schizophrenia.

    • Preview on-going Kent research; invitation to join final-year/placement projects.

Key Diagnostic Concepts

The “Four D’s” of Psychopathology

  • Statistical Deviation / Deviance

    • Traits lie on spectra; extreme ends trigger clinical concern.

    • E.g. most people score >0 on depression or psychosis questionnaires.

  • Distress

    • Sufferer’s anguish or distress caused to others (societal dilemma of individual vs. public safety).

  • Dysfunction

    • Interference with work, study, relationships, social functioning.

    • Auditory hallucinations: commonplace (≈10\% lifetime) but clinical only if distressing/impairing.

  • Danger

    • Risk of harm to self (e.g.
      suicidality) or others.

    • Statistically, people with mental disorders are more likely to be victims than perpetrators of violence.

Classification Manuals

  • DSM-5 & ICD-10 = “Bibles” of psychiatry.

  • Diagnosis relies on structured interviews & checkbox criteria—still categorical even as research moves to dimensional/ symptom‐level focus (e.g. grants now demand mechanistic targets like paranoia, not “50 schizophrenics vs 50 controls”).

  • Pros & Cons of labels:

    • + Facilitate communication, treatment protocols, research measurement.

    • – Stigma, confirmation bias (“everything they do = because of X”).

Biopsychosocial Model Reminder

  • Need to integrate biological, psychological, social domains; today’s emphasis = first two, but social factors invariably interact (e.g. hormones × support network; poverty × stress).

Major Depressive Disorder (MDD)

Epidemiology

  • Lifetime prevalence: 15\%.

  • Point prevalence: 5!-!10\%.

  • Average onset: 27 yrs; bimodal pattern (adolescence & late-life peaks).

  • Gender ratio: ≈2:1 (women > men).

    • Possible explanations: male alexithymia, externalising (aggression), substance misuse masking depression.

  • Socio-economic stress elevates risk but disorder is cross-cultural.

  • \sim 2/3 recover within 4!-!6 months; treatment-resistant minority exists.

Core Symptom Clusters (DSM emphasis)

  • Affective/Cognitive: worthlessness, hopelessness, helplessness, suicidal ideation.

  • Anhedonia: absence of anticipated pleasure—often more reliable than overt sadness.

  • Energy/Motor: psychomotor retardation, fatigue.

  • Sleep/Appetite: insomnia or hypersomnia; weight change.

  • Cognitive: impaired concentration, executive dysfunction.

  • Duration: ≥2 weeks (usually longer) & not attributable to substances/medical illness.

Cognitive Models

  • Beck’s Negative Cognitive Triad

    • Internal (“It’s me”), Global (“Everything”), Stable (“Always”) attribution style.

  • Rumination Cycle

    • Humans uniquely simulate past/future; ineffective disengagement → repetitive negative thought.

    • Requires cognitive control (frontoparietal networks) to interrupt.

Biological Bases
Genetics

  • Heritability ≈40\%.

  • Massive GWAS (n \approx 1.3\text{ million}) ⇒ polygenic: hundreds of variants, each ≤0.2\% risk; combined polygenic risk score (PRS) explains ≈5\% variance.

  • PRS modestly predicts:

    • Higher risk for other disorders (pleiotropic “p-factor”).

    • Lower performance on executive & social-cognition tasks.

  • Many risk SNPs cluster on glutamate & GABA receptor genes → drug-development targets.

Infections & Immune Factors

  • Borna disease: only 2\% victims remain euthymic; \sim 30\% develop severe depression.

  • COVID-19 / Long-COVID: global spike in depression, anxiety, psychosis irrespective of lockdown rules.

Hormonal Influences

  • Post-partum depression: 20\% incidence; linked to estrogen & progesterone crash.

  • Male postpartum / andropause: testosterone drop ↔ mood decline.

  • Menstrual cycle & menopause: phase-specific mood/cognition fluctuations; active Kent research project.

  • Adolescence: pubertal hormone surges + social upheaval.

Neuroimaging

  • Meta-analysis highlights subtle, non-diagnostic differences:

    • ↓ volume & activity: hippocampus, dorsolateral PFC.

    • ↑ activity: ventromedial PFC (self-referential focus).

    • Amygdala & putamen alterations (salience, reward blunting).

  • Treatment response pattern: remission ↔ ↑ dorsolateral PFC, ↓ vmPFC hyperactivity.

Neurochemical Models & Medication

  • Traditional focus: serotonin, dopamine, norepinephrine.

    • SSRIs discovered serendipitously; serotonin deficiency theory contested (e.g. rare serotonin-null patient not depressed).

  • Placebo ≈30\% response; meds & CBT each ≈50\%; combined often used.

  • Novel approaches: glutamatergic modulators (ketamine, esketamine).

Somatic & Neurostimulation Therapies

  • Electroconvulsive Therapy (ECT)

    • For treatment-resistant, suicidal, or psychotic depression; rapid effect, relapse common (~6 mo).

  • Deep Brain Stimulation (DBS)

    • Electrodes in subgenual cingulate; reserved for extreme, refractory cases.

  • Transcranial Magnetic Stimulation (TMS) / tDCS

    • Non-invasive targeting left DLPFC; growing evidence base, more portable.

  • Neurofeedback (“brain training”) clinics use real-time fMRI/EEG—evidence tentative.

Schizophrenia

Epidemiology & Impact

  • Prevalence: \approx 1\% worldwide (culture-invariant).

  • Onset: late adolescence/early adulthood; earlier & more severe in men.

  • Chronic, debilitating; contributes heavily to global Disability‐Adjusted Life Years (DALYs).

  • High comorbidity: substance misuse, smoking, homelessness; reduced life expectancy.

DSM-5 Criteria (simplified)

  • ≥2 of: delusions, hallucinations, disorganised speech, disorganised/catatonic behaviour, negative symptoms.

  • Continuous disturbance ≥6 months; functional decline; not due to substances or medical disorders.

Symptom Typology

  • Positive (excess): hallucinations (esp. auditory-verbal), delusions, thought disorder.

  • Negative (deficit): avolition, anhedonia, alogia, flat affect.

  • Disorganised: incoherent “word salad,” tangentiality, bizarre behaviour.

Neuropsychology & Cognition

  • Generalised impairment across working memory, attention, executive function, social cognition.

  • Not tightly correlated with severity of hallucinations/delusions ⇒ partly independent domain.

  • “Rock-in-the-shoe” metaphor: intrusive voices distract like a pebble, lowering performance globally.

Cognitive/Computational Models

  1. Predictive Processing (Bayesian Brain)

    • Perception = prior beliefs + sensory evidence.

    • Schizophrenia ≈ aberrant priors (too strong/too weak) ⇒ mis-weighting evidence; explains hallucinations/delusions.

    • Illustration: Hollow-mask illusion

      • Neurotypicals see convex face twice; patients less susceptible ⇒ weaker face prior.

  2. Social Brain Hypothesis

    • Psychotic content is highly social (persecution, agency).

    • Human brains hyper-tuned to social cues; over-interpretation → paranoia.

  3. Source Monitoring Deficit

    • Failure to tag self-generated inner speech ⇒ external attribution (“voices”).

Biological Bases
Genetics

  • Heritability ≈80\% (higher than MDD).

  • GWAS: highly polygenic; many variants in synaptic, glutamatergic, calcium-channel genes.

Environmental/Biological “Hits”

  • Prenatal viral infection (influenza, rubella, polio) during 2nd trimester ↑ later risk.

  • Post-partum psychosis: rare but dramatic; hormone crash + predisposition.

  • Cannabis / Methamphetamine: heavy adolescent use can precipitate psychosis (dose-dependent).

Neuroimaging & Connectivity

  • Enlarged ventricles & widespread gray-matter loss (esp. fronto-temporal) in many but not all patients.

  • Functional hypoactivity in DLPFC, superior temporal gyrus; hyperactivity in language/auditory cortices during hallucinations.

  • Dysconnectivity hypothesis: inefficient structural & functional network integration; partly reversible with antipsychotic treatment (connectivity normalises in responders).

Developmental Frameworks

  • Neurodevelopmental hypothesis: early lesion/genetic insult silent until brain maturation.

    • Animal DLPFC lesion study: behavioural deficit emerges post-puberty.

  • Two-hit model: congenital vulnerability + later environmental stressor (e.g. social adversity, drugs).

  • Neurodegenerative view (historical “dementia praecox”) now deemphasised but acknowledges progressive gray-matter change.

Treatments (brief)

  • Antipsychotics (D2 blockade ± 5-HT): cornerstone; normalise some connectivity.

  • Psychosocial rehab, CBT for psychosis, family interventions.

  • Research into TMS, tDCS, cognitive remediation, and social-synchrony interventions.

Kent Research Highlights (Dr Martin Lab)

  • Themes: Social Cognition, Reality/Source Monitoring, Negative & Self‐Referential Biases.

  • Toolkits: Virtual Reality, EEG + fNIRS, brain stimulation (TMS/tDCS), interpersonal synchrony paradigms.

  • Ongoing projects:

    1. Menstrual phase × mood & cognition longitudinal study (placement student presenting 25/03 Cognitive Seminar).

    2. Effects of social isolation on paranoia & trust.

    3. Brain-stimulation modulation of reality monitoring in early psychosis.

  • Opportunities:

    • Final-Year Projects (FYP), placement year, MSc/PhD; email Dr Martin to discuss ideas.

Illustrative Examples & Metaphors Recalled in Lecture

  • “Rock in the shoe”: constant hallucination distracts like pebble ⇒ broad cognitive under-performance.

  • Paranoia as hypersocial vigilance: over-interpretation of other people’s intentions.

  • Hollow-mask illusion: evidences Bayesian prior mismatch in schizophrenia.

  • Internal monologue mistaken for external voice: source-monitoring failure explanation of AVHs.

Statistical & Numerical References

  • 15\% lifetime MDD, 5!-!10\% point prevalence.

  • 2:1 female : male depression diagnosis ratio.

  • 10\% population experiences auditory hallucinations non-clinically.

  • 20\% post-partum depression; \sim 1\% prevalence schizophrenia.

  • SSRIs & CBT ≈50\% efficacy; placebo ≈30\%.

  • Depression GWAS n=1.3\text{M}; polygenic risk explains ≈5\% variance.

  • Post-parturient psychosis far less common than PPD (exact % not specified but “much rarer”).

Ethical, Philosophical & Practical Implications

  • Balance personal liberty vs. public safety (danger criterion).

  • Label stigma vs. treatment facilitation.

  • Genetic testing companies over-promise (PRS modest predictive power).

  • Equity: higher disorder burden in low socio-economic status; importance of social support (e.g. buffers post-partum mood shifts).

  • Need for dimensional, mechanism-driven funding replacing blanket diagnostic comparisons.

Connections to Earlier Coursework & Broader Principles

  • Revisits Year-1 material on classification, neuropsych methods, cognitive biases.

  • Illustrates application of biopsychosocial & Bayesian brain frameworks introduced previously.

  • Links executive‐function lectures (frontoparietal networks) to rumination control & disorganised speech.

  • Reinforces research-methods topics: GWAS, meta-analysis, twin/adoption designs, placebo-controlled trials.