23/24: Autism, ADHD, Depression

neurodevelopmental disorders

→ lifelong disabilities that are often clearly evident from birth and/or throughout childhood

• Differ from psychiatric disorders (which can be episodic and incident at any age)

prevalences’ sex differences

No sex bias: Schizophrenia, BD

Female sex bias (more common for women):

• 2x - mood and anxiety disorders; MDD, OCD, PTSD

  • Attributed to social-cultural stressors that often relate to hormonal fluctuations throughout development

• 3x - anorexia nervosa

• 10x - bulimia nervosa

Male sex bias (more common for men):

• 2x - general intellectual disabilities

• 3x - Tourette’s syndrome

• 4x - autism spectrum disorder, ADHD

“hot flashes”

→ sensation produced by the hypothalamus mistakenly believing body temperature to be too high

• In women: Often caused by sudden menopause-related changes in hormone signalling

sex chromosomes

→ explain ↑ male predisposition to neurodevelopmental disorders

Heterogametic sex → sex chromosomes differ; establishes developmental instability and tends to show more variability at a young age on many traits

• XY - male mammals or insects

• ZW - female non-mammals or insects

Homogametic sex → sex chromosomes are alike; promotes developmental robustness

• XX - female mammals or insects

• ZZ - male non-mammals or insects

gene copy number variations

CNVs → section of genome is duplicated or missing

• Rare CNVs are more often transmitted from mothers (less affected) than fathers (more affected)

Caveats with autism diagnoses:

• ↑ incidence rate for males (recall 4x)

• Males diagnosed with autism have less rare and harmful CNVs than females, BUT

• Within families, females with CNVs present with much fewer and less severe symptoms than their male counterparts (are protected somehow)

autism spectrum disorder

→ encompasses a wide range of developmental disorders with diverse underlying causes, characterized by troubles with social interaction, communication (abnormal or non-existent language), and restricted and repetitive behaviour

Etiology: Genetic and some environmental factors that disrupt early brain development

• 70-90% normally heritable, 10% linked to rare chromosomal abnormalities

Prevalence: 2% of general population

Prognosis: Symptoms usually present within first years of life (usually by age 3)

Comorbidity:

• 1/3 of patients also have an intellectual disability

• 1/3 of patients also have epilepsy (seizure disorder)

Treatment: Lessening the impact of symptomatology on patient, reducing distress on caretakers/family + improving quality of life and functional independence

• Practical:

  • Sustained special education programs (usually have accommodations to help patients learn, develop, and acquire self-care and life skills catered to them)

  • Behavioural therapies (to correct maladaptive behaviours)

• Pharmacological:

  • Anticonvulsants (↑ GABA receptors)

  • Antidepressants (↑ serotonin receptors)

  • Antipsychotics (↓ dopamine receptors)

  • Stimulants (↑ dopamine receptors)

autistic symptomology

Behavioural deficits:

• Stereotyped movements include back-and-forth motions (rocking themselves, flapping their hand)

• Ritualistic or compulsive tendencies

• Communicative deficits: 1/3 of autistic people don’t eventually develop enough natural speech to meet daily communication needs

  • Echo responses (parrot syndrome)

  • Referring to self in other POVs

Cognitive deficits:

• Reduced imaginative ability (not always)

• Emotional deficit (?): Asperger’s syndrome → involves deficient or absent social interactions, atypical and obsessive interests in narrow subjects, and other hallmark autistic behavioural deficits

• ↓ Facial recognition (fMRI studies revealed hypoactive fusiform face area when autistic patients reviewed human faces)

attention-deficit/hyperactivity disorder

ADHD → childhood condition characterized by problems paying attention and/or difficulty controlling behaviour in an age-appropriate manner

Etiology: Genetic and many environmental factors (parental substance abuse, prenatal infections, trauma, etc.)

• 75-90% normally heritable, but varies widely across communities from 1-16% of children

Prevalence: 5% of general population

• Boys are diagnosed 3-4x more than girls

Prognosis: Symptoms usually present before age 12

• Last at least 6 months; significant enough to cause impairments in frequented environments (school, home, etc.)

• Usually first identified in the classroom

• Precursor to conduct disorder

Treatment:

• Counselling

• Medication (often stimulants or antidepressants that block or reverse dopamine and/or serotonin reuptake transporters)

ADHD symptoms

• Not particularly well-defined since attention spans vary by many factors, especially personal interest

Inattentive:

• Difficulty sustaining attention

• Easily distracted

Hyperactive:

• Impetious actions, impulsivity

• Recklessness

• Allowing things to interfere with task at hand

• Difficulty withholding responses

major affective disorders

→ mood disorders, characterized by disordered affects (feelings or emotions) resulting in dangerous self-perceived symptoms

bipolar disorder

BD → serious mood disorder characterized by cyclical periods of mania and depression

• Mania → sense of euphoria not justified by circumstances

  • Abnormally hyper behaviours: Fleeting thoughts and speech, nonstop motor activity, intense affects, etc.

Etiology: Genetic and many environmental factors (mainly trauma or ACEs)

• 80% of risk attributed to genetics

Prevalence: 2% of general population

Treatment:

• Lithium (chemical element)

  • Effective for treating manic phase (plus depression usually doesn’t follow after if done)

  • Unknown mechanism, but noticeably swift

• Mood stabilizers

  • Could be anticonvulsants (particularly those that are voltage-gated sodium channel blockers that reduce neural activity)

  • Could be combined with antipsychotics or antidepressants

major depressive disorder

MDD → serious mood disorder characterized by unremitting depression or periods of depression (that don’t alternate with mania)

Etiology: Genetic and many environmental factors (mainly trauma or ACEs)

• 40% of risk attributed to genetics

Prevalence: 7% in women, 3% in men

Treatment: Everything ever

• See attached photo my god

antidepressants

• Tricyclic antidepressants (TCAs) → inhibit the reuptake of serotonin and norepinephrine (but affects other neurotransmitters)

• Selective-serotonin reuptake inhibitors (SSRIs) → inhibit the reuptake of serotonin (WITHOUT affecting other neurotransmitters)

• Serotonin and norepinephrine reuptake inhibitors (SNRIs) → inhibit the reuptake of serotonin AND norepinephrine (WITHOUT affecting other neurotransmitters)

monoamine hypothesis

→ depression may relate to insufficient monoamine (serotonin, norepinephrine, and dopamine) receptor activity

• Developed largely based on the success of antidepressant treatments (agonists for serotonin and norepinephrine, not so much dopamine however)

Serotonin depletion:

• Tryptophan → amino acid that makes serotonin (5-HT)

  • Diet with ↓ [ ] can ↓ synthesis, triggering a depressive episode

  • Easily remedied with antidepressants

subgenual anterior cingulate cortex

→ fMRIs reveal less activity after depression symptoms remiss

• Though clinical trials targeting this region with biomedical electrical treatments have been unsuccessful thus far

electroconvulsive therapy

ECT → biomedical treatment that electrically induces seizures to therapeutically alleviate severe depression and/or bipolarity

• Effective within days (not too delayed unlike antidepressants)

depressive implications on sleep

• Disordered sleep is a prominent symptom of depression

Depressed people’s sleep …

• Spends more time in shallow, rapid-wave stages (1 & 2)

  • Enters REM sooner (earlier in a cycle) after falling asleep

  • Becomes more fragmented, with insomniac symptoms also occuring

• Spends little time in deeper, slow-wave stages (3 & 4)

  • Brain is supposed to rest this way!!!

total sleep deprivation

→ not sleeping to produce a non-pharmacological antidepressant effect

• Quickly effective (within days);

• But is short-lived (effect can reverse after just a normal night’s sleep)

  • Perhaps attributed to generating an accumulation of excitatory chemicals (that is usually cleaned during sleep)

• Can also lead to some degree of mania

• Possible to do with REM sleep (though this method takes longer, like weeks)