(neu 320) exam 3

psychiatric disorder characterized by disturbances of mood and/or emotion

(a) 5 (or more) of the following present during the same 2-week period; at least one of the symptoms is either 1 or 2

1. depressed mood

2. lost of interest or pleasure

3. weight loss/gain

4. insomnia or hypersomnia

5. psychomotor agitation or retardation

6. fatigue, loss of energy

7. feelings of worthlessness or guilt

8. diminished ability to think or concentrate, indecisiveness

9. recurrent thoughts of death, suicidal ideation without a plan, or a suicide attempt/specific plan

(b) symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning

(c) episode not attributable to physiological effects of a substance or other medical condition

(e) there has never been a manic or hypomanic episode

• clinical interview

• DSM-5 criteria

• assessment tools

  • Beck Depression 21 Item Inventory

• liftime risk: 10-20%

• ~ 1 in 3 women, ~ 1 in 5 men

  • by age 65

  • women 2x higher diagnosis rate

• 3x higher in LGBTQ+ community

• affects all age groups & ethnicities

• veterans 5X higher rates

• most individuals do not seek treatment

• ~20% of those with untreated MDD attempt suicide

• ~60% of those who attempt suicide have MDD

• heterogeneous disorder

• first written accounts in 2nd millennium BC in Mesopotamia

• similar writings in many cultures, including ancient Greeks, Romans, Babylonians, Chinese, Egyptians

  • Hippocrates (Greek physician) said melancholia caused by excess of black bile in spleen

    • recommended treatments like bloodletting, baths, exercise, dietary changes

• historically viewed as a spiritual condition caused by demonic possession

  • treated by both physicians and priests

  • trepanation

• 1917: Freud theorized depression as a response to real or symbolic loss, leading to unconscious anger & malaise, manifested as depression

  • psychoanalysis (talk therapy) to resolve unconscious feelings

• late 19th, early 20th centuries: depression still thought to be bio based, physiological treatments ensued

  • frontal lobotomies

    • go in thru eye socket to remove part of frontal lobe

  • ECT

• 1950s: beginning of frequent medication use

  • stimulants, like Ritalin

    • still used off-label to augment SSRIs

    • not FDA-approved

    • effective at reducing self harm, suicide attempts

• drilling hole in skull to release evil spirits

  • did not penetrate brain

• used throughout history by Aztecs, Incas, and others

• also used during US civil war to remove bullets, fragments, etc.

• variation still used today: CRANIOTOMY

  • relieve pressure in brain due to build up of fluid, blood, pus

  • also used to relieve build up of blood under toenail

• monoamine theory

• familial/genetic

• structural & functional brain differences

• diathesis-stress

depression is due to reduced or “imbalanced” levels of monoamines (serotonin, DA, NE) in the brain, particularly serotonin

• early 1960s: Reserpine found to produce depressive-like effects in animals and humans treated for hypertension (high BP)

  • inhibits the vesicular monoamine transporter, depleting monoamine levels

    • theory was advanced

• WRONG

  1. antidepressants alter NTs but many people don’t improve

  2. monoamine depletion in healthy participants DOES NOT produce depressive symptoms

     • but associated with severity of symptoms

       • monoamines may play a modulatory role

  3. tryptophan depletion did not rapidly worsen symptoms in patients with MDD

• 85-90% of the public believes this theory

• offspring of depressed parents are 3-4x more likely to develop a depressive disorder

• MDD does tend to run in families

  • no gene has been identified as causing MDD

• likely result of combined risk factors that may interact with multiple genes

  • serotonin transpoter gene, COMT gene, TPH, 5-HT, NT receptor genes

• wide variety of differences found in those with MDD compared to control

  • none are unique to MDD

• differences in structure of hypothalamus and cerebellum

• large volume reductions in the frontal regions

• moderate volume reductions in hippocampus, putamen, caudate nucleus

• alterations in brain regions presiding over emotional recognition and evaluation

  • amygdala, hippocampus, insula, prefrontal cortex

• medication

  • antidepressants (SSRIs) & augmentation

    • Prozac, Paxil, Zoloft, etc.

    • not more effective than older antidepressants (tricyclics), but fewer side effects

    • SNRIs (e.g., Effexor) can also be effective

• cognitive behavioral therapy (CBT)

• family therapy

• mindfulness interventions

• exercise

• deep brain stimulation (DBS)

  • for severe / treatment resistant MDD

• core principles

  • our thoughts & feelings affect our behavior

  • our behavior affects our thoughts & feelings

• therapy

  • identify & alter the negative, irrational, distorted thoughts

  • induce behavior change

• more effective over time than meds

  • changing thought + behavior patterns

• NMDA (glutamate) receptor antagonist

  • blocks glutamate postsynaptic receptors (NMDA) and pre synaptic dopamine transporters

    • unclear if these or other downstream (e.g., increase BDNF) result in the improvement of symptoms

• nasal spray (esketamine) FDA approved March 2019 for treatment resistant depression

• risk of sedation, dissociation, abuse and misuse, suicidal thoughts and behaviors

• genetic testing to identify whether an individual is a poor, ultra/rapid, intermediate, or essential metabolizer of an antidepressant or antipsychotic med before prescription

  • antidepressant response could be from 42-50% genetically determined

  • variants of ABCB1 gene associated with concentration levels of various meds in the brain

• current or recent Major Depressive Episode

• previous Manic Episode or Mixed Episode (at least one)

• mood episodes not due to Schizoaffictive Disorder or part of other disorders

• current or history of major depressive episodes (one or more)

• current or history of hypomanic episode (at least one)

  • elevated moods that do NOT meet the threshold for mania

• no history of manic episode or mixed episode

• mood symptoms not due to other disorders

  • mood swings, but less intense than BP I

• symptoms cause significant distress & impairment in social, occupational, or other important areas of functioning

• the current episode meets appropriate criteria for hypomania or depression

distinct period of abnormally & persistently elevated, expansive, or irritable mood and goal-directed behavior or energy, lasting at least 1 week and present most of the day, nearly every day

• ~ 2.5% of adult population

• both BP I and II are more common in females than males

  • women more likely to experience rapid cycling

• manifestation similar across racial/ethnic groups

• average age of onset: 25

• 2/3 have a family member or relative with the disorder

• high suicide rate (1 in 5)

• consistent concordance rate

  • identical: ~ 0.8

  • fraternal: ~ 0.2

• higher incidence of BP in children with BP parents

• no specific gene currently identified as “causing” BP

  • SEE TEXTBOOK for areas of focus

  • AKAP11 gene

    • provides instructions for proteins that may interact with lithium

  • CACNA1C gene

    • Ca2+ channel regulation

  • COMT gene

    • deactivates monoamines

  • BDNF gene

    • associated with increased susceptibility of BP in children & adolescents

• highly variable findings, not unique to BP

• structural differences predominantly observed in

  • prefrontal & temporal cortex

  • cingulate gyrus

  • subcortical regions

• greater ventricle enlargement

• greater subcortical decline over time

• decreased grey matter

• mania

  • cortical thickness remains stable or increases during periods of mania compared to control

• longitudinal studies needed

• confounding variables

  • comorbidity, medication + substance use

• larger sample sizes needed

• inconsistencies across studies

1. hypoactivity (decreased activity) of the ventral prefrontal cortex in the right (sometimes left) hemisphere

2. hyperactivity of the amygdala, basal ganglia, & anterior cingulate cortex in the left (sometimes right) hemisphere

   1. during manic episodes, decreased neural activity response throughout ventrolateral & prefrontal regions during tasks designed to elicit emotional response

• medication

  • mood stabilizers (lithium)

  • antipsychotics (Abilify)

  • anticonvulsants (Tegretol)

  • 2/3 don’t response favorably to first med

• CBT

  • more for depressive symptoms

• family therapy

• mindfulness interventions

• WHO: ~ 700,000 people die by suicide each year

• in USA, ~ 45,000 each year

  • suicide rates in USA have increased by 30% in past 20 years

• compared to pre-pandemic, more suicides during COVID-19 in preteens 5-12, young adults 18-24, across all ethnicities

• compared to white peers, black youth in USA 2x more likely to attempt without telling anyone

• to date, biomarkers do NOT have the sensitivity + specificity needed for clinical utility

• examples

  • cortisol levels

  • blood protein levels

    • inflammation C-reactive protein

  • fMRI scans

    • resting state activation, functional connectivity, grey matter volumes, etc.

• ADHD

• motor disorders (Tourette’s, tic disorder)

• ASD

• disorders of learning

1. Tourette’s

2. persistent motor OR vocal tic disorder

   • specify “motor/vocal tics only”

3. provisional tic disorder

   • motor AND/OR vocal

   • tics < 1 year

4. other

   • specified: criteria not met (ex: onset after 18)

     • unspecified: chooses not to specify, insufficient info

sudden, rapid, recurrent, non-rhythmic stereotyped motor movement or vocalization

• simple

  • eye blinking

  • shoulder shrugging

  • eye darting

  • mouth movements

• complex

  • touching/smelling objects

  • repeating observed movements

  • stepping in a certain pattern

  • obscene gesturing

  • bending or twisting

  • hopping

• simple

  • grunting

  • throat clearing

• complex

  • palilalia: repeating one’s own words or phrases

  • echolalia: repeating others’ words or phrases

  • coprolalia: using vulgar, obscene, or swear words

• both multiple motor + at least one vocal tic present

  • not necessarily concurrently

  • motor tics usually appear first

• tics occur many times a day, nearly every day or intermittently thru a 1 year period

  • never a tic-free period of more than 3 consecutive months

• onset before 18

• disturbance not due to direct physiological effects of a substance or condition

• 1% worldwide prevalence in children 5-18 yrs

• onset: common but typically transient in childhood

• tics usually emerge in early childhood (4-6), wax + wane

  • but similar in expression across lifespan

• peak severity: 10-12

  • gradual decline in most cases

  • small % worsen & continue into adulthood

• boys:girls :: 2:1-4:1

• occurs in all cultures

  • 2x less common in african-americans and hispanic-americans

• symptom characteristics similar across gender, race, ethnicity, and culture

• motor tics usually appear first

• EF deficits correlated with symptom severity

• stress, anxiety, and fatigue worsen symptoms

• comorbid disorders

  • ADHD

  • OCD

  • anxiety

  • depression

    • suicide risk

      • 4x greater risk of both committing and attempting suicide

      • persistence of tics beyond young adulthood and previous attempt are strongest predictors of death by suicide

• no conclusive genetic findings

• identical: 50%, fraternal 8%

• rates are 3x higher if one or both parents have Tourette’s

• focus on DA genes

  • motor symptoms

  • worsening of tics with stimulants

  • improvement with antipsychotics

    • block DA postsynaptic receptors

    • 80% improve with DA antagonists

  • brain stimulation in globus pallidus (rich in DA) often improves symptoms

• no anatomical pattern for all patients with Tourette’s

• several structures + regions smaller in some studies

  • basal ganglia

  • anterior cingulate

  • corpus callosum

  • occipital

• some studies found enlargement of cerebral ventricles

• white matter increases in frontal and parietal regions

• lower white matter volume bilaterally in prefrontal cortex

• greater gray volume in thalamus, hypothalamus, midbrain, insula and sensorimotor cortex

• antipsychotic medications

  • clozapine

• educational

• combo of meds

• nicotine patch

• THC

• DBS

• botulism toxin

• surgery

  • lesioning of anterior cingulate

• psychotherapy/counseling

• biofeedback, relaxation

• family therapy

• similar to psychological evaluations conducted for other disorders

• background info & present symptoms (DSM-5)

• interviews, observations, assessment tools (rating scales)

  • Obsessive-Compulsive Inventory (OCI)

1. presence of obsessions, compulsions, or both

2. the behaviors are aimed at preventing or reducing anxiety/distress

   • excessive, unrealistic

3. OC symptoms are not caused by substance or other condition

4. disturbance not better explained by symptoms of another disorder

• ~ 1-2% of global population

• can occur during childhood, adolescence, or adulthood

• typically gradual onset with fluctuations over time

• average age of onset varies among studies

  • before 25

  • slightly earlier for men than women

• extremely limited info regarding minorities

• symptoms differ across cultures and genders

  • childhood: more common in males

  • adulthood: more common in females

• comorbid with anxiety, depression, PTSD, Tourette’s, anorexia

• contamination

• harming others

• symmetry

• sexual

• superstitions

• cleaning

• checking

• ordering

• primarily focused on serotonin, DA, glutamate systems

  • SSRIs can improve symptoms, serotonin antagonists worsen

  • dopamine antagonists can improve symptoms, dopamine agonists (stimulants) can worsen symptoms

  • SAPAP3 gene knock out mice (altered glutamate system) induce or worsen OCD-like behaviors

    • improvement with glutamate antagonists

• heritability component, but values differ among studies

• concordance rate for identical twins: 60-80%

• pathways from basal ganglia to prefrontal cortex are most often implicated in OCD

• heightened activation in caudate nucleus, putamen, thalamus, frontal cortex at rest + during provocation

• these patterns look similar to controls following ~ 12 weeks of CBT and/or antidepressant therapy

• CBT

  • desensitization, exposure therapy

• antidepressants

  • SSRIs and tricyclics

  • 40-60% effective

  • augmentation with antipsychotic/seizure/anxiety med or CBT improves response rate

• severe cases

  • surgery

    • cingulotomy: lesioning anterior cingulate

    • capsulotomy: lesioning part of internal capsule pathways

  • DBS

  • TMS

A neurodevelopmental disorder characterized by inappropriate levels of inattention, impulsivity, and hyperactivity

1. Individual presents 1 or both of the following patterns:

   (a) For 6 months or more, individual frequently displays at least 6 of the following symptoms of inattention, to a degree that is maladaptive and beyond that shown by most similarly aged persons

   • Unable to properly attend to details, or frequently makes careless errors

   • Finds it hard to maintain attention

   • Fails to listen when spoken to by others

   • Fails to carry out instructions and finish work

   • Disorganized

   • Dislikes or avoids mentally effortful work

   • Loses items that are needed for successful work

   • Easily distracted by irrelevant stimuli

   • Forgets to do many everyday activities

   (b) For 6 months or more, individual frequently displays at least 6 of the following symptoms of hyperactivity and impulsivity, to a degree that is maladaptive and beyond that shown by most similarly aged persons

   • Fidgets, taps hands/feet, or squirms

   • inappropriately wanders from seat

   • inappropriately runs or climbs

   • unable to play quietly

   • in constant motion

   • talks excessively

   • interrupts questioners during discussions

   • unable to wait for turn

   • barges in on others convos and activities

2. Individual displayed some of the symptoms before 12 years of age

3. Individual shows symptoms in more than 1 setting

4. individual experiences impaired functioning

1. predominantly inattentive

   • more common in females

2. hyperactive-impulsive

   • more common in males

3. combined

   • more common in males

• ~5-7% US school age population, 3.5% worldwide prevalence

• ~2.5% of the adult population

• Male to female ratio 2:1 in children, adults 1.6:1

• Symptoms continued into adulthood, although may attenuate

• Commonly co-occurs with depression, conduct disorder, learning disorder, oppositional defiant disorder (behavioral)

• inconsistent results across studies

• hypoconnectivity in frontal and parietal regions

• hyperconnectivity in regions implicated in decision-making and self-referential thinking

• reduced global blood flow in prefrontal regions

• increase in prefrontal D2 receptors, dopamine transporters, concentration of dopamine and NE metabolites in prefrontal and striatum regions

• overactive dopamine transporter system, particularly in basal ganglia

• increased presynaptic dopamine activity in caudate and putamen

• widespread volumetric reductions

  • overall cerebral volume

  • overall cortical thickness

  • frontal regions

  • cerebellum

  • corpus callosum

  • amygdala, caudate, hippocampus

  • reduced white matter density (frontal-stratal tracts)

    • in normal brain, prefrontal white matter associated with improved inhibition, cognitive skills, reading performance, executive function

    • not unique to ADHD

• largely fMRI studies, some PET and SPECT scans

• frontostriatal pathways have been primary focus

  • less activation during inhibition tasks

    • poor task performance

    • stimulate medication associated with more activation

  • reduced rCBF and glucose metabolism in frontal regions

    • stimulants increases rCBF and reduces behavioral symptoms

• inconsistent findings with respect to

  • density of DAT

  • density of postsynaptic DA receptors

• biological relatives 5-10x more likely than adoptive

• concordance rate higher in identical twins (0.78) than fraternal (0.45)

• heritability estimate 70-80%

• primary focus is DA related genes

  • presynaptic DAT gene

  • postsynaptic DA receptor genes

  • inconsistent findings

• serotonin and other genes also investigated

  • no definitive answers

• cigarette smoking

• drugs/alcohol

• inadequate nutrition

• pesticide exposure

• prematurity

• medication

  • FDA approved

    • stimulant medications (Adderall, methylphenidate)

    • non-stimulants (Strattera)

    • pro-stimulants (Vynanse)

  • off-label

    • antidepressants

• trigeminal nerve stimulation

• behavioral support programs

• CBT

• child and family education

• exercise, meditation, yoga, etc.

Includes but is not limited to:

• Gender dysphoria typically emerges in childhood & persistence rates into adolescence or adulthood range from 2% to 50% (APA, 2013).

• Most individuals report experiencing gender dysphoria for the first time between ages 3 and 7 years (Zaliznyak, 2021).

• APA reports 2 to 6 times as many males transition to female than females transition to male.

• Talk Therapy

• Gender Affirming Surgeries

• Hormonal Treatments

• Gender-Affirming Care