Psychobio Chapter 18: Psychiatric Disorders

psychiatric disorders

• disorders of psychological function that require treatment

• diagnosis is guided by the DSM of the APA

positive symptoms of schizophrenia

• presence of problematic behaviors

  • hallucinations (illusory perceptions), especially auditory

  • delusions (illusory beliefs), especially persecutory

  • bizarre behaviors

• MORE responsive to treatment

negative symptoms of schizophrenia

• absence of healthy behaviors

  • flat affect (no emotion showing in the face)

  • reduced social interaction

  • anhedonia (no feeling of enjoyment)

  • avolition (less motivation, initiative, focus on tasks)

  • alogia (speaking less)

  • carania (moving less)

factors of schizophrenia

• evidence for genetic contribution

  • inherit an increased risk for the disorder

  • concordance rate among monozygote twins is 45%

• multiple causes

  • several different chromosomes implicated

  • associated with various early insults — infections, autoimmune reactions, toxins, traumatic injury, stress

• appears that interference with the normal development of susceptible individuals may lead to development of disorder

mesolimbic pathway

positive symptoms of schizophrenia are due to excess dopamine in….

mesocortical pathway

negative symptoms of schizophrenia are due to deficiency in dopamine…

nigrostriatal pathway

NORMAL and involved in the regulation of movement

tuberoinfundibular pathway

responsible for inhibiting the release of prolactin (release of milk from breasts)

dopamine theory of schizophrenia

• chlorpromazine is a receptor blocker at dopamine synapse

• chlorpromazine was the first receptor blacker to be identified

  • its discovery changed psychopharmacology

• the positive correlation between ability of various neuroleptics to being to D2 receptors and their clinical potency

  • based on Synder 1978

  • drug that does this is called haloperidol — more successful than chlorpromazine

chlorpromazine

• receptor blocker at dopamine synapse

• first receptor blocker to be identified

  • its discovery changed psychopharmocology

haloperidol

• more successful than chlorpromazine

• DRUG that has positive correlation between ability of various neuroleptics to bind to D2 receptors and their clinical potency

classical antipsychotics

• D2 receptor blockade — antipsychotic action

• extrapyramidal side effects and hyperprolactinemia due to strong D2 blockade — side effects

• effective against positive symptoms

atypical antipsychotics

• 5HT2, D4, and weakD2 blockade-antipsychotic action

• lesser incidence of EPS and hyperprolactinemia due to weak D2 blockade

• effective against positive and negative symptoms

• effective in patients refractory to classical drugs

psychodynamic

• approach is concerned with unconscious processes

  • this causes “inner turmoil” which leads to schizophrenia behavior → according to psychodynamic approach abnormality is caused by unresolved conflict between ID, Ego, and Superego that has been repressed into the unconscious

hypoactivity in N-methyl-D-aspartate receptor (NMDAR)

• reduced the stimulation of mesocortical dopamine release

  • negative of cognitive symptoms of schizophrenia

• reduced stimulation of GABA release

  • increase stimulation of mesolimbic dopamine release

  • positive symptom of schizophrenia

^^^schizophrenia

affective disorders

1. major depressive disorder (MDD)

2. bipolar disorder (manic-depressive)

3. seasonal affective disorder (SAD)

casual factors in affective disorders

• ______ are very common

  • ~5% suffer from unipolar ______ (MDD) at some point

    • ~1% from bipolar

• genetics

  • concordance rate higher for bipolar than unipolar

seasonal affective disorder

1. light exposure triggers a signal from retina in eye to suprachiasmatic nucleus (the brain’s peacemaker)

2. signal relayed in roundabout fashion in pineal gland

3. pineal gland secrete melatonin (“darkness” hormone)

4. too much melatonin, or secretion of the hormone that’s out of phase with sleep-wake signals, may be cause of SAD

monoamine oxidase inhibitors (MAOIs)

• Ex: Iproniazid

  • prevent breakdown of monoamines

  • must avoid foods high in tyramine — “cheese effect”

• tyramine reactions

  • tyramine → increase in norepinephrine → hypertensive crisis (heart attack)

    • tyramine = MAO-A inhibitors

    • tyramine-rich foods lead to increase in norepinephrine

      • ex: cheese, wine, meats, chocolate, smoked/pickles foods

tricyclic antidepressants (TCAs)

• ex: Imipramine

  • blocks reuptake of norepinephrine and serotonin

  • safer than MAOIs

selective monoamine reuptake inhibitors

1. selective serotonin-reuptake inhibitors (SSRIs)

   • ex: prozac, paxil, zoloft

   • no more effective than TCAs, but side effects are few and they are effective at treating other disorders

2. selective norepinephrine-reuptake inhibitors (SNRIs)

   • ex: cymbalta

selective serotonin-reuptake inhibitors (SSRIs)

• ex: prozac, paxil, zoloft

• no more effective than TCAs, but side effects are few and they are effective at treating other disorders

selective norepinephrine-reuptake inhibitors (SNRIs)

• ex: cymbalta

effectiveness of drugs in the treatment of affective disorders

• 2002 study: results are about the same for MAOIs, tricyclics, and SSRIs

  • about 50% improves, compared to 25% of controls

brain pathology of bipolar affective disorder

• structural MRIs of healthy volunteers with a genetic predisposition to developing depression reveals cell loss in the:

  1. anterior cingulate

  2. amygdala

monoaminergic

• ↓ serotonin

• ↓ noradrenaline

• ↓ dopamine

neurotrophic

• ↓ BDNF/TrkB

• ↓ NGF

• ↓ neurons

• ↓ hippocampal volume

HPA axis

• ↑ corticosterone

• ↓ glucocorticoid receptors

• ↑ adrenal gland volume

immunological

• ↑ inflammation

• ↑ cytokines

• ↑ leukocytosis

• ↑ monocytosis

• ↑ T-helper lymphocytes

• ↓ T-suppressor lymphocytes

glutamatergic system

• ↑ glutamate

• ↓ GABA

treatment of depression with brain stimulation

• 2008 study found that chronic electrical stimulation near the anterior cingulate gyrus helped relieve depression in treatment-resistant patients

ketamine on depression

• Blocker of glutamate NMDA

• Analgesic, anesthetic, and sedative

  • For hemodynamically stable patients

  • Preserves airway reflexes; tends to reduce aspiration risk

• A potent antidepressant than can induce laboratory model of schizophrenia

• A key veterinary anesthetic

• A drug abuse, often called super K or special K or horse tranquilizer

• Active via the intravenous, intramuscular, subcutaneous, oral, rectal, topical, intranasal, sublingual, epidural, and caudal routes

• Antidepressant action has rapid onset and peaks within 24 hours

• Drug’s effects are transient and short-lived

  • Lasting 1 or 2 weeks in most patients after a single dose

• Repeated infusion of this has been studied for 2 weeks duration but questions remain regarding the safety and efficacy of repeated treatment and longer duration of therapy

• Protocols for this infusion for treatment-resistant depression should include proper monitoring, including adequate involvement of anesthesia services and monitoring of blood pressure and other vital signs

• Spavato = FDA approved nasal spray form of Ketamine for treatment of resistant depression

spavato

• FDA approved nasal spray form of Ketamine for treatment of resistant depression

pharmacological treatment for anxiety disorders

1. benzidiazepines (librium, valium)

   • also used as hypnotics, anticonvulsants, muscle relaxants

   • GABA_A agonists = binds to receptor and facilitate effects of GABA (highly addictive)

2. serotonin agonists (Buspirone, SSRI)

   • reduce anxiety without sedation, side effects

   • antidepressants = effective due to comorbidity of anxiety and depression

benzodiazepines

• librium, valium

• Also used as hypnotics, anticonvulsants, muscle relaxants

• GABA_A agonists = bind to receptor and facilitate effects of GABA (highly addictive)

GABA_A agonists

bind to receptor and facilitate effects of GABA (highly addictive)

serotonin agonists

• buspirone, SSRI

• Reduce anxiety without sedation, side effects

• Antidepressants = effective due to comorbidity of anxiety and depression

Antidepressants

effective due to comorbidity of anxiety and depression

animal models of anxiety

• Assess anxiolytic potential of drugs; assume that defensive behaviors triggered by fear, and that fear and anxiety are comparable

• Validated by effectiveness of benzodiazepines (diazepam or Valium)

neural basis of anxiety disorders

• Drugs suggest a role of serotonin and GABA

• Amygdala, due to its role in fear and defensive behavior, thought to be involved

  • No obvious structural pathology yet identified

• Some evidence for over-activity in the amygdalae of patients with a phobia viewing the feared object