Psychiatric Disorders

Mental disorders

A combination of how a person behaves, feels, perceives or thinks

Neurology

Branch of medicine concerned with the diagnosis and treatment of nervous system disorders

Neurological disorders

Diseases of the brain, spine, and nerves.

Illustrate the role of physiological processes in normal brain function

Psychiatry

Branch of medicine concerned with the diagnosis and treatment of disorders that affect the mind or psyche

Examples of psychiatric disorders

-Anxiety disorders

-Affective disorders

-Schizophrenia

Psychological mental disorders

Traumatic or stressful experiences

Maladaptive learned associations and cognitions or distorted perceptions

What were the antipsychotics established in 1950's-70s?

Haloperidol, fluphenazine, loxapine and thioridazine

Clinical efficacy linked to dopamine D2 receptor binding and dampening

Functions of the DSM-5

-Denomination

-Qualification

-Prediction

Categorical classification in DSM-5

-Diagnostic criteria for each disorder

Allow for easy communication from one clinician to another

Dimensional classification of DSM-5

Symptoms

Approach based on patient

View the symptoms across number of dimensions

Avoid setting a particular threshold

Neurodevelopment Disorders

Impairments of the growth and development of the brain and/or central nervous system

Non-pharmacological treatments

Examples of neurodevelopment disorders

-Intellectual disabilities

-Communication disorders

-Autism Spectrum Disorder

-Attention-Deficit/Hyperactivity disorder

-Specific learning Disorder

-Motor disorders

Schizophrenia

Severe mental disorder

Loss of contact with reality

Positive symptoms of Schizophrenia

-Delusions

-Hallucinations

-Disorganised speech

-Grossly disorganised or catatonic behaviour

Negative symptoms of Schizophrenia

-Reduced expression of emotion, poverty of speech

-Difficulty initiating goal-directed behaviour

-Memory impairment

Cognitive Symptoms of Schizophrenia

-Poor memory

-Difficulty in decision making

-Poor judgment and insight

-Poor connection and attention

-Impaired sensory perception

Risk factors of Schizophrenia

-100s genetic risk factors

-Small (SNPs) to large (CNVs)

-Environmental factors

eg CACNA1C (voltage-gated Ca2+ channel)

Gene x environment interaction of schizophrenia

Faulty genes= vulnerable to environmental factors

Are there changes in to the brain with Schizophrenia?

Larger ventricle-to-brain size ratio

What is the dopamine hypothesis for Schizophrenia?

Psychotic episodes triggered by activation of dopamine receptors

Glutamate Hypothesis for Schizophrenia

Reflects diminished activation of NMDA receptors in the brain

scPCP model

What did the Glutamate hypothesis observe?

Behavioural effects of phencyclidine (PCP) and ketamine:

-Neither effect dopaminergic transmission

-Both affect synapses that use glutamate

-Inhibit NMDA receptors

Neuroleptics to treat Schizophrenia

Chlorpromazine and haloperidol

D2 receptors:

-Reduce positive symptoms

-Numerous side effects

Affective Disorders

Mood disorders:

-Recurrent depression

-Bipolar disorder or manic-depressive disorder

Type I Affective Disorder

Mania:

-Increased goal-directed activity

-Grandiosity

-Diminished need for sleep

Type II of Affective Disorder

Hypomania:

-Periods of current or past major depressive episodes interspersed with current or past hypomania

Monoamine hypothesis of affective disorders

Depletion of monoaminergic neurotransmitters in CNS

Deficit in central diffuse modulatory systems

Studied by effects of drugs

What drugs were used to study the monoamine hypothesis of affective disoder?

-Resperpine

-Monoamine oxidase (MAO) inhibitors

-Imipramine

What does the treatment for the monoamine hypothesis of mood disorders focus on?

Central serotonergic and/or noradrenergic synapses

Diathesis-stress hypothesis of affective disorders

-Genetic predisposition (diathesis) influence stress responses

-Role of HPA axis

-Impact of CRH

-HPA becomes hyperactive

-Glucocorticoid receptor gene expression regulated by early experience

What did the diathesis-stress hypothesis show about the resting-state metabolic activity?

In anterior cingulate cortex increased in depression

Antidepressants used for affective diosrders

MAO inhibitors

Tricyclics

SSRIs

Electroconvulsive therapy (ECT) for affective disorders

Localised electrical stimulation

Unknown mechanism

Affects temporal lobe

What are the advantages of Electroconvulsive therapy (ECT) for affective disorders?

Quick relief of depression and mania

What are the adverse effects of Electroconvulsive therapy (ECT) for affective disorders?

Loss of prior memories

Impaired storage of new information

Psychotherapy for affective disorders

Help patients overcome negative views

Effective for mild to moderate depression

Deep brain stimulation (DBS) for affective disorders

When severe depression fails to respond to other treatment

Electrode implanted deep in the brain

Where in the brain would an electrode implanted in the brain for deep brain stimulation?

Anterior cingulate cortex (Brodmann's area 25)

Anhedonia pathways

How does deep brain stimulation work?

Electrical stimulation=decrease activity in brain circuits that are chronically overactive

Where does the negative affect of DBA occur?

-Subcallosal cingulate cortex (SCC)

-Lateral habenula (LHb)

Where does the Anhedonia/reward pathway occur in the brain?

-Ventral capsule and ventral striatum (VC/VS)

-Medial forebrain bundle (MFB)

-Inferior thalamic peduncle (ITP)

What is the genetic factors that affect many anxiety disorders?

-30% genetic heritability

eg 5-HTT, NPSR1, MAOA, CRHR1, RGS2

fear evoked by threatening stimulus

Stressor

Manifested by stress response

Stimulus-response relationship strengthened or weakened by experience

Stress response

Humoral response:

Corticotropin-releasing hormone (CRH)->adrenocorticotropic hormone (ACTH)->Cortisol

What regulated HPA axis in anxiety disorders?

Amygdala and hippocampus

Amygdala and HPA axis

Regulate CRH neurons

Projects to bed nucleus of stria terminalis

Activates HPA axis

Hippocampus and HPA axis

Deactivates HPA axis

Anxiolytic medications for anxiety

Role of GABA

Benzodiazepines

Serotonin-selective reuptake inhibitors (SSRIs)

Endocannabinoid system

Endogenous cannabinoid system

Use of endocannabinoid system for anxiety

G-protein coupled receptors express:

-CB1 and CB2

-Retrograde inhibition of neuronal signalling

-Postsynaptic effects on presynaptic membrane