21. Psychiatric Disorders

Psychiatric Disorders

• Psychiatry and neurodegenerative disorders are large fields; the 4-hour lecture is a brief overview.
• Wider reading and analysis are essential.
• Psychiatry is not just about dramatic or visible symptoms.

Learning Objectives

• To summarize the history of mental disorders.
• To understand the different diagnostic methods.
• To list mental disorders under the DSM-5 classification.
• To describe the main characteristics of mental disorders.

Mental Health and Illness

• Mental disorders are defined by a combination of how a person behaves, feels, perceives, or thinks according to the WHO (2014).
• Mental disorder is characterized as a syndrome with significant disturbance in cognition, emotion regulation, or behavior due to psychological, biological, or developmental dysfunctions from APA, 2013.

Neurological vs. Psychiatric Disorders

• Neurology is the branch of medicine focused on diagnosing and treating nervous system disorders.
• Neurological disorders range from multiple sclerosis to aphasia, helping clarify physiological processes in normal brain function.
• Psychiatry is the branch of medicine focused on diagnosing and treating disorders that affect the mind or psyche.
• Psychiatric disorders include anxiety disorders, affective disorders, and schizophrenia.

History of Mental Disorders

• Supernatural explanations attribute mental illness to possession by evil or demonic spirits, displeasure of gods, eclipses, planetary gravitation, curses, and sin.
• Biological explanations identify disturbances in physical functioning due to illness, genetic inheritance, or brain damage/imbalance.
• Psychological explanations attribute mental illness to traumatic or stressful experiences, maladaptive learned associations and cognitions, or distorted perceptions.

Biological Approach

• Emil Kraepelin (1856-1926) discovered that symptoms occurred regularly in clusters that called syndromes.
• Julius von Wagner-Jauregg (1917) induced fever (pyrotherapy) to treat conditions such as syphilis and malaria.
• Electric shock was used as a treatment for melancholia.
• From 1950 onwards, psychotropic drugs improved symptoms and led to deinstitutionalization.

Psychological Approach

• Freud's theory (1856-1939) states unconscious and conscious parts of the psyche create conflict.
• Treatment involves uncovering unconscious secrets
• Skinner (1904-1990) suggests behaviors are learned maladaptive responses to the environment.
• Treatment by "unlearning" through behavior modification.
• Psychosocial approaches to mental illness have a neurobiological basis.
• Psychotherapy is a treatment method.

Biopsychosocial Approach

• This model considers biological (genetics, disease), psychological (beliefs, emotions), and social (family, poverty) factors in mental health.

Modern Treatments - Antipsychotics

• The 1950s-70s saw a "pharmacological revolution" with drugs like haloperidol, fluphenazine, loxapine, and thioridazine, which are typical antipsychotics.
• Clinical efficacy correlates to dopamine D2 receptor binding and dampening.
• These treatments have side effects and a lack of novel therapeutic compounds.

Mental Illness Classification

• Classification reduces complex phenomena into categories based on shared characteristics.
• Classification functions includes:
  • Denomination: Assigning a common name to a group of phenomena.
  • Qualification: Adding relevant descriptive features.
  • Prediction: Statement about expected course, outcome, and treatment response.
• There are two forms of diagnostic approach:
• Categorical:
• Dimensional:

Categorical Classification

• The fundamental diagnostic element is the syndrome (group or pattern of symptoms).
• Diagnostic criteria for each disorder represent if the clinical presentation meets requirements.
• This classification method is used in other medical fields.
• It facilitates communication with codes.

Dimensional Classification

• The fundamental diagnostic element is symptoms.
• Dimensions extend the psychiatric symptomatology across a number of dimensions.
• Avoids setting specific thresholds to distinguish between pathology and normality.
• Approach is based on the patient.

Diagnostic & Statistical Manual of Mental Disorders

• Two widely established systems classify mental disorders.
• ICD-11 Chapter V: Mental and behavioral disorders, WHO, since 1949
• Diagnostic and Statistical Manual of Mental Disorders (DSM-5), APA, since 1952.

Neurodevelopmental Disorders

• These are impairments of the growth and development of the brain and/or central nervous system, which can be specific or global.
• Non-pharmacological treatment:
  • Intellectual Disabilities
  • Communication Disorders
  • Autism Spectrum Disorder
  • Attention-Deficit/Hyperactivity Disorder
  • Specific Learning Disorder
  • Motor Disorders
  • Other Neurodevelopmental Disorders
• Schizophrenia?

Schizophrenia Spectrum and Other Psychotic Disorders

• Severe mental disorder with loss of contact with reality.
• Positive symptoms: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior.
• Negative symptoms: reduced expression of emotion, poverty of speech, difficulty initiating goal-directed behavior, memory impairment.
• Cognitive symptoms.

Biological Basis of Schizophrenia (1 & 2)

• Gene × environment interaction: "Faulty" genes can lead to vulnerability to environmental factors.

• Associated with Physical changes in the brain, such as a larger ventricle-to-brain size ratio.

• There is the dopamine hypothesis, psychotic episodes are triggered by activation of dopamine receptors.

• Neuroleptic drugs are strong DA receptor blockers

• There is also the glutamate hypothesis.

• PCP and ketamine Observed behavioral effects.

• Do not affect dopaminergic transmission.

• Affect synapses that use glutamate as a neurotransmitter and inhibit NMDA receptors.

• Hypothesis: Schizophrenia mirrors diminished activation of NMDA receptors in the brain, as per the scPCP model.

Treatments for Schizophrenia

• Treatment includes drug therapy alongside psychosocial support.
• Conventional neuroleptics, like chlorpromazine and haloperidol, act at D₂ receptors, reducing positive symptoms.
• They have numerous side effects, inclduding Parkinson's disease symptoms and tardive dyskinesia.
• Newest research is NMDA receptors and new mechanisms?

Affective Disorders

• "Mood" disorders include recurrent depression and bipolar disorder.
• Recurrent depression includes major depression (MDD) and dysthymia ('mild' depression).
• Bipolar disorder, or manic-depressive disorder, involves recurrent, repeated episodes.
  • Type I: mania (increased goal-directed activity, grandiosity, diminished need for sleep).
  • Type II: hypomania (periods of current or past major depressive episodes interspersed with current or past hypomania).

Biological Basis of Affective Disorders (1 & 2)

• The monoamine hypothesis suggests that there is a depletion of monoaminergic neurotransmitters (serotonin, norepinephrine, and/or dopamine) in CNS.

• Deficit in central Diffuse modulatory systems

• Studied by effects of drugs, such as:

• Reserpine.

• Monoamine oxidase (MAO) inhibitors.

• Imipramine.

• Pharmacological compounds elevate monoamine levels in CNS.

• Treatment focused on serotonergic and/or noradrenergic synapses.

• The diathesis-stress hypothesis suggests genetic predisposition (diathesis) influences stress responses; role of HPA axis and Impact of CRH.

• HPA function becomes hyperactive.

• Glucocorticoid receptor (GR) gene expression regulated by early experience.

• Resting-state metabolic activity in anterior cingulate cortex increased in depression.

Treatments for Affective Disorders (1 & 2)

• Antidepressants includes: MAO inhibitors, tricyclics, and SSRIs.

• Electroconvulsive Therapy (ECT): used localised electrical stimulation

• Alleviates Depression, affects temporal lobe.

• Provides Quicker relief for both depression and mania

• Side effects are is loss of older memories

• Psychotherapy for patients to overcome the more negative views.

• Effective for mild to moderate depression.

• Not usually recommended as first line treatment as TCA;s produce more adverse effects, OD risk

• Deep brain stimulation (DBS)is for people whom severe depression in not responsive

• Electrode is surgically places into the brain.

• Negative is subcallosal Cingulate Cortex(SCC), Lateral Habenula(LHb)

• Anhedonia/Reward: Ventral capsule and ventral striatum(VC/VS), Medial Forebrain bundle(MFB), Inferior Thalamic peduncle (ITP)

Biological Basis of Anxiety Disorders (1 & 2 & 3)

• Genetic predisposition for many anxiety disorders (e.g. generalized anxiety disorder, GAD). ~30% genetic heritability i.e 5-HTT, NPSR1, COMT, MAOA, CRHR1, RGS2

• Fear evoked by threatening stimulus: stressor. Manifested by stress response. Strengthen of Stimulus response is weakened with experience

• Stress response: Humoral response: corticotropin-releasing hormone (CRH) adrenocorticotropic hormone (ACTH) cortisol.

• Concerns the Regulation of the HPA axis by the amygdala and hippocampus

• The amygdala and hippocampus both regulate CRH neurons.

• The amygdala projects to bed nucleus of the stria terminalis, which activates the HPA axis.

• The hippocampus deactivates the HPA axis.

• Glucocorticoid receptors Feedback loop Push-pull regulation.

• Central Amygdala for central nucleus, bed stimulus for stria stimulus, dorsal Raphe Nuclei

• The basolateral amygdala(BNA), pontine reticular nuclei(PNC) , for serotonin

Treatments for Anxiety (1 & 2)

• Psychotherapy
• Anxiolytic medications, such as: Role of GABA, Benzodiazepines
• Serotonin-selective reuptake inhibitors (SSRIs).
• Target for new drugs: CRH receptors. Endocannabinoid system — endogenous cannabinoid system.
• GPCRs expressed:
  • CB1 and CB2
  • Retrograde inhibition of neuronal signaling
  • Postsynaptic effects on presynaptic membranes
  • Exogenous cannabinoids for use in anxiety, may cause unknown safety efficacy and development effects.