ETIOLOGY of PSYCHOPATHOLOGY

VIVIENNE S. CAGUIOA-CLEOFAS, MD, FPPA, FCLPPI

ETIOLOGY of PSYCHOPATHOLOGY

SYMPTOMS

BIOLOGICAL DIATHESIS

SYMPTOMS

PSYCHOLOGICAL DIATHESIS

SOCIAL DIATHESIS

SYMPTOMS
Adapted from: Sadock & Sadock, 2003.

STRESS-DIATHESIS MODEL STRESS

BIOLOGICAL

DIATHESIS (VULNERABILITY)

PSYCHOLOGICAL SOCIAL

SYMPTOMS
Adapted from: Sadock & Sadock, 2003.

STRESS-DIATHESIS MODEL
A person has a specific vulnerability (diathesis) that, when acted on by a stressful influence, allows the symptoms of psychopathology to develop Diathesis or stress can be biological, psychological, social or a combination of these

Adapted from: Sadock & Sadock, 2003.

BIOLOGICAL DIATHESIS
NEUROCHEMICAL GENETIC

NEUROSTRUCTURAL

NEUROIMMUNOLOGICAL

BIOLOGICAL DIATHESIS NEUROENDOCRINOLOGICAL

PSYCHOPATHOLOGY
Adapted from: Sadock & Sadock, 2003.

GENETIC BASIS of SCHIZOPHRENIA

Prevalence of schizophrenia in specific populations General population = 1% Nontwin sibling of a patient = 8% Child with one parent with schizophrenia = 12% Dizygotic twin of patient with schizophrenia = 12% Child of two parents with schizophrenia = 40% Monozygotic twin of patient with schizophrenia = 48%

GENETIC BASIS of MAJOR DEPRESSION

Family studies First-degree relatives 1.5-2.5 times more likely to have Bipolar I Disorder 2-3 times more likely to have Major Depression Twin studies (concordance rates) Monozygotic = 50% Dizygotic = 10-25%

GENETIC BASIS of MAJOR DEPRESSION

Adoption studies
Prevalence of mood disorders in adoptive parents is similar to baseline prevalence in general population - Biological children of affected parents at increased risk of mood disorder even if reared in nonaffected adoptive families Biological parents of adopted children with mood disorder have prevalence of mood disorder similar to that of parents of nonadopted children with mood disorder

GENETIC ASPECT of BIPOLAR I DISORDER

Genetic markers found in Chromosome 5: D2 receptor gene Chromosome 11: gene for tyrosine hydroxylase (rate-limiting enzyme for catecholamine synthesis) X chromosome

NEUROSTRUCTURAL BASIS of SCHIZOPHRENIA

Primary site of pathology may be the limbic system (emotional brain) Thalamus Hypothalamus Amygdala Hippocampus

NEUROSTRUCTURAL BASIS of SCHIZOPHRENIA

Decrease in size of amygdala, hippocampus and parahippocampal gyrus

Disorganization of neurons in hippocampus

NEUROSTRUCTURAL BASIS of SCHIZOPHRENIA

Basal ganglia (controls movement) Odd movements found in patients: awkward gait, facial grimacing, stereotypies Movement disorders involving basal ganglia commonly associated with psychosis Connected with frontal lobe; abnormalities in frontal lobe may be due to disease in basal ganglia

NEUROSTRUCTURAL BASIS of SCHIZOPHRENIA

Enlargement of the lateral and third ventricle Some reduction of cortical volume Reduced number of neurons of the medial dorsal nucleus of the thalamus

NEUROSTRUCTURAL BASIS of MOOD DISORDERS

Increased frequencies of hyperintensities in subcortical regions
Periventricular regions Basal ganglia Thalamus

NEUROSTRUCTURAL BASIS of MOOD DISORDERS

Ventricular enlargement Cortical atrophy Sulcal widening Reduced hippocampal or caudate nucleus volumes

NEUROSTRUCTURAL BASIS of ALZHEIMERS DEMENTIA

Diffuse atrophy (parietal-temporal areas) Flattened cortical sulci Enlarged cerebral ventricles

NEUROSTRUCTURAL BASIS of ALZHEIMERS DEMENTIA

Senile/amyloid plaques B/A4 protein Astrocytes Dystrophic neuronal processes Microglia

SENILE PLAQUES

NEUROSTRUCTURAL BASIS of ALZHEIMERS DEMENTIA

Neurofibrillary tangles Cytoskeletal proteins, primarily phosphorylated tau protein
Found in cortex, hippocampus, substantia nigra, locus ceruleus

NEUROFIBRILLARY TANGLES
AMYGDALA

HIPPOCAMPUS

SENILE PLAQUES and NEUROFIBRILLARY TANGLES

NEUROCHEMICAL BASIS of SCHIZOPHRENIA

NEGATIVE SYMPTOMS POSITIVE SYMPTOMS

Too little dopaminergic activity in frontal cortex

Too much dopaminergic activity in subcortical limbic areas (eg, nucleus accumbens)

NEUROCHEMICAL BASIS of SCHIZOPHRENIA

Which dopaminergic tracts are involved? Mesocortical Mesolimbic

Dopaminergic neurons in these tracts connect to neurons in the limbic system and cerebral cortex

The Dopamine Hypothesis of Schizophrenia

Mesofrontal and Mesolimbic Dopamine Pathways
Frontal cortex Hypoactivity Limbic system Hyperactivity

Negative symptoms

Positive symptoms

NEUROCHEMICAL BASIS of SCHIZOPHRENIA

Serotonin (5-HT2 receptor) Norepinephrine may have a modulatory effect on dopaminergic system Amino acids GABA Glutamate

NEUROCHEMICAL BASIS of BIPOLAR DISORDER

Increased activity of dopamine mania Increased intracellular Na+ mania or depression

Shank, 1998; Kasper, 1999

NEUROCHEMICAL BASIS of BIPOLAR DISORDER

Increased calcium
Calcium controls functions of synapse and neurotransmitters

Decreased GABA mania or depression

Shank, 1998; Kasper, 1999

NEUROCHEMICAL BASIS of ANXIETY DISORDERS

Norepinephrine Cell bodies in locus coeruleus in rostral pons Axons projected to cortex, limbic system, brainstem, and spinal cord In anxiety: poorly regulated noradrenergic system with occasional bursts of activity

NEUROCHEMICAL BASIS of ANXIETY DISORDERS

Serotonin Cell bodies in platelets, GIT, raphe nuclei of rostral brainstem Axons projected to limbic system (amygdala and hippocampus) and hypothalamus Serotonergic antidepressants have therapeutic effects on some anxiety disorders

NEUROCHEMICAL BASIS of ANXIETY DISORDERS

Gamma Amino Butyric Acid Undisputed efficacy of benzodiazepines GABA activity enhancement at GABAA receptor

NEUROCHEMICAL BASIS of DEPRESSION

Dysregulation of biogenic amines
Norepinephrine - downregulation of b-adrenergic receptors - presynaptic a2-adrenergic receptor Serotonin - reduced serotonergic activity Dopamine - reduced in depression - increased in mania

NEUROCHEMICAL BASIS of DEPRESSION

Other neurochemical factors GABA Neuro-active peptides

NEUROCHEMICAL BASIS of DEPRESSION

Pathologically upgraded brain 5HT2 receptors may mediate hippocampalglucocorticoid resistance Loss of normal hippocampusmediated negative feedback controlling hypothalamic-corticotropic releasing hormone release Subsequent activation of pituitary and adrenal components of HPA axis

NEUROENDOCRINOLOGICAL BASIS OF ANXIETY DISORDERS

H-P-A Axis
HYPOTHALAMUS CRH PITUITARY ACTH

FOREBRAIN AND LIMBIC STRUCTURES - frontal cortex - amygdala - stria terminalis

BRAINSTEM - locus coeruleus - nucleus parabrachialis

ADRENAL fight CORTISOL flight

Dysregulation in Anxiety

H-P-T Axis
HYPOTHALAMUS
TRH PITUITARY

FOREBRAIN AND LIMBIC STRUCTURES - frontal cortex - amygdala - stria terminalis

BRAINSTEM - locus coeruleus - nucleus parabrachialis

TSH

THYROID

THYROID HORMONE

Dysregulation in Anxiety

NEUROENDOCRINOLOGICAL BASIS OF DEPRESSION

H-P-A Axis
HYPOTHALAMUS CRH PITUITARY ACTH

FOREBRAIN AND LIMBIC STRUCTURES - frontal cortex - amygdala - stria terminalis

BRAINSTEM - locus coeruleus - nucleus parabrachialis

ADRENAL fight CORTISOL flight

NEUROENDOCRINOLOGICAL BASIS OF DEPRESSION

Adrenal (H-P-A) axis
correlation between cortisol and depression 50% of depressed patients fail to have the normal cortisol suppression response to a single dose of dexamethasone

NEUROENDOCRINOLOGICAL BASIS OF DEPRESSION

Thyroid (H-P-T) axis
Blunted release of TSH in response to an infusion of TRH

PSYCHOLOGICAL DIATHESIS
COGNITIVE/ BEHAVIORAL

PSYCHOANALYTIC

PSYCHOLOGICAL DIATHESIS

PSYCHOPATHOLOGY

SOCIAL DIATHESIS

FAMILY

ENVIRONMENT

SOCIAL DIATHESIS

PSYCHOPATHOLOGY

PSYCHOANALYTIC BASIS of SCHIZOPHRENIA

Sigmund Freud Developmental fixation at the time when ego was just being established Ego defects Ego defect affects interpretation of reality and control of inner drives these functions are impaired

PSYCHOANALYTIC BASIS of SCHIZOPHRENIA

Margaret Mahler Distortions in the reciprocal relationship of infant and mother Child unable to separate from and progress from complete dependence on mother in oral phase Persons identity never becomes secure

PSYCHOANALYTIC BASIS of SCHIZOPHRENIA

Harry Stack Sullivan Disturbance in interpersonal relatedness Massive anxiety creates sense of unrelatedness that is transformed into parataxic distortions (persecutory) in order to avoid panic, terror and disintegration of sense of self

PSYCHOANALYTIC BASIS of DEPRESSION

Freud and Karl Abraham 1. disturbances in infant-mother relationship during oral phase 2. real or imagined object loss 3. introjection of departed objects 4. object lost regarded with love and hate, feelings of anger directed inward at the self
Sadock & Sadock, 2003.

PSYCHOANALYTIC BASIS of BIPOLAR DISORDER

Melanie Klein: defense against depression Bertram Lewin: ego is overwhelmed by pleasurable impulses (such as sex) or by feared impulses (such as aggression)

Sadock & Sadock, 2003.

PSYCHOANALYTIC BASIS of BIPOLAR DISORDER

Karl Abraham
Inability to tolerate a developmental tragedy (eg, loss of parent) Tyrannical superego (produces intolerable self-criticism) is replaced by euphoric self-satisfaction

Sadock & Sadock, 2003.

BEHAVIORAL/COGNITIVE BASIS of SCHIZOPHRENIA

Learning theories Children imitate parents who have their own emotional problems Poor models for learning during childhood lead to poor interpersonal relationships

SOCIAL BASIS of SCHIZOPHRENIA

Family dynamics Double bind (Gregory Bateson and Donald Jackson) Children receive conflicting parental messages about their behavior, attitudes and feelings Children withdraw into psychotic state to escape the unsolvable confusion of the double bind Remains to be a hypothesis; not validated successfully

SOCIAL BASIS of SCHIZOPHRENIA

Family dynamics Schisms and skewed families (Theodore Lidz) Schism: one parent is overly close to a child of the opposite sex Skewing: power struggle between the parents resulting in the dominance of one parent

SOCIAL BASIS of SCHIZOPHRENIA

Family dynamics Pseudomutual and pseudohostile families (Lyman Wynne) Suppression of emotional expression resulting in a unique verbal communication that may be incomprehensible to other people

SOCIAL BASIS of SCHIZOPHRENIA

Family dynamics Expressed emotion (EE) Overt criticism, hostility and overinvolvement toward person with schizophrenia High EE predicts high relapse rate

SOCIAL BASIS of SCHIZOPHRENIA

Social theories

Industrialization and urbanization

Causes of schizophrenia?

Major effects on schizophrenia Timing of onset Severity

SOCIAL BASIS of SOMATOFORM DISORDERS

Social communication To avoid obligations and unwelcome challenges (eg, going to a job one does not like) To express emotions (eg, anger at a spouse) Symbolize a feeling or belief (eg, a pain in the guts) Need for special consideration and treatment (primary gain) Controlling and manipulating others (secondary gain)

INTERACTION BETWEEN BIOLOGICAL and PSYCHOSOCIAL FACTORS in MOOD DISORDERS

Life events and environmental stress

Biological changes increase risk of undergoing future episodes of mood disorder even without an external stressor

INTERACTION BETWEEN BIOLOGICAL and PSYCHOSOCIAL FACTORS in MOOD DISORDERS

Stress of first episode

Long-lasting changes in brains biology
Changes in functional states of neurotransmitter and interneuronal signaling systems
Loss of neurons Excessive reduction in synaptic contacts

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