Depression Mania Anxiety

1
DepressionManiaAnxiety
2
Depression un-relievable sense of despair and
uselessness, accompanied by the incapability of
feeling pleasure or interest in any activity and
major sleep dysfunction In spite of a clear
genetic component EVERYBODY can enter periods of
depression, if subject to strong and prolonged
stress Because of the absence of more organic
symptoms and evidence, one component of the
problem is that family, friends and colleagues of
the depressed person may not understand or even
believe that the patient is deep and serious
suffering
3

• Three of more of the following symptoms need to
  be present for satisfying the clinical
  definition of depression
• Disturbed sleep
• Disturbed appetite
• Loss of energy
• Decreased sex drive
• Psychomotor agitation (restlessness)
• Psychomotor retardation (slowing down of thoughts
  and actions)
• Attention impairment (difficulty in
  concentrating)
• Indeciseveness
• Feelings of worthlessness
• Guilt
• Pessimistic thoughts
• Thoughts about death, dying and/or suicide
• Other accompanying symptoms are constipation,
  decreased salivation (dry mouth), and a diurnal
  variation in the gravity of the symptoms (usually
  worse at morning).
• Exclusion criteria schizophrenia and recent
  death of close relative

4
Depression 1) Melancholic depression (the
patient is inconsolable) 2) Atypical depression
(the patient temporarily cheers up) 3) Disthymia
(persistent but milder mood impairment) Bipolar
disease characterized by the frequency,
duration, and intensity of the positive and
negative phases Anxiety 1) Panic disorder 2)
Post Traumatic Stress Disorder 3)Generalized
anxiety disorder 4) Obsessive Compulsive Disorder
5
The three syndromes all have two major
components 1) A strong genetic predisposition
(probably with the involvement of multiple genes
polygenic-) 2) The environment external or
internal - (different source of stress disease,
social, metabolic, family, financial)
6
Hypothalamus Pituitary Adrenal axis
(HPA) Another specialized system activates a
whole series of organs of the body and brain
areas for responding to conditions which can
compromise the integrity of the organisms in the
short or in the long span (stress), and that
contributes to information processing and storage
meant to minimize current and future disruption
of organism homeostasis
7
(No Transcript)
8
Anatomy and hormones of the adrenal gland
9

• Brain input to CRF-producing neurons
• Many brain areas are involved in the
  stress-mediated response to CRF, produced locally
  or released there by the hypothalamus
• - Amygdala
• Peribrachial nucleus
• locus cerouleus (LC)
• nucleus of the solitary tract (NTS)
• neocortex
• Neocortical areas show CRF-positive neurons
  (probably bipolar interneurons), in layer 2-3 of
  prefrontal, cingulate, insular cortices, all
  regions with abnormal function in depressed
  patients

10
Neurotransmitters and modulators regulating
CRF-producing cells
11
(No Transcript)
12
(No Transcript)
13
(No Transcript)
14
(No Transcript)
15
(No Transcript)
16
Role of CRF in anxiety and stress CRF
administration produces dose-dependent
long-lasting behavioral and autonomic effect
ranging from arousal to anxiety like behavior. In
animal models Increase in locomotor activity
(low dose) Increase in freezing behavior (high
dose) Increased grooming (anxiety) Decreased
response in shock-motivated operant
tasks Enhancement of startling response Antagonis
t administration or peripheral benzodiazepine
injection block these behaviors. Many animal
models and human experiment using many techniques
demonstrate that CRF is necessary and sufficient
to define stress
17
Chronic Stress Genetic Predisposition Adapti
ve response Maladaptive response Subject-
operated unexpected Psychoses Obsessive Depressi
on (Schizophrenia) Compulsive (unipolar
or Disorder bipolar) stressor
removal with or without anxiety stre
ssor still present OR absent
18

• Risks associated with hyperactive HPA axis
• Debilitating effects in many life areas
• job
• family relationships
• sex life
• self esteem
• general quality of life
• A large percentage of suicides are caused by a
  persistent
• presence of either depressions or schizophrenia
• depression, OCD and ADD or ADHD (Attention
  Deficit disorder with or without hyperactivity)
  present a high degree of co-morbidity (they can
  be present at the same time)

19
Long-term changes (memory and learning) in
cerebral (cortical and subcortical) uses
different circuits (carrot and stick)
20
Role of the amygdala
The amygdala builds emotions as associations
between neutral stimuli and reinforcers, which
are then communicated to higher areas (prefrontal
cortex and others)
21
The amygdala is in a central positions for
creating emotional content and using it in
decision making acting on important structures of
the executive circuit -prefrontal
cortex -thalamus -basal ganglia
22
Repeated and persistent stress may induce
amygdala sensitization (hyper-responsivity)
An abnormal behavior of the amygdala could be an
important factor (not necessarily the only) to
explain different pathological outcomes
23
Stress cascade
Stress, NE release
Hypothalamus Corticotropin Releasing Hormone
(CTRH)
Pituitary Adrenocortropin Hormone (ACTH)
Amygdala (hyper-) activation
Adrenal cortex Cortisol
Alertness ACh nuclei
An increase in cortisol release is detected in
many depressed patients
Consequences of cortisol release - Increased
use of protein in metabolism - Increased storage
of fat in adipose tissue - Decreased immune
response - Maladaptive behavior (positive
feedback to the CNS)
24
Brain areas affected by long-lasting stress
Chronic Stress Genetic Predisposition Adapti
ve response Maladaptive response Subject-
operated unexpected Psychoses Obsessive Depressi
on (Schizophrenia) Compulsive (unipolar
or Disorder bipolar) with or
without anxiety stressor
removal stressor still present OR absent
PFC hyperactivity
Bas. Gan. dysfunction
PFC hypoactivity