Mood disorders Flashcards
Unipolar depression epidemiology
Avg age of onset 29 ave # of lifetime episodes: 4 Prevalence: 12 month - 7% lifetime - 17% all depression life-time prevalence: 21
Unipolar depression risk factors
female sex - 1.5-3x starting in early adolescence divorce age non-black&nonhispanic, non-white non-studying adolescent
Major depression diagnosis
MDD = major depressive disorder; (MDE: episode) Neurovegetative/vegetative symptoms DSIGECAPS: >=5 of the following for >= 2 weeks, one of criteria must be either depressed mood or anhedonia: Depressed mood Sleep disturbance loss of Interest in pleasurable activities Guilt low Energy Concentration difficulties Appetite disturbance Psychomotor retardation Suicidal ideation
Major depressive disorder comorbidities
borderline personality disorder anxiety disorders OCD eating disorders substance misuse
BAD-I diagnosis
>=1 manic episode +/- MDEs Expansive/irritable mood nad persistently increased goal-directed activity or energy plus >=3 (or >=4 if mood is only irritable) of the following, lasting >=1 week: DIGFAST Distractiliby Increase in goal-directed activity Grandiosity Flight of ideas Activities with high potential for painful consequences Sleep decreased Talkative/pressure of speech
Marked FUNCTIONAL IMPAIRMENT
BAD-II diagnosis
Abnormally/persistently elevated, expansive, or irritable mood plus abnormally & persistently increased activity/energy lasting >-4 days, during which >=3 of following occur:
DIGFAST
Unequivocal change in functioning observable by OTHERS
Episode is not severe enough to cause marked impairment in function/require hospitalization
Bipolar affective disorder comorbidities
ADHD
substance misuse
anxiety disorders
Bipolar I overview
> =1 manic episode +/- depressive episodes
Bipolar II overview
> =1 hypomanic episode +/- >=1 depressive episodes
never had full mania
Cyclothymic disorder diagnosis
> =2 y (1 in children/adolescents), numerous periods with hypomanic symptoms that do not meet criteria for hypomanic episode + numerous periods with depressive diagnoses that do not meet criteria for MDE
No symptom-free period >=2 mo at a time
during 2 y period, hypomanic/depressive symptoms have been present for at least half of the time
Have never met criteria for MDE, manic episode or hypomanic episode
Symptoms cause clinically significant distress or impairment
GMC rule out
general medical condition!
TSH, Na, B12, UTI
Liver disease, renal disease, cardiac disease, dementia, neurological disease
Dysthymia diagnosis
persistent depressive disorder
Depressed mood for most of day, for more days than not, for >=2 years (1 in children/adolescents)
While depressed, >=2 of :
- vegetative symptoms: appetite/sleep/energy changes
- psychological symptoms: low self-esteem, poor concentration/indecisiveness, feeling of hoplelessness
No symptom free period >=2 months at a time
clinically significant distress or impairment
Biogenic amine hypothesis
changes in neurotransmitter levels and regulation
deficiencies in dopamine, serotonin, norepinephrine
leading to receptor upregulation
Neurobiology of mood disorders
Biogenic amine hypothesis
post-synaptic receptor changes
neuropeptide, neuroendocrine and hormonal changes (cortisol, TSH)
regional brain dysfunction (blood flow, regional metabolism alterations)
Signal transduction abnormalities
Norepinephrine role in mood
energy
interest
motivation
anxiety, irritability
Serotonin role in mood
impulsivity sex appetite aggression anxiety irritability
Dopamine role in mood
motivation drive sex appetite aggression
Signal transduction abnormalities in depression
Brain Derived Neuropathic factor (BDNF)
sustains viability of neurons
Repressed under stress, potentially leading to atrophy of hippocampus
5HT/NE can help regulate BDNF
Imaging studies confirm reduced volume of hippocampus in depression and anxiety
Pathophysiology of bipolar disorders
not well understood! NT theories Changes in GABA, ACh Sensitization/kindling theories Hormones (cortisol, thyroid) changes in electrolyte balance alterations in membrane/secondary messenger systems Circadian rhythm theories genetics
Risk factors for bipolar disorder
Family history - 75% concordance in twins
Seasonal changes
Environmental stressors
Hx of antidepressant use/electroconvulsive therapy
Catecholamine theory
depression related to decreased catecholaminergic NT caused by NE deficiency
Depletion studies showed relapse in previously controlled depression
Animal models of altered catecholamine metabolism show abnormal exploratory behaviour, conditioned avoidance and reward-seeking behaviour
Serotonin production metabolism
Tryptophan –> 5-hydroxy tryptophan –> serotonin
Serotonin in depression
low levels of 5HT metabolite 5HIAA reported in CSF in depressed patients
Relapse in patients previously well-controlled with SSRIs
Consequences of interference with serotonin metabolism
irritability
insomnia
hyperactivity
hypersexual behaviours
Monoamine hypothesis of depression
Depression caused by decreased levels of centrally available monoamines (NE, 5HT)
Cause unknown
Evidence: antidepressants increase monoamine levels
Reserpine: depletion of monoamines by irreversibly blocking vesicular monoamine transporter may precipitate depression in some patients
Biochemical effect of antidepressants immediate, but clinical effect takes a while (antidepressants lead to compensatory adaptive changes in receptors - desensitization)
5HT/NE/DA depletion does not induce depression in healthy subjects
Antidepressants are not effective in all patients
Newer theories of depression
Anti-depressants produce secondary transcriptional and translational changes –> mediate molecular/cellular plasticity –> normalize limbic/cortical circuits
Neuroanatomy in depression
Dysfunctional connectivity between regions of frontal cortical and limbic system
Decreased size of frontal/cingulate cortices, amygdala
Activity of amygdala increased
Hippocampal volume reduced (associated with greater lifetime depression, stressful life events)
Hippocampus is the major site of neurogenesis in adult brain
Prefrontal cortex symptoms in depression
guilt, suicidality, worthlessness
mood
psychomotor fatigue (mental)
concentration, interest, pleasure
Amygdala symptoms in depression
guilt
suicidality
worthlessness
mood
HPA axis in mood disorders
Dysfunction of HPA axis established in depression –> excess secretion of cortisol
Dexamethasone non-suppression more common in depression (impaired feedback regulation)
Changes in HPA axis only present in ~50% of patients
Chronic secretion of cortisol can alter cognitive function, decrease hippocampal volume
Brain changes likely take place after first episode
Amygdala stimulates hypothalamus to produce CRF, Hippocampal inhibits hypothalamus
Cortisol –> hippocampal volume
Direct toxic effects / neurotrophic factors
Chronic stress suppresses BDNF
Genetics of depression
twin concordance 35-50% for major depression (lower than bipolar)
No specific genes
Carriers of short form of serotonin transporter –> higher risk for depression if they also experience stressful life experiences
- associated with increased activation of amygdala in response to fearful faces
Depression and immune system
Viral/bacterial infection –> sickness behaviour
Overlap significantly with symptoms of depression
Inflammatory disease/taking interferons –> increased risk of psychiatric disorders
Pathophysiology of bipolar disorder
Less known
Manic: increased catecholamines
Likely due to dysfunction of same circuits as depression (GABA/glutamate, HPA axis)
Abnormalities in cellular signal transduction cascades, second messenger systems, oxidative stress, dysregulation of energy metabolism, myelination
Highly heritable, genetic overlap with schizophrenia
SAD PERSONS scale
for suicide risk Sex (male) Age (15-24, >65) Depression Prior history Ethanol abuse Rational thinking loss (psychosis) Support system loss Organized plan No SO Sickness
IS PATH WARM
dynamic factors of suicide risk to determine need for further assessment Ideation Substance abuse Purposelessness Anxiety Trapped HOpelessness Withdrawal Anger Recklessness Mood change
