PNIE DIFFERENCES BETWEEN UNIPOLAR AND BIPOLAR DEPRESSION

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PNIE DIFFERENCES BETWEEN UNIPOLAR AND BIPOLAR
DEPRESSION

• ANDREA MARQUEZ LOPEZ MATOINSTITUTE OF BIOLOGICAL
  PSYCHIATRY
• BUENOS AIRES, ARGENTINA
• www.ipbi.com.ar

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• The author declares
• that she has no conflicts of interest
• including any financial, personal
• or other relationship
• with other people or organizations
• that could have
• inappropriately influenced her work

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UD and BD are a CONTINUUM ??YESKraepelin,
Angst, AkiskalPERHAPS Joffe, Kraepelin?
NO Perris, Winokur, Leonhard, Lopez Mato
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PNIE Differences between Unipolar and Bipolar
Depression

• The objective of this presentation is
• to determine if
• unipolar and bipolar depression are
• a unique disorder or different entities
  
• from a PNIE point of view

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PNIE Differences between
Unipolar and Bipolar Depression

• Several PNIE challenges in 103 drug free patients
  at the Biological Institute of Psychiatry, Buenos
  Aires, Argentina.
• Performed on a clinical basis as part of the
  clinical record of every patient accesing our
  Institute (1998-2008)

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PNIE-Differences between Unipolar and Bipolar
Depression

• Unipolar and bipolars underwent a clinical
  diagnose based on DSM IV criteria and
  special mood questionaries
• Research was made reviewing past and present
  medical records
• 66 and/or 95 unipolar depressive patients
• 37 and/or 48 bipolar depressive patients

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PNIE-Differences between Unipolar and Bipolar
Depression

• - Adrenal axis
• Circadian cortisol secretion
• DST
• CLU
• - Thyroid axis
• T3, T4, basal TSH
• TRHST
• - Urine determination of NT catabolites

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PNIE-Differences between
Unipolar and Bipolar Depression
ADRENAL AXIS

• Hypercortisolemia
• Circadian cortisol secretion alteration
• UFC
• DST

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Adrenal axis disturbances
in depression
Most published data

• Circadian rhythm alteration
• Non supression DST
• Blunted CRH/ACTH test
• CRH increased in CSF
• Pituitary enlargement
• Adrenal enlargement
• Decrease in CRH receptors in frontal cortex of
  suicidal individuals
• Desensitization of steroid receptors in
  hipocampus

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Adrenal axis disturbances
in depressionCortisol circadian rhythm

• REMEMBER THAT
• Cortisol secretion has a circadian rhythm
• 8 AM 5-25 ng/dL----- 4 PM 2-9 ng/dL
• Depressive patients have afternoon hypersecretion
  with inverse or flat circadian rhythm
• Biological explanation of diurnal symptomatic
  peak described by Kraepelin more than a century
  ago

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Adrenal axis disturbances
in depression

• RATIONALE
• Severe depression has been associated with
  hypercortisolism and loss of the normal diurnal
  variation of cortisol secretion
• Both appear to be a state-related finding,
  normalizing after clinical recovery
• Urinary free cortisol (UFC) is reported high in
• depressed patients

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Adrenal axis disturbances
in depression

• RATIONALE (cont)
• Bipolar depressive inpatients had a significantly
  higher prevalence rate of cortisol hypersecretion
  than unipolar

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PNIE- Differences between Unipolar and Bipolar
Depression Cortisol Rythm
66 unipolar depression 37 bipolar depression
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PNIE- Differences between Unipolar and Bipolar
Depression UFC
66 unipolar depression 37 bipolar depression
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Adrenal axis disturbances
in depresssionDST

• RATIONALE
• DST abnormality represents an increasing degree
  of severity of depression and/or a distinct
  subtype of depression
• The DST may prove particularly helpful in
  distinguishing patients with psychotic affective
  disorders from patients with schizophrenia or
  nonaffective psychoses

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Adrenal axis disturbances
in depressionDST
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Adrenal Axis Disturbances
In DepressionPositive DST

• 14 patients with depressive symptoms
• 48 patients with major depression
  without melancholia
• 78 patients with major depression
  with melancholia
• 95 patients with major depression
  with psychosis
• Evans, Burnett and Nemeroff 1983

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Adrenal axis disturbances
in depressionPositive DST

• More frequent in
• Younger patients
• More motor inhibition
• More psychotic symptoms
• More agression
• More suicidal risk
• Bipolars share these condition more than
  unipolars do

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PNIE- Differences between Unipolar and Bipolar
Depression DST no supression
66 unipolar depression 37 bipolar depression
DST revealed no supression in both group of
patients with a robust tendency to more altered
results related to the severity of clinical
presentation or risk for psychotic symptoms
((bipolars)
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PNIE- Differences between
Unipolar and Bipolar Depression
THYROID AXIS

• Basal T3, T4, TSH
• TRHST

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PNIE- Differences between Unipolar and Bipolar
DepressionBasal Hormone Determination

• RATIONALE
• Investigators are aware of the association
  between Grade II and III hypothyroidism and
  pathological behaviour, particularly severe mood
  disorder.
• It is published a 92 incidence of elevated TSH
  levels in rapid-cycling bipolar patients

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PNIE- Differences between Unipolar
and Bipolar Depression

• RATIONALE (cont)
• There is anecdotal evidence that treatment with
  thyroxine is effective in rapid-cycling bipolar
  patients
• Our own experience suggests that those who do
  respond seem to require hypermetabolic doses of
  thyroxine

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PNIE- Differences between Unipolar and Bipolar
Depression Basal Hormone Determination

• Patients with endocrinological disease are
  excluded
• 95 unipolar depression
• 48 bipolar depression
• All basal levels range between those described in
  general population
• No differences between unipolars and bipolars

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PNIE- Differences between Unipolar and Bipolar
DepressionTRHST
RATIONALE

• A blunted TSH Response ( characterized as a delta
  TSH 5 to 7 µIU/ml) has been reported in
  many patients with effective disease
• It has been reported to occur about 25 to 30
  in patients with MDD, but can also be present
  in bulimia, alcoholism, BLP, panic disorder
• A positive TRHST is related to severity of
  depression and a history of violent suicide
  attempts

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PNIE- Differences between Unipolar and Bipolar
Depression TRHST

• 34 depressive patients
• 33 had normal response
• 33 had blunted response
• (Strong correlation with unipolar
  presentation)
• 33 had hyperreponsiveness
• (Strong correlation with bipolar presentation
  and young age of onset)
• 38 had positive antibodies (antiperoxidase)

Lopez Mato A et al. Alcmeon 1996
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PNIE- Differences between
Unipolar and Bipolar DepressionTRHST in Rapid
cycling bipolar patients

• In 34 patients TRHST hyperresponsivenes seems to
  be predictor of rapid cycling
• Lopez Mato A et al 1996
• In 1000 patients TRHST hyperresponsiveness is a
  predictor of switch
• Moller HJ
  Flores Amargos D. Berlín, 2001

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PNIE Differences between Unipolar and Bipolar
DepressionTRHST (1998-2008)
95 unipolar depression 48 bipolar depression
16/48 patients
23/95 patients
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PNIE Differences between Unipolar and Bipolar
DepressionUrinary excretion of NT catabolytes

• RATIONALE
• It has been shown a frequent correlation between
  any type of depression and lower excretion of
  Phea, PhAA, 5HT, 5HIAA, DA, Epinephrine or NE in
  24 hs urine samples
• Screened at ipbi in 350 patients in 10 years
  (data not published)

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PNIE Differences between Unipolar and Bipolar
DepressionUrinary excretion of NT catabolytes
95 unipolar depression 48 bipolar depression
Plus 20
Plus 10
Normal range
Minus 10
Minus 20
Minus 30
Minus 40
Minus 50
Bipolar depression
Unipolar depression
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PNIE- Differences between Unipolar and Bipolar
DepressionUrinary excretion of NT catabolytes

• CONCLUSIONS
• Urinary excretion of PhEA, PhAA, HVA
  were similar in both unipolar and bipolar
  depressive patients
• Metoxiphenilglicol (MHPG) excretion was lower in
  bipolars

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PNIE- Differences between Unipolar
and Bipolar Depression DISCUSSION BEFORE
CONCLUSIONS

• Unipolar and bipolar depressive patients received
  a clinical diagnose based on DSM IV criteria and
  different mood questionaries administerd by
  different professionals at ipbi
• Research was made reviewing past and present
  medical records
• Laboratorial findings were performed by different
  biochemical techniques

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PNIE-Differences between Unipolar and Bipolar
Depression
CONCLUSIONS

• Some observations may lead towards a PNIE
  difference between unipolar and bipolar
  depression
• Neurobiological findings can mark a clear cut
  space for unipolar depression

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THANK YOU

• ANDREA MARQUEZ LOPEZ MATOINSTITUTE OF BIOLOGICAL
  PSYCHIATRY
• BUENOS AIRES, ARGENTINA
• www.ipbi.com.ar
• www.aapb.org.ar

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PNIE- Differences between Unipolar
and Bipolar DepressionTRHST

• REMEMBER
• TSH determination at 30-60-90 min post TRH
• TSH peak tends to occur 20-30 min
• Delta TSH (substraction of baseline TSH from
  peak) in normal individual TRH challenge causes
  serum TSH to increase 5 to 25 µIU/ml within 15-20
  min
• After TRH injection, TSH returns to baseline over
  about two hours postinjection