Download PNIE Differences between Unipolar and Bipolar Depression

PNIE DIFFERENCES
BETWEEN UNIPOLAR
AND BIPOLAR DEPRESSION
ANDREA MARQUEZ LOPEZ MATO
INSTITUTE OF BIOLOGICAL PSYCHIATRY
BUENOS AIRES, ARGENTINA
www.ipbi.com.ar
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
UD and BD are a CONTINUUM ??
YES
Kraepelin, Angst, Akiskal
PERHAPS
Joffe, Kraepelin?
NO
Perris, Winokur, Leonhard, Lopez Mato
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
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)
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
PNIE-Differences between
Unipolar and Bipolar Depression
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Adrenal axis
Circadian cortisol secretion
DST
CLU
Thyroid axis
T3, T4, basal TSH
TRHST
Urine determination of NT catabolites
PNIE-Differences between
Unipolar and Bipolar Depression
ADRENAL AXIS
• Hypercortisolemia
• Circadian cortisol
secretion alteration
• UFC
• DST
Adrenal axis disturbances
in depression
Most published data
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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
Adrenal axis disturbances
in depression
Cortisol 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
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
Adrenal axis disturbances
in depression
•
RATIONALE (cont)
Bipolar depressive inpatients had a significantly
higher prevalence rate of cortisol hypersecretion
than unipolar
PNIE- Differences between
Unipolar and Bipolar Depression
Cortisol Rythm
20
15
10
5
8
AM
4
PM
8
AM
0
66 unipolar depression
37 bipolar depression
unipolar
depression
bipolar
depression
4
PM
PNIE- Differences between
Unipolar and Bipolar Depression
UFC
140
120
100
80
60
40
20
0
66 unipolar depression
37 bipolar depression
Bipolars
Unipolars
Adrenal axis disturbances
in depresssion
DST
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
Adrenal axis disturbances
in depression
DST
Adrenal Axis Disturbances
In Depression
Positive 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
Adrenal axis disturbances
in depression
Positive 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
PNIE- Differences between
Unipolar and Bipolar Depression
DST no supression
66 unipolar depression
37 bipolar depression
80
70
60
50
40
30
20
10
0
Bipolars
Unipolars
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)
PNIE- Differences between
Unipolar and Bipolar Depression
THYROID AXIS
• Basal T3, T4, TSH
• TRHST
PNIE- Differences between
Unipolar and Bipolar Depression
Basal 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
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
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
PNIE- Differences between
Unipolar and Bipolar Depression
TRHST
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
PNIE- Differences between
Unipolar and Bipolar Depression
TRHST
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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
PNIE- Differences between
Unipolar and Bipolar Depression
TRHST 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
PNIE Differences between
Unipolar and Bipolar Depression
TRHST (1998-2008)
95 unipolar depression
48 bipolar depression
basal
30 m
60 m
90 m
23/95 patients
24 %
unipolars
33%
bipolars
16/48 patients
PNIE Differences between
Unipolar and Bipolar Depression
Urinary 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)
PNIE Differences between Unipolar
and Bipolar Depression
Urinary excretion of NT catabolytes
95 unipolar depression
48 bipolar depression
Plus 20%
Plus 10%
Normal range
Minus 10%
Phea
PhAA
HVA
MHPG
Minus 20%
Minus 30%
Minus 40%
Minus 50%
Unipolar
depression
Bipolar
depression
PNIE- Differences between
Unipolar and Bipolar Depression
Urinary 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
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
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
THANK YOU
ANDREA MARQUEZ LOPEZ MATO
INSTITUTE OF BIOLOGICAL PSYCHIATRY
BUENOS AIRES, ARGENTINA
www.ipbi.com.ar
www.aapb.org.ar
PNIE- Differences between
Unipolar and Bipolar Depression
TRHST
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