PNIE DIFFERENCES BETWEEN UNIPOLAR AND BIPOLAR DEPRESSION ANDREA MARQUEZ LOPEZ MATO INSTITUTE OF...
-
Upload
ashlie-willis -
Category
Documents
-
view
224 -
download
0
Transcript of PNIE DIFFERENCES BETWEEN UNIPOLAR AND BIPOLAR DEPRESSION ANDREA MARQUEZ LOPEZ MATO INSTITUTE OF...
PNIE DIFFERENCES BETWEEN UNIPOLAR
AND BIPOLAR DEPRESSION
ANDREA MARQUEZ LOPEZ MATOINSTITUTE 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 ??
YESKraepelin, 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
- 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
• Hypercortisolemia• Circadian cortisol
secretion alteration• UFC• DST
ADRENAL AXIS
Adrenal axis disturbances in depression
• 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
Most published data
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
0
5
10
15
20
unipolar depression
bipolar depression
8 AM
4 PM
8 AM
4 PM
66 unipolar depression37 bipolar depression
PNIE- Differences between Unipolar and Bipolar Depression
UFC
66 unipolar depression37 bipolar depression
0
20
40
60
80
100
120
140
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
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
• 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
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
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
0
10
20
30
40
50
60
70
80
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)
66 unipolar depression37 bipolar depression
PNIE- Differences between Unipolar and Bipolar Depression
• Basal T3, T4, TSH• TRHST
THYROID AXIS
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
• 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
RATIONALE
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)
PNIE- Differences between Unipolar and Bipolar Depression
TRHST
Lopez Mato A et al. Alcmeon 1996
PNIE- Differences between Unipolar and Bipolar Depression
TRHST in Rapid cycling bipolar patients
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
• 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)
24 %unipolars
33%bipolars
basal
30 m60 m
90 m
23/95 patients 16/48 patients
95 unipolar depression48 bipolar depression
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)
PNIE Differences between Unipolar and Bipolar Depression
Urinary excretion of NT catabolytes
PheaPhAAHVAMHPG
Bipolardepression
Minus 10%
Minus 20%
Minus 30%
Minus 40%
Minus 50%
Plus 10%
Plus 20%
Unipolardepression
Normal range
95 unipolar depression48 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
Some observations may lead towards a PNIE difference between unipolar and bipolar
depression
Neurobiological findings can mark a clear cut space for unipolar depression
CONCLUSIONS
THANK YOU
ANDREA MARQUEZ LOPEZ MATOINSTITUTE 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