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