1. PNIE DIFFERENCES BETWEEN UNIPOLAR AND BIPOLAR DEPRESSION ANDREA MARQUEZ LOPEZ MATO INSTITUTE OF BIOLOGICAL PSYCHIATRY BUENOS AIRES, ARGENTINA www.ipbi.com.ar

2. 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

3. UD and BD are a CONTINUUM ?? YES Kraepelin, Angst, Akiskal PERHAPS Joffe, Kraepelin? NO Perris, Winokur, Leonhard, Lopez Mato

4. 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

5. 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)

6. 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

7. 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

8. PNIE-Differences between Unipolar and Bipolar Depression Hypercortisolemia Circadian cortisol secretion alteration UFC DST ADRENAL AXIS

9. 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

10. 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

11. 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

12. Adrenal axis disturbances in depression RATIONALE (cont) Bipolar depressive inpatients had a significantly higher prevalence rate of cortisol hypersecretion than unipolar

13. PNIE- Differences between Unipolar and Bipolar Depression Cortisol Rythm 66 unipolar depression 37 bipolar depression

14. PNIE- Differences between Unipolar and Bipolar Depression UFC 66 unipolar depression 37 bipolar depression 0 20 40 60 80 100 120 140 BipolarsUnipolars

15. 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

16. Adrenal axis disturbances in depression DST

17. 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

18. 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

19. PNIE- Differences between Unipolar and Bipolar Depression DST no supression 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 depression 37 bipolar depression

20. PNIE- Differences between Unipolar and Bipolar Depression Basal T3, T4, TSH TRHST THYROID AXIS

21. 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

22. 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

23. PNIE- Differences between Unipolar and Bipolar Depression B asal 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

24. 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

25. 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

26. 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

27. PNIE Differences between Unipolar and Bipolar Depression TRHST (1998-2008) 23/95 patients 16/48 patients 95 unipolar depression 48 bipolar depression

28. 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)

29. PNIE Differences between Unipolar and Bipolar Depression Urinary excretion of NT catabolytes Bipolar depression Minus 10% Minus 20% Minus 30% Minus 40% Minus 50% Plus 10% Plus 20% Unipolar depression Normal range 95 unipolar depression 48 bipolar depression

30. 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

31. 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

32. 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

33. THANK YOU ANDREA MARQUEZ LOPEZ MATO INSTITUTE OF BIOLOGICAL PSYCHIATRY BUENOS AIRES, ARGENTINA www.ipbi.com.ar www.aapb.org.ar

34. 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