This material was presented in the 25th European Congress of Psychiatry which was organised by the European Psychiatry Association in Florence, Italy from 1-4th April 2017. I had access to the material as I attended the full Congress. Please note that this material remains the intellectual property of the European Psychiatry Association and its authors and any citation should include a full reference to it. For more information on the EPA and how to become a member, please visit: http://www.europsy.net/

1. OBESITY AND OBSTETRIC COMPLICATIONS ARE
ASSOCIATED WITH RAPID-CYCLING IN ITALIAN
PATIENTS WITH BIPOLAR DISORDER
Alice Caldiroli1, Massimiliano Buoli1, Bernardo Dell’Osso1,2, Greta Silvia Carnevali1,
Marta Serati1, Trisha Suppes2, Terence A. Ketter2, A. Carlo Altamura1
1Department of Psychiatry, University of Milan, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico,
Via F. Sforza 35, 20122, Milan, Italy
2Department of Psychiatry and Behavioral Sciences, Stanford University, School of Medicine, Stanford, CA, USA.

2. Faculty Disclosure
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X No, nothing to disclose
Yes, please specify:

3. Rapid cycling (RC) is one of the several factors associated with poor prognosis in bipolar
patients, as well as early onset, long duration of untreated illness and lifetime history of
psychotic symptoms.
The greater clinical severity of RCBD might reflect underlying biological vulnerabilities in
these patients.
Higher IL-6 and IL-18 plasma levels  more prominent inflammatory response in
hypomanic/manic RC bipolar patients compared to patients without RC (Munkholm et al.,
2015).
Introduction
RC worsens the course of bipolar disorder (BD) being associated with poor response to
pharmacotherapy (Schneck et al., 2004; Buoli et al., 2014).

4. TO CHOOSE A PROPER TREATMENT: NO antidepressants, particularly tricyclics –
YES combined therapies with stabilizer + atypical antipsychotic in the maintenance
treatment (Fountoulakis et al., 2013; Buoli et al., 2014)
TO PREDICT THE LONG-TERM OUTCOME: bipolar patients with RC have more
frequently medical comorbidity and higher suicidal risk than bipolar patients without RC
(Gigante et al., 2016; Buoli et al., 2017)
BIOMARKERS of RCBD: why is so important to find them?
TO PREDICT THE TREATMENT RESPOSE: bipolar patients with rapid cycling present a
poorer response to stabilizers in the long-term than bipolar patients without rapid cycling
(Fountoulakis et al., 2013)
An early diagnosis should be the goal to properly treat RCBD patients.

5. Past studies investigating clinical variables associated with RCBD:
 Discordant results (e.g. regarding the effect of antidepressant treatment) (Amsterdam et
al., 2015)
 Not replicated (e.g. regarding the role of inflammatory factors in causing RC)
(Munkholm et al., 2015).
Purpose of the study
To compare RC versus non-RC bipolar patients in terms of socio-demographic and clinical
variables with the aim to
 confirm/disconfirm previous data
 find new possible associations in a substantial sample of patients with BD
Hypotheses:
- RC patients have a more severe course of illness;
- praecox insults (obstetric complications) may be predictive of RC.

6. - Cross-sectional study;
- N=238 BD patients from 3 different community mental health centers;
- RC = presence of at least 4 mood episodes in the prior year according to DSM-5 criteria.
Methods (i)
Exclusion criteria:
- patients not examined in the last 12 months;
- incomplete clinical information;
- diagnosis of dementia, mental retardation or other medical conditions associated with an
increased risk of psychotic symptoms or causing medical conditions included in the
analysis of the present study (e.g., untreated Cushing syndrome and diabetes/obesity).

7. - Descriptive analyses of the total sample were performed;
- the subgroups (presence/absence of RC) were compared by multivariate analyses of
variance (MANOVAs) for continuous variables and Chi-Square tests for qualitative
variables, corrected, when appropriate, by Bonferroni's tests;
- a binary logistic regression was performed considering presence of RC as dependent
variable, and presence of obesity and history of obstetric complications as independent
variables.
Methods (ii)

8.  28 patients (11.8%) had RC;
 The two groups were not different in terms of age, age at onset, gender distribution, type
of family history, type of substance use disorder, history of antidepressant therapy, main
antidepressant, psychotic symptoms, comorbid anxiety disorders, suicide attempts, thyroid
diseases, diabetes, type of BD, duration of untreated illness, illness duration, duration of
antidepressant treatment and GAF scores;
 RC patients had more often a history of obstetric complications (p<0.05), obesity
(p<0.05) and a trend to hypercholesterolemia (p=0.08);
 RC bipolar patients presented more frequently lifetime MDMA misuse (p<0.05) than
patients without RC.
Results

9. 1. Obesity and obstetric complications are risk factors for the development of RC in BD.
Conclusions
Obesity and RC in BD:
- Association between RC and medical conditions, such as hypothyroidism, that can promote obesity
(Galvez et al., 2014);
- Common genetic susceptibility (Winham et al., 2014);
- Obesity as the clinical manifestation of a prominent inflammatory state: the tendency of RC patients to
have hypercholesterolemia is consistent with increased pro-inflammatory activity among RC compared to
non-RC BD patients (Lee et al., 2013).
Perinatal complications:
- are a well-established clinical risk factor for schizophrenia (Suvisaari et al., 2013);
- might be a risk factor for more severe forms of illness (e.g., RC) in subjects with genetic predisposition
to BD.

10. Conclusions
2. Lifetime MDMA misuse may be more frequent in RC bipolar patients.
- Consistent with pre-existing data (Carvalho et al., 2014);
- stimulants may hamper clinical stabilization of bipolar subjects and favor the onset of
RC;
- extended bed rest prevented RC development (Wehr et al., 1998)  prolonged
wakefulness may increase the risk of RC.

11. Limitations
 Patients treated with different drugs (type of last pharmacological treatment did not
differ significantly in the two groups);
 the study design and the heterogeneity of number of subjects in the two subgroups of
patients;
 small number of patients with bipolar II disorder (n=17);
 TSH is not usually carried out in the absence of clinical symptoms  possible failure to
diagnose new cases of full-blown thyroid diseases as well as subclinical hypothyroidism in
the last year of observation.
Longitudinal studies with larger samples and uniform methodologies are needed to confirm
the existing data in the literature.

12. THANK YOU!