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Background: second-generation (“atypical”) antipsychotics are widely used for the treatment of bipolar disorder, although they may be associated, to a different degree, according to the specific antipsychotic, with metabolic side effects. The aim of this study is to review the available literature on clinical and therapeutic strategies to manage metabolic syndrome in patients with bipolar disorder. Subjects and methods: a PubMed/Medline research was performed on papers with regards to metabolic adverse events induced by second-generation antipsychotics in bipolar disorder. Articles published from 1st January 1990 to 31st January 2015 were selected. Results: the following issues were discussed: a) identification of patients at risk for developing metabolic side effects (the following clinical features were found associated with an increased risk: young males, older subjects at baseline, and patients in treatment with olanzapine or risperidone both in the short and long-term); b) monitoring metabolic parameters such as cholesterol, triglycerides, glycated hemoglobin, body mass index, waist circumference, weight: bipolar patients taking atypical antipsychotics should be monitored more carefully in the first year of treatment; c) managing the antipsychotic treatment with regard to metabolic side effects (e.g. switching strategies); non-pharmacological interventions aimed at promoting regular lifestyles, in particular ABCDE approach promoted by Johns Hopkins Hospital. Conclusions: psychiatrists or general practitioners may consider the aforementioned strategies in order to limit the metabolic side effects induced by atypical antipsychotics in patients with bipolar disorder. Future researches should try to identify genetic risk factors associated with the onset of metabolic side effects in order to predict the onset of this phenomenon.

Background Lithium is recommended as a first-line treatment for Bipolar Disorder (BD). Thyroid and renal alterations are well known lithium side-effects, while effects on parathyroids are less studied. The aim of this case-control cross-sectional study is to compare parathyroid hormone (PTH) and calcium levels in lithium-exposed bipolar patients and in subjects who had never been exposed to lithium. Methods 112 BD patients were enrolled, 58 on lithium since at least 1 month (mean exposure 60.8±74.8 months) and 54 in the control group. Blood exams included complete blood count, PTH, total and ionized calcium, TSH, T3 and T4, creatinine, urea, sodium and potassium, and lithium serum levels. The Student's t-test and the Pearson's Chi-square test were used for bivariate analyses. A linear regression model was used to analyze the relationship between the duration of exposure to lithium and PTH and calcium levels. Results PTH and ionized calcium levels were significantly higher in lithium-exposed patients; the proportions of subjects with hyperparathyroidism (8.6%) and hypercalcaemia (24.1%) were significantly greater in lithium-exposed patients. The linear regression analyses showed a significant effect of exposure to lithium in months on ionized calcium levels but not on PTH levels. Limitations Given the cross-sectional design of the study we could not identify the exact time of occurrence of hyperparathyroidism. Conclusions Our results indicate that lithium-associated stimulation of parathyroid function is more common than assumed to date. Among parameters to be evaluated prior to lithium implementation and during long-term lithium maintenance, calcium (and eventually PTH) should be added.

Background Recent evidence indicates the possible involvement of adenosine and the purinergic system in the pathophysiology of bipolar disorder (BD). The aim of this study is to compare serum uric acid (UA) levels in a large group of BD patients (in mania, depression and euthymia) vs. a control group of patients with different psychiatric disorders. Methods 150 BD (SCID-I; DSM-IV) patients were compared to 150 age- and gender-matched subjects with MDD, OCD, or Schizophrenia. Mean serum UA values were compared with the ANOVA, with Bonferroni׳s post-hoc tests. Results Mean serum UA levels (5.06±1.45 vs. 4.17±1.05 mg/dL) and rates of hyperuricaemia (30.7% vs. 6.7%) were significantly higher in the bipolar than in the control group. No differences were detected between bipolars in different phases of illness, with all three groups (manic, depressive and euthymic bipolars) showing significantly higher UA levels as compared to controls. No correlations were found between UA levels and YMRS or HAM-D scores. Mean UA levels were also higher in bipolars never exposed to mood stabilizers vs. controls (5.08±1.43 vs. 4.17±1.05 mg/dL), with no differences compared to other bipolars. Limitations Our study suffers from the lack of a healthy comparison group; moreover, longitudinal data are missing. Conclusions Our study provides further evidence of a purinergic dysfunction associated with BD, in all phases of the illness. It is possible that increased UA levels are a trait marker of higher vulnerability to bipolar disorder, and are even more increased during mania (mostly in the first manic episode of drug-naive patients).

Background Specific dysfunctional beliefs have been identified as candidate endophenotypes for Obsessive–Compulsive Disorder (OCD). Rector, Cassin, Richter, and Burroughs (2009) investigated cognitive vulnerability for OCD and their results support both the notion of familial-based origin of obsessive beliefs, and the hypothesis that inflated responsibility/overestimation of threat, could represent candidate endophenotypes for OCD. Aims The primary aim of this study was to replicate previous findings of a familial cognitive vulnerability for OCD. The secondary purpose was to test the hypothesis that obsessive beliefs of patients with OCD and those of their first-degree relatives (FDRs) are correlated, supporting dysfunctional beliefs as candidate endophenotypes for OCD. Method 65 patients with DSM-IV-TR (SCID-I) OCD were included together with one healthy FDR. 77 non-affected FDRs of patients with Bipolar Disorder were enrolled as a control group. Obsessive beliefs were measured with the OBQ-44. Results First-degree relatives of subjects with OCD scored significantly higher than controls on the total score and on the domain tapping inflated responsibility and overestimation of threat. There was no significant correlation between each obsessive belief in patients with OCD and their non-affected FDRs. Conclusions Our study provides evidence of a specific cognitive vulnerability for OCD in FDRs of probands with OCD.

Lithium is recommended by all treatment guidelines for bipolar disorder (BD) as a first-line maintenance treatment. However, the potential side effects and risks associated with long-term lithium use may at times make the implementation of these recommendations in daily practice challenging. The aim of the study is to review available literature on potential long-term side effects of lithium.A PubMed/Medline search was performed on papers dealing with long-term treatment with lithium and side effects. Articles published from January 1980 to February 2013 were selected.Long-term lithium treatment is associated with a reduced urinary concentrating ability, with subsequent polyuria and polidypsia and nephrogenic diabetes insipidus (in 10-40% of patients). Lithium also reduces glomerular filtration rate, and increases risk of renal failure, although the absolute risk is small (0.5% of patients). Lithium treatment is associated with significant higher TSH levels, with a 6-fold greater risk of hypothyroidism in lithium-treated than in control subjects. Less known is the increase of PTH and calcium levels induced by lithium. An exacerbation of psoriasis is also frequently associated with lithium treatment.Lithium remains a fundamental tool for the treatment of BD. Clinicians should know potential side effects (renal, endocrine and dermatological) associated with long-term treatment with lithium, for a correct management of the patient. A specialist referral is often necessary; the question is how to deal with long-term side effects more than whether or not withdrawing lithium. This decision should remain a psychiatrist's competence.

Umberto Albert,1 David De Cori,1 Andrea Aguglia,1 Francesca Barbaro,1 Fabio Lanfranco,2 Filippo Bogetto,1 Giuseppe Maina3 1Anxiety and Mood Disorders Unit, Rita Levi Montalcini Department of Neuroscience, University of Turin, Torino, Italy; 2Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Torino, Italy; 3Department of Mental Health, San Luigi-Gonzaga Hospital, University of Turin, Orbassano, Italy Objective: The aim of this retrospective longitudinal naturalistic study was to evaluate the effects of maintenance lithium treatment on parathyroid hormone (PTH) and calcium levels. Methods: A retrospective longitudinal naturalistic study design was used. Data were collected from the database of a tertiary psychiatric center covering the years 2010–2014. Included were bipolar patients who had never been exposed to lithium and had lithium started, and who had PTH, and total and ionized calcium levels available before and during lithium treatment. Paired t-tests were used to analyze changes in PTH and calcium levels. Linear regressions were performed, with mean lithium level and duration of lithium exposure as independent variables and change in PTH levels as dependent variable. Results: A total 31 patients were included. The mean duration of lithium treatment was 18.6±11.4 months. PTH levels significantly increased during lithium treatment (+13.55±14.20 pg/mL); the rate of hyperparathyroidism was 12.9%. Neither total nor ionized calcium increased from baseline to follow-up; none of our patients developed hypercalcemia. Linear regressions analyses did not show an effect of duration of lithium exposure or mean lithium level on PTH levels. Conclusion: Lithium-associated stimulation of parathyroid function is more common than assumed to date. Among parameters to be evaluated prior to lithium implementation, calcium and PTH should be added. Keywords: bipolar disorder, follow-up study, lithium side-effects&nbsp