Major Depressive Disorder (MDD) is one of the most common mental illnesses worldwide and is strongly associated with suicidality. Commonly used treatments for MDD with suicidality include crisis intervention, oral antidepressants (although risk of suicidal behavior is high among non-responders and during the first 10-14 days of the treatment) benzodiazepines and lithium. Although several interventions addressing suicidality exist, only few studies have characterized in detail patients with MDD and suicidality, including treatment, clinical course and outcomes. Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D)-study is an investigator-initiated trial funded by Janssen-Cilag GmbH.

For population 1 out of 3 OASIS-D populations, to assess the sub-population of patients with suicidality and its correlates in hospitalized individuals with MDD.

The ongoing OASIS-D study consecutively examines hospitalized patients at 8 German psychiatric university hospitals treated as part of routine clinical care. A sub-group of patients with persistent suicidality after >48 hours post-hospitalization are assessed in detail and a sub-group of those are followed for 6 months to assess course and treatment of suicidality associated with MDD. The present analysis focuses on a preplanned interim analysis of the overall hospitalized population with MDD.

Of 2,049 inpatients (age=42.5±15.9 years, females=53.2%), 68.0% had severe MDD without psychosis and 21.2% had moderately severe MDD, with 16.7% having treatment-resistant MDD. Most inpatients referred themselves (49.4%), followed by referrals by outpatient care providers (14.6%), inpatient care providers (9.0%), family/friends (8.5%), and ambulance (6.8%). Of these admissions, 43.1% represented a psychiatric emergency, with suicidality being the reason in 35.9%. Altogether, 72.4% had at least current passive suicidal ideation (SI, lifetime=87.2%), including passive SI (25.1%), active SI without plan (15.5%), active SI with plan (14.2%), and active SI with plan+intent (14.1%), while 11.5% had attempted suicide ≤2 weeks before admission (lifetime=28.7%). Drug-induced mental and behavioral disorders (19.6%) were the most frequent comorbid disorders, followed by personality disorders (8.2%). Upon admission, 64.5% were receiving psychiatric medications, including antidepressants (46.7%), second-generation antipsychotics (23.0%), anxiolytics (11.4%) antiepileptics (6.0%), and lithium (2.8%). Altogether, 9.8% reported nonadherence to medications within 6 months of admission.

In adults admitted for MDD, suicidality was common, representing a psychiatric emergency in 35.9% of patients. Usual-care treatments and outcomes of suicidality in hospitalized adults with MDD require further study.

None Declared

The corticotropin-releasing hormone receptor 2 (CRHR2) gene encodes CRHR2, which is an important element in the hypothalamic-pituitary-adrenal physiologic response towards stress culminating in hyperglycemia, insulin resistance, mood disorders and depression (MDD). CRHR2-/- mice are hypersensitive to stress, and the CRHR2 locus in humans has been linked to type 2 diabetes (T2D) and MDD.

Several variants in the CRHR2 gene have been reported in patients with bipolar disorder, post-traumatic stress disorder, and T2D, but variants in the gene have not been investigated in families with T2D and MDD.

We genotyped 212 Italian families with T2D and MDD. We tested 17 SNPs in the CRHR2 gene using two-point parametric-linkage and linkage-disequilibrium (LD) analysis with the following models: dominant with complete-penetrance (D1), dominant with incomplete-penetrance (D2), recessive with complete-penetrance (R1) and recessive with incomplete-penetrance (R2).

We detected linkage to and/or LD with: MDD for 3 SNPs/D1, 2 SNPs/D2, 3 SNPs/R1, and 3 SNPs/R2; and, T2D for 3 SNPs/D1, 2 SNPs/D2, 2 SNPs/R1 and 1 SNP/R2. Two independent SNPs were comorbid. Interestingly, the variants linked to or in LD with MDD had in general higher statistical significance level than the variants linked to T2D, despite that the families were primarily ascertained for T2D.

Our study shows for the first time that the CRHR2 gene which encodes CRHR2 is in linkage to and linkage disequilibrium with MDD and T2D, thereby contributing, in families with T2D, to both disorders and underlying the shared genetic pathogenesis of their comorbidity

No significant relationships.

Serotonin syndrome (SS) is a toxic state characterized by increased serotonin activity. It has been suggested that severe serotonin syndrome usually involves monoaminoxidase inhibitors (MAOIs).

To quantify in how far severe SS is associated with MAOIs.

Systematic review and quantitative analysis of all SS cases published between 1 January 2004 and 31 December 2014. Severe SS was defined as cases, either requiring intensive care or resulting in death. Cases were included if they met the diagnostic criteria for SS according to at least one of the three diagnostic criteria systems (Hunter, Radomski and Sternbach).

Of the 299 included cases, 118 (39%) met the definition for severe SS. Eight cases had insufficient information to enable severity classification. Of the severe cases, 48 (40%) involved a MAOI. Of these, 67% related to psychiatric MAOIs, such as phenelzine and moclobemide and 33% to a somatic MAOI, such as methylene blue and linezolid. Of the remaining 173 non-severe SS cases, 24 cases (13%) involved a MAOI. In these, 12% related to a psychiatric MAOI and 83% to a somatic MAOI. One case (4%) had a combination of both. The odds ratio for MAOI involvement in severe versus non-severe serotonin syndrome was 4.3 (CI 2.4 – 7.5; p < 0.001).

In the majority of published case reports, drugs other than MAOIs are involved in serotonin syndrome, even in severe cases. MAOIs are, however, more common in severe serotonin syndrome than in non-severe cases.

M. Ott: scientific advisory board member of Astra Zeneca, Sweden. U. Werneke: received funding for educational activities on behalf of Norrbotten Region; Astra Zeneca, Eli Lilly, Janssen, Novartis, Otsuka/Lundbeck, Servier, Shire, Sunovion. Others: None

Evidence for lithium as a maintenance treatment for bipolar disorder type II remains limited since most treatment-prevention studies focus on bipolar disorder type I or do not distinguish between types of bipolar disorder.

To compare the impact of lithium discontinuation on hospital utilisation in patients with bipolar disorder type I or schizoaffective disorder and patients with bipolar disorder type II or other bipolar disorder.

Mirror-image study, examining hospital utilisation within two years before and after lithium discontinuation as part of LiSIE, a retrospective cohort study into effects and side-effects of lithium for the maintenance treatment of bipolar disorder as compared to other mood stabilisers.

For the whole sample, the number of admissions increased from 86 to 185 admissions after lithium discontinuation, with the mean number of admissions/patient/review period doubling from 0.44 to 0.95 (p < 0.001). The number of bed days increased from 2218 to 4240, with the mean number of bed days/patient/review period doubling from 11 to 22 (p = 0.025). This increase in admissions and bed days was exclusively attributable to patients with bipolar disorder type I or schizoaffective disorder.

Our findings suggest that due to a higher relapse risk in patients with bipolar disorder type I or schizoaffective disorder there is a need to apply a higher threshold for discontinuing lithium than for patients with bipolar disorder type II or other bipolar disorder.

Michael Ott has been a scientific advisory board member of Astra Zeneca Sweden, Ursula Werneke has received funding for educational activities on behalf of Norrbotten Region (Masterclass Psychiatry Programme 2014–2018 and EAPM 2016, Luleå, Sweden): Astra

The association between lithium and thyroid dysfunction has long been known. Yet it is not known whether lithium-associated hypothyroidism is reversible, once lithium treatment has been stopped.

To determine whether lithium-associated hypothyroidism was reversible in patients who subsequently discontinued lithium.

Retrospective cohort study in the Swedish region of Norrbotten into the effects and side- effects of lithium treatment and other drugs for relapse prevention (LiSIE). For this particular study, we reviewed medical records between 1997 and 2015 of patients treated with lithium.

Of 1340 patients screened, we identified 90 patients with lithium-associated hypothyroidism who subsequently discontinued lithium. Of these, 27% had overt hypothyroidism at the time when thyroid replacement therapy was initiated. The mean delay from lithium start to thyroid replacement therapy start was 2.3 (SD 4.7) years. Fifty percent received thyroid replacement therapy within 10 months of starting lithium. Of 85 patients available for follow up, 35 (41%) stopped thyroid replacement therapy after lithium discontinuation. Six patients reinstated thyroid replacement therapy subsequently. Only one of these had overt hypothyroidism, occurring 13 days after stopping lithium and 11 days after stopping thyroid replacement therapy.

Lithium-associated hypothyroidism seems reversible in most patients, once lithium has been discontinued. In such cases, thyroid replacement therapy discontinuation could be attempted much more often than currently done. Based on the limited evidence of our study, we can expect hypothyroidism to recur early after discontinuation of thyroid replacement therapy if at all.

MO: scient adv. board member Astra Zeneca Sweden; UW: educ. activities Norrbotten Region: Astra Zeneca, Eli Lilly, Janssen, Novartis, Otsuka/Lundbeck, Servier, Shire and Sunovion. All others: none.

Currently, our understanding remains limited of how co-occurring bipolar disorder and attention deficit hyperactivity disorder (ADHD) should be treated.

To evaluate the impact of central stimulant treatment on self-injurious behaviour in patients with a dual diagnosis of bipolar disorder or schizoaffective disorder and ADHD.

Retrospective cohort study (LiSIE) into effects and side-effects of lithium as compared to other mood stabilisers. Here, using a mirror-image design, we compared suicide attempts and non-suicidal self-injury events within 6 months and 2 years before and after central stimulant treatment start.

Of 1564 eligible patients, 206 patients met inclusion criteria; having a dual diagnosis of bipolar disorder or schizoaffective disorder and ADHD at first central stimulant initiation. In these, suicide attempts and non-suicidal self-injury events decreased significantly within both 6 months (p = 0.004) and 2 years (p = 0.028) after central stimulant start. After multiple adjustments, this effect was preserved 2 years after central stimulant start (OR 0.63, 95% CI; 0.40 – 0.98, p = 0.041).

Central stimulant treatment may reduce the risk of self-injurious behavior in patients with a dual diagnosis of bipolar disorder or schizoaffective disorder and ADHD. However, to reduce the risk of manic switches, concomitant mood stabilising treatment remains warranted.

Michael Ott has been a scientific advisory board member of Astra Zeneca Sweden, Ursula Werneke has received funding for educational activities on behalf of Norrbotten Region (Masterclass Psychiatry Programme 2014–2018 and EAPM 2016, Luleå, Sweden): Astra

Previous research indicates that prisoners have severe psychological distress. To assess their distress level and potential need for treatment, the present study compared the subjective psychological distress of long- and short-term prisoners with that of psychiatric and forensic patients.

Long- (n = 98) and short-term prisoners (n = 94) and forensic (n = 102) and psychiatric (n = 199) patients completed the German versions of the Symptom Checklist Revised (SCL-90-R) and Brief Symptom Inventory (BSI).

In general, long-term prisoners showed the same level of mental distress as psychiatric patients and more than that reported by forensic patients. Short-term prisoners reported the least level of distress. Long- but not short-term prisoners showed clinically significant results on the scales for depression, paranoid ideation, and psychosis.

The improvements in psychiatric treatment for inmates demanded by many stakeholders need to differentiate between long- and short-term prisoners. Because depression seems to cause the most psychological distress among inmates, suicide prevention seems to be an important issue in prisons.

The authors have not supplied their declaration of competing interest.

Across psychopathologies, trauma-exposed individuals suffer from difficulties in inhibiting emotions and regulating attention. In trauma-exposed individuals without psychopathology, only subtle alterations of neural activity involved in regulating emotions have been reported. It remains unclear how these neural systems react to demanding environments, when acute (non-traumatic but ordinary) stress serves to perturbate the system. Moreover, associations with subthreshold clinical symptoms are poorly understood.

The present fMRI study investigated response inhibition of emotional faces before and after psychosocial stress situations. Specifically, it compared 25 women (mean age 31.5 ± 9.7 years) who had suffered severe early life trauma but who did not have a history of or current psychiatric disorder, with 25 age- and education-matched trauma-naïve women.

Under stress, response inhibition related to fearful faces was reduced in both groups. Compared to controls, trauma-exposed women showed decreased left inferior frontal gyrus (IFG) activation under stress when inhibiting responses to fearful faces, while activation of the right anterior insula was slightly increased. Also, groups differed in brain–behaviour correlations. Whereas stress-induced false alarm rates on fearful stimuli negatively correlated with stress-induced IFG signal in controls, in trauma-exposed participants, they positively correlated with stress-induced insula activation.

Neural facilitation of emotion inhibition during stress appears to be altered in trauma-exposed women, even without a history of or current psychopathology. Decreased activation of the IFG in concert with heightened bottom-up salience of fear related cues may increase vulnerability to stress-related diseases.