The aim of this study was to evaluate the predictive validity of the apathy subsyndrome in patients with therapy-resistant depression in the dose–remission study with transcranial pulsating electromagnetic fields (T-PEMF).

The apathy subsyndrome consists of the symptoms of fatigue, concentration and memory problems, lack of interests, difficulties in making decisions, and sleep problems. We evaluated 65 patients with therapy-resistant depression. In total, 34 of these patients received placebo T-PEMF in the afternoon and active T-PEMF in the morning, that is, one daily dose. The remaining 31 patients received active T-PEMF twice daily. Duration of treatment was 8 weeks in both groups. The Hamilton Depression Scale (HAM-D17) and the Bech-Rafaelsen Melancholia Scale (MES) were used to measure remission. We also focused on the Diagnostic Apathia Scale, which is based on a mixture of items from the MINI and the HAM-D17/MES.

In patients without apathy, the remission rate after T-PEMF was 83.9% versus 58.8% in patients with apathy (p≤0.05). In patients without apathy receiving one active dose daily 94.4% remitted versus 50% for patients with apathy (p≤0.05). In patients without apathy who received two active doses 69.9% remitted versus 66.7% for patients with apathy (p≤0.05).

Taking the baseline diagnosis of the apathy syndrome into consideration, we found that in patients without apathy one daily dose of T-PEMF is sufficient, but in patients with apathy two daily doses are necessary. Including the apathy syndrome as predictor in future studies would seem to be clinically relevant.

Although severe hoarding symptoms have been considered rare among obsessive-compulsive disorder (OCD) samples, the prevalence of animal hoarding in OCD is unknown. To help clarifying this issue, we searched for cases of animal hoarding among patients attending a university OCD clinic (n=420).

Chart review.

Only two patients from our sample exhibited animal hoarding (<0.5%) and only one of them presented additional obsessive-compulsive symptoms. Both cases also collected inanimate objects, presented low insight, exhibited poor response to serotonin reuptake inhibitors and did not adhere to therapy.

There seems to be a lack of relationship between animal hoarding and OCD. However, further studies with larger numbers of patients are needed to better define their psychopathological profile and more appropriate nosological insertion.

Although poor sleep accompanies depression, it is unknown which specific sleep abnormalities precede depression. This is similarly the case for depression developing during interferon-α (IFN-α) therapy. Because vulnerability becomes evident in those who slept poorly before IFN-α, we prospectively determined which specific aspect of sleep could predict subsequent depression.

Two nights of polysomnography with quantitative electroencephalogram (EEG) were obtained in 24 adult, euthymic subjects – all subsequently treated with IFN-α for hepatitis C. Every 2 weeks, a Beck Depression Inventory-II (BDI-II) score was obtained, and the maximal increase in BDI-II from pre-treatment baseline – excluding the sleep question – was determined.

The delta sleep ratio (DSR; an index of early-night restorative delta power) was inversely associated with BDI-II increases (p<0.01), as was elevated alpha power (8–12 Hz; p<0.001). Both delta (0.5–4 Hz) and alpha power exhibited high between-night correlations (r=0.83 and 0.92, respectively). In mixed-effect repeated-measure analyses, there was an interaction between alpha power and DSR (p<0.001) – subjects with low alpha power and elevated DSR were resilient to developing depression. Most other sleep parameters – including total sleep time and percentage of time in slow wave sleep – were not associated with subsequent changes in depression.

Both high DSR and low alpha power may be specific indices of resilience. As most other aspects of sleep were not associated with resilience or vulnerability, sleep interventions to prevent depression may need to specifically target these specific sleep parameters.

Glucagon-like peptide 1 (GLP-1) receptor agonists are a new group of antidiabetic medications quickly gaining popularity. We aimed to examine behavioural and neuroendocrine changes following chronic treatment with GLP-1 receptor agonists in animal models.

The effects of chronic treatment with GLP-1 receptor agonists were determined on behavioural parameters [anxiety level in the light–dark compartment test, the motor activity in automated activity cages, immobility in the forced swimming test (FST)] and on corticosterone release in mice. The possible antidepressant effect of chronic liraglutide treatment was also studied in Flinders Sensitive Line (FSL) rats, a genetic model of depression.

Two weeks of treatment with exenatide (10 µg /kg twice daily) or liraglutide (1200 µg/kg once daily) did not affect the anxiety level in a light–dark compartment test nor induce an antidepressant-like effect in the FST in mice. Moreover, chronic treatment with liraglutide had no effect on depression-related behaviour in FSL rats. Interestingly, hypolocomotion induced by the drugs in mice disappeared after chronic dosing. Both of the GLP-1 receptor agonists induced robust increases in corticosterone levels in mice under basal conditions as well as in the case of combination with swimming stress. Remarkably, exenatide was as potent a stimulator of corticosterone release after 2 weeks as after acute administration.

The increases in corticosterone release seen after acute exenatide or liraglutide treatment do not abate after 2 weeks of treatment demonstrating that tolerance does not develop towards this particular effect of GLP-1 agonists.

In this study, we aimed to find out whether sexual dysfunction in patients with Parkinson’s Disease (PD) was associated to PD-related disability and whether this relationship was modulated by depressive and anxiety symptoms.

Eighty-nine consecutive patients with idiopathic PD who attended to our movement disorders outpatient clinics between January 2011 and June 2014 were included in this study. The diagnosis of PD was confirmed by a movement disorders specialists in Neurology, according to UK Parkinson’s Disease Society Brain Bank Criteria. The Unified PD Rating Scale (UPDRS) motor was used to assess motor disability and Hoehn and Yahr stage (H&Y) was used to establish disease severity. Cognitive function was assessed by the Mini-Mental State Examination. Patients were also administered the Hamilton depression (HAMD) and anxiety (HAMA) rating scales. The sexual functions of the patients were rated by applying the Turkish version of the Arizona Sexual Experiences Scale (ASEX).

The mean age at the time of the study visit was 67.74±9.05. Male/female ratio was 1.87. Mean UPDRS total was 29.06±13.96 and mean UPDRS motor was 17.62±9.07. Mean HAMD score was 13.92±10.86, 58.4% of the patients had minor or major depression; and mean HAMA score was 7.94±6.49, 56.2% of the patients had minor or major anxiety. The mean ASEX score was 18.54±7.27 out of a maximum of 30. ASEX total scores were correlated with age, H&Y stage and HAMA scores. Age and also age at onset were correlated with ASEX subdomains except sexual desire. There was no correlation between disease duration and ASEX subdomains. UPDRS motor score was correlated with erection/lubrication. HAMD was only correlated with orgasm satisfaction. HAMA score was correlated with stimulation and orgasm.

In patients with PD, there may be a common factor that modulates both depression, anxiety and sexual function. Further studies are needed to clarify the exact relationship.

Autosomal recessive intellectual disability (ID) is genetically heterogeneous and most of the genes causing it remain undiscovered.

We have ascertained 11 consanguineous families multiplex for IDs in order to identify new loci for autosomal recessive genes for non-syndromic ID, or to aid pinpointing mutations in known causative gene/loci.

Microarray genotyping (Affymatrix 250K) was performed to identify homozygosity-by-descent (HBD) in all affected families.

Analysis of genotypes revealed 45 potential HBD regions across the families, although these may be rationalised down to 39. Two families share an overlapping HBD region on 7q11.21. In one family, X-linkage also looks plausible, and a new ID gene near the centromere may be a likely cause. In one family, no HBD region was found, and thus we exclude autosomal recessive mutation as the likely cause in this family. Copy-number variation (CNV) was also performed and revealed no CNVs, homozygous or heterozygous, segregating with the phenotype.

The homozygous loci identified in this study might harbour candidate genes for ID in these studied families. Therefore, we are proceeding with next-generation sequencing analysis of the families, using whole-exome approaches, and anticipate that this will identify the causative gene/mutation within the identified HBD regions for many of the families studied here.

Dipyrone is one of the most commonly used non-opioid analgesic and antipyretic drug. Its anti-nociceptive and hypothermic effects have long been suspected to be centrally mediated. The involvement of the most recently discovered opioid peptide, nociceptin/orphanin FQ (N/OFQ), and its receptor (NOP) in pain transmission is controversial. It appears to be pro-nociceptive when administered supra-spinally, but exerts anti-nociceptive effects when injected spinally or systemically.

Investigation of the role of the N/OFQ system in paracetamol-induced anti-nociception and hypothermia led us to determine its role in the anti-nociceptive and hypothermic effects of dipyrone.

Hot-plate and tail-flick tests were used to assess nociception, and a rectal thermometer was used to measure rectal temperature in mice.

Mice injected with dipyrone (150, 300, 600 mg/kg, i.p.) displayed dose-related anti-nociception and hypothermia. The NOP receptor antagonist JTC-801 (3 mg/kg, i.p.), at a dose that exerted no effect when used alone, alleviated dipyrone-induced anti-nociception but did not reverse dipyrone-induced hypothermia.

We conclude that NOP receptors participate in the anti-nociceptive, but not in the hypothermic, effects of dipyrone.

A case of agomelatine-induced hepatotoxicity is described in a 47-year female patient who has received the drug, 25 mg/day, for 4 months, for the treatment of depression.

The patient was admitted to the Department of Gastroenterology because of fatigue and nausea, with concomitant elevation of alanine aminotransferase (ALT), 550 U/L, and asparagine aminotransferase (AST), 300 U/L.

Liver biopsy showed diffuse lymphocyte infiltration in the dilated portal spaces without lesion of hepatic lobules. Several weeks after stopping agomelatine, the liver enzymes returned to normal. Subsequently, small gallstones in common bile duct were detected and removed by the endoscopic sphincterotomy.

It is hypothesized that choledocholithiasis could theoretically increase a risk of developing agomelatine-induced hepatotoxicity in this patient. Any pre-existing liver disease should be a contraindication for treatment with agomelatine.