Accumulating evidences suggest that pro-inflammatory cytokines such as interleukin-6 (IL-6) play a role in the pathophysiology of depression. In the learned helplessness (LH) paradigm, ~35% rats are resilient to inescapable stress.

Levels of IL-6 in the serum and medial prefrontal cortex (mPFC) of LH rats (susceptible) and non-LH rats (resilience) were measured using enzyme-linked immunosorbent assay and western blot analysis, respectively.

Serum levels of IL-6 in the LH rats were significantly higher than those of control and non-LH rats. In contrast, tissue levels of IL-6 in the mPFC were not different among three groups.

The results suggest that peripheral IL-6 may contribute to resilience versus susceptibility to inescapable stress.

Severe depression may be a risk factor for diagnostic conversion into bipolar disorder (BD), and psychotic depression (PD) has been consistently associated with BD. The aims of the present study were to investigate the stability of the diagnosis of severe depression and the differences between PD and non-psychotic severe depression (non-PD), as well as to assess the effectiveness of electroconvulsive therapy (ECT).

Patients who were hospitalised for severe depression (diagnosed according to ICD-10) both with and without psychotic symptoms (n=89; mean age=55.6 years, SD=13.9) from 2001 to 2010 were retrospectively assessed.

By the 75th month of follow-up assessments, 11(12.4%) patients had developed BD. Among these 11 converters, nine had developed BD within 1 year after admission. Only sub-threshold hypomanic symptoms were significantly related to developing BD. The number of depressive episodes and history of physical diseases were significantly increased in non-PD compared with PD patients, whereas ECT was significantly increased in PD compared with non-PD patients. There was a significant association between length of stay at the hospital and the number of days between admission and ECT.

Sub-threshold hypomanic symptoms may represent a prodrome of BD or an indicator of an already manifest phenotype, especially in older patients, which suggests cautious use of antidepressants. In severe depression, non-PD may often occur secondary to physical diseases and patients may experience increased recurrences compared with PD patients, which may be a more ‘primary’ disorder and often requires ECT treatments. ECT is effective for severe depression regardless of the presence of any psychotic feature; the earlier ECT is introduced, the better the expected treatment outcome.

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.

The aim of the present study was to analyse demographic and clinical characteristics, as well as psychiatric diagnoses to identify gender differences in patients with attempted suicide in a Mexican population.

Between September 2010 and September 2012, 140 suicide attempts were documented in the Department of Psychiatry at the General Hospital of Comalcalco (Hospital General de Comalcalco in Spanish) in Tabasco, Mexico. Diagnoses were established using the DSM-IV questionnaire in which Axis I and II were considered. The Suicide Intent Scale was also applied.

In our sample, 63.6% were females and 36.4% males. With regard to socio-demographic characteristics, the predominant marital status in males was single, and in females married (χ2=5.93, df=2, p=0.05). In occupation the male group was mainly unemployed and housewife in females (χ2=55.51, df=4, p<0.001). Male subjects were more likely to consume alcohol (χ2=20.40, df=1, p≤0.001), cannabis (χ2=16.62, df=1, p≤0.001) or tobacco. The prevalence of psychiatric diagnosis was significantly different because, the male group was mainly diagnosed with substance-related disorders, whereas female participants showed a prevalence of stress-related disorders (χ2=34.17, gl=4, p=0.0001).

Our results provide evidence that the characteristics of suicide attempt are different by gender in the Mexican population. Interventions are necessary for the development of prevention strategies that may lead to a reduction in suicidal behaviour. These preventive activities should consider the occupation for the female group and consumption of alcohol, cannabis or tobacco in the male group.

Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioural disorder. It is conceivable that Gamma aminobutyric acid (GABA) neurotransmission is implicated in the pathophysiology of ADHD. This study investigated the effect of GABA transporter 1 (GAT-1) on the anxiety-like behaviours and cognitive function in knockout mice.

In all, 20 adult male mice were divided into two groups: wild-type (WT) group and GAT-1−/− group. The open field test, elevated O-maze (EZM) and Morris water maze were used to evaluate behavioural traits relevant to ADHD.

Compared with WT mice, the GAT-1−/− mice travelled longer and displayed an enhanced kinematic velocity with the significant reduction of rest time in the open field test (p<0.05). The EZM showed that GAT-1−/− mice displayed a significant increase in total entries into the open sectors and the closed sectors compared with the WT mice. The WT mice showed shorter latencies after the training session (p<0.01), whereas the GAT-1−/− mice made no difference during probe test, the GAT-1−/− mice spent less time in the target quadrant (p<0.01).

Our results demonstrated that GAT-1−/− mice have phenotypes of hyperactivity, impaired sustained attention and learning deficiency, and the performance of GAT-1−/− mice is similar to ADHD symptoms. So, the study of the GAT-1−/− mice may provide new insights into the mechanisms and the discovery of novel therapeutics for the treatment of ADHD.

Chronic inflammation is implicated in numerous diseases, including major depression and type 2 diabetes mellitus (T2DM). Since depression and T2DM often co-exist, inflammatory pathways are suggested as a possible link. Hence, the establishment of an immune-mediated animal model would shed light on mechanisms possibly linking depression and metabolic alterations.

In this study we investigated a behavioural and metabolic paradigm following chronic infusion with low doses of lipopolysaccharide (LPS) using osmotic minipumps in male rats.

Behavioural testing consisted of evaluating activity level in the open field and depressive-like behaviour in the forced swim test. Metabolic assessment included measurement of body weight, food and water intake, and glucose and insulin levels during an oral glucose tolerance test.

LPS-infused rats showed acute signs of sickness behaviour, but chronic LPS infusion did not induce behavioural or metabolic changes.

These results suggest that although inflammation is immediately induced as indicated by acute sickness, 4 weeks of chronic LPS administration via osmotic minipumps did not result in behavioural changes. Therefore, this paradigm may not be a suitable model for studying the underlying mechanisms that link depression and T2DM.

We have made a 2-year follow-up study to evaluate the effect of repeated transcranial pulsating electromagnetic fields (T-PEMF) augmentation in patients who had achieved remission but later on relapsed, as well as to identify factors contributing to treatment-resistant depression in patients who did not respond to T-PEMF.

Using the Longitudinal Expert Assessment of All Data approach the patients were classified in four groups: A: patients who achieved remission; B: patients with doubtful effect; C: patients with no effect; and D: patients who were hard-to-assess.

In group A, comprising 27 patients, 13 had relapsed; they obtained a clear remission after a repeated course of T-PEMF augmentation. In group D, comprising 16 patients, we identified misdiagnostic factors both concerning the event of remission after the previous T-PEMF augmentation and concerning the aetiology (psychosocial stressors and co-morbid conditions). Compared with the other groups, the group D patients had a smaller number of previous episodes (p=0.09) and a longer duration of the current episode (p=0.01).

T-PEMF has an effect among patients who relapsed after remission with the first series of T-PEMF. Treatment-resistant depression is a condition that has a high degree of multivariate problems. Misuse of alcohol or drugs, severe somatic disorders and other psychosocial problems may need other kinds of treatment before T-PEMF augmentation.

Autoimmune NMDA-R encephalitis (ANRE) shares clinical features with schizophrenia. Recent research also indicates that both disorders are associated with dysfunction of the N-Methyl-D-Aspartate glutamate receptors (NMDA-R) subunit 1.

We present the case of Ms A, 16 years old. Ms A presented with acute personality change, bizarre behaviour, delusional ideas and atypical seizures. She had a family history of psychotic disorders, and autistic traits diagnosed in childhood. She was initially diagnosed with a psychotic disorder. Delayed testing of CSF indicated ANRE. As the patient was a Jehovah's witness the treating team was unable to use gammaglobulin therapy; they instead relied on combined plasmapheresis and rituximab. To exclude the possibility that the affected members of this family shared a gene coding for an abnormal configuration of the NMDA receptor subunit 1 we sequenced the region of the GRIN1 gene in DNA extracted from blood in both Ms A and her grandmother.

Ms A’s condition improved dramatically, though her long-term memory is still demonstrably impaired. No genetic abnormality was detected.

This case emphasizes how important it is, for a first episode psychosis, to exclude ANRE and other autoimmune synaptic encephalitides, even in the face of significant family history, and if seronegative, the importance of testing for CSF autoantibodies.

Tramadol hydrochloride (HCl) is a centrally acting synthetic opioid analgesic. Psychotic symptoms are relatively rare in reported adverse events. Here, we report a patient who presented with tramadol-related psychotic symptoms.

A 59-year-old female had underlying bipolar I disorder and received lithium treatment with stable affective status. 1 month before hospitalisation, she had been taking tramadol HCl/acetaminophen for joint pain. She then developed obvious persecutory delusion. However, her clinical picture did not meet the criteria of any mood episode. After treatment of risperidone in addition to lithium, she was discharged without any psychotic symptom. She remained euthymic without any psychotic symptom on monotherapy of lithium (300 mg) three tablets once daily.

Tramadol HCl is commonly prescribed in clinical practice and psychotic symptoms related to it are uncommon. We should be careful about the rare but important adverse events while prescribing tramadol HCl.

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.

Heat stroke is a medical emergency. Psychiatric patients are particularly susceptible to heat stroke. Therefore, awareness and preventive measures of heat stroke are important for both clinicians and patients.

A 49-year-old man with schizophrenia, who was under maintenance treatment with olanzapine 20 mg/day, trihexyphenidyl 4 mg/day, and trazodone 50 mg/day, suffered from heat stroke in a heat wave and required intensive care. He recovered with the medical treatment provided.

Several factors could have contributed to the impaired thermoregulation and the occurrence of heat stroke in this case: schizophrenia, the psychotropic regimen, and lack of preventive measures. Possible differential diagnoses of heat stroke in this case include infection, neuroleptic malignant syndrome, and serotonin syndrome.

Heat stroke can occur during the maintenance treatment of olanzapine, trihexyphenidyl, and trazodone for schizophrenia. Clinicians should be proactive to reduce the risk of heat stroke in psychiatric patients.