Stressful life events play an important role in the aetiology of human mood disorders and are frequently modelled by chronic social defeat (SD) in rodents. Exploratory phenotype in rats is a stable trait that is likely related to inter-individual differences in reactivity to stress. The aim of the study was to confirm that low levels of exploratory activity (LE) are, in rodents, a risk factor for passive stress coping, and to clarify the role of medium (ME) and high (HE) exploratory disposition in the sensitivity to SD.

We examined the effect of SD on male Wistar rats with LE, ME, and HE activity levels as measured in the exploration box. After SD, the rats were evaluated in social preference, elevated zero maze, and open-field tests. Brain tissue levels of monoamines were measured by high-performance liquid chromatography.

Rats submitted to SD exhibited lower weight gain, higher sucrose consumption, showed larger stress-induced hyperthermia, lower levels of homovanillic acid in the frontal cortex, and higher levels of noradrenaline in the amygdala and hippocampus. Open-field, elevated zero maze, and social preference tests revealed the interaction between stress and phenotype, as only LE-rats were further inhibited by SD. ME-rats exhibited the least reactivity to stress in terms of changes in body weight, stress-induced hyperthermia, and sucrose intake.

Both low and high novelty-related activity, especially the former, are associated with elevated sensitivity to social stress. This study shows that both tails of a behavioural dimension can produce stress-related vulnerability.

ADHD is a prevalent and highly heritable mental disorder associated with significant impairment, morbidity and increased rates of mortality. This combination of high prevalence and high morbidity/mortality seen in ADHD and other mental disorders presents a challenge to natural selection-based models of human evolution. Several hypotheses have been proposed in an attempt to resolve this apparent paradox. The aim of this study was to review the evidence for these hypotheses.

We conducted a systematic review of the literature on empirical investigations of natural selection-based evolutionary accounts for ADHD in adherence with the PRISMA guideline. The PubMed, Embase, and PsycINFO databases were screened for relevant publications, by combining search terms covering evolution/selection with search terms covering ADHD.

The search identified 790 records. Of these, 15 full-text articles were assessed for eligibility, and three were included in the review. Two of these reported on the evolution of the seven-repeat allele of the ADHD-associated dopamine receptor D4 gene, and one reported on the results of a simulation study of the effect of suggested ADHD-traits on group survival. The authors of the three studies interpreted their findings as favouring the notion that ADHD-traits may have been associated with increased fitness during human evolution. However, we argue that none of the three studies really tap into the core symptoms of ADHD, and that their conclusions therefore lack validity for the disorder.

This review indicates that the natural selection-based accounts of ADHD have not been subjected to empirical test and therefore remain hypothetical.

Transcranial direct current stimulation (tDCS) is a non-invasive and well-tolerated brain stimulation technique with promising efficacy as an add-on treatment for schizophrenia and for several other psychiatric disorders. tDCS modulates neuroplasticity; psychiatric disorders are established to be associated with neuroplasticity abnormalities. This review presents the summary of research on potential genetic basis of neuroplasticity-modulation mechanism underlying tDCS and its implications for treating various psychiatric disorders.

A systematic review highlighting the genes involved in neuroplasticity and their role in psychiatric disorders was carried out. The focus was on the established genetic findings of tDCS response relationship with BDNF and COMT gene polymorphisms.

Synthesis of these preliminary observations suggests the potential influence of neuroplastic genes on tDCS treatment response. These include several animal models, pharmacological studies, mentally ill and healthy human subject trials.

Taking into account the rapidly unfolding understanding of tDCS and the role of synaptic plasticity disturbances in neuropsychiatric disorders, in-depth evaluation of the mechanism of action pertinent to neuroplasticity modulation with tDCS needs further systematic research. Genes such as NRG1, DISC1, as well as those linked with the glutamatergic receptor in the context of their direct role in the modulation of neuronal signalling related to neuroplasticity aberrations, are leading candidates for future research in this area. Such research studies might potentially unravel observations that might have potential translational implications in psychiatry.

A prominent theory of depression focusses on neural plasticity and stress as central issues in seeking to develop a pattern of identifiable biological markers for the depressive disorders. Relative neglect, however, of clinical factors in that theory limits the uncovering of markers and opens to question their methodological approach. A conflicting theory, the ‘opposed neurobehavioral states’, based on dimensional analysis of monoamine neurotransmitter systems and behavioural factors is presented. This perspectives paper contrasts the two approaches viewing the biomarkers theory as premature at this point in the progress of depression research.

Studies developed to support the biomarkers theory and the opposed neurobehavioral states theory are examined for their strengths and limitations in explaining the nature of the disorder and the actions of therapeutic drugs. Reference is made to reviews of the many studies on biomarkers and the recent work that supports the opposed neurobehavioral states theory.

Main issue: the biomarkers theory sets important goals, but despite the many advances in the neural investigations of factors underlying depression, is still not successful in specifying markers. Thus, it is believed to be applying the wrong methodologic approach and premature in its claims. Perspective: the ‘opposed neurobehavioral’ theory is limited in its breadth of research. It applies, however, the dimensional approach to the clinical side of the problem, a methodological approach more likely to be effective in selecting the best clinical treatment and open to a more productive path to understanding of the nature of the disorder in future research.

The discipline of clinical neuropsychiatry currently provides specialised services for a number of conditions that cross the traditional boundaries of neurology and psychiatry, including non-epileptic attack disorder. Neurophysiological investigations have an important role within neuropsychiatry services, with video-electroencephalography (EEG) telemetry being the gold standard investigation for the differential diagnosis between epileptic seizures and non-epileptic attacks. This article reviews existing evidence on best practices for neurophysiology investigations, with focus on safety measures for video-EEG telemetry.

We conducted a systematic literature review using the PubMed database in order to identify the scientific literature on the best practices when using neurophysiological investigations in patients with suspected epileptic seizures or non-epileptic attacks.

Specific measures need to be implemented for video-EEG telemetry to be safely and effectively carried out by neuropsychiatry services. A confirmed diagnosis of non-epileptic attack disorder following video-EEG telemetry carried out within neuropsychiatry units has the inherent advantage of allowing diagnosis communication and implementation of treatment strategies in a timely fashion, potentially improving clinical outcomes and cost-effectiveness significantly.

The identified recommendations set the stage for the development of standardised guidelines to enable neuropsychiatry services to implement streamlined and evidence-based care pathways.

Although cognitive behavioural therapy (CBT) has been shown to be an effective treatment for depression, the biological mechanisms underpinning it are less clear. This review examines if it is associated with changes identifiable with current brain imaging technologies.

To better understand the mechanisms by which CBT exerts its effects, we undertook a systematic review of studies examining brain imaging changes associated with CBT treatment of depression.

Ten studies were identified, five applying functional magnetic resonance imaging, three positron emission tomography, one single photon emission computer tomography, and one magnetic resonance spectroscopy. No studies used structural MRI. Eight studies included a comparator group; in only one of these studies was there randomised allocation to another treatment. CBT-associated changes were most commonly observed in the anterior cingulate cortex (ACC), posterior cingulate, ventromedial prefrontal cortex/orbitofrontal cortex (VMPFC/OFC) and amygdala/hippocampus.

The evidence, such as it is, suggests resting state activity in the dorsal ACC is decreased by CBT. It has previously been suggested that treatment with CBT may result in increased efficiency of a putative ‘dorsal cognitive circuit’, important in cognitive control and effortful regulation of emotion. It is speculated this results in an increased capacity for ‘top-down’ emotion regulation, which is employed when skills taught in CBT are engaged. Though changes in activity of the dorsal ACC could be seen as in-keeping with this model, the data are currently insufficient to make definitive statements about how CBT exerts its effects. Data do support the contention that CBT is associated with biological brain changes detectable with current imaging technologies.

In bipolar disorder, treatment with antidepressants without concomitant use of mood stabilisers (antidepressant monotherapy) is associated with development of mania and rapid cycling and is therefore not recommended. The present study aimed to investigate the psychopharmacological treatment patterns in bipolar disorder over time, with a focus on antidepressant monotherapy.

Cohort study with annual cross-sectional assessment of the use of psychotropic medications between 1995 and 2012 for all Danish residents aged 10 years or older with a diagnosis of bipolar disorder registered in the Danish Psychiatric Central Research Register. Users of a given psychotropic medication were defined as individuals having filled at least one prescription for that particular medication in the year of interest.

We identified 20 618 individuals with bipolar disorder. The proportion of patients with bipolar disorder using antidepressants, atypical antipsychotics and anticonvulsants increased over the study period, while the proportion of patients using lithium, typical antipsychotics and benzodiazepines/sedatives decreased. The proportion of patients treated with antidepressant monotherapy decreased from 20.5% in 1997 to 12.1% in 2012, and among antidepressant users, the proportion in monotherapy decreased from 47.7% to 23.9%, primarily driven by a decrease in the use of tricyclic antidepressants.

The results show an increase in the proportion of patients with bipolar disorder being treated with antidepressants in the period from 1997 to 2012. However, in accordance with international treatment guidelines, the extent of antidepressant monotherapy decreased during the same period.

Previous morphology and diffusion-imaging studies have suggested that structural changes in white matter is an important part of the pathophysiology of obsessive–compulsive disorder (OCD). However, different methodological approaches and the heterogeneity of patient samples question the validity of the findings.

In total, 30 patients were matched for age and sex with 30 healthy controls. All participants underwent T1-weighted magnetic resonance imaging, diffusion tensor imaging and T2 fluid-attenuated inversion recovery. Voxel-based morphometry and tract-based spatial statistics were used to compare white matter volumes and diffusion tensor imaging between groups. These data were analysed correcting for the effects of multiple comparisons, age, sex, severity and duration of illness as nuisance covariates. White matter hyperintensities were manually identified.

Increase in fractional anisotropy in cerebellum was the most prominent result. A decrease in fractional anisotrophy in patients comparable with previous studies was located in forceps minor. There were no differences in the white matter morphology or in the white matter hyperintensities between patients and healthy controls.

Decrease in fractional anisotrophy in forceps minor and increase in cerebellum were found, and they were not due to neither white matter hyperintensities nor morphology of the white matter. Cerebellar hyperconnectivity could be an important part of OCD pathophysiology.

The aim of this study was to evaluate the dynamic thiol–disulphide homeostasis as an oxidative stress parameter, using a newly proposed method, in patients with Alzheimer’s disease.

In total, 97 participants were included in the study. Among them, 51 had been diagnosed with Alzheimer’s disease, and the remaining 46 were healthy individuals. Total thiol (–SH+–S–S–) levels and native thiol (–SH) levels in serum of each participant were measured. The amount of dynamic disulphide bonds (–S–S–) and (–S–S–) ×100/(–SH), (–S–S–) ×100/(–SH+–S–S–), and –SH×100/(–SH+–S–S–) ratios were calculated from these values. The obtained data were used to compare Alzheimer’s disease patients with healthy individuals.

The average total thiol and native thiol levels of patient with Alzheimer’s disease in the study were found to be significantly lower than those levels of healthy individuals. In addition, in the patient group, the –S–S–×100/–S–S+–SH ratio was found to be significantly higher, whereas the –SH×100/–S–S+–SH ratio was found to be significantly lower compared with healthy individuals. Total thiol and native thiol levels, dynamic disulphide bond amount, and –S–S–×100/–SH, –S–S–×100/–S–S+–SH, and –SH×100/–S–S+–SH ratios were not found to be correlated with mini mental state examination score or duration of disease.

Recent studies have shown that oxidative stress is the one of the molecular changes underlying the pathogenesis of Alzheimer’s disease. In this study, we have investigated the dynamic thiol–disulphide homeostasis in patients with Alzheimer’s disease, using a novel method.

Stress increases DNA methylation and decreases the expression of genes involved in neural plasticity, while treatment with DNA methyltransferase inhibitors (DNMTi) increases gene expression and induces antidepressant-like effects in preclinical models. Therefore, the aim of the present work was to further investigate the potential antidepressant-like effect induced by DNMTi by evaluating the behavioural effects induced by associating DNMTi treatment with conventional antidepressant drugs in mice submitted to the forced swimming test (FST). In addition, brain levels of DNA methylation were also investigated.

Mice received systemic injections of 5-aza-2'-deoxycytidine (5-AzaD, 0.1, 0.2 mg/kg), RG108 (0.1, 0.2, 0.4 mg/kg), desipramine (DES, 2.5, 5, 10 mg/kg) or fluoxetine (FLX, 5, 10, 20, 30 mg/kg) and were submitted to the FST or to the open field test (OFT). Additional groups received a combination of subeffective doses of 5-AzaD or RG108 (DNMTi) with subeffective doses of DES or FLX (antidepressants).

Subeffective doses of RG108 (0.1 mg/kg) or 5-AzaD (0.1mg/kg) in association with subeffective doses of DES (2.5 mg/kg) or FLX (10 mg/kg) induced significant antidepressant-like effects. Effective doses of RG108 (0.2 mg/kg), 5-AzaD (0.2 mg/kg), DES (10 mg/kg) and FLX (20 mg/kg) atenuated stress-induced changes in DNA methylation levels in the hippocampus and prefrontal cortex. None of the treatments induced locomotor effects in the OFT.

These results suggest that DNMTi potentiate the behavioural effects of antidepressant drugs in the FST and that antidepressants, as well as DNMTi, are able to modulate stress-induced changes in DNA methylation in brain regions closely associated with the neurobiology of depression.

The study investigated the effectiveness of an 8-week intensive residential treatment programme based on principles from intensive short-term dynamic psychotherapy for patients with known treatment-resistant anxiety- and/or depressive disorders (mainly with comorbid personality disorders).

Patients (N=95) with prior repeated treatment failure were included. Changes in self-reported target complaints, symptom severity, and overall interpersonal problems have been presented for these patients in two previous articles. We now expand upon the existing knowledge by presenting novel data from a number of important observer-based and self-reported outcome domains (diagnostic changes on Axis I and II, changes in overall personality dysfunction, disorder complexity, medication use, health care utilisation, and occupational activity).

There were pervasive and significant improvements on all measures during treatment, which were maintained or further improved during follow-up. Fourteen months after the end of treatment, 46.26% of patients had recovered in terms of Axis I pathology, 63.79% had recovered in terms of Axis II pathology, 71.18% had returned to work, and there was a 28.62% reduction in regular use of psychotropic medications. Health care utilisation was reduced by 65.55%, and there were large improvements in disorder complexity and levels of personality dysfunction.

The treatment programme was highly effective for patients with common and complex treatment-resistant mental disorders. Results are encouraging for the relatively large number of patients who tend not to benefit from standard formats of treatment for debilitating psychological problems.

The Germanwings 9525 incident drew significant attention to the ‘plane-assisted suicide’ construct, yet little scientific literature exists on this topic. This paper reviews the available literature and applies lessons from the suicide-homicide and men’s mental health literature to better understand this construct from a scientific perspective.

A systematic review of the relevant clinical literature was undertaken.

Multiple lines of evidence suggests the applicability and relevance of suicide-homicide research and men’s mental health to the plane-assisted suicide phenomenon. Plane-assisted suicides occur within an overwhelmingly male, middle aged population who, in addition to suicide, commit large scale acts of murder. Issues of divorce, separation, and threats to masculinity appear integral to an effective prevention program.

Further research in the understanding of plane-assisted suicide as a product of neuropsychiatric disorder may advance such prevention efforts and have the opportunity to reduce the loss of life in future tragedies.

The present research explored the cortical correlates of rewarding mechanisms and cortical ‘unbalance’ effect in internet addiction (IA) vulnerability.

Internet Addiction Inventory (IAT) and personality trait (Behavioural Inhibition System, BIS; Behavioural Activation System, BAS) were applied to 28 subjects. Electroencephalographic (EEG, alpha frequency band) and response times (RTs) were registered during a Go-NoGo task execution in response to different online stimuli: gambling videos, videogames or neutral stimuli. Higher-IAT (more than 50 score, with moderate or severe internet addiction) and lower-IAT (<50 score, with no internet addiction).

Alpha band and RTs were affected by IAT, with significant bias (reduced RTs) for high-IAT in response to gambling videos and videogames; and by BAS, BAS-Reward subscale (BAS-R), since not only higher-IAT, but also BAS and BAS-R values determined an increasing of left prefrontal cortex (PFC) activity (alpha reduction) in response to videogames and gambling stimuli for both Go and NoGo conditions, in addition to decreased RTs for these stimuli categories.

The increased PFC responsiveness and the lateralisation (left PFC hemisphere) effect in NoGo condition was explained on the basis of a ‘rewarding bias’ towards more rewarding cues and a deficit in inhibitory control in higher-IAT and higher-BAS subjects. In contrast lower-IAT and lower-BAS predicted a decreased PFC response and increased RTs for NoGo (inhibitory mechanism). These results may support the significance of personality (BAS) and IAT measures for explaining future internet addiction behaviour based on this observed ‘vulnerability’.

A number of atypical antipsychotic drugs were demonstrated to have anxiolytic effects in patients and in animal models. These effects were mostly suggested to be the consequence of the drugs’ affinity to the serotonin system and its receptors. Asenapine is a relatively new atypical antipsychotic that is prescribed for schizophrenia and for bipolar mania. Asenapine has a broad pharmacological profile with significant effects on serotonergic receptors, hence it is reasonable to expect that asenapine may have some anxiolytic effects. The present study was therefore designed to examine possible effects of asenapine on anxiety-like behaviour of mice.

Male ICR mice were repeatedly treated with 0.1 or 0.3 mg/kg injections of asenapine and then tested in a battery of behavioural tests related to anxiety including the open-field test, elevated plus-maze (EPM), defensive marble burying and hyponeophagia tests. In an adjunct experiment, we tested the effects of acute diazepam in the same test battery.

The results show that diazepam reduced anxiety-like behaviour in the EPM, the defensive marble burying test and the hyponeophagia test but not in the open field. Asenapine has anxiolytic-like effects in the EPM and the defensive marble burying tests but had no effects in the open-field or the hyponeophagia tests. Asenapine had no effects on locomotor activity.

The results suggest that asenapine may have anxiolytic-like properties and recommends that clinical trials examining such effects should be performed.