The present paper is devoted to evaluation of clinical and immunomodulatory effect of ultra-high dilutions of antibodies to human interferon γ, included in the complex therapy of patients with schizophrenia.

The study was carried out at the Mental Health Research Institute, Tomsk, Russian Federation. This double-blind, placebo-controlled randomised in parallel-group study enrolled 40 patients. As a part of complex therapy, patients from the main group (n=20) received anaferon, a drug containing ultra-high dilutions of affinity-purified antibodies to human interferon γ as the active pharmaceutical ingredient; patients from the comparative group (n=20) received placebo. Duration of the therapy was 30±5 days. Assessment of severity of symptoms and changes in them were made using clinical scales: Positive and Negative Syndrome Scale, Clinical Global Impression, Abnormal Involuntary Movements Scale. Spontaneous and phytohemagglutinin-induced production of interferon γ by immunocompetent cells in supernatants of 48 h whole blood culture of patients was measured by enzyme-linked immunosorbent assay (ELISA) method.

The reduction of interferon-producing potential by immunocompetent cells in comparison with reference normal value was shown in total group of patients (n=40) before combined therapy. During the treatment, increase of spontaneous interferon γ production and favourable changes in psychopathological symptoms as compared with placebo were shown in subjects receiving anaferon. It was found that favourable changes in clinical symptoms assessed using clinical scales with a high degree of confidence correlated with high level of spontaneous interferon γ production.

Anaferon as a part of complex therapy of patients with schizophrenia contributes to enhancement of its efficacy acting via mechanism of psychoimmunomodulation.

The occurrence of a relapse during abstinence is an important issue that must be addressed during treatment for drug addiction. We investigated the influence of drug exposure pattern on morphine-seeking behaviour following withdrawal. We also studied the role of the hippocampus in this process to confirm its involvement in drug relapse.

Male Sprague–Dawley rats that were trained to self-administer morphine (1.0 mg/kg) using 2, 4, 6, 8, or 10 h daily sessions underwent withdrawal in their home cages and were re-exposed to the operant chamber to evaluate morphine-seeking behaviour. During the relapse session, rats were intravenously injected with morphine (0.25 mg/kg) or saline before re-exposure to the chamber. In the second experiment, rats were administered a microinjection of saline or cobalt chloride (CoCl2, 1 mM), a synaptic blocker, into the CA1 of the hippocampus prior to the relapse test.

In the first experiment, more morphine-seeking behaviour was observed in the 2 h group (animals trained to self-administer morphine during a 2 h daily session spread over 21 days) during the relapse session, despite all groups being exposed to similar amounts of morphine during the training period before withdrawal. In the second experiment, pretreatment with CoCl2 markedly reduced morphine-seeking behaviour in the 2 h group.

The present findings suggest that the exposure pattern influences the degree of relapse and that control of memorisation is important for prevention of relapse.

Quercetin, one of the most potent flavonol in the family of flavonoids, has been shown to have benefits against diabetes and its complications. In the present study, we investigated effects of quercetin on depression-like behaviours and hypothalamic–pituitary–adrenal (HPA) axis in diabetic rats.

Experimental diabetes was induced by using streptozotocin, and either 50 or 100 mg/kg quercetin was intraperitoneally administered for 21 days. Following the last treatment, animals were subjected to the forced swim test, and subsequently, the blood was obtained by cardiac puncture to measure plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels.

A significant increase of the total immobile time, accompanied by a decrease in the immobility latency, which suggests a depressive status, was observed in diabetic animals that was reversed by the treatment of 50 mg/kg quercetin. However, the higher dose of quercetin (100 mg/kg) was ineffective in alleviating depression-like behaviours. The plasma concentrations of ACTH, and total- and free-CORT were not affected by both doses of quercetin.

Therefore, we concluded that the antidepressant-like effects of quercetin in diabetes are independent of the HPA axis.

For centuries, cannabinoids have been known to be effective in pain states. Itch and pain are two sensations sharing a lot in common.

The goal of this research was to observe whether the cannabinoid agonist WIN 55,212-2 reduces serotonin-induced scratching behaviour and whether neurotoxic destruction of descending serotonergic and noradrenergic pathways mediate the antipruritic effect of WIN 55,212-2.

Scratching behaviour was induced by intradermal injection of serotonin (50 µg/50 µl/mouse) to Balb/c mice. The neurotoxins 5,7-dihydroxytryptamine (5,7-DHT, 50 μg/mouse) and 6-hydroxydopamine (6-OHDA, 20 μg/mouse) are applied intrathecally to deplete serotonin and noradrenaline in the spinal cord. WIN 55,212-2 (1, 3, 10 mg/kg, i.p.) dose-dependently attenuated serotonin-induced scratches. Neurotoxic destruction of neither the serotonergic nor the noradrenergic systems by 5,7-DHT and 6-OHDA, respectively, had any effect on the antipruritic action of WIN 55,212-2.

Our findings indicate that cannabinoids dose-dependently reduce serotonin-induced scratching behaviour and neurotoxic destruction of descending inhibitory pathways does not mediate this antipruritic effect.

To examine the unique neuropsychological presentation in adults with high functioning autism spectrum disorders (HF-ASD) by comparison with adults with attention deficit hyperactivity disorder (ADHD).

Adults with ASD referred to a specialty clinic (n=26) were compared to two non-ASD groups with (n=52) and without (n=52) ADHD of similar age and sex.

No differences in IQ were found. Subjects with HF-ASD were significantly more impaired than both comparison groups in processing speed, cognitive flexibility and sight words. Subjects with HF-ASD were more impaired than controls in working memory, but not the ADHD group.

These findings suggest that there may be specific neuropsychological correlates of HF-ASD differing from ADHD that could have significant implications for identifying individuals at risk for ASD.

Behavioural and psychological symptoms of dementia (BPSD) are commonly present in patients with Alzheimer’s disease (AD). Disturbed sleep quality is also observed in AD patients. However, the effects of memantine on sleep architecture have not been investigated. The purpose of this study was to investigate the effects of memantine on polysomnography (PSG) variables and BPSD.

In total, 12 patients with AD (mean age: 79.0±4.1 years old) were enrolled in this study. The following tests were performed: the Neuropsychiatric Inventory for the assessment of BPSD, the Mini-Mental State Examination (MMSE) for cognitive function, and PSG for evaluation of sleep architecture. After baseline examinations, patients were treated with memantine according to a standard prescription protocol. After being treated with 20 mg/day of memantine for 4 weeks, examinations were carried out again.

All subjects completed the trial. The mean MMSE and NPI scores were 22.6±3.4 and 13.8±12.9, respectively. Treatment with memantine significantly decreased the NPI score (5.8±4.3, p<0.01). There were significant decreases in the scores of subscales for anxiety (p=0.04) and irritability/lability (p=0.04). PSG demonstrated a longer total sleep time (TST) (p<0.01), increases in sleep efficiency (p<0.01) and time spent in stage II (% TST, p=0.02), and decreases in nocturnal awakening (p<0.01), the periodic limb movement index (p<0.01), and time spent in stage I (% TST, p=0.02).

Memantine was effective for reducing fragmented sleep and improving BPSD, and was well tolerated.

We performed functional magnetic resonance imaging (fMRI) to discriminate the differential brain activation patterns in patients with obsessive compulsive disorder (OCD) and healthy controls during implicit retrieval tasks with emotionally neutral and unpleasant words.

Sixteen patients with OCD (mean age: 31.4±10.1 years) and 16 healthy controls (mean age: 32.6±5.8 years) with no history of neurological or psychiatric illness underwent 3-T fMRI. The stimulation paradigm consisted of the following cycle: rest, encoding of a string of two-syllable words, rest, and retrieval of the previously encoded words with the first consonant omitted.

During the implicit retrieval task with emotionally neutral words, no distinct brain activity was observed in either the patients with OCD or healthy controls. On the other hand, during the retrieval task with unpleasant words, the patients with OCD showed predominant activity in the superior/middle temporal pole, medial superior frontal gyrus, and orbitofrontal cortex (uncorrected p<0.001, extent threshold: 30 voxels), whereas the healthy controls did not show any distinct regions of activation.

This study revealed the differential brain activation patterns between patients with OCD and healthy controls during implicit memory tasks with unpleasant words. Our results suggest that the impact of negative emotion on implicit memory task may be associated with the symptomatology of OCD. This finding may be helpful for understanding the neural mechanisms that underlie implicit memory retrieval, particularly the interaction between emotion and cognition, in patients with OCD.

The purpose of the present study was to test whether individuals with Internet addiction disorder (IAD) presented analogous characteristics of working memory, executive function and impulsivity compared with pathological gambling (PG) patients.

The subjects included 23 individuals with IAD, 23 PG patients and 23 controls. All of the participants were measured with the digit span task, Wisconsin Card Sorting Test, go/no-go task and Barratt Impulsiveness Scale-11 (BIS-11) under the same experimental conditions.

The results of this study showed that the false alarm rate, total response errors, perseverative errors, failure to maintain set and BIS-11 scores of both the IAD and PG groups were significantly higher than that of the control group. In addition, the forward scores and backwards scores, percentage of conceptual level responses, number of categories completed and hit rate of the IAD and PG groups were significantly lower than that of the control group. Furthermore, the false alarm rate and BIS-11 scores of the IAD group were significantly higher than those of PG patients, and the hit rate was significantly lower than that of the PG patients.

Individuals with IAD and PG patients present deficiencies in working memory, executive dysfunction and impulsivity, and individuals with IAD are more impulsive than PG patients.

Fluid intelligence (Gf) has been related to executive functioning (EF) in previous studies, and it is also known to be correlated with crystallized intelligence (Gc). The present study includes representative measures of Gf, Gc, and EF frequently used in clinical practice to examine this Gf–EF relation. It is hypothesised that the Gf–EF relation is higher than the Gc–EF relation, and that working memory in particular (as a measure of EF) shows a high contribution to this relation.

Confirmatory factor analysis was performed on a mixed neuropsychiatric and non-clinical sample consisting of 188 participants, using the Kaufman Adolescent and Adult Intelligence Test, and three executive tasks of the Cambridge Neuropsychological Test Automated Battery, covering working memory, planning skills, and set shifting.

The model fitted the data well [χ2(24)=35.25, p=0.07, RMSEA=0.050]. A very high correlation between Gf and EF was found (0.91), with working memory being the most profound indicator. A moderate to high correlation between Gc and EF was present. Current results are consistent with findings of a strong relation between Gf and working memory.

Gf and EF are highly correlated. Gf dysfunction in neuropsychiatric patients warrants further EF examination and vice versa. It is discussed that results confirm the need to distinguish between specific versus general fluid/executive functioning, the latter being more involved when task complexity and novelty increase. This distinction can provide a more refined differential diagnosis and improve neuropsychiatric treatment indication.

Asenapine is an atypical antipsychotic that is currently available for the treatment of schizophrenia and bipolar I disorder. Although the atypical antipsychotics clozapine and olanzapine are effective for depression and anxiety in schizophrenia, as demonstrated by animal model studies, this has not been clarified for asenapine. Therefore, we compared the effects of asenapine in the conditioned fear stress model with those of clozapine and olanzapine.

Rats were individually fear conditioned using electrical foot shock in a Skinner box. Approximately 24 h later, individual animals were returned to the same Skinner box (without electrical shock) and their freezing behaviour was observed for 5 min. Animals were treated with asenapine, clozapine, olanzapine, the 5-HT1A receptor partial agonist buspirone, or the 5-HT2C receptor antagonist SB242084 at 30 min before freezing behaviour assessment. The 5-HT1A receptor antagonist WAY100635 or the 5-HT2C receptor agonist Ro60-0175 was also used concomitantly with asenapine. The effects of asenapine, clozapine, and olanzapine on serotonin release in the rat hippocampus were also measured using in vivo microdialysis.

Asenapine reduced freezing behaviour, while neither clozapine nor olanzapine reduced freezing behaviour. Buspirone and SB242084 also reduced freezing behaviour. The effect of asenapine in reducing freezing behaviour was not altered by the concomitant administration of WAY100635 or Ro60-0175. Both asenapine and clozapine, but not olanzapine, increased serotonin release in the rat hippocampus.

Asenapine may have superior therapeutic effect on anxiety symptoms than other agents, although the underlying mechanism of its anxiolytic activity remains unknown.

The escalating tendency of elderly population aged 65 and over, which grown up to 9% since 2001 in Taiwan, remarks the important issue of mental health among ageing population. Depression in the elderly is frequently undetected or inadequately treated. This study aimed to investigate the pharmacotherapy of elderly patients with depression by comparing the patterns of prescribing psychotropic drugs (psychotropics) of psychiatrists and non-psychiatrists.

A random sampling of 5% of inpatients from the National Health Insurance (NHI) database in Taiwan from 2001 to 2003 was selected. In all, 1058 (0.9%) inpatients aged 65 and older with a diagnosis of any depressive disorder were included. The psychotropic prescribing pattern and the dosages used were analysed and compared. Physician specialties were based on the record of NHI database. Non-psychiatrists were defined by physicians other than psychiatry.

A total of 88% of elderly depressed inpatients had two or more comorbid physical illnesses. The most commonly prescribed psychotropics were: antidepressants (71.4%), anxiolytics (62.6%) and hypnotics (51.4%). Psychiatrists had a higher rate of prescribing psychotropics, except anxiolytics, than non-psychiatrists. Although selective serotonin reuptake inhibitors were commonly prescribed, non-psychiatrists preferred the use of tricyclic antidepressants and moclobemide. Trazodone was the most preferred antidepressant, but was generally used in low dosages.

Psychiatrists generally utilised higher dosages of newer antidepressants than non-psychiatrists. Differences in the prescribing pattern of psychotropics existed between physician specialties. Further investigations are warranted to determine how the selection and dosing of drugs influence the outcome of depression on the elderly.

To determine the prevalence of and factors associated with depression and stress with perceived quality of life and the salivary cortisol levels in Community Health Agent (CHA).

Cross-sectional descriptive study of CHAs in Pelotas-RS, Brazil. Data collection, including sociodemographic information and factors related to work and health. Beck Depression Inventory (BDI) II was used to assess depressive symptoms, Inventory of Stress Symptoms Lipp (ISSL) was used for the analysis of stress and the WHOQOL-BREF was used to investigate quality of life. Salivary cortisol was quantified via ELISA test.

The assessments showed that 71.0% are in a state of stress resistance, 30.5% were in the alert state of stress and 32.8% were in the stress state of exhaustion. Depressive episodes (BDI≥12) were observed in 28.2%. The environmental domain had the lowest score for quality of life. We observed significantly higher salivary cortisol levels in CHAs with less than 1 year of service and with the lowest quality of life scores in the environmental subsection.

A high prevalence of stress and depression was observed in this sample of CHAs. In addition, the worst levels of quality of life were identified in the environmental subsection. Cortisol levels corroborate these findings regarding quality of life within the environmental domain and began working less than a year previously.

It has been reported that lithium may inhibit lipid peroxidation and protein oxidation. Lithium salts also appear to stimulate cell proliferation, increase neurogenesis, and delay cell death. Oxidative stress and neurodegeneration may play an important role in the pathophysiology of bipolar disorder and the disease course thereof. The aim of this research is to estimate the influence of lithium (alone and in combination with haloperidol) on the parameters of oxidative stress and viability of SH-SY5Y cell lines in neutral and pro-oxidative conditions.

The evaluated oxidative stress parameter was lipid peroxidation. The viability of the cell lines was measured utilising the MTT test.

In neutral conditions, higher levels of thiobarbituric acid reactive substances were observed in those samples which contained both haloperidol and lithium than in other samples. However, these differences were not statistically significant. Cell viability was significantly higher in therapeutic lithium samples than in the controls; samples of haloperidol alone as well as those of haloperidol with lithium did not differ from controls.

The results of our study may indicate that lithium possess neuroprotective properties that may be partly due to antioxidative effects. The combination of lithium and haloperidol may generate increased oxidative stress.

Recent genome-wide analysis has indicated that the autism susceptibility candidate 2 (AUTS2) gene is involved in the regulation of alcohol consumption. We hypothesised that AUTS2 might be associated with the development of alcohol dependence. Therefore, in this exploratory study, we compared the genotype and allele frequencies of the polymorphisms rs6943555 and rs9886351 in the AUTS2 gene between patients with alcohol dependence and healthy control subjects living in a Japanese provincial prefecture. We also examined whether or not the haplotypes consisting of these polymorphisms are related to alcohol dependence.

The subjects of this study consisted of 64 patients with alcohol dependence and 75 unrelated healthy people. The AUTS2 genotypes were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method.

No significant differences in the genotype and allele frequencies of the polymorphisms AUTS2 rs6943555 and rs9886351 were found between alcohol dependence and control subjects. On the other hand, the frequencies of the AUTS2 haplotypes were significantly different between them, and the rs6943555 and rs9886351 A-A haplotype was associated with alcohol dependence (p=0.0187).

This suggests that the rs6943555 and rs9886351 A-A haplotype might affect the vulnerability to alcohol dependence pathogenesis. Further studies are needed to confirm the reproducibility of the results of this study with increased numbers of subjects.

Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) study, we aimed to present the rates and clinical correlates of suicidal thoughts/acts in patients recruited from a total of 40 centres in 10 Asian countries/areas: China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Singapore, Taiwan, and Thailand.

Data from 1122 patients with depressive disorders in the REAP-AD study were used. The ICD-10 was employed to diagnose depressive episodes and recurrent depressive disorder. The presence or absence of suicidal thoughts/acts and profile of other depressive symptoms was established using the National Institute for Health and Clinical Excellence guidelines for depression. Country/area differences in rates of suicidal thoughts/acts were evaluated with the χ2 test. In addition, depressive symptom profiles, other clinical characteristics, and patterns of psychotropic drug prescription in depressed patients with and without suicidal thoughts/acts were compared using analysis of covariance for continuous variables and logistic regression analysis for discrete variables to adjust the effects of covariates.

The rates of suicidal thoughts/acts in 10 countries/areas varied from 12.8% in Japan to 36.3% in China. Patients with suicidal thoughts/acts presented more persistent sadness (adjusted odds ratio [aOR]=2.64, p<0.001), loss of interest (aOR=2.33, p<0.001), fatigue (aOR=1.58, p<0.001), insomnia (aOR=1.74, p<0.001), poor concentration (aOR=1.88, p<0.001), low self-confidence (aOR=1.78, p<0.001), poor appetite (aOR=2.27, p<0.001), guilt/self-blame (aOR=3.03, p<0.001), and use of mood stabilisers (aOR=1.79, p<0.001) than those without suicidal thoughts/acts.

Suicidal thoughts/acts can indicate greater severity of depression, and are associated with a poorer response to antidepressants and increased burden of illness. Hence, suicidal thoughts/acts can provide a clinical index reflecting the clinical status of depressive disorders in Asians.

Brain-derived neurotrophic factor (BDNF) seems to play an important role in the course of depression including the response to antidepressants in patients with depression. We aimed to study the effect of an antidepressant intervention on peripheral BDNF in healthy individuals with a family history of depression.

We measured changes in BDNF messenger RNA (mRNA) expression and whole-blood BDNF levels in 80 healthy first-degree relatives of patients with depression randomly allocated to receive daily tablets of escitalopram 10 mg versus placebo for 4 weeks.

We found no statistically significant difference between the escitalopram and the placebo group in the change in BDNF mRNA expression and whole-blood BDNF levels. Post hoc analyses showed a statistically significant negative correlation between plasma escitalopram concentration and change in whole-blood BDNF levels in the escitalopram-treated group.

The results of this randomised trial suggest that escitalopram 10 mg has no effect on peripheral BDNF levels in healthy individuals.

We investigated how different levels of prenatal exposure to testosterone influence physiological reactions to dyadic interactions, hypothesising that higher levels of prenatal testosterone are linked to greater physiological responses.

Autonomic nervous system responses to dyadic interactions focussed on social or physical norms were measured. Physiological assessment of excitability (heart rate, facial temperature) and a behavioural assessment (Likert items judgements) were run on 25 neurotypical participants who had distinct testosterone exposure levels in utero. In utero exposure to testosterone was assessed measuring 2D : 4D (ratio between the lengths of the index and the ring fingers).

Higher testosterone exposure participants showed greater physiological arousal: a greater heart rate decrease, independent from scenario type (p<0.05), and opposite facial temperature changes in response to social (increase) (vs.) physical scenarios (decrease) were found (Left-cheek: p<0.05; Right-cheek: p<0.05).

These findings suggest a long-term influence of prenatal environment on adults’ physiological responses during social situations.

To assess the relationship between states of anger and stroke.

Systematic review of the literature.

In total, 21 papers were selected for the systematic review of data published on the subject of anger and stroke. A state of anger may be a risk factor for stroke, as well as a consequence of brain lesions affecting specific areas that are caused by a stroke. Scales to assess anger varied among authors. There was no consensus regarding the area of brain lesions that might lead to a state of anger. Although some authors agreed that lesions on the right side led to angrier behaviour, others found that lesions on the left side were more relevant to anger. Likewise, there was no consensus regarding the prevalence of anger pre or post-stroke. Some authors did not even find that these two conditions were related.

Although most authors have accepted that there is a relationship between anger and stroke, studies with uniform methodology need to be conducted if this association is to be properly evaluated and understood.

The brainstem-derived neuropeptide S (NPS) has a multidirectional regulatory activity, especially as a potent anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signalling in various brain structures. However, there is no information regarding the influence of haloperidol on NPS and NPS receptor (NPSR) expression.

We assessed NPS and NPSR mRNA levels in brains of rats treated with haloperidol using quantitative real-time polymerase chain reaction.

Chronic haloperidol treatment (4 weeks) led to a striking upregulation of NPS and NPSR expression in the rat brainstem. Conversely, the NPSR mRNA expression was decreased in the hippocampus and striatum.

This stark increase of NPS in response to haloperidol treatment supports the hypothesis that this neuropeptide is involved in the dopamine-dependent anxiolytic actions of neuroleptics and possibly also in the pathophysiology of mental disorders. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications.