The aim of this review is to provide an overview of the fundamental features of the neurosphere assay (NSA), which was initially described in 1992, and has since been used not only to detect the presence of stem cells in embryonic and adult mammalian neural tissues, but also to study their characteristics in vitro. Implicit in this review is a detailed examination of the limitations of the NSA, and how this assay is most accurately and appropriately used. Finally we will point out criteria that should be challenged to design alternative ways to overcome the limits of this assay.

NSA is used to isolate putative neural stem cells (NSCs) from the central nervous system (CNS) and to demonstrate the critical stem cell attributes of proliferation, extensive self-renewal and the ability to give rise to a large number of differentiated and functional progeny. Nevertheless, the capability of neural progenitor cells to form neurospheres precludes its utilisation to accurately quantify bona fide stem cell frequency based simply on neurosphere numbers. New culture conditions are needed to be able to distinguish the activity of progenitor cells from stem cells.

A commonly used, and arguably misused, methodology, the NSA has provided a wealth of information on precursor activity of cells derived from the embryonic through to the aged CNS. Importantly, the NSA has contributed to the demise of the ‘no new neurogenesis’ dogma, and the beginning of a new era of CNS regenerative medicine. Nevertheless, the interpretations arising from the utilisation of the NSA need to take into consideration its limits, so as not to be used beyond its specificity and sensitivity.

Evidence for a possible association between a low level of cholesterol and increased suicidal behaviour has accumulated in the recent 3 decades. The present study investigates whether lipid levels can make state-dependent markers of suicidal behaviour in Polish patients with mood disorder recently admitted to a psychiatric hospital owing to an acute depressive episode.

The study was conducted on 223 patients (73 male and 150 female) with unipolar (n=171) and bipolar (n=52) depression. They were interviewed to assess any occurrence of suicidal thoughts, suicidal tendencies and/or suicidal attempts during the 3 months before admission. Laboratory measurements [total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides and total lipids] were obtained within 24–72 h after hospital admission.

Suicidal thoughts, tendencies, and attempts were associated with low total cholesterol, LDL cholesterol, and total lipids in both male and female patients, in both diagnostic categories. Triglycerides were significantly lower in male and female patients with suicidal thoughts compared with their non-suicidal counterparts. No association with suicidality was found with HDL cholesterol.

The results of our study support a majority of research showing the association in depressed patients between suicidal behaviour and low levels of total and LDL cholesterol. In addition, the data suggest a similar association with low total lipids, and in some instances, with low triglycerides.

The cannabinoid receptor 1 (CB1) and transient receptor potential cation channel subfamily V member 1 (TRPV1) are proposed to mediate opposite behavioural responses. Their common denominator is the endocannabinoid ligand anandamide (AEA), which is believed to mediate antidepressant-like effect via CB1-R stimulation and depressive-like effect via TRPV1 activation. This is supposed to explain the bell-shaped dose-response curve for anandamide in preclinical models.

We investigated this assumption by administering the dual inhibitor of AEA hydrolysis and TRPV1 activation N-arachidonoyl-serotonin (AA-5HT) into the medial prefrontal cortex of rats. AA-5HT was given in three different doses (0.125, 0.250, 0.500 nmol/0.4 µl/side) and rat behaviour was assessed in the forced swim test.

Our results show significant antidepressant-like effect of AA-5HT (0.250 nmol) but no effects of low or high doses. The effect of 0.250 nmol AA-5HT was partially attenuated when coadministering the inverse CB1-agonist rimonabant (1.6 µg).

A 0.250 nmol of AA-5HT administration into the medial prefrontal cortex induced a significant antidepressant-like effect that was partially attenuated by locally blocking CB1-receptor.

To evaluate the absence and size of massa intermedia (MI), a midline thalamic structure, and its gender-specific alteration in patients with schizophrenia and bipolar disorder.

Thirty-five patients with schizophrenia (17 females and 18 males), 21 patients with bipolar disorder (15 females and 6 males) and 89 healthy controls (50 females and 39 males) were evaluated by magnetic resonance imaging. Thin-slice magnetic resonance images of the brain were evaluated. MI was determined in coronal and sagittal images, and area of the MI was measured on the sagittal plane.

Females had a significantly lower incidence of absent MI compared with males in the healthy control group. The absence of MI in schizophrenia and bipolar patients was not higher than the incidence in healthy controls. The size of MI showed a gender difference. The mean MI area size was smaller in female schizophrenia patients than in female controls, while no significant difference was observed between male schizophrenia patients and their controls.

The size of MI, a gender difference midline structure, is smaller in females with schizophrenia, and the results of this study support other studies of structural aberration of the thalamus and other midline structures in the brains of patients with schizophrenia.

Cryotherapy has a long tradition in somatic medicine. Yet we know very little about its impact on psyche and mood disturbances in particular. Therefore there is a real need for scientific investigations into this problem.

The study reported here was an initial approach to whole-body cryotherapy (WBCT) as a potential treatment modality for depression and was expected to provide rough data helping to design a future project with extended methodology, larger sample groups and longer follow-up.

Twenty-three patients aged 37–70 years gave informed consent to participate in the study. Ten WBCT procedures (160 s, −150°C) were applied within 2 weeks. Participants were recruited from depressed day hospital patients. Antidepressive medication was not ceased. Symptoms were rated at the beginning and end of this intervention using the 21-item Hamilton Depression Rating Scale (HDRS). Changes in scores were analyzed in the group of patients for every item separately as well as for the sum of all items for each patient.

Almost for each individual HDRS item, the overall score for all patients together was significantly lower after WBCT. This means that all symptoms, except for day–night mood fluctuations, were presumably positively influenced by cryotherapy. The HDRS sum-score for each patient after WBCT was lower than that of the baseline and reached statistical significance in a paired samples t-test. Every patient was therefore considerably relieved after WBCT.

It appears that WBCT helps in alleviating depression symptoms. Should this be confirmed in the extended study we are currently implementing, WBCT may become an auxiliary treatment in depression.

Intrauterine growth restriction (IUGR) has been associated with metabolic disorders later in life such as obesity and diabetes as well as psychiatric disorders such as depression and schizophrenia. Therefore, we wanted to investigate whether behavioural, metabolic or neuroendocrine abnormalities could be provoked or exacerbated by a high-fat diet (HFD) in an experimental model of IUGR.

Pregnant dams were exposed to dexamethasone (DEX) in the third gestational week to induce IUGR. Late adolescent male offspring of DEX- and vehicle-treated dams were then fed a HFD or standard chow for 8 weeks and subjected to a variety of assessments.

Only diet affected the hypothalamus-pituitary-adrenal (HPA) axis stress response, as HFD doubled the observed corticosterone levels following acute restraint. HFD and prenatal DEX exposure concomitantly exacerbated depressive-like behaviour in the forced swim test, even though no interaction was seen. Prenatal DEX treatment tended to increase the basal acoustic startle response (ASR), while an interaction between HFD and DEX was present in the ASR pre-pulse inhibition suggestive of fundamental changes in neuronal gating mechanisms. Metabolic parameters were only affected by diet, as HFD increased fasting glucose and insulin levels.

We conclude that chronic HFD may be more important in programming of the HPA axis stress responsiveness than an adverse foetal environment and therefore potentially implies an increased risk for developing psychiatric and metabolic disease.

Recent studies have proposed the existence of three distinct subgroups of bipolar 1 disorder based on age at onset (AAO). The present study aims to investigate potential clinical and functional differences between these subgroups in an Australian sample.

Participants (n = 239) were enrolled in the Bipolar Comprehensive Outcomes Study (BCOS), a 2-year longitudinal, observational, cross-sectional study. Assessment measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD21), Clinical Global Impressions Scale (CGI-BP), SF-36, SLICE/Life Scale, and the EuroQol (EQ-5D). Participants were also asked about their age at the first major affective episode.

Three AAO groups were compared: early (AAO < 20, mean = 15.5 ± 2.72; 44.4% of the participants); intermediate (AAO 20–39, mean = 26.1 ± 4.8; 48.14% of the participants) and late (AAO > 40, mean = 50.6 ± 9.04; 7.4% of the participants). Higher rates of depression, suicidal ideation and binge drinking were reported by the early AAO group. This group also reported poorer quality of life in a number of areas. The early AAO group had a predominant depressive initial polarity and the intermediate group had a manic predominance.

Early AAO is associated with an adverse outcome.

This article describes an exploratory study of MMPI-2 administration to 20 patients with Korsakoff's disease, all admitted to the Korsakoff unit of a major psychiatric hospital in the Netherlands.

We compared their MMPI-2 basic profiles with those of an inpatient alcohol-dependent non-Korsakoff group. Attention was also given to content scales and some selected supplementary scales. Furthermore, we explored the differences between MMPI-2 profiles of Korsakoff patients with and without insight into oneself and one's disease.

Compared with both the Dutch norms and the scale means of the non-Korsakoff alcoholics, Korsakoff patients showed an extraordinary flat profile. Illness insight appeared to be related to the levels of the various scales.

The results show the potential usefulness of the MMPI-2 in the differential diagnosis of chronic alcoholism and Korsakoff's disease.

Chronic stress responses can lead to physical and behavioural health problems, often experienced and observed in the care of people with intellectual disabilities or people with dementia. Electrodermal activity (EDA) is a bio-signal for stress, which can be measured by wearables and thereby support stress management. However, the how, when and to what extent patients and healthcare providers can benefit is unclear. This study aims to create an overview of available wearables enabling the detection of perceived stress by using EDA.

Following the PRISMA-SCR protocol for scoping reviews, four databases were included in the search of peer-reviewed studies published between 2012 and 2022, reporting detection of EDA in relation to self-reported stress or stress-related behaviours. Type of wearable, bodily location, research population, context, stressor type and the reported relationship between EDA and perceived stress were extracted.

Of the 74 included studies, the majority included healthy subjects in laboratory situations. Field studies and studies using machine learning (ML) to predict stress have increased in the last years. EDA is most often measured on the wrist, with offline data processing. Studies predicting perceived stress or stress-related behaviour using EDA features, reported accuracies between 42% and 100% with an average of 82.6%. Of these studies, the majority used ML.

Wearable EDA sensors are promising in detecting perceived stress. Field studies with relevant populations in a health or care context are lacking. Future studies should focus on the application of EDA-measuring wearables in real-life situations to support stress management.

Sleep disturbances are one of the most common underdiagnosed and undertreated health problems among the adult population.

The aim of the study was to assess the prevalence of sleeping problems and their relation to sociodemographic characteristics in the Polish population, based on the results of the National Health Interview Survey carried out by the Central Statistical Office in 1996.

A stratified sampling scheme, involving two steps, was used. Standardized prevalence ratios (SPRs and their 95% confidence intervals) were calculated. Assessment of sleep-related problems was based on six questions. A representative Polish sample (47 924 non-institutionalized, adult respondents) was interviewed.

Nearly one-fourth of Polish inhabitants suffered from insomnia. The percentage was significantly higher among women (28.1%) than among men (18.1%). The prevalence of insomnia increased with age and was highest in divorced respondents. Respondents of both sexes with higher educational levels suffered from insomnia less often than individuals with lower levels of education. The problem of insomnia applies in a similar degree to inhabitants of both rural and urban regions. About one-twentieth of inhabitants of Poland experienced recent sleep deterioration related to problems. It was associated positively with age, female gender and lower education. About 20% of the population get up not rested in the morning, women significantly more often than men, urban residents more often than rural ones.

Sleep-related problems are common and the results are comparable with those from other countries. The findings have important implications, such as the necessity of better education of the public community about the identification and possibilities of treatment of sleep disturbance.

Depression and coronary heart disease (CHD) are highly comorbid conditions. Brain-derived neurotrophic factor (BDNF) plays an important role in cardiovascular processes. Depressed patients typically show decreased BDNF concentrations. We analysed the relationship between BDNF and depression in a sample of patients with CHD and additionally distinguished between cognitive-affective and somatic depression symptoms. We also investigated whether BDNF was associated with somatic comorbidity burden, acute coronary syndrome (ACS) or congestive heart failure (CHF).

The following variables were assessed for 225 hospitalised patients with CHD: BDNF concentrations, depression [Patient Health Questionnaire-9 (PHQ-9)], somatic comorbidity (Charlson Comorbidity Index), CHF, ACS, platelet count, smoking status and antidepressant treatment.

Regression models revealed that BDNF was not associated with severity of depression. Although depressed patients (PHQ-9 score >7) had significantly lower BDNF concentrations compared to non-depressed patients (p = 0.04), this was not statistically significant after controlling for confounders (p = 0.15). Cognitive-affective symptoms and somatic comorbidity burden each closely missed a statistically significant association with BDNF concentrations (p = 0.08, p = 0.06, respectively). BDNF was reduced in patients with CHF (p = 0.02). There was no covariate-adjusted, significant association between BDNF and ACS.

Serum BDNF concentrations are associated with cardiovascular dysfunction. Somatic comorbidities should be considered when investigating the relationship between depression and BDNF.

Altered cardiac autonomic function has been proposed in schizophrenia, but the results are mixed. Therefore, analyses with larger sample sizes and better methodology are needed.

To examine whether acute schizophrenia is associated with cardiac autonomic dysfunction, 314 unmedicated patients with acute schizophrenia and 409 healthy volunteers, aged 18–65 years, were recruited for a case–control analysis. The severity of schizophrenia symptoms was assessed with the Positive and Negative Syndrome Scale. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV) parameters during the supine–standing–supine test. Frequency-domain indices of HRV were obtained.

Unmedicated patients with acute schizophrenia consistently exhibited reduced mean RR interval and HRV levels in a supine rest and standing position compared with healthy volunteers. The severity of psychopathology, in particular positive symptoms, was negatively correlated with cardiac vagal control.

These data suggest that acute schizophrenia is accompanied by cardiac autonomic dysregulation. In view of the higher risk for cardiac complications in these patients, one might also consider the antipsychotic treatment in favour of improving cardiac autonomic modulation. Further studies using larger patient groups and controlled therapeutics may better understand the influence of antipsychotic treatment on cardiac autonomic regulation in schizophrenia.

Interleukin-6 (IL-6) is a pleiotropic proinflammatory cytokine that plays a key role in the injuries and diseases of the central nervous system (CNS). A voltage-gated Na+ channel (VGSC) is essential for the excitability and electrical properties of the neurons. However, there is still limited information on the role of IL-6 in voltage-gated sodium channels. Our study aimed to investigate the effects of IL-6 on Na+ currents in cultured spinal-cord neurons.

VGSC currents were activated and recorded using whole-cell patch-clamp technique in the cultured rat spinal cord neurons. The effects of IL-6 concentration and exposure duration were examined. To determine whether any change in the number of channels in the plasma membrane can inhibit IL-6 on VGSC currents, we examined the expression of α1A (SCN1α) subunit mRNA level and protein level in the neurons before and after IL-6 induction using real-time polymerase chain reaction.

We verified that IL-6, through a receptor-mediated mechanism, suppressed Na+ currents in a time- and dose-dependent manner, but did not alter the voltage-dependent activation and inactivation. Gp130 was involved in this inhibition. Furthermore, the spike amplitude was also inhibited by IL-6 in the doses that decreased the Na+ currents.

VGSC currents are significantly inhibited by IL-6. Our findings reveal that the potential neuroprotection of IL-6 may result from the inhibitory effects on VGSC currents.

In major depressive disorder (MDD), single nucleotide polymorphisms (SNPs) in monoaminergic genes may impact disease susceptibility, treatment response, and brain volume. The objective of this study was to examine the effect of such polymorphisms on hippocampal volume in patients with treatment-resistant MDD and healthy controls. Candidate gene risk alleles were hypothesised to be associated with reductions in hippocampal volume.

A total of 26 outpatients with treatment-resistant MDD and 27 matched healthy controls underwent magnetic resonance imaging and genotyping for six SNPs in monoaminergic genes [serotonin transporter (SLC6A4), norepinephrine transporter (SLC6A2), serotonin 1A and 2A receptors (HTR1A and HTR2A), catechol-O-methyltransferase (COMT), and brain-derived neurotrophic factor (BDNF)]. Hippocampal volume was estimated using an automated segmentation algorithm (FreeSurfer).

Hippocampal volume did not differ between patients and controls. Within the entire study sample irrespective of diagnosis, C allele-carriers for both the NET−182 T/C [rs2242446] and 5-HT1A−1019C/G [rs6295] polymorphisms had smaller hippocampal volumes relative to other genotypes. For the 5-HTTLPR (rs25531) polymorphism, there was a significant diagnosis by genotype interaction effect on hippocampal volume. Among patients only, homozygosity for the 5-HTTLPR short (S) allele was associated with smaller hippocampal volume. There was no association between the 5-HT2A, COMT, and BDNF SNPs and hippocampal volume.

The results indicate that the volume of the hippocampus may be influenced by serotonin- and norepinephrine-related gene polymorphisms. The NET and 5-HT1A polymorphisms appear to have similar effects on hippocampal volume in patients and controls while the 5-HTTLPR polymorphism differentially affects hippocampal volume in the presence of depression.

Sustained immune activation leads to cognitive dysfunctions, depression-, and anxiety-like behaviours in humans and rodents. It is modelled by administration of lipopolysaccharides (LPS) to induce expression of pro-inflammatory cytokines that then activate indoleamine 2,3 dioxygenase (IDO1), the rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism. Here, we ask whether chronic IDO1 inhibition by 1-methyl-tryptophan (1-MT, added at 2 g/l in the drinking water) or chronic inhibition of tryptophan 2,3 dioxygenase (TDO2), another enzyme capable of converting tryptophan to kynurenine, by 680C91 (15 mg/kg per os), can rescue LPS-induced (0.83-mg/kg intraperitoneally) anxiety and cognitive deficits. We also investigate the acute effects of 680C91 on serotonergic, dopaminergic, and kynurenine pathway metabolites.

We examined LPS-induced deficits in trace fear conditioning and anxiety in the light–dark box and elevated plus maze (EPM) in group-housed C57Bl6/N mice. Kynurenine pathway metabolites and monoamine levels were measured via high-performance liquid chromatography.

Chronic blockade of IDO1 with 1-MT did not rescue cognitive deficits or abrogate the anxiogenic behaviour caused by LPS despite a decrease in the brain kynurenine:tryptophan ratio. However, 1-MT by itself demonstrated anxiolytic properties in the EPM. Acute and chronic inhibition of TDO2 elevated brain levels of tryptophan, while chronic inhibition of TDO2 was unsuccessful in rescuing cognitive deficits and abrogating the anxiety caused by LPS.

In line with previous studies, we show that LPS administration induces anxiety and cognitive dysfunctions in mice that however were not reversed by chronic blockade of IDO1 or TDO2 at the doses used.

Electroconvulsive therapy (ECT) is one of the most efficient treatments for severe major depression, but some patients suffer from retrograde memory loss after treatment. Electroconvulsive seizures (ECS), an animal model of ECT, have repeatedly been shown to increase hippocampal neurogenesis, and multiple ECS treatments cause retrograde amnesia in hippocampus-dependent memory tasks. Since recent studies propose that addition of newborn hippocampal neurons might degrade existing memories, we investigated whether the memory impairment after multiple ECS treatments is a cumulative effect of repeated treatments, or if it is the result of a delayed effect after a single ECS.

We used the hippocampus-dependent memory task Morris water maze (MWM) to evaluate spatial memory. Rats were exposed to an 8-day training paradigm before receiving either a single ECS or sham treatment and tested in the MWM 24 h, 72 h, or 7 days after this treatment, or multiple (four) ECS or sham treatments and tested 7 days after the first treatment.

A single ECS treatment was not sufficient to cause retrograde amnesia whereas multiple ECS treatments strongly disrupted spatial memory in the MWM.

The retrograde amnesia after multiple ECS is a cumulative effect of repeated treatments rather than a delayed effect after a single ECS.