Dense attention network identifies EEG abnormalities during working memory performance of patients with schizophrenia.

Introduction: Patients with schizophrenia typically exhibit deficits in working memory (WM) associated with abnormalities in brain activity. Alterations in the encoding, maintenance and retrieval phases of sequential WM tasks are well established. However, due to the heterogeneity of symptoms and complexity of its neurophysiological underpinnings, differential diagnosis remains a challenge. We conducted an electroencephalographic (EEG) study during a visual WM task in fifteen schizophrenia patients and fifteen healthy controls. We hypothesized that EEG abnormalities during the task could be identified, and patients successfully classified by an interpretable machine learning algorithm. Methods: We tested a custom dense attention network (DAN) machine learning model to discriminate patients from control subjects and compared its performance with simpler and more commonly used machine learning models. Additionally, we analyzed behavioral performance, event-related EEG potentials, and time-frequency representations of the evoked responses to further characterize abnormalities in patients during WM. Results: The DAN model was significantly accurate in discriminating patients from healthy controls, ACC = 0.69, SD = 0.05. There were no significant differences between groups, conditions, or their interaction in behavioral performance or event-related potentials. However, patients showed significantly lower alpha suppression in the task preparation, memory encoding, maintenance, and retrieval phases F(1,28) = 5.93, p = 0.022, η2 = 0.149. Further analysis revealed that the two highest peaks in the attention value vector of the DAN model overlapped in time with the preparation and memory retrieval phases, as well as with two of the four significant time-frequency ROIs. Discussion: These results highlight the potential utility of interpretable machine learning algorithms as an aid in diagnosis of schizophrenia and other psychiatric disorders presenting oscillatory abnormalities.

A pilot predictive model based on COVID-19 data to assess suicidal ideation indirectly.

The COVID-19 pandemic has had a negative impact on the mental health of the population. Many studies reported high levels of psychological distress and rising rates of suicidal ideation (SI). Data on a range of psychometric scales from 1790 respondents were collected in Slovenia through an online survey between July 2020 and January 2021. As a worrying percentage (9.7%) of respondents reported having SI within the last month, the goal of this study was to estimate the presence of SI, as indicated by the Suicidal Ideation Attributes Scale (SIDAS). The estimation was based on the change of habits, demographic features, strategies for coping with stress, and satisfaction with three most important aspects of life (relationships, finances, and housing). This could both help recognize the telltale factors indicative of SI and potentially identify people at risk. The factors were specifically selected to be discreet about suicide, likely sacrificing some accuracy in return. We tried four machine learning algorithms: binary logistic regression, random forest, XGBoost, and support vector machines. Logistic regression, random forest, and XGBoost models achieved comparable performance with the highest area under the receiver operating characteristic curve of 0.83 on previously unseen data. We found an association between various subscales of Brief-COPE and SI; Self-Blame was especially indicative of the presence of SI, followed by increase in Substance Use, low Positive Reframing, Behavioral Disengagement, dissatisfaction with relationships and lower age. The results showed that the presence of SI can be estimated with reasonable specificity and sensitivity based on the proposed indicators. This suggests that the indicators we examined have a potential to be developed into a quick screening tool that would assess suicidality indirectly, without unnecessary exposure to direct questions on suicidality. As with any screening tool, subjects identified as being at risk, should be further clinically examined.

Depression, Anxiety, Stress, and Suicidality Levels in Young Adults Increased Two Years into the COVID-19 Pandemic.

BACKGROUND: The severity of both the COVID-19 clinical picture and confinement measures in Slovenia was higher during the initial phase of the pandemic in 2020 than during the Omicron wave in 2022. This could lead us to expect a higher level of distress during the initial phase. On the other hand, prolonged stress can have a detrimental effect on mental health. This study aimed to explore how the prolonged stress of the COVID-19 pandemic and the accompanying changes affected the mental health of young adults in Slovenia. We analyzed and compared the levels of depression, anxiety, stress, and suicidal ideation in young adults during the initial phase of the pandemic and the Omicron wave, as well as between the COVID-19-infected and non-infected individuals. METHODS: An online survey was used to survey 587 young adults in the first wave (July-December 2020) and 511 in the Omicron wave (January-February 2022). Levels of depression, anxiety, stress, and suicidal ideation were compared using Mann-Whitney U test. RESULTS: Results show that the Omicron wave significantly worsened depression, anxiety, stress, and suicidal ideation. Young adults who had tested positive for COVID-19 reported no worse or only slightly worse mental health than those who never tested positive. CONCLUSIONS: The current study provides new evidence about the mental health of young adults during the Omicron wave. Our results show that two years into the pandemic, they expressed more negative emotions and suicidal thoughts than at the beginning.

Risk of Depression, Anxiety, and Stress During the Second Wave of COVID-19 in Slovenia.

The spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) pandemic has led to numerous negative consequences on the mental health of the population throughout the world. The main aim of our study was to compare the risk for depression, anxiety, and stress during the second wave of the pandemic in Slovenia. An additional goal was to analyze the association of depression, anxiety, and stress, with the most relevant subjective factors that define the quality of life. Furthermore, we aimed at determining whether health workers have a higher risk for depression following the course of the pandemic. The study was conducted on the general population, between July 2020 and January 2021 through an online survey. The data of 1,728 respondents in two samples of respondents (782 at baseline - first measurement point and 946 during the second measurement point) of the second wave were analyzed using zero-inflated negative binomial regression and Mann-Whitney U-test. The findings of this study show that the rise the second wave was associated with a higher risk for depression, anxiety and stress. The risk for all three was higher for younger participants. Women showed a higher risk for anxiety and stress. Finances, relationships, and housing dissatisfaction were relevant predictors for depression, anxiety and stress. Health workers in our sample showed a higher risk for stress, but not for depression or anxiety, than the general population. Our findings highlight the urgent need for coordinating and developing mental health services and tailored interventions to reduce the mental health burden, especially in the younger.

Differences in SNP genotype distributions between complex and simple suicides.

Dysregulations in serotonin neurotransmission can be a strong contributing factor in suicide and impulsive-aggressive personality traits. Victims of suicide form a heterogeneous group in terms of planning, lethality and number of used methods. In this study, we tested single nucleotide polymorphisms (SNPs) of the monoamine oxidase (MAO) A and B genes on the Slovenian population, which has one of the highest suicide rates in the world. Genotyping was performed on 77 victims of complex suicide, 406 victims of simple suicide and 289 controls. The differences in allele distribution were investigated with the two-tailed χ2 test. Haplotype analysis was performed on 740 subjects. Significant or tendency for significant differences in distribution was observed for all studied polymorphisms in the MAOA gene when comparing male victims of complex suicide, victims of simple suicide and controls. Minor allele frequencies in male victims of complex suicide were A 6.7% for rs3027407, C 13% for rs909525 and T 12.7% for rs1137070; in victims of simple suicide, A 36.3% for rs3027407, C 39.5% for rs909525 and T 36.4% for rs1137070; and in controls, A 25.2% for rs3027407, C 30.4% for rs909525 and T 25.8% for rs1137070. The distribution analysis of polymorphism rs1799836 in the MAOB gene and all studied polymorphisms in the MAOA gene in females failed to show any significant results. GTC haplotype (for rs3027407, rs909525, rs1137070) in MAOA polymorphisms was more frequent in victims of complex suicide compared to that in controls and victims of simple suicide. Compared to victims of complex suicide, male victims of simple suicide were more often carriers of MAOA alleles that are, according to literature, associated with higher levels of impulsivity and anger. These differences in SNP distribution could serve as an additional method of differentiating between victims of complex and victims of simple suicide. Further studies including psychological autopsies should be carried out in order to identify personality traits and behavioural differences among distinct groups of suicide victims.

Association of the Five-Factor Model personality traits and opioid addiction treatment outcome.

Many patients with opioid addiction continue to use opioids during and after treatment, and their career of drug taking is usually punctuated by repeated treatment admissions and relapses. Personality traits are considered risk factors for drug use, and, in turn, the psychoactive substances impact individuals' traits. The most widely used system of traits is called the Five-Factor Model (FFM). Studies have shown that persons who use heroin are consistently depicted as high on Neuroticism and higher Extroversion, also they are described as more impulsive and less sociable. Those who maintain abstinence are characterized by a higher Agreeableness and Conscientiousness. Treatment programs for opioid addiction vary substantially in treatment processes, and an early identification of patients traits that address their strengths and weaknesses within specific treatment settings could be useful in decreasing the possibility of relapse.

Completed suicide, depression, and RELN polymorphisms.

OBJECTIVE: Suicidal behavior is a complex phenomenon, an outcome of both environmental and genetic factors. In the present study, we looked for a potential association between suicide and the reelin gene as reelin has been associated previously with several psychiatric disorders, including depression. MATERIALS AND METHODS: We analyzed three single nucleotide polymorphisms (SNPs) in the reelin gene, rs2965087, rs7341475, and rs362691, in a population of 483 suicide victims and 332 healthy controls, all Caucasians. An analysis was carried out according to sex and the method of suicide. In a group of 77 suicide victims with psychological autopsy data, suicide threats, suicide in the family, and number of depression symptoms were also considered. RESULTS: Analysis of all three polymorphisms did not confirm an association with suicide in general. However, for subjects included in psychological autopsy study, association with previous announcement of suicide in the group of subjects with TT genotype for polymorphism rs2965087 was determined. Furthermore, the results pointed to an association with reported suicide in the family of suicide victims in case of the TT genotype. In contrast, the number of depressive symptoms, besides suicidal threats, was lower in the group with the TT genotype. LIMITATIONS: Psychological autopsies can be associated with recall bias and the sample was rather small and therefore underpowered. CONCLUSION: The present investigation, performed on a study sample from a population with one of the highest suicide rates in the world, indicated an association between rs2965087 in the reelin gene and the expression of suicidal threats a month before suicide in contrast to other symptoms of depression.

Relationship of suicide rates with climate and economic variables in Europe during 2000-2012.

BACKGROUND: It is well known that suicidal rates vary considerably among European countries and the reasons for this are unknown, although several theories have been proposed. The effect of economic variables has been extensively studied but not that of climate. METHODS: Data from 29 European countries covering the years 2000-2012 and concerning male and female standardized suicidal rates (according to WHO), economic variables (according World Bank) and climate variables were gathered. The statistical analysis included cluster and principal component analysis and categorical regression. RESULTS: The derived models explained 62.4 % of the variability of male suicidal rates. Economic variables alone explained 26.9 % and climate variables 37.6 %. For females, the respective figures were 41.7, 11.5 and 28.1 %. Male suicides correlated with high unemployment rate in the frame of high growth rate and high inflation and low GDP per capita, while female suicides correlated negatively with inflation. Both male and female suicides correlated with low temperature. DISCUSSION: The current study reports that the climatic effect (cold climate) is stronger than the economic one, but both are present. It seems that in Europe suicidality follows the climate/temperature cline which interestingly is not from south to north but from south to north-east. This raises concerns that climate change could lead to an increase in suicide rates. The current study is essentially the first successful attempt to explain the differences across countries in Europe; however, it is an observational analysis based on aggregate data and thus there is a lack of control for confounders.

Increased libido associated with donepezil treatment: a case report.

Inappropriate verbal and physical sexual behaviour is not common among individuals with dementia, but when it does occur, it can have profound consequences. We report a case of 79-year-old woman with dementia of the Alzheimer's type who complained of increased libido after an increased dose of donepezil, which was being used along with tianeptine. Donepezil withdrawal led to the resolution of increased libido, but when it was reintroduced, increased libido reappeared once again (Naranjo score: 7). Increased libido was not reported by the patient during the 6-year follow-up period after donepezil withdrawal. A potential mechanism of acetylcholinesterase inhibitor-induced increased libido and the current literature on hypersexuality as a side-effect of donepezil treatment are discussed.

Relationship of suicide rates to economic variables in Europe: 2000-2011.

BACKGROUND: It is unclear whether there is a direct link between economic crises and changes in suicide rates. AIMS: The Lopez-Ibor Foundation launched an initiative to study the possible impact of the economic crisis on European suicide rates. METHOD: Data was gathered and analysed from 29 European countries and included the number of deaths by suicide in men and women, the unemployment rate, the gross domestic product (GDP) per capita, the annual economic growth rate and inflation. RESULTS: There was a strong correlation between suicide rates and all economic indices except GPD per capita in men but only a correlation with unemployment in women. However, the increase in suicide rates occurred several months before the economic crisis emerged. CONCLUSIONS: Overall, this study confirms a general relationship between the economic environment and suicide rates; however, it does not support there being a clear causal relationship between the current economic crisis and an increase in the suicide rate.

Blood alcohol concentration of suicide victims by partial hanging.

During the investigated period, 2000-2007, 4249 suicides were reported in Slovenia, and 1061 autopsies of suicide deaths from the central, northwestern, and southwestern parts of Slovenia were conducted at the Institute of Forensic Medicine in Ljubljana. To identify a possible role of alcohol use in the selection of suicide method blood samples were collected during medicolegal autopsies of suicide victims in order to establish their blood alcohol concentration (BAC) level at the time of death. The study group consisted of 844 suicide victims that used violent suicide methods and 174 suicide victims that used non-violent suicide methods. Out of the group with violent suicide methods 184 (21.8%) suicide victims by partial hanging and 112 (13.3%) suicide victims by complete hanging were identified. The average age was higher in the group of suicide victims by partial hanging than in the group of suicide victims by complete hanging (p < 0.001; T = 3653; df = 294). The mean BAC was higher (T = 1.604; df = 278; p < 0.05) in the group of suicide victims by partial hanging (0.57 g/kg; SD ± 0.92) than in the group of suicide victims by complete hanging (0.40 g/kg; SD ± 0.82). The proportion of BAC positive suicide victims with blood alcohol concentration above 0.1 g/kg at the time of death was higher in the group of suicide victims who used non-violent suicide methods in comparison to the group of suicide victims who used violent suicide methods (p < 0.001; χ(2) = 14.988, df = 1). Partial hanging was almost twice as common as complete hanging. Higher BAC in the group of suicide victims by partial hanging and more BAC positive suicide victims in the group who died by non-violent suicide methods could give indications about the role of alcohol in the selection of suicide method.

Availability of mental health service providers and suicide rates in Slovenia: a nationwide ecological study.

AIM: To investigate the influence of socioeconomic factors, mental health service availability, and prevalence of mental disorders on regional differences in the suicide rate in Slovenia. METHODS: The effects of different socioeconomic factors, mental health service availability, and mental disorders factors on suicide rates from 2000-2009 were analyzed using a general linear mixed model (GLMM). Pearson correlations were used to explore the direction and magnitude of associations. RESULTS: Among socioeconomic factors, unemployment rate ranked as the most powerful predictor of suicide and an increase of one unit in the unemployment rate increased regional suicide rate by 2.21 (ß=2.21, 95% confidence intervals [CI]=1.87-2.54, P<0.001). On the other hand, higher marriage/divorce ratio was negatively related to the suicide rate and an increase of one unit in marriage/divorce ratio reduced regional suicide rate by 1.16 (ß=-1.16, 95% CI=-2.20 to -0.13, P<0.031). The most influential mental health service availability parameter was higher psychiatrist availability (4 psychiatrists and more working at outpatient clinics per 100 000 inhabitants), which was negatively correlated with the suicide rate and reduced regional suicide rate by 2.95 (ß=-2.95, 95% CI=-4.60 to -1.31, P=0.002). Another negatively correlated factor was the antidepressant/anxiolytic ratio higher than 0.5, which reduced the regional suicide rate by 2.32 (ß=-2.32, 95% CI=-3.75 to -0.89, P=0.003). Among mental health disorders, only the prevalence of alcohol use disorders was significantly related to the regional suicide rates and an increase of one unit in the prevalence of alcohol use disorders per 1000 inhabitants increased the regional suicide rate by 0.02 (ß=0.02, 95% CI=0.01- 0.03, P=0.008). CONCLUSIONS: Besides unemployment, which was a very strong predictor of suicide rates, unequal availability of mental health services and quality of depressive disorder treatment may contribute to variations in suicide rates in different regions.

Psychopharmacotherapy prescription and suicidal behaviour.

Suicidal behaviour has multiple causes. Psychiatric disorder is a major contributing factor. Consecutively, diagnosis and treatment of mental disorders has an impact on suicide rate. The studies that investigated the possible impact of psychopharmacotherapy prescription practise on suicide rate have been gathered in the present article. Ongoing discussion of potential benefits and risks of antidepressant treatment with respect to suicidal behaviours includes many ecological, or population- based, correlational studies of temporal or regional trends in suicide rates and rates of usage of modern antidepressants including SSRIs. A number of studies have found a relationship between increase in national antidepressant prescribing and declining suicide rates, with general agreement but some exceptions. In general, studies showed that increased prescribing of antidepressants may indicate improved diagnosis and treatment of depression. On the other hand, studies that investigated the impact of prescription of anxyolitics on suicide rate were scarce, although the ratio of anxiolytics to antidepressants has been described as a quality indicator regarding treatment of depression, which is in most cases combined with anxiety and increased suicide risk. Importantly, sedatives and hypnotics are widely prescribed to elderly persons with symptoms of depression, anxiety, and sleep disturbance, but studies demonstrated that sedatives and hypnotics were both associated with increased risk for suicide in the elderly. Finally, studies on antipsychotic prescription demonstrated that particularly treatment with clozapine decreased suicide mortality among individuals with schizophrenia and schizoaffective disorders and on the other hand lithium reduced suicide rate among individuals with mood disorders.

Tryptophan hydroxylase 2 (TPH 2) single nucleotide polymorphisms, suicide, and alcohol-related suicide.

BACKGROUND: Suicide has been identified as a serious public health problem that is often accompanied by alcohol misuse and dependence. It seems that suicide is a result of an interplay between distal (e.g. genetic loading, family history of suicide) and proximal factors (e.g. existence of psychiatric disorder, events conferring acute stress), as well as their interactions. However, like suicide, alcohol dependence seems to be a multifactorial disorder caused by genetic and environmental factors. Serotonergic dysfunction has been implicated to be involved in the pathophysiology of substance abuse, and has also an important role in suicidal behaviour. Studies investigating suicide, alcohol-related suicide and the rate limiting enzyme of serotonin synthesis, tryptophan hydroxylase 2 (TPH2), remain to date rather limited. RESULTS: Recent studies of TPH2 showed a range of strong, mild or no association with suicide and alcohol-related suicide, depending on a study group and genetic variants tested. Overall, to date the clinical effects seems to be quite modest. Among suicide victims with more impulsive and verbal aggressive behaviour more alcohol misuse or dependency was present. CONCLUSIONS: Suicide and alcoholism are often comorbid disorders with a complex nature. They are both strongly linked to serotonin modulation, and therefore association studies of SNPs in genes from the serotonergic system could provide an insight into the genetic background of such disorders. However, based on current results we cannot draw any conclusions, but further research to clarify the interplay between serotonergic system dysfunction, suicide, alcohol dependence, impulsivity and the role of TPH2 enzyme is needed.

Factors associated with the outcome of drug addiction treatment.

Despite different treatment approaches many patients with drug addiction continue to use drugs during and after treatment. Approximately 50 percent of the patients in substance abuse treatment do not complete the first month of treatment ,and this is associated with poor outcome. Attempts have been made to improve outcomes of addiction treatment by addressing patient characteristics that predict continued drug use. Appropriate instruments have been developed in order to facilitate assessment and outcome research. It could be concluded that different psychosocial factors could serve as a predictor of drug addiction treatment outcome. However the interplay of these factors is still poorly understood and further research is needed.

The role of brain-derived neurotrophic factor in the pathophysiology of suicidal behavior.

Suicidal behaviour is a major public health concern. It is known that the pathogenesis of suicidal behaviour involves altered neural plasticity, resulting in the aberrant stress response of the central nervous system to environmental factors. Indeed, altered brain structure and function was found in suicide victims. Neurotrophins are growth factors that are involved in the regulation of structural, synaptic, and morphological plasticity and in the modulation of the strength and number of synaptic connections and neurotransmission. Brain-derived neurotrophic factor (BDNF) the most studied and the most widely distributed among neurotrophins binds to a tropomyosin-related kinase B (TrkB) receptor and to a pan75 neurotrophins receptor. It has been reported that BDNF production is decreased in all patients with suicidal behaviour and in all suicide victims regardless of a psychiatric diagnosis. It was also found that the mRNA and protein level of BDNF was significantly lower in both the prefrontal cortex and the hippocampus of suicide subjects. Different mechanisms could be involved in the regulation of BDNF gene expression, among which epigenetic mechanisms seem to play a key role. However, also for a functional polymorphism (rs6265) Val66Metit has been shown that the Met allele is associated with the reduced BDNF activity. Further, a recent meta-analysis including 12 studies showed a trend for the Met-carrying genotypes and Met allele conferring risk for suicide. Among included studies, our study with the largest sample size, indicated that the combined Met/Met and Met/Val genotypes of the BDNF Val66Met variant could be the risk factor for violent suicide in female subjects and for suicide in victims exposed to childhood trauma. In accordance with previous reports, our findings demonstrate that aberrant regulation of BDNF synthesis is associated with suicidal behaviour.

Preliminary data on validity of the Drug Addiction Treatment Efficacy Questionnaire.

BACKGROUND: This study describes the validation process for the Slovenian version of the Drug Addiction Treatment Efficacy Questionnaire (DATEQ). SUBJECTS AND METHODS: DATEQ was constructed from the questionnaires used at the Centre for the Treatment of Drug Addiction, Ljubljana University Psychiatric Hospital, and within the network of Centres for the Prevention and Treatment of Drug Addiction in Slovenia during the past 14 years. The Slovenian version of the DATEQ was translated to English using the 'forward-backward' procedure by its authors and their co-workers. The validation process included 100 male and female patients with established addiction to illicit drugs who had been prescribed opioid substitution therapy. The DATEQ questionnaire was used in the study, together with clinical evaluation to measure psychological state and to evaluate the efficacy of treatment in the last year. To determinate the validity of DATEQ the correlation with the clinical assessments of the outcome was calculated using one-way ANOVA. RESULTS: The F value was 44.4, p<0.001 (sum of squares: between groups 210.4, df=2, within groups 229.7, df=97, total 440.1, df=99). At the cut-off 4 the sensitivity is 81% and specificity 83%. CONCLUSION: The validation process for the Slovenian DATEQ version shows metric properties similar to those found in international studies of similar questionnaires, suggesting that it measures the same constructs, in the same way and as similar questionnaires. However, the relatively low sensitivity and specificity suggests caution when using DATEQ as the only measure of outcome.

Risk factors for fatal outcome in patients with opioid dependence treated with methadone in a family medicine setting in Croatia.

AIM: To determine the risk factors for fatal outcome in patients with opioid dependence treated with methadone at the primary care level. METHODS: A group of 287 patients with opioid dependence was monitored prospectively from 1995 to 2007. At the beginning of the study, we collected the data on patient baseline characteristics, treatment characteristics, and living environment. At the annual check-up, we collected the data on daily methadone dose, method of methadone therapy administration, and family physician's assessment of the patient's drug use status. RESULTS: Out of 287 patients, 8% died. Logistic regression analysis showed that the predictors of fatal outcome were continuation of drug use during previous therapeutic attempts (odds ratio [OR], 19.402; 95% confidence interval [CI], 1.659-226.873), maintenance therapy as the planned treatment modality (OR, 3.738; 95% CI, 1.045-13.370), living in an unstable relationship (OR, 9.275; 95% CI, 2.207-38.984), and loss of continuity of care (OR, 12.643; 95% CI, 3.001-53.253). CONCLUSION: The patients presenting these risk factors require special attention. It is important for family physicians to insist on compliance with the treatment protocol and intervene when they lose contact with the patient to prevent the fatal outcome.

Suppression of collagen Q expression in the extrajunctional regions of rat fast muscles is encoded in their stem cells (satellite cells).

In rat fast muscles, collagen Q (ColQ) expression is restricted to the neuromuscular junctions. In contrast, it is high also extrajunctionally in the slow soleus muscles. Fast muscles activated by chronic low-frequency electrical stimulation, similar to neural activation of the soleus muscles, did not increase their extrajunctional expression of ColQ. We assumed that the myogenic stem cells (satellite cells) in fast and slow muscles were intrinsically different in regard to the capacity that they convey to their respective muscle fibers to increase the extrajunctional ColQ expression upon innervation. ColQ mRNA levels were determined by quantitative real-time PCR. Extensive neural suppression of the extrajunctional ColQ expression in regenerating fast muscles during maturation is a very slow process requiring 30-60 days. If the immature regenerating fast EDL muscles were indirectly or directly electrically stimulated immediately after innervation by chronic low-frequency impulse pattern for 8 days, no significant increase of the extrajunctional ColQ mRNA levels was observed in stimulated regenerates in comparison to non-stimulated ones. In contrast, the extrajunctional ColQ mRNA levels in the regenerates of the soleus muscles, trans-innervated by the EDL nerve at the time of muscle injury, increased 4- to 5-fold after 8 days of the same chronic low-frequency electrical stimulation in comparison to those in the stimulated EDL regenerates. Since both fast and slow muscles completely regenerated only from their own myogenic stem cells and were innervated by the same nerve and later activated by the same tonic pattern of impulses, these results demonstrated that the mechanism causing incapacity of regenerating fast muscles to increase their extrajunctional ColQ expression upon tonic activation is encoded in their satellite cells, which in this respect differ from those in the slow muscles.