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OBJECTIVE: Cognitive alterations play an important role in the pathophysiology and treatment of anorexia nervosa (AN). Previous studies suggest that some implicit learning processes may be inhibited in AN. However, this has not yet been fully explored. The purpose of this study is to analyze implicit learning in patients with AN in comparison to healthy controls. METHODS: In this pilot-study, a total of 21 patients diagnosed with AN and 21 matched controls were administered the weather prediction task (WPT), a probabilistic implicit category learning task that consists of two sub-variants. During the feedback (FB) version of the task, participants learn associations between tarot cards and weather outcomes via an operant learning model through which they receive immediate FB on their answers, whereas during the paired associate (PA) variant, participants are directly asked to memorize given associations. RESULTS: AN patients showed selective impairment on the FB task where they scored significantly lower both in comparison to controls (p = .001) who completed the same task and when compared to their own performance on the PA variant (p = .006). Clinical measures showed no significant correlations with test scores. DISCUSSION: Our results demonstrate implicit FB learning deficiencies in adult patients with AN. These impairments may have an impact on the effect of psychotherapeutic interventions and could partially explain the lack of treatment response in AN. Further studies are necessary to derive when and through which mechanisms these alterations originate, and to what extent they should be considered during treatment of the disorder. PUBLIC SIGNIFICANCE: Cognitive impairments pose a challenge in the management of anorexia nervosa. Improved comprehension of cognitive alterations could lead to a greater understanding of the disease and adaptation of psychotherapeutic treatments. In this study, we found that implicit feedback learning in anorexia nervosa is impaired compared to healthy controls. This could indicate the necessity of treatment adaptations in the form of therapy tools without feedback and a larger focus on psychoeducation.
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Anorexia Nervosa , Aprendizagem por Probabilidade , Adulto , Humanos , Anorexia Nervosa/complicações , Anorexia Nervosa/terapia , Projetos Piloto , Aprendizagem/fisiologiaRESUMO
INTRODUCTION: Sleep disturbances are highly prevalent across most major psychiatric disorders. Alterations in the hypothalamic-pituitary-adrenal axis, neuroimmune mechanisms, and circadian rhythm disturbances partially explain this connection. The gut microbiome is also suspected to play a role in sleep regulation, and recent studies suggest that certain probiotics, prebiotics, synbiotics, and fecal microbiome transplantation can improve sleep quality. METHODS: We aimed to assess the relationship between gut-microbiota composition, psychiatric disorders, and sleep quality in this cross-sectional, cross-disorder study. We recruited 103 participants, 63 patients with psychiatric disorders (major depressive disorder [n = 31], bipolar disorder [n = 13], psychotic disorder [n = 19]) along with 40 healthy controls. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The fecal microbiome was analyzed using 16S rRNA sequencing, and groups were compared based on alpha and beta diversity metrics, as well as differentially abundant species and genera. RESULTS: A transdiagnostic decrease in alpha diversity and differences in beta diversity indices were observed in psychiatric patients, compared to controls. Correlation analysis of diversity metrics and PSQI score showed no significance in the patient and control groups. However, three species, Ellagibacter isourolithinifaciens, Senegalimassilia faecalis, and uncultured Blautia sp., and two genera, Senegalimassilia and uncultured Muribaculaceae genus, were differentially abundant in psychiatric patients with good sleep quality (PSQI >8), compared to poor-sleep quality patients (PSQI ≤8). CONCLUSION: In conclusion, this study raises important questions about the interconnection of the gut microbiome and sleep disturbances.
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Transtorno Depressivo Maior , Microbioma Gastrointestinal , Transtornos Mentais , Transtornos do Sono-Vigília , Humanos , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , Estudos Transversais , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Transtornos Mentais/diagnóstico , SonoRESUMO
INTRODUCTION: The COVID-19 pandemic with its protective measures (e. g. lockdown) had far-reaching effects on everyone's well-being. The aim of this study was to examine lifestyle variables during the first Austrian lockdown in patients with bipolar disorder in comparison to a healthy control group and to assess subjective changes caused by the pandemic. METHOD: At the beginning of April 2020, an online survey of n=75 participants (35 people with bipolar disorder and 40 healthy controls) with standardized questionnaires (Beck Depression Inventory-2, Food Craving Inventory, Altman Self Rating Mania Scale) as well as non-standardized COVID-19-specific questions on the subject of "Psychological stress and effects of the COVID-19 pandemic in bipolar disorder" was created and distributed via LimeSurvey. RESULTS: Both groups reported a negative impact on their mental health. The participants with bipolar disorder showed significantly higher values in the Beck Depression Inventory-2 score (p<0,001), in emotional distress due to social distancing (p=0,003) and significantly lower values in muscle-strengthening exercise (p=0,039) and in sport units (p=0,003) compared to the control group. In addition, patients with bipolar disorder smoked more often than individuals of the control group. People with bipolar disorder were 42,9% more likely to report they were less efficient during the pandemic, and 22,9% experienced weight gain compared to before the pandemic. The control group, on the other hand, was less efficient at 17,5% and 5,0% reported weight gain. However, a comparison with pre-pandemic data showed a decrease in food craving in both groups. CONCLUSION: This study provided first evidence of self-reported adverse effects on mental stress and lifestyle in people with bipolar disorder at the beginning of the COVID-19 pandemic. Psychiatric care and early interventions for patients with bipolar disorder would be particularly important in times of crisis in order to help maintain a healthy lifestyle and thus counteract unfavourable developments.
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Transtorno Bipolar , COVID-19 , Humanos , Áustria/epidemiologia , Transtorno Bipolar/epidemiologia , Pandemias , Controle de Doenças Transmissíveis , Estilo de VidaRESUMO
BACKGROUND: The onset and early warning signs of episodes of bipolar disorder are often realized late by those affected. The earlier an incipient episode is treated, the more prognostically favorable the course will be. Symptom monitoring via smartphone application (app) could be an innovative way to recognize and react to early warning signs more swiftly. The aim of this study was to find out whether patients and their relatives consider technical support through an app to be useful and practical in the early warning sign detection and treatment. METHODS: In the present study, 51 patients with bipolar disorder and 28 relatives were interviewed. We gathered information on whether participants were able to perceive early warning signs in form of behavioral changes sufficiently and in a timely fashion and also whether they would use an app as treatment support tool. RESULTS: Although 94.1% of the surveyed patients and 78.6% of their relatives felt that they were well informed about the disease, 13.7% and 35.7%, respectively were not fully satisfied with the current treatment options. Early warning signs of every depressive development were noticed by 25.5% of the patients (relatives 10.7%). Every (hypo)manic development was only noticed by 11.8% of the patients (relatives 7.1%); 88.2% of the patients and 85.7% of the relatives noticed the same symptoms recurrently at the beginning of a depression and 70.6% and 67.9%, respectively, at the beginning of a (hypo)manic episode (in particular changes in physical activity, communication behavior and the sleep-wake rhythm). 84.3% of the patients and 89.3% of the relatives stated that they considered technical support that draws attention to mood and activity changes as useful and that they would use such an app for the treatment. DISCUSSION: The current options for perceiving early warning signs of a depressive or (hypo)manic episode in bipolar disorder are clinically inadequate. Those affected and their relatives desire innovative, technical support. Early detection of symptoms, which often manifest themselves in changes in behavior or activity patterns, is essentiell for managing the course of bipolar disorder. In the future, smartphone apps could be used for clinical treatment and research through objective, continuous and.
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Transtorno Bipolar , Aplicativos Móveis , Telemedicina , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Emoções , Humanos , ManiaRESUMO
INTRODUCTION: Obesity and associated risk factors have been linked to cognitive decline before. OBJECTIVES: In the present study, we evaluated potential cumulative negative effects of overweight and obesity on cognitive performance in euthymic patients with bipolar disorder (BD) in a longitudinal design. METHODS: Neurocognitive measures (California Verbal Learning Test, Trail Making Test [TMT] A/B, Digit-Symbol-Test, Digit-Span, d2 Test), anthropometrics (e.g., body mass index [BMI]), and clinical ratings (Hamilton Depression Scale, Young Mania Rating Scale) were collected over a 12-month observation period. Follow-up data of 38 patients with BD (mean age 40 years; 15 males, 23 females) were available. RESULTS: High baseline BMI predicted a decrease in the patient's performance in the Digit-Span backwards task measuring working memory performance. In contrast, cognitive performance was not predicted by increases in BMI at follow-up. Normal weight bipolar patients (n = 19) improved their performance on the TMT B, measuring cognitive flexibility and executive functioning, within 1 year, while overweight bipolar patients (n = 19) showed no change in this task. CONCLUSIONS: The results suggest that overweight can predict cognitive performance changes over 12 months.
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Transtorno Bipolar/complicações , Índice de Massa Corporal , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Função Executiva/fisiologia , Sobrepeso/complicações , Adulto , Feminino , Seguimentos , Humanos , Masculino , Testes de Memória e Aprendizagem , Pessoa de Meia-Idade , Testes Neuropsicológicos , Obesidade/complicações , Dados Preliminares , Escalas de Graduação Psiquiátrica , Teste de Sequência AlfanuméricaRESUMO
For avoiding affective episodes, patients with bipolar disorders are treated with mood stabilizers. Under that term, the substances lithium, valproic acid, lamotrigine and carbamazepine are included. In the light of upcoming new psychiatric concepts, the use of second generation antipsychotics is also taken into consideration in pharmacological treatment. In this review, the relation between brain structure and the use of lithium in bipolar disorders is examined. Therefore, results from MRI-, DTI-, SPECT-studies assessing this relation, were included.Most of the studies are cross-sectional and examined the effects of lithium. The latter is associated with increased cortical and sub-cortical gray matter volume and ameliorative white matter microstructure. 7-lithium spectroscopy showed a significant difference in brain-lithium concentrations between remitted and non-remitted patients.There are preclinical studies reporting induction of promitotic and antiapoptotic effects by lithium. This literature underpins the hypothesis of lithium-induced neurogenesis. However, osmotic and physical effects of lithium could also explain the demonstrated volume gain in bipolar human brain.Cross-sectional design and small patient groups are typical limitations of numerous studies included in this review.Notably, with the 7-lithium spectroscopy of the central nervous system, new perspectives in clinical research to clarify pharmacokinetic differences between remitted and non-remitted bipolar patients can be established in future.
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Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/patologia , Compostos de Lítio/uso terapêutico , Indução de Remissão , Antimaníacos/análise , Antimaníacos/química , Antimaníacos/uso terapêutico , Antipsicóticos/análise , Antipsicóticos/química , Antipsicóticos/uso terapêutico , Transtorno Bipolar/psicologia , Estudos Transversais , Humanos , Compostos de Lítio/análise , Compostos de Lítio/químicaRESUMO
INTRODUCTION: Cognitive dysfunction is prevalent in depressive as well as manic episodes in individuals with Bipolar Disorder (BD). Even more, after symptom remission, many individuals with BD experience persisting cognitive impairment also in euthymic periods, leading to high illness burden and low quality of life. According to a recent research in animals and healthy humans, microbiota may influence cognitive processes via the brain-gut axis. A strategy to examine the role of the microbiota in different diseases is the intake of supplements that modulate the gut microbiome. The aim of this pilot study was to analyze the impact of probiotic supplements on cognitive parameters in a cohort of euthymic individuals with BD, receiving daily probiotic treatment over a time period of 3 months. METHODS: A total of 20 euthymic individuals with BD received probiotic supplement over a time period of 3 months and completed a cognitive test battery at 3 time points (t1 at time of inclusion, t2 after one month and t3 after 3 months of probiotic intake). RESULTS: We found a significant improvement of performance concerning attention and psychomotor processing speed measured with the Digit Symbol Test after one (t2) as well as after 3 months (t3) of treatment (F = 8.60; η2 = 0.49, p < 0.01). Furthermore, executive function measured with the TMT-B, increased significantly over 3 months (F = 3.68; η2 = 0.29, p < 0.05). CONCLUSION: The results confirm the hypotheses that probiotic supplement might help stable individuals with BD to improve the cognitive function, which in turn might lead to better psychosocial, occupational, work and financial functioning. Nevertheless, the idea of this potential new treatment is challenging because of the variety of the human's gut microbiota.
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Eye Movement Desensitization and Reprocessing (EMDR) is a therapeutic method that has been shown to be especially effective in traumatic disorders. Since the concept of an addiction memory has become widely accepted, the use of EMDR also in substance use disorders (SUD) treatment might count as a separate field. This review summarizes the current state of research on treatment effects EMDR in SUD. The literature search included the databases of PubMed and PsychInfo; four studies met the inclusion criteria. EMDR was found to be related to a decreased amount of craving, fear and depression and to an improvement of emotion regulation and management and self-esteem. Initial findings indicate a high therapeutic potential of EMDR in SUD treatment.
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Dessensibilização e Reprocessamento através dos Movimentos Oculares/métodos , Transtornos Relacionados ao Uso de Substâncias/terapia , Humanos , Transtornos Relacionados ao Uso de Substâncias/psicologia , Resultado do TratamentoRESUMO
BACKGROUND: The early diagnosis of cognitive impairments is an important step in the adequate management of dementia. The project "Smart Cognition & Behaviour Screening powered by Augmented Reality" (SCOBES-AR) aims to develop a multimodal screening tool (MST) for the early detection of cognitive impairments using augmented and virtual reality. The first project phase selected validated assessments for combination with the MST and tested it in 300 healthy older adults. OBJECTIVE: This study established a protocol for the implementation and usability of a mixed reality (MR)-enhanced multidisciplinary screening tool for the early detection of cognitive impairments in older adults. The developed MST will be partially enhanced by MR, which is a combination of augmented reality (AR) and virtual reality (VR). This MR-enhanced prototype of the screening tool (MR-MST) will be tested and compared to the previously developed MST. The usability of the prototype will also be examined. METHODS: This single-center observational crossover design study screens 100 healthy participants (aged 60-75 years) for cognitive decline using a specially developed MST (assessment of cognitive functions, olfactory sensitivity, nutritional preferences, gait parameters, reaction times, and activities of daily living) and an MR-enhanced MST in which the assessments of cognitive functions, reaction time, activities of daily living, and gait will be performed using tailor-made software and AR and VR hardware. The results of the MR-enhanced MST will be compared to those without MR. The usability of the developed MR-enhanced MST will be tested on 10 investigators and 10 test participants using observed summative evaluation and the codiscovery method, and on 2 usability experts using the codiscovery and cognitive walkthrough methods. RESULTS: This study was funded by the Austrian Research Promotion Agency (grant 866873) and received approval from the ethics committee of the Medical University of Graz. The MR-MST and the experimental protocol for this study were developed. All participants gave written informed consent. As of July 15, 2022, a total of 70 participants have been screened. Data analysis and dissemination are scheduled for completion by September 2023. CONCLUSIONS: The development and testing of the MR-MST is an important step toward the establishment of the best practice procedure for the implementation of AR and VR in the screening of cognitive declines in older adults. It will help improve our knowledge of the usability and applicability of the developed prototype and promote further advancement in AR and VR technologies to be used in therapeutic settings. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39513.
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Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in widespread socioeconomic restrictions including quarantine, social distancing and self-isolation. This is the first study investigating the psychological impact of the pandemic on patients waiting for liver or kidney transplantation, a particularly vulnerable group. Methods: Twenty-seven patients on the transplantation waiting list and 43 healthy controls took part in an online survey including the Beck Depression Inventory (BDI-2), the Brief Symptom Inventory-18 (BSI-18), the Pittsburgh Sleep Quality Index (PSQI), the Alcohol Use Identification Test (AUDIT-C), the 12-item Operationalized Psychodynamic Diagnosis Structure Questionnaire (OPD-SQS) and a questionnaire to determine cognitions and beliefs, attitude and fear related to COVID-19. Results: BSI-18 Somatization was increased in waiting list patients compared to controls. Correlation analyses indicated a relationship between Somatization and the fear of contracting the coronavirus in the patient group; however this association was weak. In patients and controls, other psychologicial symptoms (depression, anxiety) correlated highly with emotional distress due to social distancing. There were no differences between patients and controls in depression scores and sleep disturbances. Alcohol consumption and personality structure were not related to COVID-19 fears. Conclusion: In times of the first lockdown during the COVID-19 pandemic, patients on the transplantation waiting list have high somatization symptoms associated with COVID-19 fears. As vulnerable group, they need psychological counseling to improve mental well-being during times of crisis.
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BACKGROUND: The coronavirus disease (COVID-19) pandemic, a global health crisis, has resulted in widespread socioeconomic restrictions including lockdown, social distancing, and self-isolation. To date, little is known about the psychological impact of the COVID-19 pandemic and lockdown on patients with bipolar disorder as a particularly vulnerable group. METHODS: An online survey was conducted in Austria at two points of measurement (T1 April 2020 during the first lockdown vs. T2 May 2020 at post-lockdown). The sample comprises 20 patients with bipolar disorder (mean age = 49.4 ± 15.6 years) and 20 healthy controls (mean age = 32.7 ± 9.6 years). A 2 × 2 factorial design to compare two time points (T1 vs. T2) and two groups (patients vs. healthy controls) was used. Main outcome measures included the Brief Symptom Inventory-18 (BSI-18) and a (non-validated and non-standardized) assessment to determine COVID-19 fears and emotional distress due to social distancing. Multiple linear regression analyses were used to assess the longitudinal association of COVID-19 fears/emotional distress due to social distancing during lockdown (T1) and psychological symptoms after lockdown (T2). RESULTS: At T1, results demonstrated higher scores in BSI-18 subscales depression, anxiety and global severity index as well as emotional distress due to social distancing in bipolar patients compared to controls. There was a significant time x group interaction in the BSI-18 subscale somatization showing a decreasing trend in patients with BD compared to controls. No time effects in BSI-18 subscales or COVID-19 fears/emotional distress due to social distancing were observed. Regression analyses showed that COVID-19 fears during lockdown predicted somatization, only in patients. CONCLUSIONS: There was a connection between the lockdown measures and somatization symptoms observed in patients. When the first steps of easing the social restrictions in May 2020 took place, somatization decreased only in the bipolar compared to the control group. Higher COVID-19 fears during lockdown predicted later symptoms at post-lockdown. Long-term impacts of the COVID-19 pandemic need further investigations to improve current therapeutic approaches and prevent fears and distress during lockdown in individuals with bipolar disorder in times of crisis.
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INTRODUCTION: The coronavirus disease (COVID-19) pandemic and consequent restrictions including social distancing had a great impact on everyday life. To date, little is known about how the restrictions affected sleep, which is commonly disturbed in bipolar disorder (BD). The aim of this study was to elucidate sleep patterns during the pandemic in Austrian BD individuals. METHODS: An online survey assessed sleep with the Pittsburgh Sleep Quality Index (PSQI) and COVID-19-associated attitudes, fears, and emotional distress of 20 BD individuals and 19 controls (HC) during the pandemic. The survey was conducted in April 2020, when very strict regulations were declared, and repeated in May, when they were loosened. RESULTS: Individuals with BD reported overall poor sleep according to PSQI sum at both time points. Subjective sleep quality, sleep latency, daytime sleepiness, and PSQI sum were worse in individuals with BD than in HC. Individuals with BD informed themselves more frequently about pandemic-related topics. Higher information frequency and more COVID-19 fears (about the virus, own infection, contracting others) correlated with worse PSQI values. Regression models found in BD group that higher information frequency as well as higher COVID-19 fears in April predicted worse sleep characteristics in May, in particular subjective sleep quality, sleep duration, sleep efficiency, and daytime sleepiness. CONCLUSION: As sufficient sleep duration and quality are essential for well-being and particularly important for vulnerable BD individuals, it is important that information about the pandemic is gathered to a reasonable extent and mental health professionals include COVID-19-related fears when currently treating BD.
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Transtorno Bipolar , COVID-19 , Transtornos do Sono-Vigília , Transtorno Bipolar/epidemiologia , Medo , Humanos , SARS-CoV-2 , SonoRESUMO
Background: Sleep disturbances are common early warning signs of an episode of bipolar disorder, and early recognition can favorably impact the illness course. Symptom monitoring via a smartphone app is an inexpensive and feasible method to detect an early indication of changes such as sleep. The study aims were (1) to assess the acceptance of apps and (2) to validate sleeping times measured by the smartphone app UP!. Methods:UP! was used by 22 individuals with bipolar disorder and 23 controls. Participants recorded their time of falling asleep and waking-up using UP! for 3 weeks. Results were compared to a validated accelerometer and the Pittsburgh Sleep Quality Index. Additionally, participants were interviewed regarding early warning signs and their feedback for apps as monitoring tools in bipolar disorder (NCT03275714). Results: With UP!, our study did not find strong reservations concerning data protection or continual smartphone usage. Correlation analysis demonstrates UP! to be a valid tool for measuring falling asleep and waking-up times. Discussion: Individuals with bipolar disorder assessed the measurement of sleep disturbances as an early warning sign with a smartphone as positive. The detection of early signs could change an individual's behavior and strengthen self-management. The study showed that UP! can be used to measure changes in sleep durations accurately. Further investigation of smartphone apps' impact to measure other early signs could significantly contribute to clinical treatment and research in the future through objective, continuous, and individual data collection.
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BACKGROUND: An impairment of self and interpersonal functioning has an impact on coping strategies, regulation of affect and stress. Little is known so far about the impairment of personality functioning in patients with bipolar disorder (BD). The aim of this study is to assess the effects of personality structure and attachment in BD patients on the symptom burden. METHODS: Forty-six patients with the diagnosis of BD were assessed by the 12-item Operationalized Psychodynamic Diagnosis Structure Questionnaire (OPD-SQS), the short version of Experience in Close Relationship-revised (ECR-R-D), and the Brief Symptom Inventory-18 (BSI 18) to determine the level of personality functioning, attachment patterns, and symptom load. RESULTS: We observed positive correlations between personality difficulties, insecure attachment, and symptom load in patients with BD. A low level of structural integration and an insecure attachment style in patients with BD were accompanied by a significantly higher symptom load (r = 0.66, p ≤ 0.01). Interestingly, there were no significant differences in the structural integration (T(1.44) = -0.93, p = 0.357) and in the attachment style attachment related avoidance: (T(1,44) = 1.50, p = 0.140); attachment related anxiety (T(1,44) = -0.781, p = 0.439) of study participants with BD when compared to the normative value of the general population. LIMITATIONS: Our limitations are the small sample size of our group and the lack of a control group. CONCLUSION: In general, our results suggest that there is a link between personality structure and affective dynamics including depressive, anxiety, and somatization symptoms in BD. These findings underline the increasing importance of assessing personality structure and attachment for diagnosis and treatment planning of BD.
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Obesity and weight gain in bipolar disorder (BD) have multifactorial underlying causes such as medication side effects, atypical depressive symptomatology, genetic variants, and disturbances in the neuro-endocrinal system. Therefore, we aim to explore the associations between food craving (FC), clinical parameters, psychotropic medication, and appetite-related hormones. In this cross-sectional investigation, 139 individuals with BD and 93 healthy controls (HC) completed the food craving inventory (FCI). In addition, blood samples (including leptin and acylated ghrelin) were analyzed and sociodemographic and anthropometric data were collected. Individuals with BD reported higher frequencies of total FC as well as craving for fat and fast food than HC. Additionally, we found a significant negative correlation between FC and ghrelin levels in BD. Smokers with BD reported significantly more craving for high fat foods than non-smokers. Age was significantly associated with FC independent of group. Individuals with BD taking olanzapine and quetiapine reported higher frequencies of craving for sweet food, while patients currently taking lithium reported less total FC compared to those without lithium therapy. Likewise, patients currently taking valproate reported less total FC and less craving for sweets than those not taking valproate. FC appears to be of clinical relevance in individuals with BD. Contrary to previous data, this does not seem to be a female phenomenon only and might encompass more than the specific craving for carbohydrates. Although due to the cross sectional design, causality cannot be determined, the association between depressive symptomatology and fast food craving warrants further research.
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Apetite , Transtorno Bipolar/fisiopatologia , Fissura , Hormônios , Acilação , Adulto , Antropometria , Estudos Transversais , Fast Foods , Feminino , Grelina , Humanos , Leptina , Masculino , Pessoa de Meia-Idade , não Fumantes , Obesidade , Fumantes , Ácido Valproico , Aumento de Peso , Adulto JovemRESUMO
BACKGROUND & OBJECTIVE: The kynurenine pathway is involved in inflammatory diseases. Alterations of this pathway were shown in psychiatric entities as well. The aim of this study was to determine whether specific changes in kynurenine metabolism are associated with current mood symptoms in bipolar disorder. METHODS: Sum scores of the Hamilton Depression Scale, Beck Depression Inventory, and Young Mania Rating Scale were collected from 156 bipolar individuals to build groups of depressive, manic and euthymic subjects according to predefined cut-off scores. Severity of current mood symptoms was correlated with activities of the enzymes kynurenine 3-monooxygenase (ratio of 3-hydroxykynurenine/ kynurenine), kynurenine aminotransferase (ratio of kynurenic acid/ kynurenine) and kynureninase (ratio of 3-hydroxyanthranilic acid/ 3-hydroxykynurenine), proxied by ratios of serum concentrations. RESULTS: Individuals with manic symptoms showed a shift towards higher kynurenine 3-monooxygenase activity (χ2 = 7.14, Df = 2, p = .028), compared to euthymic as well as depressed individuals. There were no differences between groups regarding activity of kynurenine aminotransferase and kynureninase. Within the group of depressed patients, Hamilton Depression Scale and kynurenine aminotransferase showed a significant negative correlation (r = -0.41, p = .036), displaying lower metabolism in the direction of kynurenic acid. DISCUSSION: Depression severity in bipolar disorder seems to be associated with a decreased synthesis of putative neuroprotective kynurenic acid. Furthermore, higher kynurenine 3-monooxygenase activity in currently manic individuals indicates an increased inflammatory state within bipolar disorder with more severe inflammation during manic episodes. The underlying pathophysiological mechanisms of the different affective episodes could represent parallel mechanisms rather than opposed processes.
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Transtorno Bipolar/metabolismo , Depressão/metabolismo , Cinurenina/metabolismo , Transtornos do Humor/metabolismo , Adulto , Transtorno Bipolar/sangue , Depressão/sangue , Feminino , Humanos , Cinurenina/sangue , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/sangueRESUMO
Cognitive dysfunction is a prominent feature of psychiatric disorders. Studies have shown that systemic low-grade inflammation is crucial in the development of cognitive deficits across psychiatric disorders. The aim of this study was to further examine the role of inflammation and inflammatory mediators in cognitive function in psychiatric disorders. This study included 364 inpatients (53% females) with International Classification of Diseases (ICD)-10 F3 (affective disorders) and F4 (neurotic, stress-related, and somatoform disorders) diagnoses. The mean age was 52 years (22 to 69 years) and the median body mass index was 27.6. Cognitive function was assessed with the Color-Word Interference Test after Stroop and the Trail-Making Test A/B. Multiple linear regression models were calculated to assess the predictive value of C-reactive protein and the kynurenine/tryptophan ratio on cognitive function controlling for age, sex, education, premorbid verbal intelligence quotient illness duration, depressive symptoms, and obesity-related parameters (e.g., body mass index, high-density lipoprotein). Our data confirm that in patients with psychiatric disorders, C-reactive protein serum concentration is a relevant and important predictor of Trail-Making Test B performance, measuring cognitive flexibility. The effect size of this association did not change much after adding clinical and metabolic variables into the regression model. The kynurenine/tryptophan ratio was not related to cognitive test scores. The involvement of C-reactive protein as a peripheral inflammatory marker in cognitive flexibility and psychomotor processing speed in psychiatric illness can be concluded.
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Proteína C-Reativa/análise , Disfunção Cognitiva/sangue , Mediadores da Inflamação/sangue , Transtornos Mentais/sangue , Teste de Sequência Alfanumérica , Adulto , Idoso , Biomarcadores/sangue , Disfunção Cognitiva/psicologia , Feminino , Humanos , Inflamação , Cinurenina/sangue , Modelos Lineares , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valor Preditivo dos Testes , Desempenho Psicomotor , Tempo de Reação , Teste de Stroop , Triptofano/sangue , Adulto JovemRESUMO
BACKGROUND/AIMS: Recent evidence indicates that the intake of atypical antipsychotics (AAP) is associated with gray matter abnormalities in patients with psychiatric disorders. We explored if patients with bipolar disorder (BD) who are medicated with AAP exhibit total gray matter volume (TGV) reduction compared to BD individuals not medicated with AAP and healthy controls (HC). METHODS: In a cross-sectional design, 124 individuals with BD and 86 HC underwent 3T-MRI of the brain and clinical assessment as part of our BIPFAT-study. The TGV was estimated using Freesurfer. We used univariate covariance analysis (ANCOVA) to test for normalized TGV differences and controlled for covariates. RESULTS: ANCOVA results indicated that 75 BD individuals taking AAP had significantly reduced normalized TGV as compared to 49 BD not taking AAP (Fâ¯=â¯9.995, p = .002., Eta = 0.084) and 86 HC (Fâ¯=â¯7.577, p = .007, Eta = 0.046). LIMITATIONS: Our cross-sectional results are not suited to draw conclusions about causality. We have no clear information on treatment time and baseline volumes before drug treatment in the studied subjects. We cannot exclude that patients received different psychopharmacologic medications prior to the study point. We did not included dosages into the calculation. Many BD individuals received combinations of psychopharmacotherapy across drug classes. We did not have records displaying quantitative alcohol consumption and drug abuse in our sample. CONCLUSIONS: Our data provide further evidence for the impact of AAP on brain structure in BD. Longitudinal studies are needed to investigate the causal directions of the proposed relationships.
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Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/patologia , Substância Cinzenta/patologia , Adulto , Encéfalo/patologia , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
Major depressive disorder (MDD) is a prevalent disease, in which one third of sufferers do not respond to antidepressants. Probiotics have the potential to be well-tolerated and cost-efficient treatment options. However, the molecular pathways of their effects are not fully elucidated yet. Based on previous literature, we assume that probiotics can positively influence inflammatory mechanisms. We aimed at analyzing the effects of probiotics on gene expression of inflammation genes as part of the randomized, placebo-controlled, multispecies probiotics PROVIT study in Graz, Austria. Fasting blood of 61 inpatients with MDD was collected before and after four weeks of probiotic intake or placebo. We analyzed the effects on gene expression of tumor necrosis factor (TNF), nuclear factor kappa B subunit 1 (NFKB1) and interleukin-6 (IL-6). In IL-6 we found no significant main effects for group (F(1,44) = 1.33, p = ns) nor time (F(1,44) = 0.00, p = ns), but interaction was significant (F(1,44) = 5.67, p < 0.05). The intervention group showed decreasing IL-6 gene expression levels while the placebo group showed increasing gene expression levels of IL-6. Probiotics could be a useful additional treatment in MDD, due to their anti-inflammatory effects. Results of the current study are promising, but further studies are required to investigate the beneficial effects of probiotic interventions in depressed individuals.
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Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/genética , Expressão Gênica/efeitos dos fármacos , Interleucina-6/sangue , Interleucina-6/genética , Probióticos/farmacologia , Adulto , Afeto/efeitos dos fármacos , Áustria , Cognição/efeitos dos fármacos , Transtorno Depressivo Maior/psicologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Expressão Gênica/genética , Humanos , MasculinoRESUMO
Objectives: An important aspect of bipolar disorder (BD) research is the identification of biomarkers pertaining to the somatic health state. The branched-chain essential amino acids (BCAAs), viz valine, leucine and isoleucine, have been proposed as biomarkers of an individual's health state, given their influence on protein synthesis and gluconeogenesis inhibition.Methods: BCAA levels of 141 euthymic/subsyndromal individuals with BD and 141 matched healthy controls (HC) were analysed by high-pressure lipid chromatography and correlated with clinical psychiatric, anthropometric and metabolic parameters.Results: BD and HC did not differ in valine and isoleucine, whereas leucine was significantly lower in BD. Furthermore, correlations were found between BCAAs and anthropometric and glucose metabolism data. All BCAAs correlated with lipid metabolism parameters in females. There were no associations between BCAAs and long-term clinical parameters of BD. A negative correlation was found between valine and Hamilton Depression-Scale, and Beck Depression Inventory II, in male individualsConclusions: Our results indicate the utility of BCAAs as biomarkers for the current state of health, also in BD. As BD individuals have a high risk for overweight/obesity, in association with comorbid medical conditions (e.g. cardiovascular diseases or insulin resistance), health state markers are urgently required. However, no illness-specific associations were found in this euthymic/subsyndromal BD group.