Medication Use is Associated with Distinct Microbial Features in Anxiety and Depression.

This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive disorder (MDD), as defined by DSM-IV or V criteria. The study also examined the influence of medication use, particularly antidepressants and/or anxiolytics, classified through the Anatomical Therapeutic Chemical (ATC) Classification System, on the gut microbiota. Both 16S rRNA gene amplicon sequencing and shallow shotgun sequencing were performed on DNA extracted from 666 fecal samples from the Tulsa-1000 and NeuroMAP CoBRE cohorts. The results highlight the significant influence of medication use; antidepressant use is associated with significant differences in gut microbiota beta diversity and has a larger effect size than NPD diagnosis. Next, specific microbes were associated with ANXD and MDD, highlighting their potential for non-pharmacological intervention. Finally, the study demonstrated the capability of Random Forest classifiers to predict diagnoses of NPD and medication use from microbial profiles, suggesting a promising direction for the use of gut microbiota as biomarkers for NPD. The findings suggest that future research on the gut microbiota's role in NPD and its interactions with pharmacological treatments are needed.

Personalized Definition of Surgical Targets in Major Depression and Obsessive-Compulsive Disorder: A Potential Role for Low-Intensity Focused Ultrasound?

Major Depressive Disorder (MDD) and Obsessive-Compulsive Disorder (OCD) are common and potentially incapacitating conditions. Even when recognized and adequately treated, in over a third of patients with these conditions the response to first-line pharmacological and psychotherapeutic measures is not satisfactory. After more assertive measures including pharmacological augmentation (and in the case of depression, transcranial magnetic stimulation, electroconvulsive therapy, or treatment with ketamine or esketamine), a significant number of individuals remain severely symptomatic. In these persons, different ablation and deep-brain stimulation (DBS) psychosurgical techniques have been employed. However, apart from the cost and potential morbidity associated with surgery, on average only about half of patients show adequate response, which limits the widespread application of these potentially life-saving interventions. Possible reasons are considered for the wide variation in outcomes across different series of patients with MDD or OCD exposed to ablative or DBS psychosurgery, including interindividual anatomical and etiological variability. Low-intensity focused ultrasound (LIFU) is an emerging technique that holds promise in its ability to achieve anatomically circumscribed, noninvasive, and reversible neuromodulation of deep brain structures. A possible role for LIFU in the personalized presurgical definition of neuromodulation targets in the individual patient is discussed, including a proposed roadmap for clinical trials addressed at testing whether this technique can help to improve psychosurgical outcomes.

Elevated peripheral inflammation is associated with attenuated striatal reward anticipation in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is the leading cause of years lived with disability worldwide, and up to 40% of individuals with MDD do not respond to current treatments. Studies suggest that peripheral inflammation plays an important role in the striatal mesolimbic dopamine pathway and corticostriatal reward circuitry in MDD. Although MDD patients show blunted striatal responses to reward, the link between degree of inflammation and attenuation of reward processing is unclear. We investigated whether MDD patients with elevated peripheral inflammation exhibit attenuated reward responses to enhance our understanding of MDD pathophysiology and develop more effective treatments for current non-responders. METHODS: MDD subjects varying on serum C-reactive protein (CRP) concentrations (MDD-High CRP, >3 mg/L, n = 44; MDD-Low CRP, <3 mg/L, n = 44) and healthy comparisons (HC, n = 44) completed a monetary incentive delay (MID) task and provided blood samples to measure inflammation-related markers. MDD-High and MDD-Low were propensity score-matched on age, sex, body mass index (BMI), smoking status, exercise and MID task head motion. Percent change in blood oxygen level-dependent (BOLD) signal during anticipation of wins and losses was extracted from bilateral nucleus accumbens, dorsal caudate and dorsolateral putamen regions of interest (ROIs). A linear mixed-effects model was used to test group (MDD-High, MDD-Low and HC), condition (large-win, small-win and no win), and their interaction for these ROIs as well as whole-brain voxelwise data. Analyses also tested group differences in inflammatory mediators. Correlations were used to explore the relationship between inflammatory mediators and brain regions showing differences between MDD-High and MDD-Low. RESULTS: MDD-High exhibited: (a) lower BOLD signal change in dorsal caudate, thalamus, left insula and left precuneus during anticipation of small wins than MDD-Low; and (b) higher serum soluble intercellular adhesion molecule 1 (sICAM-1) and interleukin 6 (IL-6) concentrations than MDD-Low and HC. MDD as a whole, regardless of CRP-based inflammation, exhibited: (a) lower precuneus BOLD signal change to large wins than HC; and (b) higher Interleukin 1 receptor antagonist (IL-1ra), macrophage-derived chemokine (MDC) and macrophage inflammatory protein-1 alpha (MIP-1α) concentrations than HC. Higher serum sICAM-1 concentrations were associated with lower caudate BOLD signal change to small wins only within the MDD-High group. CONCLUSION: Within MDD patients, high inflammation (CRP, sICAM-1) was linked to reduced striatal activation recruited to discriminate intermediate reward magnitudes. These findings support an association between levels of peripheral inflammation and the degree of reward-related activation in individuals with MDD. REGISTRATION OF CLINICAL TRIALS: The ClinicalTrials.gov identifier for the clinical protocol associated with data published in this current paper is NCT02450240, "Latent Structure of Multi-level Assessments and Predictors of Outcomes in Psychiatric Disorders."

Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI): neuropsychological evolution profile after one-year follow up / Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI): evolução do perfil neuropsicológico depois de um ano de seguimento

ABSTRACT The Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI) study is a longitudinal prospective cohort of 50 participants at a single institution in Buenos Aires, Argentina. Longitudinal assessments on a neuropsychological test battery were performed on 15 controls, 24 mild cognitive impairment (MCI) patients and 12 Alzheimer's disease (AD) dementia patients. In our study population, there was a high prevalence of positive AD biomarkers in the AD group, 92.3% (12/13); and a low prevalence in the normal controls, 20%; almost half (48%) of the patients diagnosed with MCI had positive amyloid detection. After a one year, the significant differences found at baseline on neuropsychological testing were similar at the follow-up assessment even though the AD group had significantly altered its functional performance (FAQ and CDR). The exception was semantic fluency, which showed greater impairment between the AD group and MCI and normal controls respectively. For these tests, the addition of AD biomarkers as a variable did not significantly alter the variations previously found for the established clinical group's model. Finally, the one-year conversion rate to dementia was 20% in the MCI cohort.

RESUMO El estudio de Argentina-Alzheimer's Disease Neuroimaging Initiative (Arg-ADNI) es una cohorte prospectiva de 50 pacientes seguidos en una misma institución. Fueron evaluados cognitivamente 15 controles normales (CN), 24 sujetos con deterioro cognitivo leve (DCL) y 12 con demencia tipo Alzheimer (DTA) leve. En los DTA, 92,3% tuvieron biomarcadores positivos para Alzheimer y 20% en los CN. Casi la mitad de los DCL presentaron biomarcadores positivos. Después de un año de seguimiento, la diferencias significativas halladas en la visita de inicio en las pruebas cognitivas fueron similares al año aunque los DTA tuvieron empeoramiento funcional medido en el FAQ y CDR. La excepción fue la fluencia semántica, la cual mostró mayor declinación entre DTA y los demás grupos. La incorporación de los biomarcadores como variable no alteró significativamente los hallazgos de grupo. La tasa de conversión a demencia anual fue del 20%.

El nuevo DSM-V o Kraepelin antes de su madurez: el oxímoron del "Trastorno esquizoafectivo" / [DSM-5: a young Kraepelin and the \"schizoaffective disorder\" oxymoron].

The last several years have witnessed the accumulation of evidence suggesting that the Kraepelinian binary system of classification of the psychoses does not capture their true nature, as Kraepelin himself had cautioned in his late years. The long-awaited new edition of the APA’s Diagnostic and Statistical Manual will in all probability incorporate symptom dimensions and suppress schizophrenia subtypes. However, the initial Kraepelinian conceptualization of the psychoses is maintained, along with the diagnostic category that epitomizes its obsolescence: schizoaffective disorder. We hereby make a brief critical appraisal of this fact, pointing out how the current classification system might be an obstacle to much-needed advances in this knowledge field.

Nonlinear relationship between electrodermal activity and heart rate variability in patients with acute schizophrenia.

We investigated to what degree tonic skin conductance levels (SCL) and cardiac autonomic dysfunction are interrelated in schizophrenia. Heart rate variability (HRV) and SCL were simultaneously assessed in 18 unmedicated patients and 18 controls matched for age, sex, weight, and smoking habits. For comparison to prior studies, phasic sympathetic skin responses (SPR) were also recorded. Compared to controls, patients had prolonged SPR latency and reduced SPR amplitude with a right-greater-than-left asymmetry, which was inversely correlated with positive symptoms. An autonomic imbalance was reflected in linear and nonlinear measures of HRV and increased SCL. Patients showed a stronger nonlinear association between SCL and heart rate than controls. HRV and SCL findings were strongly affected by group differences in breathing rate. Stronger HRV-SCL coupling in patients may suggest augmented sympathetic modulation in schizophrenia.

Mood, Th-1/Th-2 cytokine profile, and autonomic activity in older adults with acute/decompensated heart failure: preliminary observations.

In order to assess the relationships among mood, peripheral autonomic output and circulating immunoinflammatory mediators in older individuals with decompensated heart failure (CHF), 20 consecutive patients (78+/-7 years, 35% women) admitted to the coronary care unit with a clinical diagnosis of acute/decompensated CHF of coronary origin were examined. Mood was evaluated by the 21-item Hamilton Depression Scale (HAM-D). Four patients met the criteria for major depression. Heart rate variability (HRV) analysis and the levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-6 and IL-10 were measured within 24-72 h of admission. A significant positive relationship between score in HAM-D and serum IL-6 levels was detected with a similar trend as far as IL-2 levels. Circulating IL-2 levels were strongly associated with the HRV L/H quotient, an index of increased sympathetic and/or decreased parasympathetic thoracic activity. A negative correlation between vagal activity (as assessed by HRV) and IL-4 occurred. Neither TNF-alpha nor IL-10 were detectable in this group of elderly patients. The results add to the concept that mood and autonomic unbalance are associated with increased systemic inflammation in old patients with decompensated CHF, a potential mechanism for mood-related worsened prognosis of heart failure at an advanced age.

Depresión y enfermedad cardiovascular / Depression and cardiovascular disease

El presente estudio revisa las interacciones entre enfermedad cardiovascular y depresión. En pacientes con enfermedad cardiovascular conocida, la depresión empeora el pronóstico, siendo esto especialmente evidente en sobrevivientes de infarto de miocardio. Los individuos que desarrollan depresión parecen asimismo tener un riesgo aumentado de desarrollo ulterior de enfermedad cardiovascular. Se ofrece una hipótesis que vincula ambos cuadros y se revisan estrategias de manejo de la depresión en pacientes cardiológicos

Some neurovegetative correlates of Minnesota Multiphasic Personality Inventory (MMPI)

In 57 patients with psicovegetative disorders and abnormal MMPI, abnormality in MMPI scales indicating hypochondriasis, hysteria, gender deviant, paranoia, psychastenia, schizophrenia, hypomania or introversion was accompanied by increased plasma catecholamine levels and/or responses to hypoglycemia or by an increased cardiovascular reactivity. A high depression scale was associated with lower plasma catecholamine levels. Blunted plasma growth hormone responses to hypoglycemia were found in abnormal hypomania scale, and augmented responses of plasma cortisol in abnormal hysteria or schizophrenia scales. Paranoia and hypomania traits correlated with absence of morning-evening differences in blood cortisol levels. Electrodermal responses compatible with increased sympathetic activity correlated with high hysteria, gender, paranoia, schizophrenia or hypomania MMPI scales. This study indicates that most psychopathological traits in MMPI are accompanied by humoral and/or electrophysiological signs of abnormality of the autonomic nervous system