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Neurosciences. Biological psychiatry. Neuropsychiatry and RC321-571

Abstract Autism spectrum disorder (ASD) is associated with a diverse range of etiological processes, including both genetic and non-genetic causes. For a plurality of individuals with ASD, it is likely that the primary causes involve multiple common inherited variants that individually account for only small levels of variation in phenotypic outcomes. This genetic landscape creates a major challenge for detecting small but important pathogenic effects associated with ASD. To address similar challenges, separate fields of medicine have identified endophenotypes, or discrete, quantitative traits that reflect genetic likelihood for a particular clinical condition and leveraged the study of these traits to map polygenic mechanisms and advance more personalized therapeutic strategies for complex diseases. Endophenotypes represent a distinct class of biomarkers useful for understanding genetic contributions to psychiatric and developmental disorders because they are embedded within the causal chain between genotype and clinical phenotype, and they are more proximal to the action of the gene(s) than behavioral traits. Despite their demonstrated power for guiding new understanding of complex genetic structures of clinical conditions, few endophenotypes associated with ASD have been identified and integrated into family genetic studies. In this review, we argue that advancing knowledge of the complex pathogenic processes that contribute to ASD can be accelerated by refocusing attention toward identifying endophenotypic traits reflective of inherited mechanisms. This pivot requires renewed emphasis on study designs with measurement of familial co-variation including infant sibling studies, family trio and quad designs, and analysis of monozygotic and dizygotic twin concordance for select trait dimensions. We also emphasize that clarification of endophenotypic traits necessarily will involve integration of transdiagnostic approaches as candidate traits likely reflect liability for multiple clinical conditions and often are agnostic to diagnostic boundaries. Multiple candidate endophenotypes associated with ASD likelihood are described, and we propose a new focus on the analysis of “endophenotype trait domains” (ETDs), or traits measured across multiple levels (e.g., molecular, cellular, neural system, neuropsychological) along the causal pathway from genes to behavior. To inform our central argument for research efforts toward ETD discovery, we first provide a brief review of the concept of endophenotypes and their application to psychiatry. Next, we highlight key criteria for determining the value of candidate endophenotypes, including unique considerations for the study of ASD. Descriptions of different study designs for assessing endophenotypes in ASD research then are offered, including analysis of how select patterns of results may help prioritize candidate traits in future research. We also present multiple candidate ETDs that collectively cover a breadth of clinical phenomena associated with ASD, including social, language/communication, cognitive control, and sensorimotor processes. These ETDs are described because they represent promising targets for gene discovery related to clinical autistic traits, and they serve as models for analysis of separate candidate domains that may inform understanding of inherited etiological processes associated with ASD as well as overlapping neurodevelopmental disorders.

Cascade Training, Task-sharing, Primary healthcare, Low- and middle-income countries, Perinatal depression, Neurosciences. Biological psychiatry. Neuropsychiatry, and RC321-571

Abstract Background Task-shared care is a demonstrated approach for integrating mental health into maternal and child healthcare (MCH) services. Training and continued support for frontline providers is key to the success of task sharing initiatives. In most settings this is provided by mental health specialists. However, in resource constrained settings where specialists are in short supply, there is a need to explore alternative models for providing training and supportive supervision to frontline maternal care providers. This paper reports on the impact of a cascade training (train-the-trainers) approach in improving the knowledge and attitudes of primary healthcare workers (PHCW) to perinatal depression. Methods Senior primary health care providers selected from across participating local government areas were trained to provide training to other PHCWs. The training sessions facilitated by these trainers were observed and rated for fidelity by specialist trainers, while the trainees provided their impression of and satisfaction with the training sessions using predesigned assessment forms. Training outcomes assessed included knowledge of depression (using mhGAP training questions and knowledge of depression questionnaire) and attitude towards providing care for depression (revised depression attitude questionnaire (R-DAQ)) measured pre and post training as well as six months after training. Results Trainees were 198 PHCWs (94.4% female), who routinely provide MCH services in 28 selected primary care clinics and had between 6- and 34-years’ experience. Training was provided by 11 trained trainers who were general physicians or senior nurses. Training sessions were rated high in fidelity and on training style. Sessions were rated excellent by 77.8% of the trainees with the trainers described as knowledgeable, effective and engaging. Knowledge of depression mean score improved from a pre-training level of 12.3 ± 3.5 to 15.4 ± 3.7, immediately post-training and 14.7 ± 3.2, six months post-training (both comparisons: p

Special aspects of education, LC8-6691, Neurosciences. Biological psychiatry. Neuropsychiatry, and RC321-571

Abstract The income-achievement gap is a significant and stubborn problem in the United States, which has been exacerbated by the Covid-19 pandemic. In this article, we link two emerging literatures that have historically been disparate: the neurobiology of poverty as a form of early life stress, and research on educational policies with the potential to reduce SES-based disparities in academic achievement. In doing so, we (1) integrate the literature on poverty-related mechanisms that contribute to early life stress, alter neurobiology, and lead to educational inequities, and (2) based on this research, highlight policies and practices at the school/classroom level and broader structural level that have the potential to address the problem of inequity in our educational systems. We emphasize that educational inequity is a systemic issue, and its resolution will require coordination of local, state, and national policies.

Butyrate, Inflammation, Hypothalamus, PCOS, GABA, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, and QP351-495

Abstract Polycystic ovarian syndrome (PCOS) is a known endocrine disorder that has affected many women of childbearing age, and is accompanied by various neurodegenerative conditions. Hence, this study investigates the impact of butyrate in reversing hypothalamic-related disorder, possibly through γ aminobutyric acid (GABA) in a rat model of PCOS. Eight-week-old female Wistar rats were allotted into four groups (n = 5), which include control, butyrate, letrozole, and letrozole + butyrate groups. PCOS was induced by administering 1 mg/kg of letrozole (oral gavage) for 21 days. After confirmation of PCOS, 200 mg/kg of butyrate (oral gavage) was administered for 6 weeks. Rats with PCOS were characterized by elevated levels of plasma insulin and testosterone. Increases in plasma and hypothalamic triglyceride levels, inflammatory biomarker (SDF-1), apoptotic marker (caspase-6), and decreased plasma GnRH were observed. Additionally, a decrease in hypothalamic GABA was revealed. Nevertheless, the administration of butyrate attenuated these alterations. The present study suggests that butyrate ameliorates hypothalamic inflammation in an experimental model of PCOS, a beneficial effect that is accompanied by enhanced GABA production.

Mental health, Muslim, Help-seeking, Barriers, Beliefs, CBT, Neurosciences. Biological psychiatry. Neuropsychiatry, and RC321-571

Abstract Background Muslims experience the lowest recovery rate from mental health difficulties across all religious groups. The aim of this research is to understand the barriers that prevent Muslims from accessing Cognitive Behavioral Therapy (CBT) and the extent to which these may vary across country of residence. Methods Systematic review and thematic synthesis for quantitative, qualitative, and mixed methods studies published in English and Arabic informed by the SPIDER search tool. Methodological quality and risk of bias of included papers were critically appraised independently according to the Mixed Methods Appraisal Tool. Results A search of seven databases in the Arabic and English language yielded 3836 studies with 210 studies assessed for eligibility. Employing the Mixed Methods Appraisal Tool resulted in 14 studies included in the thematic synthesis. Seven studies adopted a qualitative methodology employing semi-structured interviews and seven were quantitative descriptive studies. Conclusions Muslim communities experience barriers accessing Cognitive Behavioral Therapy at the level of the individual, culture, provider and management. The main barriers were experienced at the individual level which was dominated by the influence of Islam regarding the cause of mental health difficulties, which also influenced the way in which difficulties were managed. Systematic review registration: PROSPERO and registration number: CRD42020192854.

Brain injury, Cognitive assessment, Classification, Immersive virtual reality, Unilateral visuospatial neglect, Neurosciences. Biological psychiatry. Neuropsychiatry, and RC321-571

Abstract Background In neurorehabilitation, problems with visuospatial attention, including unilateral spatial neglect, are prevalent and routinely assessed by pen-and-paper tests, which are limited in accuracy and sensitivity. Immersive virtual reality (VR), which motivates a much wider (more intuitive) spatial behaviour, promises new futures for identifying visuospatial atypicality in multiple measures, which reflects cognitive and motor diversity across individuals with brain injuries. Methods In this pilot study, we had 9 clinician controls (mean age 43 years; 4 males) and 13 neurorehabilitation inpatients (mean age 59 years; 9 males) recruited a mean of 41 days post-injury play a VR visual search game. Primary injuries included 7 stroke, 4 traumatic brain injury, 2 other acquired brain injury. Three patients were identified as having left sided neglect prior to taking part in the VR. Response accuracy, reaction time, and headset and controller raycast orientation quantified gameplay. Normative modelling identified the typical gameplay bounds, and visuospatial atypicality was defined as gameplay beyond these bounds. Results The study found VR to be feasible, with only minor instances of motion sickness, positive user experiences, and satisfactory system usability. Crucially, the analytical method, which emphasized identifying 'visuospatial atypicality,' proved effective. Visuospatial atypicality was more commonly observed in patients compared to controls and was prevalent in both groups of patients—those with and without neglect. Conclusion Our research indicates that normative modelling of VR gameplay is a promising tool for identifying visuospatial atypicality after acute brain injury. This approach holds potential for a detailed examination of neglect.

Cognitive complaints, Objective cognitive trajectories, Depression, Comorbidity-polypharmacy, Loneliness, Blood-based AD biomarkers, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, and RC346-429

Abstract Background Cognitive complaints are often regarded as an early sign of Alzheimer’s disease (AD) but may also occur in several other conditions and contexts. This study examines the correlates of cognitive complaint trajectories over a 5-year period in individuals who shared similar objective cognitive trajectories. Methods We analyzed a subsample (n = 1748) of the MEMENTO cohort, consisting of individuals with subjective cognitive decline or mild cognitive impairment at baseline. Participants were stratified based on their latent MMSE trajectory over a 5-year period: “high and increasing,” “subtle decline,” and “steep decline.” Within each of the three strata, we used a latent-class longitudinal approach to identify distinct trajectories of cognitive complaints. We then used multiple logistic regressions to examine the association between these complaint trajectories and several factors, including AD biomarkers (blood pTau/Aβ42 ratio, cortical thickness, APOE genotype), anxiety, depression, social relationships, a comorbidity-polypharmacy score, and demographic characteristics. Results Among participants with high and increasing MMSE scores, greater baseline comorbidity-polypharmacy scores (odds ratio (OR) = 1.30, adjusted p = 0.03) were associated with higher odds of moderate and increasing cognitive complaints (as opposed to mild and decreasing complaints). Baseline depression and social relationships also showed significant associations with the complaint pattern but did not survive correction for multiple comparisons. Among participants with subtle decline in MMSE scores, greater baseline depression (OR = 1.76, adjusted p = 0.02) was associated with higher odds of moderate and increasing cognitive complaints (versus mild and decreasing). Similarly, baseline comorbidity-polypharmacy scores and pTau/Aβ42 ratio exhibited significant associations, but they did not survive correction. Among participants with a steep decline in MMSE scores, greater baseline comorbidity-polypharmacy scores increased the odds of moderate complaints (versus mild, OR = 1.38, unadjusted p = 0.03, adjusted p = 0.32), but this effect did not survive correction for multiple comparisons. Conclusions Despite similar objective cognitive trajectory, there is heterogeneity in the subjective perception of these cognitive changes. This perception was explained by both AD-related and, more robustly, non-AD-related factors. These findings deepen our understanding of the multifaceted nature of subjective cognitive complaints in individuals at risk for dementia and underscore the importance of considering a range of factors when interpreting cognitive complaints.

Aging, Cognitive stimulation, Quality of life, Reminiscence, Specific memory, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, and RC346-429

Abstract Background There are increasing reports on the cognitive and emotional benefits of positive reminiscence therapy in older people. The objective of this study is to assess the differential improvement of the quality of life for older people in different vital situations (three different types of aging) and from different countries by implementing a positive reminiscence therapy program (REMPOS). Methods The participants were 144 older adults above the age of 65, 77 participants from Spain (45 experimental groups, 32 control groups) and 67 from Mexico (34 experimental groups, 33 control groups). The participants were recruited from nursing and retirement homes. A factorial randomized design with pre–post measurement with three independent variables: country (Mexico, Spain), condition (experimental, control), and types of aging (healthy aging, HA., mild cognitive impairment, MCI., Alzheimer’s disease, AD). The experimental groups received REMPOS therapy and control groups received standard cognitive stimulation program. The quality of life was measured with the Life Satisfaction Inventory for adults (LSI-A) and autobiographical memory test (AMT) before and after REMPOS therapy. Results The REMPOS intervention showed significantly higher positive effects than the control condition on the recall of specific positive memories across countries and types of aging, except for the Spanish MCI group. Life satisfaction in the Alzheimer’s and MCI group only improved with REMPOS in the Mexican sample. Conclusions The REMPOS effects showed generalizable effects across countries, but the cross-cultural differences shown highlight the necessity of running studies to test those differential effects.

Retention, Alzheimer’s disease, Clinical trials, Trial duration, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, and RC346-429

Abstract Background Participant retention is a key factor that affects clinical trial integrity. Trial protocols estimate attrition as a function of sample size calculations. Alzheimer’s disease (AD) is an area of active treatment development. We aimed to quantify the association between trial duration and completion rates and provide guidance for estimating attrition in AD trial protocols. Methods Using the Alzforum and ClinicalTrials.gov databases, we analyzed retention data from 125 mild-to-moderate AD and 12 mild cognitive impairment (MCI) clinical trials. We compared the rates of completion between trial arms (active vs. control) and ran regression models to test the hypothesis that trials with longer study duration have lower trial completion using all available data and restricting to placebo data. Our primary outcome was the odds of trial completion for a 6-month increase in trial duration. From the regression model, we estimated the proportion of participants completing 6-, 12-, and 18-month trials. Results We found that 21 (17%) mild-to-moderate AD trials and 1 (8%) MCI trial demonstrated greater dropout in treatment compared to placebo arms. For every 6-month increase in trial duration, there was a 27% decrease in the odds of trial completion (OR = 0.73; 95% CI 0.66, 0.81; p

Cerebral sparganosis, Craniotomy, Refractory epilepsy, Spirometra mansoni, Tunnel sign, Surgery, RD1-811, Neurosciences. Biological psychiatry. Neuropsychiatry, and RC321-571

Abstract Spirometra is larval cestode that involve humans as accidental intermediate hosts. Although the incidence of central nervous system infestation with sparganum is low, the diagnosis of the disease can cause delayed with an increased possibility of severe brain damage and neurological deficits. The present case reports a case of a 19-year male student and describes the imaging findings, histopathological characteristics, and management of this rare disease. The patient was treated surgically with good outcome.

Trigeminal neuralgia, Microvascular decompression, Trigeminal nerve, Neuralgic pain, Tic douloureux, Surgery, RD1-811, Neurosciences. Biological psychiatry. Neuropsychiatry, and RC321-571

Abstract Aim We retrospectively analyse and review the results of microvascular decompression performed for trigeminal neuralgia. We also discuss the surgical nuances, complication avoidance and compare our results with other reported studies. Materials and methods This is a retrospective study in which the data of eighty-four patients who underwent microvascular decompression for trigeminal neuralgia in the last ten years from 2013 till May 2023 at our institute (Neuron hospital and SSG Hospital, Vadodara, India) was reviewed. The preoperative pain characteristics, radiology reports and the degree and duration of post-operative pain relief and neurologic outcome was assessed. MRI was done preoperatively in all the cases to rule out a secondary cause for trigeminal neuralgia. All the cases of secondary trigeminal neuralgia were excluded from the study. A favourable outcome was defined as a post-operative Barrow Neurological Institute pain intensity score of 1. Results Eighty patients had excellent immediate postoperative pain relief without any need for medications. None of these patients have developed any recurrence of pain till date. Four operated patients did not experience any pain relief after surgery. Conclusion Microvascular decompression for trigeminal neuralgia is a safe and effective procedure which treats the root cause of the disease and hence provides good long term pain relief.

Rheumatoid arthritis, Cervical spine, Instability, Neurological symptoms, Surgery, RD1-811, Neurosciences. Biological psychiatry. Neuropsychiatry, and RC321-571

Abstract Introduction Rheumatoid arthritis (RA) is a chronic, progressive, and systemic disease that broadly affects connective tissues, especially synovial joints. The aim of this study was to investigate the prevalence of cervical spine instability in patients diagnosed with RA. Material and methods Fifty patients with rheumatoid arthritis referred to Imam Khomeini Hospital in Urmia were selected by the census. After taking a history, the neck X-ray was taken from the lateral view in static, flexion, and extension. Results Among 50 patients, 11 were male (22%) and 39 were female (78%). The average disease duration period was 5.63 ± 5.21 years. 43 patients (86%) had normal AADI, 5 patients (10%) had abnormal dynamic AADI, and 2 patients (4%) had abnormal AADI static. Basilar invagination instability was not found in the studied patients. There was no significant difference in terms of gender between normal and abnormal cases of AADI. Among normal AADI cases, 40 cases (93%) were taking drugs and among abnormal AADI cases, 4 cases (57.1%) were taking drugs and 3 patients (42.9%) were not receiving drug treatment. There is a significant difference between normal and abnormal cases of AADI in terms of drug use. Conclusions In our study, 7 cases of abnormal AADI were found among 50 patients, of which 2 had abnormal static AADI, which indicates the worsening of cervical spine instability. The study also found that those not treated with DMARDS were more likely to have cervical spine instability.

Cervical stenosis, Laminectomy, Lateral mass, Myelopathy, Surgery, RD1-811, Neurosciences. Biological psychiatry. Neuropsychiatry, and RC321-571

Abstract Background Multisegment cervical canal stenosis is one of the most common causes of spinal cord dysfunction. Cervical laminectomy affords direct relief from dorsal stenosis, but many concerns were raised regarding its effect on spinal stability and cervical sagittal alignment. Laminectomy in conjunction with lateral mass screws is aiming to prevent recurrence of stenosis and to achieve much improvement of the cervical spine range of motion and curvature. Objectives To compare the clinical and radiological outcome of laminectomy alone versus laminectomy with lateral mass screw fixation in the treatment of patients with multisegment cervical canal stenosis. Patients and methods A retrospective study conducted on 46 patients with multisegment cervical canal stenosis who were treated between April 2018 and April 2021. Patients were divided into two groups. The 20 cases in group (A) underwent conventional laminectomies and the 26 cases in group (B) underwent laminectomies with lateral mass screw fixation. Operative complications, visual analogue scale (VAS), neurological functional recovery and cervical curvature changes were compared between the two groups. Results Operative times in group A were significantly less than it was in group B (P

Neurosciences. Biological psychiatry. Neuropsychiatry and RC321-571

Abstract Background Increase pressure on arteries branching points and curves (hyperdynamic theory) is the most popular theory to explain the aneurysms formation that augmented by the observation of high incidence of anomalies (either A1 aplasia or hypoplasia) and the anterior communicating artery (ACoA) aneurysms. It still underestimated the correlation between these anatomical anomalies and aneurysm occurrence and its rupture. We aim to estimate the incidence and type of anatomical anomalies of the anterior cerebral circulation, including the A2 segment in patients with ACoA aneurysms and their predictive value for aneurysm occurrence and rupture parallel to the risk of hypertension. Also, we study the impact of these anomalies on the configuration of the aneurysm, including the neck and size. Results A1 hypoplasia and aplasia were significantly higher in AcoA aneurysms group than in the control group (P

Essential tremor, Autonomic function tests, Heart rate variability, Sympathetic skin response, Neurosciences. Biological psychiatry. Neuropsychiatry, and RC321-571

Abstract Background Essential tremor (ET) is a prevalent movement disorder that may be linked to neurodegenerative changes. It is marked by a mix of motor and non-motor symptoms, which include disturbances in the autonomic nervous system. Aim of the study: We aimed to assess autonomic dysfunction in individuals with essential tremor. Thirty patients with essential tremor (Group 1) and 30 age and sex-matched healthy subjects as the control group (Group 2) were recruited. Comprehensive medical and neurological examinations were conducted on all participants, followed by electrophysiological assessments of autonomic function, including heart rate variability (HRV) tests (E/I ratio, Valsalva ratio, 30:15 ratio), adrenergic tests (blood pressure responses to active standing and sustained hand grip), and sympathetic skin response (SSR) tests. Finally, the results of these tests were classified according to the Ewing classification of autonomic failure. Results: The study revealed significant differences between ET patients and the control group. Heart rate variability tests showed a marked difference between the groups. Adrenergic tests, measuring sympathetic innervation, also displayed a significant difference. The sudomotor function test exhibited noteworthy differences in onset latencies and amplitudes in the palm and sole, with ET patients showing prolonged onset latencies and decreased amplitudes. Moreover, the study found a significant correlation between disease severity and autonomic function test results and the Ewing score. Conclusion: The study highlights the presence of autonomic dysfunction in essential tremor patients, with disease severity being associated with the level of autonomic affection, as evidenced by various autonomic function tests and the Ewing score.

Ependymoma, Extramedullary, Intradural, Anaplastic, Spinal, Neurosciences. Biological psychiatry. Neuropsychiatry, and RC321-571

Abstract Background Ependymomas are neuroectodermal tumors that grow from the ependymal cells of the ventricles or the central canal of the spinal cord. When the ependymoma is anaplastic, extramedullary, intradural and multifocal, it is a very rare anatomical entity, same as case described by us. Case presentation A 44-year-old man had been admitted to our hospital for progressive paralysis of both legs over the past 5 weeks. Contrast-enhanced MRI showed intradural extramedullary tumor at T11 with cord compression and an other more little tumor at T6 level, also intradural and extramedullary. The largest lesion was completely removed by laminectomy. Histology documented an anaplastic ependymoma. Contrast-enhanced brain and spinal MRI showed the results of the previous surgery. Conclusion Multifocal intradural extramedullary anaplastic ependymomas are very rare entity. Surgery is the main treatment that can improve prognosis, while radiotherapy is useful, after surgery, in the treatment of residues, recurrences, anaplastic transformations, metastases and multifocal lesions.

Neurosciences. Biological psychiatry. Neuropsychiatry and RC321-571

Abstract Electroconvulsive therapy (ECT) is an effective therapy for depression, but its cellular effects on the human brain remain elusive. In rodents, electroconvulsive shocks increase proliferation and the expression of plasticity markers in the hippocampal dentate gyrus (DG), suggesting increased neurogenesis. Furthermore, MRI studies in depressed patients have demonstrated increases in DG volume after ECT, that were notably paralleled by a decrease in depressive mood scores. Whether ECT also triggers cellular plasticity, inflammation or possibly injury in the human hippocampus, was unknown. We here performed a first explorative, anatomical study on the human post-mortem hippocampus of a unique, well-documented cohort of bipolar or unipolar depressed patients, who had received ECT in the 5 years prior to their death. They were compared to age-matched patients with a depressive disorder who had not received ECT and to matched healthy controls. Upon histopathological examination, no indications were observed for major hippocampal cell loss, overt cytoarchitectural changes or classic neuropathology in these 3 groups, nor were obvious differences present in inflammatory markers for astrocytes or microglia. Whereas the numbers of proliferating cells expressing Ki-67 was not different, we found a significantly higher percentage of cells positive for Doublecortin, a marker commonly used for young neurons and cellular plasticity, in the subgranular zone and CA4 / hilus of the hippocampus of ECT patients. Also, the percentage of positive Stathmin 1 cells was significantly higher in the subgranular zone of ECT patients, indicating neuroplasticity. These first post-mortem observations suggest that ECT has no damaging effects but may rather have induced neuroplasticity in the DG of depressed patients.

Neurosciences. Biological psychiatry. Neuropsychiatry and RC321-571

Abstract An increased understanding of the interrelations between depressive symptoms among older populations could help improve interventions. However, studies often use sum scores to understand depression in older populations, neglecting important symptom dynamics that can be elucidated in evolving depressive symptom networks. We computed Cross-Lagged Panel Network Models (CLPN) of depression symptoms in 11,391 adults from the English Longitudinal Study of Ageing. Adults aged 50 and above (mean age 65) were followed over 16 years throughout this nine-wave representative population study. Using the eight-item Center for Epidemiological Studies Depression Scale, we computed eight CLPNs covering each consecutive wave. Across waves, networks were consistent with respect to the strength of lagged associations (edge weights) and the degree of interrelationships among symptoms (centrality indices). Everything was an effort and could not get going displayed the strongest reciprocal cross-lagged associations across waves. These two symptoms and loneliness were core symptoms as reflected in strong incoming and outgoing connections. Feeling depressed was strongly predicted by other symptoms only (incoming but not strong outgoing connections were observed) and thus was not related to new symptom onset. Restless sleep had outgoing connections only and thus was a precursor to other depression symptoms. Being happy and enjoying life were the least central symptoms. This research underscores the relevance of somatic symptoms in evolving depression networks among older populations. Findings suggest the central symptoms from the present study (everything was an effort, could not get going, loneliness) may be potential key intervention targets to mitigate depression in older adults.

Neurosciences. Biological psychiatry. Neuropsychiatry and RC321-571

Abstract There are only a few studies reporting on the immunological profiles of methamphetamine (MA) use, MA dependency, or MA-induced psychosis (MAP). This study measured M1 macrophage, T helper (Th)-1, Th-2, growth factor, and chemokine profiles, as well as the immune inflammatory response system (IRS) and compensatory immunoregulatory system (CIRS) in peripheral blood samples from patients with MA use (n = 51), MA dependence (n = 47), and MAP (n = 43) in comparison with controls (n = 32). We discovered that persistent MA use had a robust immunosuppressive impact on all immunological profiles. The most reliable biomarker profile of MA use is the combination of substantial CIRS suppression and a rise in selected pro-inflammatory cytokines, namely CCL27 (CTACK), CCL11 (eotaxin), and interleukin (IL)-1α. In addition, MA dependency is associated with increased immunosuppression, as demonstrated by lower stem cell factor levels and higher IL-10 levels. MAP is related to a significant decrease in all immunological profiles, particularly CIRS, and an increase in CCL5 (RANTES), IL-1α, and IL-12p70 signaling. In conclusion, long-term MA use and dependency severely undermine immune homeostasis, whereas MAP may be the consequence of increased IL-1α – CCL5 signaling superimposed on strongly depleted CIRS and Th-1 functions. The widespread immunosuppression established in longstanding MA use may increase the likelihood of infectious and immune illness or exacerbate disorders such as hepatitis and AIDS. Furthermore, elevated levels of CCL5, CCL11, CCL27, IL-1α, and/or IL-12p70 may play a role in the peripheral (atherosclerosis, cutaneous inflammation, immune aberrations, hypospermatogenesis) and central (neuroinflammation, neurotoxic, neurodegenerative, depression, anxiety, and psychosis) side effects of MA use.

Neurosciences. Biological psychiatry. Neuropsychiatry and RC321-571

Abstract Exposure to stress can lead to long lasting behavioral and neurobiological consequences, which may enhance the susceptibility for the onset of mental disorders. However, there are significant individual differences in the outcome of stress exposure since only a percentage of exposed individuals may show pathological consequences, whereas others appear to be resilient. In this study, we aimed to characterize the effects of prenatal stress (PNS) exposure in rats at adolescence and to identify subgroup of animals with a differential response to the gestational manipulation. PNS adolescent offspring (regardless of sex) showed impaired emotionality in different pathological domains, such as anhedonia, anxiety, and sociability. However, using cluster analysis of the behavioral data we could identify 70% of PNS-exposed animals as vulnerable (PNS-vul), whereas the remaining 30% were considered resilient (PNS-res). At the molecular level, we found that PNS-res males show a reduced basal activation of the ventral hippocampus whereas other regions, such as amygdala and dorsal hippocampus, show significant PNS-induced changes regardless from vulnerability or resilience. Taken together, our results provide evidence of the variability in the behavioral and neurobiological effects of PNS-exposed offspring at adolescence. While these data may advance our understanding of the association between exposure to stress during gestation and the risk for psychopathology, the investigation of the mechanisms associated to stress vulnerability or resilience may be instrumental to develop novel strategies for therapeutic intervention.