Basal and Adrenocorticotropic Hormone Stimulated Plasma Cortisol Levels Among Egyptian Autistic Children: Relation to Disease Severity

<p>Abstract</p> <p>Background</p> <p>Autism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviors. The hypothalamic-pituitary-adrenocortical (HPA) axis deserves special attention, since it is the basis for emotions and social interactions that are affected in autism.</p> <p>Aim</p> <p>To assess basal and stimulated plasma cortisol, and adrenocorticotropic hormone (ACTH) levels in autistic children and their relationship to disease characteristics.</p> <p>Methods</p> <p>Fifty autistic children were studied in comparison to 50 healthy age-, sex- and pubertal stage- matched children. All subjects were subjected to clinical evaluation and measurement of plasma cortisol (basal and stimulated) and ACTH. In addition, electroencephalography (EEG) and intelligence quotient (IQ) assessment were done for all autistic children.</p> <p>Results</p> <p>Sixteen% of autistic patients had high ACTH, 10% had low basal cortisol and 10% did not show adequate cortisol response to ACTH stimulation. Autistic patients had lower basal (p = 0.032) and stimulated cortisol (p = 0.04) and higher ACTH (p = 0.01) than controls. Childhood Autism Rating Scale (CARS) score correlated positively with ACTH (r = 0.71, p = 0.02) and negatively with each of basal (r = -0.64, p = 0.04) and stimulated cortisol (r = -0.88, p < 0.001). Hormonal profile did not differ in relation to EEG abnormalities, IQ and self- aggressive symptoms.</p> <p>Conclusions</p> <p>The observed hormonal changes may be due to a dysfunction in the HPA axis in autistic individuals. Further studies are warranted regarding the role of HPA axis dysfunction in the pathogenesis of autism.</p

The relationship between associative learning, transfer generalization, and homocysteine levels in mild cognitive impairment

Previous studies have shown that high total homocysteine levels are associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI). In this study, we test the relationship between cognitive function and total homocysteine levels in healthy subjects (Global Dementia Rating, CDR = 0) and individuals with MCI (CDR = 0.5). We have used a cognitive task that tests learning and generalization of rules, processes that have been previously shown to rely on the integrity of the striatal and hippocampal regions, respectively. We found that total homocysteine levels are higher in MCI individuals than in healthy controls. Unlike what we expected, we found no difference between MCI subjects and healthy controls in learning and generalization. We conducted further analysis after diving MCI subjects in two groups, depending on their Global Deterioration Scale (GDS) scores: individuals with very mild cognitive decline (vMCD, GDS = 2) and mild cognitive decline (MCD, GDS = 3). There was no difference among the two MCI and healthy control groups in learning performance. However, we found that individuals with MCD make more generalization errors than healthy controls and individuals with vMCD. We found no difference in the number of generalization errors between healthy controls and MCI individuals with vMCD. In addition, interestingly, we found that total homocysteine levels correlate positively with generalization errors, but not with learning errors. Our results are in agreement with prior results showing a link between hippocampal function, generalization performance, and total homocysteine levels. Importantly, our study is perhaps among the first to test the relationship between learning (and generalization) of rules and homocysteine levels in healthy controls and individuals with MCI

The effects of clinical motor variables and medication dosage on working memory in Parkison's disease

In this study, we investigate the interrelationship between clinical variables and working memory (WM) in Parkinson's disease (PD). Specifically, the aim of the study was to investigate the relationship between disease duration, dopaminergic medication dosage, and motor disability (UPDRS score) with WM in individuals with PD. Accordingly, we recruited three groups of subjects: unmedicated PD patients, medicated PD patients, and healthy controls. All subjects were tested on three WM tasks: short-delay WM, long-delay WM, and the n-back task. Further, PD encompasses a spectrum that can be classified either into akinesia/rigidity or resting tremor as the predominant motor presentation of the disease. In addition to studying medication effects, we tested WM performance in tremor-dominant and akinesia-dominant patients. We further correlated WM performance with disease duration and medication dosage. We found no difference between medicated and unmedicated patients in the short-delay WM task, but medicated patients outperformed unmedicated patients in the long-delay WM and n-back tasks. Interestingly, we also found that akinesia-dominant patients were more impaired than tremor-dominant patients at various WM measures, which is in agreement with prior studies of the relationship between akinesia symptom and basal ganglia dysfunction. Moreover, the results show that disease duration inversely correlates with more demanding WM tasks (long-delay WM and n-back tasks), but medication dosage positively correlates with demanding WM performance. In sum, our results show that WM impairment in PD patients depend on cognitive domain (simple vs. demanding WM task), subtype of PD patients (tremor- vs. akinesia-dominant), as well as disease duration and medication dosage. Our results have implications for the interrelationship between motor and cognitive processes in PD, and for understanding the role of cognitive training in treating motor symptoms in PD

Factors underlying probabilistic and deterministic stimulus-response learning performance in medicated and unmedicated patients with Parkinson's disease

Objective: Prior studies have not tested individual differences or effects of medication dosage on stimulus-response learning in patients with Parkinson's disease (PD). In the current study, we investigated the effects of motor variables (including tremor, akinesia, and disease duration) as well as dopaminergic medication dosage on learning in unmedicated PD patients, medicated PD patients, and healthy controls. Method: We tested all subjects on probabilistic and deterministic learning tasks, and also collected awareness measures data using postexperimental questionnaires. Importantly, we tested learning performance in tremor-dominant and akinesia-dominant PD patients, and further correlated learning performance with disease duration and medication dosage. Results: Results show that akinesia-dominant patients were more impaired than tremor-dominant patients at probabilistic rewardbut not punishment-based learning, which is in agreement with prior studies of the relationship between akinesia and basal ganglia dysfunction. We also found no difference between medicated and unmedicated PD patients in reward- or punishment-based deterministic learning, but medicated patients were better than unmedicated patients at reward-based probabilistic learning. Our results show that awareness measures explain differences among probabilistic and deterministic learning performance. Moreover, we found that disease duration and motor severity are inversely correlated, and medication dosage is positively correlated, with reward-based probabilistic learning. Conclusion: Our results suggest that stimulus-response learning performance in patients with PD depends on the type of learning (probabilistic vs. deterministic), medication status (on vs. off medication, dopaminergic medication dosage), disease duration as well as motor severity and subtype in PD patients (tremor- vs. akinesia-dominant)

Neural substrates and potential treatments for levodopa-induced dyskinesias in Parkinson's disease

Parkinson's disease (PD) is primarily a motor disorder that involves the gradual loss of motor function. Symptoms are observed initially in the extremities, such as hands and arms, while advanced stages of the disease can effect blinking, swallowing, speaking, and breathing. PD is a neurodegenerative disease, with dopaminergic neuronal loss occurring in the substantia nigra pars compacta, thus disrupting basal ganglia functions. This leads to downstream effects on other neurotransmitter systems such as glutamate, gamma-aminobutyric acid, and serotonin. To date, one of the main treatments for PD is levodopa. While it is generally very effective, prolonged treatments lead to levodopa-induced dyskinesia (LID). LID encompasses a family of symptoms ranging from uncontrolled repetitive movements to sustained muscle contractions. In many cases, the symptoms of LID can cause more grief than PD itself. The purpose of this review is to discuss the possible clinical features, cognitive correlates, neural substrates, as well as potential psychopharmacological and surgical (including nondopaminergic and deep brain stimulation) treatments of LID

Homocysteine levels in schizophrenia and affective disorders : focus on cognition

Although homocysteine (Hcy) has been widely implicated in the etiology of various physical health impairments, especially cardiovascular diseases, overwhelming evidence indicates that Hcy is also involved in the pathophysiology of schizophrenia and affective disorders. There are several mechanisms linking Hcy to biological underpinnings of psychiatric disorders. It has been found that Hcy interacts with NMDA receptors, initiates oxidative stress, induces apoptosis, triggers mitochondrial dysfunction and leads to vascular damage. Elevated Hcy levels might also contribute to cognitive impairment that is widely observed among patients with affective disorders and schizophrenia. Supplementation of vitamins B and folic acid has been proved to be effective in lowering Hcy levels. There are also studies showing that this supplementation strategy might be beneficial for schizophrenia patients with respect to alleviating negative symptoms. However, there are no studies addressing the influence of add-on therapies with folate and vitamins B on cognitive performance of patients with schizophrenia and affective disorders. In this article, we provide an overview of Hcy metabolism in psychiatric disorders focusing on cognitive correlates and indicating future directions and perspectives

Homocysteine levels in neurological disorders

Homocysteine (Hcy) is a sulphur-containing amino acid synthesized in one-carbon metabolic cycle. It is metabolized either by transsulfuration to cysteine or by remethylation to methionine. Plasma Hcy levels are often measured by collecting blood samples using the Hcy enzyme immunoassay (EIA) method. Several factors are known to increase hcy level including male gender, older age, higher body weight, lower folic acid and vitamin B dietary intake, cigarette smoking, alcohol abuse, chronic renal disease, as well as certain medications such as diuretics and fibrates. Interindividual differences in Hcy levels might be also attributed to certain genetic risk factors that influence the activity of one-carbon metabolism. Two single nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) –C677T and AI298C—are among the most important genetic predictors of Hcy level and have been widely studied in numerous diseases that might be linked to alterations in one-carbon metabolism. Primarily, high Hcy levels have been exclusively regarded as a risk factor for cardiovascular diseases. Indeed, it has been found that Hcy may lead to endothelial injury triggering a cascade of processes resulting in atherosclerosis

Cognitive correlates of psychosis in patients with Parkinson's disease

Introduction. Psychosis and hallucinations occur in 20-30% of patients with Parkinson's disease (PD). In the current study, we investigate cognitive functions in relation to the occurrence of psychosis in PD patients. Methods. We tested three groups of subjects-PD with psychosis, PD without psychosis and healthy controls-on working memory, learning and transitive inference tasks, which are known to assess prefrontal, basal ganglia and hippocampal functions. Results. In the working memory task, results show that patients with and without psychosis were more impaired than the healthy control group. In the transitive inference task, we did not find any difference among the groups in the learning phase performance. Importantly, PD patients with psychosis were more impaired than both PD patients without psychosis and controls at transitive inference. We also found that the severity of psychotic symptoms in PD patients [as measured by the Unified Parkinson Disease Rating Scale Thought Disorder (UPDRS TD) item] is directly associated with the severity of cognitive impairment [as measured by the mini-mental status exam (MMSE)], sleep disturbance [as measured by the Scales for Outcome in Parkinson Disease (SCOPA) sleep scale] and transitive inference (although the latter did not reach significance).Conclusions. Although hypothetical, our data may suggest that the hippocampus is a neural substrate underlying the occurrence of psychosis, sleep disturbance and cognitive impairment in PD patients

Sexual dysfunctions in male schizophrenia patients

Background: Sexuality involves a complex interaction of biological, cultural, and developmental factors. Growing awareness of sexual dysfunctions in schizophrenia, as well as the adverse effects of psychotropic drugs (i.e., drugs affecting the mind and brain), have led to attempts to use different kinds of treatments to manage sexual dysfunction in these patients. The aim of this study is to investigate clinical factors underlying sexual dysfunction, especially highlighting clinical data in schizophrenia patients associated with sexual and erectile dysfunction, in order to improve clinical treatment. Methods: The male version of the Sexual Behavioral Questionnaire was applied to 214 schizophrenia patients. Of those patients, the Arabic version of the Marital Satisfaction Inventory and the International Index of Erectile Function was given to married patients, while their wives were given the Woman Abuse Scale. Results: 84.2% of the patients were dissatisfied with their sexual life. A negative correlation was found between sexual enjoyment and age. About 35% (n=33) of the patients receiving mixed treatment and 40% (n=21) of patients who are on typical antipsychotic treatment were dissatisfied with their sexual life (p=0.002, 0.05). A nonsignificant difference in sexual satisfaction was found in patients on atypical antipsychotics. Significant differences are found regarding mild erectile dysfunction, sudden onset of erectile dysfunction, erectile dysfunction with their partner only, and the presence of morning erection (p=0.05, 0.02, 0.04, and 0.05, respectively). Significant positive correlations were found between receiving mixed drugs with mild erectile dysfunction and sudden onset of erectile function (p=0.005, r=0.87 and p=0.01, r=0.081, respectively); these results were not found with atypical antipsychotics. Significant differences were found between patients with mild erectile dysfunction and their dissatisfaction with their financial issues (p=0.04). Significant differences were also found between married patients receiving mixed treatment and their wives who experienced physical, sexual, and psychological abuse. Conclusions: Sexual dysfunction in schizophrenia should be carefully diagnosed and treated. This study shows significant correlations between sexual dysfunction and receiving typical antipsychotics and mixed medications. The use of atypical antipsychotics was associated with fewer sexual problems in male patients with schizophrenia

The thalamus as a relay station and gatekeeper : relevance to brain disorders

Here, we provide a review of behavioural, cognitive, and neural studies of the thalamus, including its role in attention, consciousness, sleep, and motor processes. We further discuss neuropsychological and brain disorders associated with thalamus function, including Parkinson's disease, Alzheimer's disease, Korsakoff's syndrome, and sleep disorders. Importantly, we highlight how thalamus-related processes and disorders can be explained by the role of the thalamus as a relay station