Is there a connection between estrogen and Parkinson's disease?

Increasing evidence suggests that estrogens may protect the nigrostriatal dopaminergic pathway affected in Parkinson's disease (PD). Animal studies show that estrogens influence the synthesis, release, and metabolism of dopamine and can modulate dopamine receptor expression and function. Some clinical studies suggest that PD symptoms may be exacerbated after menopause and delayed or alleviated with hormone replacement therapy, but others have failed to observe positive estrogenic effects. The conflicting findings suggest that several variables, including age, estrogen dose and formulation, and timing and length of dosing period, may determine whether benefits are seen and the nature of these benefits. Further investigation is therefore needed for the relationship between estrogens and the nigrostriatal dopaminergic system.     

Are there differences between women's and men's antidepressant responses?

OBJECTIVE: The study examined a large data set to determine whether patients' sex affected the outcome of antidepressant treatment. METHOD: Data for 1,746 patients aged 18-65 years who had been treated with tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), fluoxetine, or placebo were examined in a retrospective analysis to determine whether men and women differed in their responses to antidepressants. To examine the effect of menopausal status in the absence of data on individual patients' menopausal status, results for female patients younger or older than age 50, 52, 54, and 56 were compared. RESULTS: Men and women both younger and older than age 50 had equivalent response rates to tricyclics and fluoxetine. Women had a statistically superior response to MAOIs. Placebo response was equivalent across all groups. CONCLUSIONS: Neither sex nor menopausal status may be relevant in antidepressant treatment of adult depressed patients up to 65 years of age. Although women had a statistically superior response to MAOIs, this difference may not be clinically relevant.     

Are dementia and depression in Parkinson's disease related?

INTRODUCTION: Depression and dementia are common problems in PD. As the depression and dementia of PD share many symptoms such as apathy, anhedonia, anergia, and agitation, it is reasonable to ask if they are related. METHODS: 106 consecutive PD patients, unselected for depression or dementia were evaluated for depression using the Hamilton Depression Scale (Ham-D21). They were also evaluated using a modified neuropsychiatric inventory (NPI). Following the above, 100 consecutive PD patients were evaluated for dementia using Folstein's Mini Mental Status Examination (MMSE). They were also evaluated using the modified NPI. RESULTS: 29 of the first series of patients, 27%, were depressed, score of > or =14 on the Ham-D21. 8 of the second series of consecutive patients, 18%, were demented, score < or =24 on the MMSE. Depressed and demented patients were significantly more likely to suffer from apathy, anhedonia, mood lability, daytime drowsiness, paranoia, and hallucinations. Demented patients were significantly older, had PD longer, were more disabled and more likely to be depressed. COMMENT: The commonality of certain symptoms in demented and depressed patients suggests that dementia and depression in PD may be related and that, in PD depression may be a fore-runner of dementia. Five year follow-up of these patients supports this suggestion.     

Is there a relationship between Parkinson's disease and obsessive-compulsive disorder?

Obsessive-compulsive (OC) symptoms and obsessive-compulsive disorder (OCD) have been reported in Parkinson's disease (PD). This is interpreted as an indirect evidence for the involvement of frontobasal ganglia circuitry in OCD. However, the evidence for relationship between the OC symptoms and PD is inconsistent. This study systematically assessed OC symptoms and OCD in non-demented idiopathic PD patients (n=69) and matched medically ill controls (n=69). The cases did not differ from controls with respect to OC symptoms, clinical and subclinical OCD, tics and other psychiatric diagnoses. There was no relationship between severity of PD and OC symptoms. The findings do not support relationship between OCD and PD. While the findings of this study do not in any way rule out the involvement of frontobasal ganglia circuitry in OCD, it is speculated that the involvement of different circuitry in the pathophysiology of OCD and PD explain the lack of association between PD and OCD.     

Functional connectomes of akinetic-rigid and tremor within drug-naïve Parkinson's disease

Aims

To detect functional connectomes of akinetic-rigid (AR) and tremor and compare their connection pattern.

Methods

Resting-state functional MRI data of 78 drug-naïve PD patients were enrolled to construct connectomes of AR and tremor via connectome-based predictive modeling (CPM). The connectomes were further validated with 17 drug-naïve patients to verify their replication.

Results

The connectomes related to AR and tremor were identified via CPM method and successfully validated in the independent set. Additional regional-based CPM demonstrated neither AR nor tremor could be simplified to functional changes within a single brain region. Computational lesion version of CPM revealed that parietal lobe and limbic system were the most important regions among AR-related connectome, and motor strip and cerebellum were the most important regions among tremor-related connectome. Comparing two connectomes found that the patterns of connection between them were largely distinct, with only four overlapped connections identified.

Conclusion

AR and tremor were found to be associated with functional changes in multiple brain regions. Distinct connection patterns of AR-related and tremor-related connectomes suggest different neural mechanisms underlying the two symptoms.     

Are quantitative and clinical measures of bradykinesia related in advanced Parkinson's disease?

Introduction

Bradykinesia is usually assessed using clinical rating scales. In some circumstances, a laboratory assessment of bradykinesia using tools of higher resolution is required. One task often used for the evaluation of bradykinesia is a rapid alternating movement (RAM) of the hand. However, the relationship between clinical scores of bradykinesia and the properties of a RAM task assessed quantitatively has yet to be determined.

Objective

Identify which of the commonly used properties of a RAM task are related to a clinical score of bradykinesia and assess the strength of this relationship.

Methods

Nineteen patients with idiopathic Parkinson's disease were tested ON and OFF medication. They performed three trials of the RAM task and were assessed clinically using the Unified Parkinson's disease rating scale in each condition and with each hand.

Results

A statistically significant correlation was observed between the clinical score of bradykinesia and two of the properties of the RAM task; namely mean and maximal velocity.

Comparison with existing methods

These results indicate that a RAM task does provide a measure of bradykinesia but it is only moderately correlated to a clinical rating of this motor symptom.

Conclusion

We propose that the results from the RAM task represent a measure of “core bradykinesia” while a clinical evaluation represents a composite score of bradykinesia, movement amplitude and motor coordination.     

Patterns of α-synuclein pathology in incidental cases and clinical subtypes of Parkinson's disease

Parkinson's disease (PD) is characterized by a gradual accumulation of neuropathology that may begin many years before a clinical diagnosis can be made using currently accepted criteria. Here, we first review the prevalence of α-synuclein neuropathology in elderly and discuss its clinical relevance in Parkinson patients. Subsequently, the results of a retrospective study focussing on the distribution of neuropathology in Parkinson patients with a tremor-dominant (TD), non-tremordominant (NTD) or rapid disease progression (RDP) subtype are presented. The study population recruited by the Netherlands Brain bank consisted of 149 non-neurological donors, 26 donors with incidental Lewy body disease (iLBD) and 111 Parkinson patients. In total, 89% of these cases could be classified in accordance with the Braak staging when taking into account the severity of α-synuclein pathology and adding an amygdala-predominant category of synucleinopathy. The pathological progression seemed to be non-linear. Interestingly, a strong correlation between neuronal loss and α-synuclein pathology was observed in the substantia nigra in Braak stages 3-6 (P < 0.01). However, there was no correlation between Hoehn & Yahr and Braak stages. Neuropathological progression may, however, vary between subtypes as cortical Lewy body load and Braak stages were higher in patients with NTD compared to TD and Alzheimer pathology was more prevalent in RDP patients. Recognition of clinical subtypes in neuropathological studies is essential to identify selective vulnerability to protein accumulation that may determine the clinical phenotype in PD.     

Are there temperament differences between major depression and dysthymic disorder in adolescent clinical outpatients?

AimsThe aim of the study was to explore possible differences in temperament and character dimensions between 2 monodiagnostic adolescent groups of depression, namely, one with a present episode of major depression and subjects with the other being their dysthymic peers.SampleFrom a multisite Western Hungarian sample of consecutively referred 14- to 18-year-old new psychiatric adolescent outpatients, 2 groups were compared: group I, n = 56 (9 males, 47 females), with major depressive disorder (MDD) and group II, n = 27 (6 males, 21 females), with a diagnosis of dysthymic disorder (DD). All other comorbid diagnoses including bipolar and double depression (MDD + DD) cases were excluded. Present suicide events, if the attempter had an underlying diagnosis of depression, were not causes for exclusion. Assessment methods used were the adapted Hungarian versions of the Mini International Neuropsychiatric Interview and the Junior Temperament (Cloninger) Character Inventory.ResultsThe only difference between the major depressive and dysthymic adolescents was harm avoidance, adolescents with major depression having a higher level practice of harm avoidance, whereas the temperament type of MDD vs DD seems to differ only in the aspect of avoiding painful stress. Expectations regarding a worse degree of self-directedness and lower levels of persistence and cooperativeness in the MDD sample were not proved.ConclusionsNo essential temperament differences were found between the 2 adolescent depressive groups. Scarce differences between temperament qualities of MDD and DD may support Akiskal's continuum theory of depressive disorders. More research and the use of closer clinical personality typologies are warranted to explore possible personality trait differences (if they exist) between clinical diagnostic groups of adolescent patients.     

Are there gender differences in the severity and consequences of sleep disordered in children?

ObjectivesIn adults there is a distinct gender difference in the prevalence and severity of sleep disordered breathing (SDB), however there have been limited studies examining the effects of gender in children with SDB. We aimed to compare the effects of gender on severity of SDB, blood pressure, sleep and respiratory characteristics, quality of life, behavior and executive function.MethodsWe included 533 children aged 3–18 years, who underwent standard pediatric overnight polysomnography (PSG) between 2004 and 2016. Blood pressure was recorded prior to each study. Quality of life, behavior and executive function were assessed with parental questionnaires. Children were grouped by gender and SDB severity based on their obstructive apnea hypopnea index (OAHI) into non-snoring controls, Primary Snoring (PS) (OAHI≤1 event/h), Mild obstructive sleep apnea (OSA) (OAHI>1-≤5 events/h) and moderate/severe (MS) OSA (OAHI>5 events/h) and data compared with 2-way ANOVA.ResultsA total of 298 boys and 235 girls were studied. There were no differences in age, BMI z-score, SDB severity sleep characteristics or blood pressure between genders. Diastolic blood pressure was elevated in females with MS OSA compared to males (P < 0.05). Quality of life, behavior and executive function scores were all elevated in the SDB groups compared to controls. Females with MS OSA exhibited more internalizing behavioral problems compared to males (59.2 ± 2.4 vs. 51.4 ± 2.3, P < 0.05).ConclusionsIn contrast to studies in adults, we identified no gender differences in the severity or consequences of SDB in children, other than females with moderate-severe OSA exhibiting more internalizing problems and higher diastolic blood pressure.     

Are there gender differences in DSM-IV personality disorders?

This study examined gender differences in DSM-IV personality disorders (PD) in outpatients. Structured diagnostic interviews were reliably administered to a consecutive series of 145 outpatients with a primary axis I diagnosis of binge eating disorder (BED). To further reduce variability due to heterogeneity of axis I, a subgroup of 75 patients with co-occurring major depressive disorder (MDD) was retested for gender differences. Overall, the proportion of males (34.4%) and females (27.4%) diagnosed with any PD did not significantly differ. Specific PD diagnoses were not differentially distributed by gender in the overall study group of patients with BED or in the subgroup of patients with BED and MDD, except for antisocial PD in males.     

Are there subtypes of suicidal schizophrenia? A prospective study

BACKGROUND: Tragically, suicide is not uncommon in schizophrenia. The principal objective of this study was to examine possible subtypes of suicidal schizophrenic patients and identify their clinical and psychopathological profiles at long-term follow-up. METHOD: The study involved 62 patients diagnosed with schizophrenia according to ICD-10 criteria, who were consecutively admitted following a suicide attempt. Of these subjects, 47 (75.8%) could be re-evaluated after 1 year. Sociodemographic, general clinical, and psychopathological variables were evaluated. RESULTS: Two predominant subgroups were identified according to suicidal motivation: psychotic motivation and depressive motivation. At re-evaluation after 1 year, the depressive motivation subgroup showed higher depression and hopelessness scores. This subgroup also had greater educational level, age, and duration of illness, and more frequent existence of previous suicide attempts compared to the psychotic motivation subgroup. Of note in the psychotic motivation subgroup was the presence of hopelessness. The variables of educational level, duration of illness, and previous suicide attempts were the ones that best distinguished these subgroups. CONCLUSION: These findings reinforce the notion that meaningful subgroups occur among suicidal schizophrenic patients. The different psychopathological profiles of the two prominent subgroups suggest the need for a different management approach in each case. The identification of these profiles in both subtypes at long-term follow-up may facilitate their detection by clinicians and, therefore, foster the adoption of appropriate preventive measures against subsequent suicidal behavior.     

Are dopaminergic pathways involved in theory of mind? A study in Parkinson's disease

The "orbitofrontal" and "cingulate" frontostriatal loops and the mesolimbic dopaminergic system that modulates their function have been implicated in theory of mind (ToM). Parkinson's disease (PD) provides a model for assessing their role in humans. Results of the handful of previous studies of ToM in PD providing preliminary evidence of impairment remain controversial, mainly because the patients included in these studies were not accurately described, making it difficult to determine whether their ToM deficits were due to general cognitive deterioration or to a more specific dopaminergic deficit. The aim of our study was therefore to re-examine previous results highlighting ToM in PD and to explore the involvement of the dopaminergic pathways in ToM. ToM was investigated in 17 newly diagnosed PD patients (early PD group), 27 PD patients in the advanced stages of the disease (advanced PD group) and 26 healthy matched controls (HC), using two ToM tasks: a visual one, which is thought to reflect the "affective" ToM subcomponent ("Reading the Mind in the Eyes"), and a verbal one, which is thought to reflect both the "affective" and the "cognitive" ToM subcomponents (faux pas recognition). Furthermore, the early PD group was studied in two conditions: with and without dopamine replacement therapy (DRT). We failed to find any significant difference in ToM between the early PD patients and the HC group. Furthermore, there was no difference between the early PD patients in the medicated and unmedicated conditions. Conversely, the advanced PD patients scored poorly on the intention attribution question ("cognitive" ToM score) in the faux pas recognition task. The present results suggest that the deficit in ToM only occurs in the more advanced stages of the disease. In addition, our results would appear to indicate that these advanced PD patients present "cognitive" ToM impairment rather than global ("cognitive" and "affective") ToM impairment. In other words, the ToM deficit would appear to be present in PD patients where the degenerative process has spread beyond the dopaminergic pathways, but not in early PD patients where neuronal loss is thought to be restricted to the nigrostriatal and mesolimbic dopaminergic systems. In conclusion, our results suggest that the dopaminergic pathways are not involved in ToM.     

Are electrophysiological autonomic tests useful in the assessment of dysautonomia in Parkinson's disease?

To assess the autonomic system in Parkinson's disease (PD), the sympathetic skin response (SSR) and the R-R interval variation (RRIV) tests were studied in 26 PD patients and in 24 healthy controls. The aim of the study was to evaluate the sympathetic and parasympathetic system function in PD, to define the pattern of autonomic abnormalities found in SSR and RRIV in parkinsonian patients as well as to analyze the usefulness of both tests in paraclinical assessment of the dysautonomia, compared with clinical symptoms and signs of the autonomic nervous system involvement. The corrrelations between both autonomic tests results were also studied. In PD patients SSR test was abnormal in about 35% and RRIV was abnormal in about 54% of patients. SSR and RRIV were both abnormal in about 27% of PD patients whereas at least one of electrophysiological autonomic tests was abnormal in about 62% of PD patients. Clinical and paraclinical signs of dysautonomia occurred in a similar proportion of patients (i.e. in about 62%). A weak correlation was found between the latency of SSR from upper limbs and the value of RRIV during deep breathing (p=0.063). Our results show that SSR and RRIV are non-invasive paraclinical electrophysiological tests that confirm clinical dysautonomia in PD and can supplement the clinical differentiation of Parkinsonian syndromes.