Striatal D2/3 Binding Potential Values in Drug-Na?ve First-Episode Schizophrenia Patients Correlate With Treatment Outcome

One of best validated findings in schizophrenia research is the association between blockade of dopamine D₂ receptors and the effects of antipsychotics on positive psychotic symptoms. The aim of the present study was to examine correlations between baseline striatal D_2/3 receptor binding potential (BP_p) values and treatment outcome in a cohort of antipsychotic-naïve first-episode schizophrenia patients. Additionally, we wished to investigate associations between striatal dopamine D_2/3 receptor blockade and alterations of negative symptoms as well as functioning and subjective well-being. Twenty-eight antipsychotic-naïve schizophrenia patients and 26 controls were included in the study. Single-photon emission computed tomography (SPECT) with [¹²³I]iodobenzamide ([¹²³I]-IBZM) was used to examine striatal D_2/3 receptor BP_p. Patients were examined before and after 6 weeks of treatment with the D_2/3 receptor antagonist amisulpride. There was a significant negative correlation between striatal D_2/3 receptor BP_p at baseline and improvement of positive symptoms in the total group of patients. Comparing patients responding to treatment to nonresponders further showed significantly lower baseline BP_p in the responders. At follow-up, the patients demonstrated a negative correlation between the blockade and functioning, whereas no associations between blockade and negative symptoms or subjective well-being were observed. The results show an association between striatal BP_p of dopamine D_2/3 receptors in antipsychotic-naïve first-episode patients with schizophrenia and treatment response. Patients with a low BP_p have a better treatment response than patients with a high BP_p. The results further suggest that functioning may decline at high levels of dopamine receptor blockade.Key words: [¹²³I]iodobenzamide, SPECT, occupancy, amisulpride, subjective well-being     

Association Between BDNF Val66Met Polymorphism and Cognitive Performance in Antipsychotic-Na?ve Patients with Schizophrenia

Cognitive impairment is one of the core symptoms in schizophrenia, which reflects the neurodevelopmental deficits in the etiology of this disease. Brain-derived neurotrophic factor (BDNF) plays an important role in various neurodevelopmental processes. Growing evidence has shown that BDNF may be involved in the etiology of schizophrenia. The aim of this study was to examine the association of the BDNF Val66Met polymorphism with cognition in patients with schizophrenia. Various neuropsychological tests including the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised, and the Wisconsin Card Sorting Test (WCST) were employed in a sample of 112 antipsychotic-na?ve patients with schizophrenia and 63 healthy controls. We examined the Val66Met polymorphism in the 112 patients and 394 controls. Among the patients, cognition was compared between Met allele carriers and non-Met allele carriers. A wide range of cognitive deficits were demonstrated in the schizophrenic patients, compared with the controls (Ps?相似文献   

P50 Suppression and Its Neural Generators in Antipsychotic-Na?ve First-Episode Schizophrenia Before and After 6 Months of Quetiapine Treatment

Background: Numerous studies have demonstrated sensory gating deficits in schizophrenia. However, only a few longitudinal studies report on the effects of antipsychotic treatment on sensory gating deficits and their results are inconsistent. In the present study, P50 suppression and its neural generators were investigated in antipsychotic-naïve first-episode patients with schizophrenia before and after 6 months of treatment with quetiapine. Methods: Thirty-four antipsychotic-naïve first-episode schizophrenia patients and age and gender matched healthy controls were tested in an auditory sensory gating paradigm at baseline and after 6 months. During this period, the patients were treated with quetiapine, while controls received no treatment. Sixteen patients completed the study. Results: Patients showed significant reduced P50 suppression compared with controls at baseline but not at follow-up. Furthermore, a significant positive correlation between baseline P50 suppression and dose of quetiapine at follow-up was found. P50 suppression in patients receiving above median dosages of quetiapine increased significantly from baseline to follow-up. At baseline, a frontocentral source was significantly more active in patients than in controls at the time of the testing stimulus. Conclusions: The present findings suggest that P50 suppression deficits are already present at an early stage of schizophrenia. Furthermore, particularly those patients with more severe gating deficits appeared to need higher dosages of quetiapine, although their clinical symptoms did not seem to indicate this. Quetiapine treatment significantly improved these gating deficits. Furthermore, a frontocentral source in the brain appeared to be involved in the deficient P50 gating of the patients.     

Decreased Cardiac Vagal Control in Drug-Na?ve Patients with Posttraumatic Stress Disorder

Objective

Decreased cardiac vagal control (CVC) has been proposed in posttraumatic stress disorder (PTSD), but the results are mixed. Analyses with larger sample sizes and better methodology are needed.

Methods

Thirty-two drug-naïve survivors with current PTSD, 32 survivors without PTSD and 192 matched controls were recruited for a case-control analysis. We used the PTSD checklist-civilian version (PCL-C) to assess posttraumatic symptoms severity. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV) parameters. Frequency-domain indices of HRV were obtained. The obtained results were evaluated in association with personality traits assessed by the Tridimensional Personality Questionnaire (TPQ).

Results

PTSD patients exhibited decreased LF-HRV and HF-HRV as compared to survivors without PTSD and to matched controls. The PTSD symptoms severity was associated with reduced mean RR intervals, Var-HRV, LF-HRV and HF-HRV. The harm avoidance score (which has been suggested to be associated with serotonergic activity) was negatively correlated with Var-HRV, LF-HRV and HF-HRV.

Conclusion

These data suggest that PTSD is accompanied by decreased CVC, highlighting the importance of assessing HRV in PTSD patients. In view of the increased risk for cardiovascular diseases in these vulnerable individuals, one might consider the treatment to restore their autonomic function while reducing PTSD symptoms.     

Is Nonverbal Communication Disrupted in Interactions Involving Patients With Schizophrenia?

Background: Nonverbal communication is a critical feature of successful social interaction and interpersonal rapport. Social exclusion is a feature of schizophrenia. This experimental study investigated if the undisclosed presence of a patient with schizophrenia in interaction changes nonverbal communication (ie, speaker gesture and listener nodding). Method: 3D motion-capture techniques recorded 20 patient (1 patient, 2 healthy participants) and 20 control (3 healthy participants) interactions. Participants rated their experience of rapport with each interacting partner. Patients’ symptoms, social cognition, and executive functioning were assessed. Four hypotheses were tested: (1) Compared to controls, patients display less speaking gestures and listener nods. (2) Patients’ increased symptom severity and poorer social cognition are associated with patients’ reduced gesture and nods. (3) Patients’ partners compensate for patients’ reduced nonverbal behavior by gesturing more when speaking and nodding more when listening. (4) Patients’ reduced nonverbal behavior, increased symptom severity, and poorer social cognition are associated with others experiencing poorer rapport with the patient. Results: Patients gestured less when speaking. Patients with more negative symptoms nodded less as listeners, while their partners appeared to compensate by gesturing more as speakers. Patients with more negative symptoms also gestured more when speaking, which, alongside increased negative symptoms and poorer social cognition, was associated with others experiencing poorer patient rapport. Conclusions: Patients’ symptoms are associated with the nonverbal behavior of patients and their partners. Patients’ increased negative symptoms and gesture use are associated with poorer interpersonal rapport. This study provides specific evidence about how negative symptoms impact patients’ social interactions.Key words: schizophrenia, nonverbal communication, rap port, symptoms, social exclusion     

Mortality in Schizophrenia and Other Psychoses: A 10-Year Follow-up of the ?SOP First-Episode Cohort

The excess mortality in people with psychotic disorders is a major public health concern, but little is known about the clinical and social risk factors which may predict this health inequality and help inform preventative strategies. We aimed to investigate mortality in a large epidemiologically characterized cohort of individuals with first-episode psychosis compared with the general population and to determine clinical and social risk factors for premature death. All 557 individuals with first-episode psychosis initially identified in 2 areas (Southeast London and Nottinghamshire, United Kingdom) were traced over a 10-year period in the ӔSOP-10 study. Compared with the general population, all-cause (standardized mortality ratio [SMR] 3.6, 95% confidence interval [CI] 2.6–4.9), natural-cause (SMR 1.7, 95% CI 1.0–2.7) and unnatural-cause (SMR 13.3, 95% CI 8.7–20.4) mortality was very high. Illicit drug use was associated with an increased risk of all-cause mortality (adj. rate ratio [RR] 2.31, 95% CI 1.06–5.03). Risk of natural-cause mortality increased with a longer time to first remission (adj. RR 6.61, 95% CI 1.33–32.77). Family involvement at first contact strongly reduced risk of unnatural-cause mortality (adj. RR 0.09, 95% CI 0.01–0.69). Our findings suggest that the mortality gap in people with psychotic disorders remains huge and may be wider for unnatural-cause mortality than previously reported. Efforts should now focus on further understanding and targeting these tractable clinical and social risk factors of excess mortality. Early intervention and dual diagnosis services may play a key role in achieving more rapid remission and carer involvement and addressing substance use problems to reduce excess mortality in psychosis.Key words: schizophrenia/, mortality/, psychosis/, risk factors     

Is Familiality Associated with Downward Occupation Drift in Schizophrenia?

Objective

Downward occupational drift has been extensively investigated in schizophrenia. It is known that certain illness related factors, such as severity, affect drift, but the impact of familial factors has not been investigated.

Methods

Occupation drift was studied among patients with schizophrenia/schizoaffective disorder (SZ/SZA)(n=523) and 130 affected sib pairs (ASPs). Drift was analyzed in relation to familiality as well as demographic and clinical variables. For comparison one proband (one of the affected siblings) from each ASP was selected. Occupation drift was measured in relation to the most responsible job held, and with regard to head of the household (HOH) occupation status.

Results

There was no significant difference between single affected and ASP probands in terms of occupational drift from the most responsible job (drifted 39.2% and 38% respectively) and with regard to HOH''s occupation (drifted 88% and 82.8% respectively). A significant part of the sample remained unemployed in both single affected and ASP samples. Thus, there was no significant impact of familiality on these variables. However, marital status, pattern of severity, age at onset, gender were found to be associated with downward occupation drift in single affected probands while the only significant factor in familial probands was pattern of severity of severity when measuring in terms of downward drift from most responsible job.

Conclusion

Though there is occupation drift in schizophrenia, there is no detectable impact of familial factors. Employment is associated with severity of delete.     

Is Taste Altered in Patients with ALS?

Amyotrophic lateral sclerosis (ALS) is a degenerative neurological disease that affects the motor systems in patients but also may affect some sensory systems. Some ALS patients report taste changes that may decrease their oral intake and nutritional status. This study examined whether focal taste damage occurs in ALS patients compared to age/gender-matched adult healthy controls. An abbreviated Spatial Taste Test was administered to the fungiform and circumvallate papillae. Compared to healthy controls, ALS patients exhibited significantly lower taste intensities across the four basic tastes and significantly lower taste intensities at both the fungiform and vallate papillae, but no significant difference in whole mouth taste intensities. Seven out of nine ALS patients with self reported altered taste had tongue fasciculations, involuntary movements within the tongue dorsum due to lower motor neuron impairment (a common sign of bulbar ALS). Additionally, for patients taking riluzole taste perception at the fungiform papillae appears to be further reduced relative to the vallate papillae. This study suggests ALS decreases taste at both the fungiform and vallate papillae. In addition, riluzole may further damage the chorda tympani. Further studies need to be conducted to examine the etiology for taste loss.     

Elevated Levels of α-Synuclein Oligomer in the Cerebrospinal Fluid of Drug-Na?ve Patients with Parkinson's Disease

Background and Purpose

The detection of α-synuclein in the body fluids of patients with synucleinopathy has yielded promising but inconclusive results, in part because of conformational changes of α-synuclein in response to environmental conditions. The aim of this study was to determine the feasibility of using α-synuclein as a biological marker for Parkinson''s disease (PD).

Methods

Twenty-three drug-naïve patients with PD (age 62.4±12.7 years, mean±SD; 11 males) and 29 age- and sex-matched neurologic control subjects (age 60.1±16.2 years; 16 males) were recruited. The levels of oligomeric and total α-synuclein in the cerebrospinal fluid (CSF) and plasma were measured using two simultaneous enzyme-linked immunosorbent assays.

Results

The level of α-synuclein oligomer in the CSF of PD patients was significantly higher in PD patients than in neurological controls, but other findings (plasma α-synuclein oligomer and total α-synuclein in CSF and plasma) did not differ significantly between the two groups. When the control subjects were divided into a symptomatic control group (11 patients who complained of parkinsonian symptoms and were diagnosed with hydrocephalus and drug-induced or vascular parkinsonism) and a neurologic control group (10 normal subjects and 8 patients with diabetic ophthalmoplegia), the level of α-synuclein oligomer in the CSF was still significantly higher in PD patients than in both of the control subgroups.

Conclusions

These findings provide further evidence for a pathogenic role of the α-synuclein oligomer and suggest that CSF levels of α-synuclein oligomer can be a reliable marker for PD.     

Comorbid Moderate–Severe Depressive Symptoms and their Association with Quality of Life in Chinese Patients with Schizophrenia Treated in Primary Care

This study described the prevalence and correlates of comorbid moderate–severe depressive symptoms (comorbid depression thereafter) and their association with quality of life (QOL) in schizophrenia patients treated in primary care. 623 schizophrenia patients were enrolled. Patients’ socio-demographic and clinical characteristics including comorbid depression [defined as a total score of 18 or above on the Montgomery–Asberg Depression Rating Scale (MADRS)] were recorded. Depressive symptoms (defined as a total score of 9 or above on the MADRS) were present in 54.1?% of patients, while 17.7?% had comorbid depression. Analysis of covariance revealed that comorbid depression was significantly associated with lower mental QOL. Multiple logistic regression analysis revealed that more severe positive and negative symptoms, anxiety symptoms, use of first-generation antipsychotics and antidepressants, were independently associated with comorbid depression. Given the negative association between comorbid depression and QOL, attempts to address comorbid depression in schizophrenia patients treated in primary care should be made.     

Dopamine Modulation of Emotional Processing in Cortical and Subcortical Neural Circuits: Evidence for a Final Common Pathway in Schizophrenia?

The neural regulation of emotional perception, learning, and memory is essential for normal behavioral and cognitive functioning. Many of the symptoms displayed by individuals with schizophrenia may arise from fundamental disturbances in the ability to accurately process emotionally salient sensory information. The neurotransmitter dopamine (DA) and its ability to modulate neural regions involved in emotional learning, perception, and memory formation has received considerable research attention as a potential final common pathway to account for the aberrant emotional regulation and psychosis present in the schizophrenic syndrome. Evidence from both human neuroimaging studies and animal-based research using neurodevelopmental, behavioral, and electrophysiological techniques have implicated the mesocorticolimbic DA circuit as a crucial system for the encoding and expression of emotionally salient learning and memory formation. While many theories have examined the cortical-subcortical interactions between prefrontal cortical regions and subcortical DA substrates, many questions remain as to how DA may control emotional perception and learning and how disturbances linked to DA abnormalities may underlie the disturbed emotional processing in schizophrenia. Beyond the mesolimbic DA system, increasing evidence points to the amygdala-prefrontal cortical circuit as an important processor of emotionally salient information and how neurodevelopmental perturbances within this circuitry may lead to dysregulation of DAergic modulation of emotional processing and learning along this cortical-subcortical emotional processing circuit.     

Does Gender Influence Outcome in Schizophrenia?

Psychiatric Quarterly - Good outcome of schizophrenia has several meanings and most of these meanings carry both positive and negative undertones depending on perspective. Currently, a...     

Sociodemographic Factors and Medication Administration Factors Affecting Re – Hospitalization in Patients with Schizophrenia – Spectrum Disorders

Psychiatric Quarterly - Schizophrenia – spectrum disorders have been shown to have large economic costs for the society due to hospitalizations. Long Acting Injections (LAIs) have been shown...     

Why Do Patients with Partial Epilepsy Improve Their IQ After Training to Self-Regulate Slow Cortical Potentials?

In patients with epilepsy, not only seizures but also cognitive, emotional, and social functioning are of increasing interest in research (Kelley, Jacobs, &; Lowenstein, 2009 Kelley , M. S. , Jacobs , M. P. , &; Lowenstein , D. H. , for the NINDS Epilepsy Benchmark Stewards . ( 2009 ). The NINDS epilepsy research benchmarks . Epilepsia , 50 , 579 – 582 . doi: doi:10.1111/j.1528-1167.2008.01813.x  [Google Scholar]). As a decrease in cognitive functions over the course of the illness is usually reported, we wanted to explore changes in Intelligence Scores observed after a neurofeedback treatment in patients with drug-resistant epilepsies. In a controlled study that compared the outcome of three different interventions (training to regulate slow cortical potentials, N = 34; training to regulate breath rate and the amount of carbon dioxide in the end tidal volume of the exhaled air, N = 11; modification of drug regime, N = 25), pre- and postmeasurements of a short version of the Wechsler Intelligence Scale were applied. The interval between the two assessments was more than 12 months, with a mean of 61 weeks. Mean age of the patients was 35, with a range from 17 to 57. The highly significant 7-point increment of IQ only after training of slow cortical potentials was not related to clinical (e.g., seizure reduction) or neuropsychological (e.g., attention and memory) variables. Instead, it was related to psychophysiological measures: IQ change was inversely related to the Latency of the P300 component of event-related brain potentials and directly related to the Latency of the P2 component and the increase of N2 Amplitude during training. We conclude that regulation training of slow cortical potentials improves IQ in patients with refractory partial epilepsy, which might be related to an improved ability for controlled allocation of cognitive resources.