CSF homocysteine is not elevated in schizophrenia

Summary. Homocysteine is a neurotoxic amino acid originally found to be an independent risk factor for cardiovascular and cerebral vascular disease and more recently suggested to be a risk factor for Alzheimers disease. Several authors have observed high plasma homocysteine levels among schizophrenia patients. We reported that such high levels characterize young male schizophrenia patients.We now studied two groups of schizophrenia patients (N=41) and controls (N=29) for CSF homocysteine levels. No difference was found for CSF homocysteine levels between schizophrenia patients and controls (p=.041 for Study A and p=.52 for Study B).     

Schizophrenic relapse after drug withdrawal is predictable

Thirty-two patients in remission were followed by regular ratings during a prospective neuroleptic withdrawal study. They were outpatients who fulfilled the DSM-III criteria of schizophrenia and who were motivated for drug withdrawal. The relapse rate was 81%. The results from the rating scales confirm the hypothesis that a symptom increase occurs before psychotic relapse. In the order statistical differences occurred, the factors predicting relapse were those concerned with positive psychopathology, motor dysfunction, impaired affects and sleep disturbances. The corresponding symptoms and signs were mainly concerned with thought disorders, paranoid ideation, overactivity, depression and insomnia middle, all of nonpsychotic degree of severity. If prodromes appear, the patient should resume his neuroleptic treatment, or other preventive measures should be taken. By such therapeutic interactions, psychotic relapse may be prevented, or can be dealt with in an outpatient setting.     

C-reactive protein is elevated in schizophrenia

BackgroundIncreased levels of inflammatory markers have been reported in schizophrenia, but few studies have examined levels of high sensitivity C-reactive protein (CRP), a non-specific inflammatory marker.MethodsLevels of high sensitivity CRP were measured in individuals with schizophrenia, bipolar disorder, and non-psychiatric controls. Linear regression analyses were used to compare the CRP levels among the three groups adjusting for demographic and clinical variables. Logistic regression analyses were used to determine the odds ratios associated with elevated levels of CRP, defined as >=75th and 90th percentile in the controls.ResultsThe sample consisted of 715 individuals: 295 with schizophrenia, 192 with bipolar disorder, and 228 without a psychiatric disorder. The levels of CRP in the schizophrenia group, but not in the bipolar disorder group, were significantly increased compared to controls adjusting for age, gender, race, maternal education, smoking status, and Body Mass Index (BMI) (t = 3.78, p = < .001). The individuals with schizophrenia had significantly increased odds of having elevated levels of CRP relative to both the 75th and 90th percentile levels of the controls adjusting for the same covariates (OR 1.79, 95% CI 1.14, 2.82; p = .012; OR 2.76, 95% CI 1.58, 4.83, p = < .001). In the multivariate linear and logistic regression analyses, levels of CRP were also associated with BMI and female gender.ConclusionsIndividuals with schizophrenia may be at risk for the adverse health consequences associated with elevated CRP in the overall population. Trials of interventions directed at lowering the level of CRP and other inflammatory markers are indicated.     

CSF somatostatin is elevated in patients with postzoster neuralgia

We evaluated the concentration of the neuropeptide somatostatin (SOM) in the CSF of patients with several neurologic diseases. Since SOM is localized in high concentrations in primary sensory pathways, such as the dorsal root ganglia and dorsal horn of the spinal cord, it might be involved in conditions of chronic pain due to functional alterations of nociceptive neurons, such as postinfectious zoster neuralgia. Our study indicated a marked elevation of SOM in patients suffering from postzoster neuralgia compared with controls. Comparison with other neurologic diseases revealed decreased CSF SOM levels in Parkinson's and Alzheimer's disease, unchanged values in patients with amyotrophic lateral sclerosis, and increased concentrations in patients with brain tumors. In neurodegenerative disorders, SOM levels in CSF seemed to reflect the anatomic distribution as well as a reduction or preservation of the peptide in certain brain areas affected by the disease process. In postzoster patients, postinfectious degeneration of dorsal root ganglia cells might cause deafferentation of dorsal horn neurons and activation of SOM-containing systems with increased release either locally from neurons in the dorsal horn of the spinal cord or from descending fiber projections. The results suggested that SOM may take part in the modulation of nociceptive responses.     

Quality of life is predictive of relapse in schizophrenia

Background

Obese and overweight people have a higher risk of both chronic physical illness and mental illness. Obesity is reported to be positively associated with psychiatric disorders, especially in people who seek obesity treatment. At the same time, obesity treatment may be influenced by psychological factors or personality characteristics. This study aimed to understand the prevalence of mental disorders among ethnic Chinese who sought obesity treatment.

Methods

Subjects were retrospectively recruited from an obesity treatment center in Taiwan. The obesity treatments included bariatric surgery and non-surgery treatment. All subjects underwent a standardized clinical evaluation with two questionnaires and a psychiatric referral when needed. The psychiatric diagnosis was made thorough psychiatric clinic interviews using the SCID. A total of 841 patients were recruited. We compared the difference in psychiatric disorder prevalence between patients with surgical and non-surgical treatment.

Results

Of the 841 patients, 42% had at least one psychiatric disorder. Mood disorders, anxiety disorders and eating disorders were the most prevalent categories of psychiatric disorders. Females had more mood disorders and eating disorders than males. The surgical group had more binge-eating disorder, adjustment disorder, and sleep disorders than the non-surgical group.

Conclusion

A high prevalence of psychiatric disorders was found among ethnic Chinese seeking obesity treatment. This is consistent with study results in the US and Europe.     

Increased CSF cortisol levels after neuroleptic treatment in schizophrenia

The cerebrospinal fluid (CSF) concentration of cortisol was determined in schizophrenic patients drug-free and on neuroleptics, compared to healthy controls, and in schizophrenics before and during neuroleptic treatment. Neuroleptics significantly increased the CSF concentrations of cortisol in these patients.     

Pupillary constriction during haloperidol treatment as a predictor of relapse following drug withdrawal in schizophrenic patients.

It has been proposed that the autonomic nervous system is dysregulated in schizophrenia. We hypothesized that measures of autonomic function, even during neuroleptic stabilization, might predict relapse following withdrawal of medication. Previously, shorter latencies to maximum pupillary constriction have been reported to differentiate acutely hospitalized schizophrenic patients from control subjects. Pupillary light reactions were recorded weekly from 19 chronic schizophrenic inpatients who were initially maintained on haloperidol and subsequently were withdrawn from medication under double-blind, placebo-controlled conditions. Patients were then classified as either relapsed or nonrelapsed (clinically stable) during the drug-free period. During the treatment phase, a shorter latency to maximum pupillary constriction significantly distinguished patients who were later to relapse from the nonrelapsers. The potential use of autonomic activity as an indicator of prodromal sensitivity was supported. In addition, these findings emphasize the need for classification of drug-free patients according to clinical status.     

CSF creatinine in schizophrenia

Concentrations of creatinine in cerebrospinal fluid (CSF) from schizophrenic patients and healthy control subjects were determined by a liquid chromatographic method. The concentration of creatinine in CSF from schizophrenic patients was lower (42.8 nmol/ml) than that of the controls (54.4 nmol/ml). The concentration of creatinine was correlated to the levels of homovanillic acid and 5-hydroxyindoleacetic acid. Treatment of the schizophrenic patients with sulpiride (800 mg daily), but not with chlorpromazine, elevated the concentration of creatinine in the CSF.     

Seven keys to relapse prevention in schizophrenia

Relapse prevention is a primary goal in the treatment of schizophrenia. Relapse can cause significant personal distress, interfere with rehabilitation efforts, and result in psychiatric hospitalization. The emergence of psychotic symptoms and disruptive behaviors can also lead to arrest and incarceration, particularly among patients who are not engaged in treatment. This article focuses on the process of relapse in schizophrenia and theoretical foundations of relapse prevention. The Program for Relapse Prevention is presented, along with the results of a recently completed controlled prospective evaluation. Based upon this study and the current literature, the author presents a series of seven clinical strategies for optimal relapse prevention.     

Clinical factors related to schizophrenia relapse

Objective: Relapses represent one of the main problems of schizophrenia management. This article reviews the clinical factors associated with schizophrenia relapse. Methods: A research of the last 22 years of literature data was performed. Two-hundred nineteen studies have been included. Results: Three main groups of factors are related to relapse: factors associated with pharmacological treatment, add-on psychotherapeutic treatments and general risk factors. Overall, the absence of a maintenance therapy and treatment with first generation antipsychotics has been associated with higher risk of relapse. Further, psychotherapy add-on, particularly with cognitive behaviour therapy and psycho-education for both patients and relatives, has shown a good efficacy for reducing the relapse rate. Among general risk factors, some could be modified, such as the duration of untreated psychosis or the substance misuse, while others could not be modified as male gender or low pre-morbid level of functioning. Conclusion: Several classes of risk factors have been proved to be relevant in the risk of relapse. Thus, a careful assessment of the risk factors here identified should be performed in daily clinical practice in order to individualise the relapse risk for each patient and to provide a targeted treatment in high-risk subjects.     

Probenecid-induced norepinephrine elevations in plasma and CSF

Probenecid administered in divided oral doses totaling 100 mg/kg increased levels of norepinephrine (NE) in plasma and cerebrospinal fluid (CSF). This technique is commonly used to measure the rate of accumulation of acidic metabolites of certain brain neurotransmitter biogenic amines in CSF after blockade of their transport into blood. Since levels of 3-methoxy-4-hydroxy-phenylethyleneglycol, a neutral metabolite of NE, are also elevated after high oral doses of probenecid, the increases of CSF and plasma NE levels may be directly related to probenecid-induced release of this amine from noradrenergic neurons. In patients who experienced nausea or vomiting there were lower levels of probenecid in CSF, probably secondary to diminished absorption of the medication. These patients also had lower levels of NE in plasma than did patients who remained asymptomatic.     

CSF norepinephrine concentrations in posttraumatic stress disorder

OBJECTIVE: Despite evidence of hyperresponsive peripheral and central nervous system (CNS) noradrenergic activity in posttraumatic stress disorder (PTSD), direct measures of CNS norepinephrine in PTSD have been lacking. The goal of this study was to determine serial CSF norepinephrine levels in patients with PTSD. METHOD: CSF samples were obtained serially over a 6-hour period in 11 male combat veterans with chronic PTSD and eight healthy men through an indwelling subarachnoid catheter. Thus the authors were able to determine hourly CSF norepinephrine concentrations under baseline (unstressed) conditions. Severity of the patients' PTSD symptoms was assessed with the Clinician-Administered PTSD Scale. RESULTS: CSF norepinephrine concentrations were significantly higher in the men with PTSD than in the healthy men. Moreover, CSF norepinephrine levels strongly and positively correlated with the severity of PTSD symptoms. Plasma norepinephrine concentrations showed no significant relationship with the severity of PTSD symptoms. CONCLUSIONS: These findings reveal the presence of greater CNS noradrenergic activity under baseline conditions in patients with chronic PTSD than in healthy subjects and directly link this pathophysiologic observation with the severity of the clinical posttraumatic stress syndrome.     

Predictors for relapse after antiepileptic drug withdrawal in seizure-free patients with epilepsy

The objective of this study was to evaluate the timing of medication withdrawal and other clinical factors as potential predictors of seizure relapse after antiepileptic drug (AED) withdrawal in patients with epilepsy. A total of 99 patients who were seizure free for more than 2 years were recruited from the Neurology Clinics of Nanjing Brain Hospital between 2001 and 2009, and were followed prospectively for at least 2 years or until seizure relapse. Kaplan–Meier survival analysis was used for calculating recurrence rates. Univariate and multivariate analyses for recurrence risk factors were performed using the Cox proportional hazards model. Thirteen patients were excluded due to loss of follow-up or incomplete seizure records. Epileptiform electroencephalography (EEG) abnormality within the first year after AED withdrawal (hazard ratio [HR] = 4.810, 95% confidence interval [CI] = 2.220–10.420) was found on multivariate analysis to be a predictor of seizure recurrence. Early AED withdrawal after a seizure-free period of 2–3 years did not significantly increase the risk of recurrence (HR = 0.999, 95% CI = 0.969–1.029) as compared with delayed AED withdrawal (patients who were seizure-free for more than 3 years). AED can be withdrawn in patients who have been seizure-free for more than 2 years. As epileptiform EEG abnormality within the first year after AED withdrawal predicts seizure relapse, it is necessary to perform EEG for patients during the first year after AED withdrawal.     

D2 but not D3 receptors are elevated after 9 or 11 months chronic haloperidol treatment: influence of withdrawal period

Previous postmortem studies have identified divergent alterations in D2 and D3 receptors in schizophrenia but those results cannot be interpreted without further understanding of whether antipsychotic regulation of the D3 receptor is different from that of the D2 receptor. Depot parenteral administration of haloperidol decanoate was utilized to achieve consistent high levels in rat brain for 9 months with 2-month withdrawal or 11 months with 48-h withdrawal and compared to vehicle control and acute haloperidol (48-h) treatment groups. Autoradiographic means for measuring levels of D2 ([(3)H]-spiperone) and D3 receptors ([(125)I]trans 7-OH-PIPAT) and of D3 mRNA by in situ hybridization histochemistry in rat caudate-putamen, nucleus accumbens, islands of Calleja, and olfactory tubercle determined that there were significant group differences for regulation of D2 receptor. Chronic haloperidol for 9 or 11 months elevated D2 but not D3 receptors or D3 mRNA in all regions measured. Acute haloperidol treatment had no significant effects for any measure. Treatment for 9 months with a 2-month withdrawal resulted in a persistent increase in D2 receptors that was greater than that observed in the 11 months with 48-h withdrawal. This effect was most noticeable in the olfactory tubercle. These data confirm previous findings that short- or long-term haloperidol treatment leads to elevations in D2 but not D3 receptors or D3 mRNA, and long-term withdrawal from chronic haloperidol does not lead to elevations in D3 receptors or D3 mRNA. This suggests that an elevation in D3 receptors identified at postmortem in schizophrenics withdrawn from antipsychotics is not the result of the previous drug history [Gurevich et al. (1997) Arch Gen Psychiatry 54:225-232].     

Social isolation is associated with elevated tumor norepinephrine in ovarian carcinoma patients

Noradrenergic pathways have been implicated in growth and progression of ovarian cancer. Intratumoral norepinephrine (NE) has been shown to increase with stress in an animal cancer model, but little is known regarding how tumor NE varies with disease stage and with biobehavioral factors in ovarian cancer patients. This study examined relationships between pre-surgical measures of social support, depressed mood, perceived stress, anxiety, tumor histology and tumor catecholamine (NE and epinephrine [E]) levels among 68 ovarian cancer patients. We also examined whether associations observed between biobehavioral measures and tumor catecholamines extended to other compartments. Higher NE levels were found in advanced stage (p = 0.006) and higher grade (p = 0.001) tumors. Adjusting for stage, grade, and peri-surgical beta blockers, patients with a perceived lack of social support had significantly higher tumor NE (β = −0.29, p = 0.012). A similar trend was seen for social support and ascites NE (adjusting for stage, peri-surgical beta blockers and caffeine: β = −0.50, p = 0.075), but not for plasma NE. Other biobehavioral factors were not related to tumor, ascites, or plasma NE (p values >0.21). Tumor E was undetectable in the majority of tumors and thus E was not further analyzed. In summary, these results suggest that tumor NE provides distinct information from circulating plasma concentrations. Tumor NE levels were elevated in relationship to tumor grade and stage. Low subjective social support was associated with elevated intratumoral NE. As beta-adrenergic signaling is related to key biological pathways involved in tumor growth, these findings may have implications for patient outcomes in ovarian cancer.     

CSF copper in schizophrenia.

The authors measured copper levels in the cerebrospinal fluid of 8 schizophrenic subjects and 6 controls. The schizophrenic subjects had significantly lower CSF copper values than the controls, which is consistent with the hypothesis that there is reduced central activity of copper-dependent enzymes in schizophrenia. These enzymes, tyrosine hydroxylase and dopamine-beta-hydroxylase, are involved in the synthesis and catabolism of dopamine.     

Plasma norepinephrine in chronic schizophrenia

Several lines of evidence indicate altered noradrenergic function in schizophrenia. The authors examined resting, standing, and change (standing minus resting) in plasma norepinephrine levels in 14 drug-free patients with chronic schizophrenia or schizoaffective disorder and in 33 age- and sex-matched healthy volunteers. Schizophrenic patients had significantly higher resting and standing plasma norepinephrine levels and significantly greater change. Resting and standing levels were significantly related to positive and negative symptoms. There was a significant positive correlation between resting plasma and CSF norepinephrine levels and a significant negative correlation between CSF homovanillic acid and resting, standing, and change in plasma norepinephrine levels.     

Time to relapse after epilepsy surgery in children: AED withdrawal policies are a contributing factor

Aim. It was recently suggested that early postoperative seizure relapse implicates a failure to define and resect the epileptogenic zone, that late recurrences reflect the persistence or re‐emergence of epileptogenic pathology, and that early recurrences are associated with poor treatment response. Timing of antiepileptic drugs withdrawal policies, however, have never been taken into account when investigating time to relapse following epilepsy surgery. Methods. Of the European paediatric epilepsy surgery cohort from the “TimeToStop” study, all 95 children with postoperative seizure recurrence following antiepileptic drug (AED) withdrawal were selected. We investigated how time intervals from surgery to AED withdrawal, as well as other previously suggested determinants of (timing of) seizure recurrence, related to time to relapse and to relapse treatability. Uni‐ and multivariable linear and logistic regression models were used. Results. Based on multivariable analysis, a shorter interval to AED reduction was the only independent predictor of a shorter time to relapse. Based on univariable analysis, incomplete resection of the epileptogenic zone related to a shorter time to recurrence. Timing of recurrence was not related to the chance of regaining seizure freedom after reinstallation of medical treatment. Conclusion. For children in whom AED reduction is initiated following epilepsy surgery, the time to relapse is largely influenced by the timing of AED withdrawal, rather than by disease or surgery‐specific factors. We could not confirm a relationship between time to recurrence and treatment response. Timing of AED withdrawal should be taken into account when studying time to relapse following epilepsy surgery, as early withdrawal reveals more rapidly whether surgery had the intended curative effect, independently of the other factors involved.