Elevated allostatic load early in the course of schizophrenia.

Stress plays a significant role in schizophrenia from disease onset to exacerbation of psychotic symptoms. Allostatic load (AL) is a measure of cumulative stress to the organism. This study is an extension of our previous work on AL and its relationship to brain structures. Here, we further determined whether elevated AL is a function of illness chronicity, or if it is already present early in the course of schizophrenia. AL was compared in schizophrenia patients early in the illness (within 5 years of disease onset), patients with chronic schizophrenia (more than 5 years of illness), and two groups of healthy controls that were age-and sex-matched to the two patient groups. This work is presented with an expanded sample and includes about two-thirds of the participants who were previously reported. We found that patients with early psychosis had significantly elevated AL score compared with their age-matched controls (p = 0.005). Chronic course patients also had elevated AL compared with age-matched controls (p = 0.003). Immune and stress hormone AL subcomponents were nominally higher in early-stage patients compared with controls (p = 0.005 and 0.04, respectively). Greater AL was also associated with more severe positive psychotic symptoms in early-stage patients (r = 0.54, p = 0.01). Elevated levels of allostatic load are already present in the early years of the schizophrenia illness, particularly in patients with more severe psychotic symptoms. AL may be a useful evaluation for the need of early intervention on psychosomatic comorbidity.

The association of cannabis use on inpatient psychiatric hospital outcomes.

BACKGROUND: The associations between cannabis use and psychosis are well documented in numerous studies. There is a need to evaluate the impact of cannabis use on inpatient psychiatric utilization and outcomes. OBJECTIVES: To evaluate the impact of cannabis use on psychiatric hospital outcomes. METHODS: This study was conducted between April 20, 2015 and October 20, 2015. All patients (n = 120) admitted to Denver Health with psychotic symptoms were administered a urine toxicology screening testing for the presence of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH, the active metabolite of cannabis). Patients with positive tests were compared to those with negative tests on several measures, including length of stay, presence or lack of 30-day readmission, Brief Psychotic Rating Scale (BPRS) score, and use of antipsychotics and/or sedatives/anxiolytics. RESULTS: There were 120 patients. Twenty nine were women and 91 were men. Patients testing positive for THC-COOH had a shorter length of stay compared to patients testing negative for THC-COOH, after adjusting for age, prior psychiatric admissions, history of a psychotic-spectrum disorder, and comorbid additional substance use (p = 0.02). There were no differences in 30-day readmissions, 30-day post-discharge presentation to the Denver Health psychiatric emergency department, BPRS scores, and medication administration. CONCLUSION: Patients presenting with psychotic symptoms and cannabis use require shorter inpatient psychiatric hospitalizations. This study is the first to quantify this observation and highlights the need for future clinical decision-making tools that would ideally correlate cannabis use with the degree of potential need for expensive and scarce mental health resources, such as psychiatric hospitalization.

Elevated hydroxylactam of hemopyrrole level in urine in perpetrators of extremely violent acts diagnosed with psychosis. / Podwyzszone stezenie hydroksylaktamu hemopyrolu u psychotycznych sprawców czynów szczególnie agresywnych.

OBJECTIVES: Hydroxylactam of hemopyrrole (HPL) is an abnormal side product of porphyrin biosynthetic pathway, which may have a devastating impact on the behavior. The link between an aggressive behavior and an increased HPL level was postulated in the 1960s. Further researches concerning HPL brought contrary results and did not clarify its function and possible role in the pathogenesis of aggression. In our research we hypothesize that a heightened level of HPL may correspond to an extreme aggressive behavior in subjects diagnosed with psychosis. METHODS: We performed an analysis of HPL level in urine samples, collected from 36 male subjects diagnosed with a mental illness who presented an extreme aggressive behavior. The control group included 22 male subjects, matched with age. RESULTS: The variable HPL/creatinine quotient differs significantly between the study group and the control group. CONCLUSIONS: We used successfully proprietary method for marking HPL level in urine, developed for the purposes of the project. The results of our study indicate that in a group of subjects with a history of an extreme aggressive behavior a corrected level of HPL may be elevated, compared to subject without history of extreme aggressive behavior. Further studies are needed to evaluate the reasons of HPL elevation and its clinical implications in this group of patients.

Lower rates of consistent urine drug tests for prescribed psychotropic medications among patients on opioid replacement therapy.

BACKGROUND: Patients on opioid replacement therapy (ORT) to treat opioid use disorder are frequently monitored for these medications, but it is not known if they are also adhering to their psychotropic medications. This is an analysis of measure of potential adherence to psychotropic medications by patients on ORT. METHODS: This is a retrospective cohort study of patients (n=1470) on antidepressants and/or antipsychotics and tested by the Millennium Health laboratory. Potential adherence to psychotropic medications was measured by urine drug test (UDT) results. The consistency of UDT for expected psychotropic medication in patients on ORT was compared to patients not on ORT (control group) during 3-months period. The study used propensity score methods to match individuals from both groups on their demographics and their psychotropic medication. RESULTS: There were 457 participants (31.09%) on ORT and 1013 participants (68.91%) in the control group. Only 55.33% of UDTs (n=1388) were consistent for expected psychotropic medications in the ORT group compared to 73.69% of UDTs (n=4953) consistent for expected psychotropic medications in the control group (χ2=172.99, p<0.001). After matching, patients in the ORT group were less likely than the control group to have consistent UDTs for expected psychotropic medications (OR: 0.81, 95% CI: 0.76-0.85, P<0.001). CONCLUSION: There is a high rate of inconsistent UDT for prescribed psychotropic medication among patients on ORT. This could reflect potential poor adherence. Monitoring adherence to psychotropic medications should be part of every clinical visit for patients on ORT.

Striatal dopamine D2/3 receptor binding following dopamine depletion in subjects at Ultra High Risk for psychosis.

Altered striatal dopaminergic neurotransmission is thought to be fundamental to schizophrenia. Increased presynaptic dopaminergic activity ([18F]-DOPA PET) may predate the onset of psychotic symptoms and correlates to clinical symptoms in subjects at Ultra High Risk (UHR) for developing psychosis. Postsynaptic dopaminergic neurotransmission has not been investigated yet in UHR patients. We hypothesized that synaptic dopamine concentration would be increased in UHR patients, and that synaptic dopamine concentration would be related to symptom severity. 14 UHR patients and 15 age and IQ matched controls completed an [123I]-IBZM SPECT scan at baseline and again after dopamine depletion with alpha-methyl-para-tyrosine (AMPT). We measured changes in radiotracer binding potential, compared these between UHR patients and controls, and correlated these to symptom severity. The UHR group as a whole did not differ significantly from controls. AMPT significantly reduced symptom severity in the UHR group (p=0.014). Higher synaptic dopamine concentration predicted larger reduction of positive symptoms following depletion in the UHR group (p=0.01). In UHR patients, positive symptoms responded to dopamine depletion, comparable to observations in schizophrenia, suggesting a similar mechanism. Higher synaptic dopamine concentration was associated with more severe positive symptoms and a greater reduction of these symptoms following depletion.

Colloidal silver ingestion with copper and caeruloplasmin deficiency.

The copper concentration in serum can be affected by the presence of other trace elements such as silver. Low serum copper may result in decreased caeruloplasmin synthesis. We report the case of a 59-year-old woman, who was admitted to hospital with acute psychosis and who had been ingesting chronically, colloidal silver.

Testosterone in newly diagnosed, antipsychotic-naive men with nonaffective psychosis: a test of the accelerated aging hypothesis.

OBJECTIVE: Schizophrenia has been associated with age-related abnormalities, including abnormal glucose tolerance, increased pulse pressure, increased inflammation, abnormal stem cell signaling, and shorter telomere length. These metabolic abnormalities and other findings suggest that schizophrenia and related disorders might be associated with accelerated aging. Testosterone activity has a progressive decline with increasing age. METHODS: We tested the hypothesis that circulating biologically active testosterone is lower in newly diagnosed, antipsychotic-naive male patients with nonaffective psychosis than in matched control subjects. RESULTS: Patients (n = 33) were matched to control subjects (n = 33) for age, sex, body mass index, socioeconomic status of the family of origin, and smoking. The free androgen index, a measure of biologically active testosterone, was significantly lower in the psychosis group (mean [standard deviation] = 57.7% [26.1]) than in control subjects (71.6% [27.0], p = .04), with an effect size of 0.53. Multivariate analysis also supported the findings. In the psychosis group, free androgen index had a significant negative correlation with the conceptual disorganization item (r = -0.35, p = .049) but not with reality distortion (r = -0.21, p = .24), negative symptoms (r = 0.004, p = .98), or depression (r = -0.014, p = .94). CONCLUSIONS: Lower testosterone level is consistent with accelerated aging in nonaffective psychosis, but further testing of this hypothesis is needed.

Reduced urinary excretion of homocysteine could be the reason of elevated plasma homocysteine in patients with psychiatric illnesses.

OBJECTIVES: Although increased plasma total homocysteine (tHcy) concentrations were reported in psychiatric diseases, currently the reasons of elevated tHcy levels were not clearly understood. In this study we aimed to investigate the contribution of renal clearance of homocysteine on plasma tHcy load in patients with depression and first episode psychosis. DESIGN AND METHODS: Thirty depression, 14 first episode psychosis patients and 34 healthy individuals (control group) were involved in the study. In patients and control groups, plasma and urine tHcy levels, urine methylmalonic acid (uMMA), serum vitamin B12 and folate concentrations were measured. RESULTS: Although there was not any difference between depression, psychosis and control groups with respect to mean (SD) values of vitamin B12 (289(131), 230 (72) and 249(79) pg/mL, respectively) and folate (6.4(4.0), 5.3(2.3) and 5.7(2.3) ng/mL, respectively), plasma tHcy levels of depression and psychosis group were higher than the control values (16.3(6.2), 15.5(4.3) and 9.9(2.1) micromol/L, respectively). Urine tHcy values of patient groups were significantly lower than those in the control group (14.5(7.6), 15.8(6.8) and 29.6(16.9) micromol/g creatinine, respectively). There were elevated uMMA levels in depression and psychosis groups compared with control group (4.9(2.4), 6.6(3.2) and 2.8(1.2) mmol/mol creatinine, respectively). There were a significant and negative correlation between urinary tHcy and plasma tHcy levels (r=-0.258 and p=0.011). CONCLUSION: In conclusion, reduced urinary tHcy levels in psychiatric patients could be one of the reasons of plasma tHcy elevations with normal folate and vitamin B12 levels. Altered renal handling mechanisms of homocysteine may lead to elevated plasma tHcy levels by reduced clearance of homocysteine via glomerular filtration.

Relationship between nocturnal urinary cortisol excretion and symptom severity in subgroups of patients with depressive episodes.

INTRODUCTION: The aim of this naturalistic study was to gain more information about the elevation of basal hypothalamic-pituitary-adrenal (HPA) activity in relationship to symptom severity in specific subtypes of depressive episodes. METHOD: Hamilton Depression Rating Scale scores and aggregated nocturnal urinary cortisol excretion were measured in 4 groups of inpatients with depressive episodes (n = 48; monopolar nonpsychotic, monopolar psychotic, bipolar nonpsychotic and bipolar psychotic) at the beginning and at the end of inpatient treatment. RESULTS: The initial elevation of nocturnal urinary cortisol excretion was most pronounced in psychotic patients. At the end of treatment, the Hamilton Depression Rating Scale scores had decreased significantly in all patients to comparable levels, whereas the nocturnal cortisol excretion values were still relatively elevated in mono- and bipolar psychotic patients compared to mono- and bipolar nonpsychotic ones. CONCLUSION: The observation that the basal HPA activity remains elevated even after remission of symptoms in patients with psychotic depression supports the concept that a dysfunctional regulation of the HPA system is possibly a trait- rather than a state-related feature.

Cannabis use and misuse prevalence among people with psychosis.

BACKGROUND: Increasing attention has been given by researchers to cannabis use in individuals with psychosis. As psychoses are relatively low-prevalence disorders, research has been mostly been restricted to small-scale studies of treatment samples. The reported prevalence estimates obtained from these studies vary widely. AIMS: To provide prevalence estimates based on larger samples and to examine sources of variability in prevalence estimates across studies. METHOD: Data from 53 studies of treatment samples and 5 epidemiological studies were analysed. RESULTS: Based on treatment sample data, prevalence estimates were calculated for current use (23.0%), current misuse (11.3%), 12-month use (29.2%), 12-month misuse (18.8%), lifetime use (42.1%) and lifetime misuse (22.5%). Epidemiological studies consistently reported higher cannabis use and misuse prevalence in people with psychosis. CONCLUSIONS: The factor most consistently associated with increased odds of cannabis prevalence was specificity of diagnosis. Factors such as consumption patterns and study design merit further consideration.

Use of case manager ratings and weekly urine toxicology tests among outpatients with dual diagnoses.

Use of drugs and alcohol by 43 predominantly male outpatients who had severe mental illness and a comorbid substance use disorder were assessed weekly through the ratings of experienced dual disorder case managers and through blinded research urine toxicology tests. The percentage of weeks in which drugs or alcohol were used was calculated on the basis of one or both assessments. The case managers often missed drug use over the weekends, which was detected by the urine toxicology tests. Agreement between the two methods varied widely, even when the ratings were made by highly experienced case managers. These findings have implications for monitoring patients with dual diagnoses and provide insight into the accuracy of case manager ratings.

Absence of myoglobinuria in acute psychotic patients with marked elevation in serum creatine phosphokinase level.

Elevated levels of serum creatine phosphokinase, muscular type (CK(MM)) are caused primarily by diseased muscle fiber. Acute psychoses are often associated with a marked increase in serum CK(MM) levels, though the reason remains obscure. Since striated muscle damage is also associated with pigmenturia and myoglobinuria, we sought to determine whether the markedly high serum CK level of acute psychosis reflects skeletal muscle damage by evaluating urinary myoglobin in affected patients. Baseline serum CK was measured on admission in 713 consecutive acute psychotic inpatients (BPRS> or =40). Those showing a serum CK levels above 1000 IU/l on the first 2 days of hospitalization underwent urine collection for myoglobin testing. Patients with physical trauma or medical conditions known to cause CKemia were excluded. Twenty-five patients were eligible for the study. In no case did myoglobinuria or pigmenturia accompany the marked CKemia. There is an unexpected dissociation between the robust increase in the serum CK(MM) levels and the absence of myoglobinuria in acute psychosis. Our negative finding may indicate that the serum CK threshold for myoglobinuria is very high (above 10000 IU/l). Alternatively, psychosis-associated CKemia may be related to an unknown, nontraumatic, pathophysiological mechanism(s).

[The action of high-intensity light on catecholamine excretion in depressive patients]. / Deistvie sveta povyshennoi intensivnosti na ékskretsiiu katekholaminov u bol'nykh depressiei.

The action of bright light (2600-2800 lux) on the catecholamine (CA) excretion was analyzed in patients with anxious (11) and melancholic (12) depressions resultant from manic-depressive psychosis and schizophrenia. The melancholic depressed patients were characterized by decreased noradrenaline (NA) and increased adrenaline (A) levels; in anxious depression NA and A were increased. The light therapy resulted in decrease of A level but NA level remained invariable in melancholic depression. Meanwhile the tendency to normalization of excretion of both CA was observed in anxious patients after light therapy. The contrary alterations in A/NA ratio as well as its considerable individual fluctuations were observed after light therapy. The A/NA ratio after light therapy depended mainly upon the initial A/NA ratio (the higher or lower ratio compared to control value).