Treating late-onset Tay Sachs disease: Brain delivery with a dual trojan horse protein.

Tay-Sachs (TS) disease is a neurodegenerative disease resulting from mutations in the gene encoding the α-subunit (HEXA) of lysosomal ß-hexosaminidase A (HexA). We report that (1) recombinant HEXA alone increased HexA activity and decreased GM2 content in human TS glial cells and peripheral mononuclear blood cells; 2) a recombinant chimeric protein composed of HEXA linked to two blood-brain barrier (BBB) entry elements, a transferrin receptor binding sequence and granulocyte-colony stimulating factor, associates with HEXB in vitro; reaches human cultured TS cells lysosomes and mouse brain cells, especially neurons, in vivo; lowers GM2 in cultured human TS cells; lowers whole brain GM2 concentration by approximately 40% within 6 weeks, when injected intravenously (IV) to adult TS-mutant mice mimicking the slow course of late-onset TS; and increases forelimbs grip strength. Hence, a chimeric protein equipped with dual BBB entry elements can transport a large protein such as HEXA to the brain, decrease the accumulation of GM2, and improve muscle strength, thereby providing potential treatment for late-onset TS.

EEG-based spatio-temporal relation signatures for the diagnosis of depression and schizophrenia.

The diagnosis of psychiatric disorders is currently based on a clinical and psychiatric examination (intake). Ancillary tests are used minimally or only to exclude other disorders. Here, we demonstrate a novel mathematical approach based on the field of p-adic numbers and using electroencephalograms (EEGs) to identify and differentiate patients with schizophrenia and depression from healthy controls. This novel approach examines spatio-temporal relations of single EEG electrode signals and characterizes the topological structure of these relations in the individual patient. Our results indicate that the relational topological structures, characterized by either the personal universal dendrographic hologram (DH) signature (PUDHS) or personal block DH signature (PBDHS), form a unique range for each group of patients, with impressive correspondence to the clinical condition. This newly developed approach results in an individual patient signature calculated from the spatio-temporal relations of EEG electrodes signals and might help the clinician with a new objective tool for the diagnosis of a multitude of psychiatric disorders.

Psychopharmacology in the Pediatric Oncology and Bone Marrow Transplant Units: Antidepressant Treatment.

Objectives: The aim of this study was to characterize the clinical profiles, tolerability, and efficacy of two groups of antidepressants, selective serotonin reuptake inhibitors (SSRIs), and the atypical antidepressant, mirtazapine, in children and adolescents treated in a large pediatric Hematology-Oncology center. Methods: A review of computerized medical charts of 32 pediatric patients with cancer, from December 2011 to April 2020, was conducted. Efficacy and tolerability of antidepressant medications were retrospectively analyzed. The Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) Scales were used to evaluate psychiatric symptoms severity before and following treatment, while the data on adverse events and drug-drug interactions were retrieved from the computerized medical records. Results: Thirty-two children and adolescents with cancer, 2-21 years of age (mean 14.1 ± 4.6 years), were treated with antidepressants. Fourteen patients (44%) received mirtazapine, whereas 18 patients (56%) received SSRIs: sertraline (25%), escitalopram (25%), or fluoxetine (6%). Treatment choice was dictated either by physician preference or informed by potential drug-drug interactions. The most common psychiatric diagnoses were major depressive disorders (47%), anxiety disorders (19%), and medication-induced psychiatric disorders (19%). The most common psychiatric-medical symptoms were depressed mood (94%) and anxiety (62%). CGI-S improved significantly (p < 0.05) between pretreatment and on-treatment assessments, with no statistically significant difference between SSRI and mirtazapine-treated patients. CGI-I scores at reassessment indicated improvement in most patients (84%). Adverse events of treatment were mild in all patients. Conclusions: The antidepressants used in this study, SSRIs and mirtazapine, were effective and well tolerated in children and adolescents with cancer and psychiatric comorbidities. Given the high rates of depression and anxiety in children with cancer, large-scale, multisite, prospective clinical trials of antidepressants are warranted.

EEG p-adic quantum potential accurately identifies depression, schizophrenia and cognitive decline.

No diagnostic or predictive instruments to help with early diagnosis and timely therapeutic intervention are available as yet for most neuro-psychiatric disorders. A quantum potential mean and variability score (qpmvs), to identify neuropsychiatric and neurocognitive disorders with high accuracy, based on routine EEG recordings, was developed. Information processing in the brain is assumed to involve integration of neuronal activity in various areas of the brain. Thus, the presumed quantum-like structure allows quantification of connectivity as a function of space and time (locality) as well as of instantaneous quantum-like effects in information space (non-locality). EEG signals reflect the holistic (nonseparable) function of the brain, including the highly ordered hierarchy of the brain, expressed by the quantum potential according to Bohmian mechanics, combined with dendrogram representation of data and p-adic numbers. Participants consisted of 230 participants including 28 with major depression, 42 with schizophrenia, 65 with cognitive impairment, and 95 controls. Routine EEG recordings were used for the calculation of qpmvs based on ultrametric analyses, closely coupled with p-adic numbers and quantum theory. Based on area under the curve, high accuracy was obtained in separating healthy controls from those diagnosed with schizophrenia (p<0.0001), depression (p<0.0001), Alzheimer's disease (AD; p<0.0001), and mild cognitive impairment (MCI; p<0.0001) as well as in differentiating participants with schizophrenia from those with depression (p<0.0001), AD (p<0.0001) or MCI (p<0.0001) and in differentiating people with depression from those with AD (p<0.0001) or MCI (p<0.0001). The novel EEG analytic algorithm (qpmvs) seems to be a useful and sufficiently accurate tool for diagnosis of neuropsychiatric and neurocognitive diseases and may be able to predict disease course and response to treatment.

Suicide-related calls to a national crisis chat hotline service during the COVID-19 pandemic and lockdown.

BACKGROUND: A COVID-19 pandemic-related rise in suicide rates has been predicted due to social isolation, fear, uncertainty, economic turndown and grief. Detecting an increase in suicide rates is difficult in the absence of real-time data. Alternative data sources for such trends in psychopathology and suicidal behavior must be sought. METHODS: Data from a national chat-based crisis hotline for the first half of 2019 (pre-COVID-19), were compared to data from the first half of 2020 (during COVID-19). Chat sessions were classified by content and demographics and the data compared between the two time periods. OUTCOME: Total chats (n = 6756) were 48% higher during COVID-19 (p < .05). Suicide-related chat (SRC) number was also higher, although the proportion relative to all chats was slightly lower during COVID-19, compared to pre-COVID-19 (p < .05). SRCs increased during the COVID-19 lockdown. The number of severe SRCs resulting in urgent police intervention, increased during the lockdown (April-May 2020) compared with the same period in 2019 (p = .04). Issues of anxiety were higher in 2020 (19.4%) vs. 2019 (16.5%) (p < .00001) while issues of depression were lower (22.4% vs 33%, respectively) (p < .00001). The overall use of chats among adults aged >50 yrs increased during COVID-19 and likewise, the rate of SRCs in this age-group increased 30-fold in this period when compared to pre-COVID-19 (p < .00001). SRCs included more women than men (p < .0001) in both pre-COVID-19 and during the COVID-19 period, when the proportion of women increased from 62% in 2019 to 73% during COVID-19 (p < .0001). INTERPRETATION: The rise in total chats, SRCs and SRCs resulting in police action, commenced during lockdown and was ameliorated by end of the lockdown, indicating that distress created by the lockdown was more impactful than mourning deaths of loved ones, fear and uncertainty, because all these factors persisted beyond the end of the lockdown. Older populations were probably more distressed due to greater risk and less adaptability to isolation, social media and staying home. More calls by women may reflect women's better help-seeking capacity. The increase in SRCs indicates the potential for more suicides and the need for bolstering mental health services and reach-out to older people during pandemic lock-downs.

Psychopharmacology in the Pediatric Oncology and Bone Marrow Transplant Units: Antipsychotic Medications Palliate Symptoms in Children with Cancer.

Objectives: The present study characterized the psychiatric diagnoses and symptoms that led to the administration of antipsychotic medications in children and adolescents with cancer, and to evaluate the benefits and tolerability of these drugs in a large hospital-based pediatric hematology-oncology practice. Methods: Efficacy and adverse effects of two second-generation antipsychotics were retrospectively analyzed in 43 patients 2.9-19.6 (mean 12.1) years of age. The Clinical Global Impression-Severity (CGI-S) Scale and Improvement (CGI-I) Scale were used to evaluate psychiatric symptom severity before and following treatment, while the incidence of side effects and drug-drug interactions were collected from medical records. Results: Olanzapine was administered to 58% of patients and risperidone to 42%; the choice of drug was at the discretion of the treating psychiatrist. The common psychiatric diagnoses among these patients included adjustment disorder (37%) and medication-induced psychiatric disorders (23%). The most common psychiatric-medical symptoms included irritability/agitation (79%) and depressed mood (74%). CGI-S improved significantly (p < 0.001) between assessments, with no statistically significant difference between olanzapine- and risperidone-treated patients. CGI-I scores at reassessment indicated superiority of olanzapine as compared with risperidone. Adverse effects of treatment were mild. Conclusions: Olanzapine and risperidone can be well tolerated and ameliorate severe psychiatric-medical symptoms in children and adolescents with cancer. The potential palliative benefits of these second-generation antipsychotics (e.g., rapid onset of action, antiemesis, sedation, and appetite stimulation) increase the utility of their use in children treated in oncology and bone marrow transplant units.

Comorbid personality disorders in manic bipolar I disorder patients is associated with increased use of long-acting injectable antipsychotic treatment and higher rates of rehospitalization.

Personality disorder comorbidity is considered a poor prognostic factor among bipolar disorder patients. However, an evidence-based pharmacological treatment for this sub-population is lacking, and only few studies investigated the impact of personality disorder on bipolar disorder-I course. Here, we studied the effect of comorbid personality disorder on the administrated psychopharmacotherapy and rehospitalization risk among manic bipolar disorder-I patients. A sample of 340 patients with bipolar disorder-I, who were hospitalized with acute manic episode between 2005 and 2013, were retrospectively followed for a mean duration of 1129 days. Drug treatment at discharge and rehospitalization rates during follow-up time were compared between bipolar disorder-I patients with (n = 55) or without (n = 285) personality disorder comorbidity. Multivariate survival analyses adjusted for covariates were conducted. During the study period, 39.4% of bipolar disorder-I patients were rehospitalized due to a mood episode. Comorbid personality disorder was significantly associated with higher rates of long-acting injectable antipsychotics administration at discharge from hospitalization (adjusted odds ratio 2.66, 95% confidence interval: 1.19-5.94, P = 0.017). Comorbid personality disorder significantly increased the adjusted risk of rehospitalization due to a mood episode (hazard ratio = 2.04, 95% confidence interval: 1.29-3.23, P = 0.002). In conclusion, comorbid personality disorder in manic bipolar disorder-I patients is associated with increased use of long-acting injectable antipsychotics and higher rates of rehospitalization.

Aggressive symptoms in children with tic disorders.

Episodes of explosive anger and aggression are reported in patients with tic disorders and probably contribute to psychosocial stress and low quality of life. The source of these symptoms is controversial. The objective of the study was to study the relationship between tic disorders, their associated comorbidities, and aggressive behavior. The cohort included 47 children and adolescents (age 7-17 years) with Tourette syndrome or other chronic tic disorders attending a tertiary pediatric Tourette clinic. Associated psychopathology was assessed with the Yale Global Tic Severity Scale, Yale Brown Obsessive Compulsive Scale, Conners ADHD Rating Scale, Screen for Child Anxiety-Related Emotional Disorders, and Child Depression Inventory. Aggression was assessed with the Overt Aggression Scale and scores were compared with a group of 32 healthy age- and sex-matched children. There were no significant differences in aggression scores between the children with tic disorders and controls. Verbal aggression was the most prevalent type of aggression, found in 70% of the patients with tic disorders. The level of aggression was not correlated to tic severity. Comorbid attention-deficit hyperactivity disorder and obsessive-compulsive disorder increased the probability of aggressive behavior in patients with tic disorders. On regression analysis, the only significant predictor of aggression was the severity of attention-deficit hyperactivity disorder. This study suggests that there is no difference in aggressive behavior between children with tics without comorbidities and healthy children. It is possible that aggressive behavior in children with tic disorders is predominantly associated with comorbid attention-deficit hyperactivity disorder.

Differences in demographic and clinical characteristics between cannabis users and non-drug users: A retrospective study of patients at first hospitalization due to psychotic symptoms.

This retrospective, chart review, cohort study compared demographic and clinical characteristics of cannabis -users and non-drug users at first admission due to psychotic symptoms at Geha Mental Health Center, Israel, between August 2002 and December 2013. We assessed the role of current cannabis use as a risk for re-hospitalization during this period as well as the stability of psychotic diagnoses at re-hospitalization. A total of 318 patients were included in the study, of which 106 (33.3%) were cannabis -users. The cannabis-user group had a shorter duration of hospitalization than the non-drug user group but without a significant difference in 5-year re-hospitalization rates. The latter had a higher rate of severe mental illness (SMI) diagnoses at first hospitalization (53.3% vs. 20.3%, respectively), but the difference disappeared at the second hospitalization. The two groups demonstrated a 79-80% rate of conversion from a non-SMI to an SMI diagnosis between the admissions. The results indicate the instability of non-SMI diagnoses at first hospitalization due to psychotic symptoms, regardless of concurrent cannabis use. The high conversion rate from non-SMI to SMI in current cannabis-users may be due to under-diagnosis of SMI at first admission or an effect of cannabis on the development of SMI.

Adjunctive antidepressants in bipolar depression: A cohort study of six- and twelve-months rehospitalization rates.

Although antidepressants (ADs) are widely used in bipolar depression, there is weak evidence for their effectiveness and safety in this condition. Furthermore, there is a paucity of studies on the risk-benefit ratio of AD maintenance treatment in bipolar disorder (BD). We compared rehospitalization rates of patients with BD-I depressive episode who were discharged with mood stabilizers (MSs) and/or atypical antipsychotics (AAPs) with or without adjunctive AD. Ninety-eight patients with BD-I who were hospitalized with a depressive episode between 2005 and 2013 were retrospectively followed for 6-months and 1-year rehospitalization rates, as well as time to rehospitalization, according to treatment at discharge: MSs and/or AAPs with or without AD. Multivariable survival models adjusted for covariates known to influence rehospitalization were conducted. Six-months and 1-year rehospitalization rates were significantly lower in the adjunctive-AD treatment group compared to the no-AD group (9.2% vs. 36.4%, P = .001, power = 0.87 and 12.3% vs. 42.4%, P = .001, power = 0.89, respectively). Time to rehospitalization within 6-months and 1-year was significantly longer in the adjunctive-AD treatment group (169.9 vs 141 days, P = .001 and 335.6 vs 252.3 days, P = .001, respectively). Adjunctive-AD treatment at discharge reduced significantly the adjusted risk of rehospitalization within 6-months (HR = 0.081, 95% CI: 0.016-0.412, P = 0.002) and 1-year (HR = 0.149, 95% CI: 0.041-0.536, P = 0.004). Moreover, adjunctive-AD treatment did not increase rehospitalization rates of manic episode. In conclusion, adjunctive-AD therapy to MS/AAP at discharge from BD-I depressive episode hospitalization is associated with a lower rate of and a longer time to rehospitalization during a 1-year follow up period.

Vitamin D Supplementation in Chronic Schizophrenia Patients Treated with Clozapine: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.

BACKGROUND: While accumulating evidence suggests that vitamin D deficiency may be involved in the risk to develop schizophrenia and its outcome, there are no studies on vitamin D supplementation in this context. We sought to assess the effect of vitamin D supplementation on psychiatric, cognitive and metabolic parameters in chronic clozapine-treated schizophrenia patients. METHODS: This eight-week, randomized, double-blind, placebo-controlled clinical trial, recruited schizophrenia patients who had been maintained on clozapine treatment for at least 18weeks and had low levels of vitamin D (<75nmol/l) and total PANSS scores >70 (to ascertain the presence of residual symptoms). Patients were randomly allocated to either weekly oral drops of vitamin D (14,000IU) or placebo and subsequently assessed at two-week intervals for psychosis severity, mood, cognition and metabolic profile. RESULTS: Twenty four patients were randomly assigned to vitamin D (aged 39.4±9.6years, 75% males) and the other 23 patients to the placebo arm (aged 42.5±11.2years, 60.9% males). After eight weeks, the vitamin D group exhibited a significant increase in vitamin D levels (31.4 vs -0.4nmol/l, p<0.0001). There was no significant effect of vitamin D on psychotic, depressive or metabolic parameters. However, in the vitamin D group, there was a trend towards improved cognition (effect size=0.17, significance lost following Bonferroni correction). CONCLUSIONS: Vitamin D supplementation was associated with a trend towards improved cognition, but did not affect psychosis, mood or metabolic status. It is possible that the robust decrease in the PANSS scores in both groups may have obscured an effect of vitamin D supplementation.

Emotional Reactivity and Regulation Following Citalopram Therapy in Children and Adolescents with Anxiety Disorders.

OBJECTIVE: Emotional dysregulation is an important element in the pathophysiology of childhood anxiety disorders and can distinguish anxious subjects from controls. Treatment with selective serotonin inhibitors (SSRIs) has been found to lessen anxiety, but its effects on emotional reactivity and regulation are less documented. The aim of the study was to prospectively assess changes in emotional reactivity and regulation in response to citalopram in children and adolescents with anxiety disorders, with special focus on the mechanism of reappraisal. METHODS: The sample included 70 children and adolescents (38 boys, 32 girls) 10-17 years of age, divided into three groups: Those with anxiety disorder treated with citalopram for 8 weeks (n = 35); untreated subjects with anxiety disorder on the waiting list for cognitive behavioral therapy (CBT) (n = 15); and subjects without anxiety disorder (controls) (n = 20). Emotional reactivity and regulation (i.e., reappraisal), were assessed at baseline and after 8 weeks (follow-up) with validated computer-based instruments, Reactivity and Regulation-Situations (REAR-S) and Reactivity and Regulation-Images (REAR-I). RESULTS: Citalopram-treated subjects showed significantly greater improvement in reappraisal ability than CBT-waitlisted subjects. Improvement in the ability to reappraise threatening images correlated significantly with the decrease in anxiety. There was a decrease in negative emotional reactivity between assessments, which was positively correlated with clinical improvement. Higher intensity of baseline reactivity (on the REAR-S) predicted more severe symptoms at follow-up. CONCLUSIONS: Citalopram therapy improves reappraisal ability in children and adolescents with anxiety. However, the improvement in other examined emotional reactivity indices occurred in both medicated and waitlisted groups. It is possible that these findings may have implications for understanding the pathophysiology of anxiety in children and adolescents.

Antipsychotic adjunctive therapy to mood stabilizers and 1-year rehospitalization rates in bipolar disorder: A cohort study.

OBJECTIVES: Antipsychotic adjunctive therapy to mood stabilizers (MSs) may improve relapse prevention; however, only a few naturalistic studies, reflecting more generalizable bipolar disorder (BD) samples, support this notion. We compared the 1-year rehospitalization rates of manic patients with bipolar I disorder (BD-I) who were discharged with MS (lithium or valproate) monotherapy or with adjunctive atypical or typical antipsychotic therapy. METHODS: A total of 201 patients with BD-I who were hospitalized with manic episodes between 2005 and 2013 were retrospectively followed for 1-year rehospitalization rates according to treatment at discharge: MS monotherapy, MS with atypical antipsychotics, and MS with typical antipsychotics. Additionally, time to rehospitalization during the 1-year period after discharge was compared between treatment groups. Multivariable survival analyses adjusted for covariates known to influence rehospitalization were conducted. RESULTS: Rehospitalization rates within 1 year were significantly lower in the MS with atypical antipsychotics group (6.3%) compared to the MS monotherapy group (24.3%, P=.008) and to the MS with typical antipsychotics group (20.6%, P=.02). Time to rehospitalization was significantly longer for the MS with atypical antipsychotics group (345.5 days) compared to the MS monotherapy group (315.1 days, P=.006) and to the MS with typical antipsychotics group (334.1 days, P=.02). The MS with atypical antipsychotics group had a significantly reduced adjusted risk of rehospitalization (hazard ratio=0.17, 95% confidence interval: 0.05-0.61, P=.007) compared to the MS monotherapy group. CONCLUSIONS: Atypical antipsychotic adjunctive therapy to MSs may be more effective than MS monotherapy in preventing rehospitalization during the 1-year period after a BD manic episode.

Seasonal pattern of manic episode admissions among bipolar I disorder patients is associated with male gender and presence of psychotic features.

BACKGROUND: Bipolar I disorder (BD-I) patients demonstrate disrupted chronobiology expressed as seasonal variation in mood symptoms. The seasonal pattern (SP) specifier of mood disorders was recently extended by the DSM-5, to be applied to manic episodes. However, the significance of seasonality of manic episodes for the course of BD-I is unknown. In the present study we sought to identify clinical and demographic features that discriminate between BD-I patients with and without SP of manic admissions. METHODS: BD-I patients (n=148) admitted at least twice with the same mood exacerbation type, were retrospectively followed between 2005 and 2013. Demographic and clinical characteristics were compared between BD-I patients with or without SP of manic admissions. RESULTS: SP of manic episode admissions, found in 31 (26%) of 117 BD-I patients with repeated manic episode admissions, was associated with higher rates of male gender (p=0.01), presence of psychotic features (p=0.01) and comorbid substance use disorder (p<0.05) compared to patients without SP. In a multivariate analysis, SP of manic episode admissions was associated with the presence of psychotic features (OR 8.42, 95% CI: 1.05-67.65, p<0.05) and male gender (OR 3.23, 95% CI: 1.08-9.65, p<0.05), but not with comorbidity of substance use disorder (OR 1.79, 95% CI: 0.71-4.50, p=0.24). LIMITATIONS: Seasonal psychological/environmental factors contributing to the emergent of mood episodes could not be ruled out. CONCLUSIONS: Our results suggest that SP of manic admissions is associated with male gender and the presence of psychotic features, thus might be associated with more severe form of the disorder.

Effect of cyclic, low dose pyrimethamine treatment in patients with Late Onset Tay Sachs: an open label, extended pilot study.

BACKGROUND: Late Onset Tay- Sachs disease (LOTS) is a rare neurodegenerative lysosomal storage disease which results from mutations in the gene encoding the α subunit (HEXA) of ß-hexosaminidase enzyme (HexA). At the present time, no effective treatment exists for LOTS and other neurodegenerative diseases involving the central nerve system (CNS). Pyrimethamine (PMT) was previously shown to act as a HexA chaperone in human fibroblasts in vitro carrying some (e.g., αG269S), but not all LOTS-related mutations. The present study assessed the effect of cyclic, low dose and long term pyrimethamine treatment on HexA in subjects with LOTS. METHODS: In an open label trial in 4 LOTS patients, PMT was initiated at an average daily dose of ~2.7 mg and administered cyclically guided by blood lymphocyte HexA activity for a mean duration of 82.8 (±22.5; SD) weeks (~1.5 year). RESULTS: HexA activity rose in all subjects, with a mean peak increase of 2.24 folds (±0.52; SD) over baseline activity (range 1.87-3). The mean treatment time required to attain this peak was of 15.7 (±4.8; SD) weeks. Following increase in activity, HexA gradually declined with the continued use of PMT, which was then stopped, resulting in the return of HexA activity to baseline. A second cycle of PMT treatment was then initiated, resulting again in an increase in HexA activity. Three of the patients experienced a measurable neuropsychiatric deterioration whereas one subject remained entirely stable. CONCLUSIONS: Cyclic low dose of PMT can increase HexA activity in LOTS patients. However, the observed increase is repeatedly transient and not associated with discernible beneficial neurological or psychiatric effects.

Association between bipolar episodes and fluid and electrolyte homeostasis: a retrospective longitudinal study.

OBJECTIVES: Imbalance of fluid and electrolyte homeostasis has been suggested to be associated with the neuropathological processes underlying bipolar disorder. However, longitudinal data regarding the association of bipolar episodes with fluid balance are still lacking. We hypothesized that mania may be associated with a relative fluid retention and hemodilution, and depression with a relative hemoconcentration. METHODS: Patients with bipolar disorder (n = 43) admitted to a mental health center, both with depressive and manic episodes, were retrospectively followed between 2005 and 2013. Fluid balance and electrolyte serum indices were compared between their manic and depressive episodes. We adjusted for physical and psychiatric comorbidities and for psychotropic treatment, using two-way analysis of variance with repeated measures. RESULTS: There was a significant reduction in serum fluid balance indices during mania compared to depression: mean hemoglobin concentration 13.9 ± 1.4 g/dL versus 14.5 ± 1.4 g/dL, paired t = -4.2, p < 0.0005; mean hematocrit 41.1 ± 4.1% versus 42.3 ± 3.7%, paired t = -3.0, p < 0.005; mean albumin concentration 4.2 ± 0.3 g/dL versus 4.5 ± 0.3 g/dL, paired t = -4.5, p < 0.0001; and mean sodium concentration 140.3 ± 2.0 mEq/L versus 141.0 ± 2.0 mEq/L, paired t = -2.1, p = 0.04, respectively. Controlling for physical and psychiatric comorbidities and psychotropic treatment did not alter these associations. CONCLUSIONS: Our results support the notion of an imbalance of fluid and electrolyte homeostasis among bipolar episodes, which is suggestive for relative hemoconcentration during depressive episodes and relative hemodilution during manic episodes. These findings may eventually lead to novel therapeutic targets.

Neuroimmunological function in parents of children suffering from cancer.

The main aim of this study is to evaluate the relationship between depression and immunological function in parents of children with cancer. Thirty-two parents participated in the study. The parents completed the following assessments: a list of major stressful events in a Hemato-Oncology ward, beck depression inventory II (BDI-II), posttraumatic diagnostic scale (PDS) and quality of life (QOL) questionnaire. A single blood sample was drawn from parents for evaluation of cortisol levels and lymphocyte cell subgroups. The parents were divided into two groups: Those who suffered from depression as defined by BDI-II cutoff score of 14 (depressed parents (DP), n = 7), and non-depressed parents (non-DP, n = 25). In parents of children with cancer the DP group had statistically significantly higher stressful event scores, dysfunction scores (from the PDS) and CD8 percentage compared to the non-DP group. QOL, CD4 percentage and CD4/CD8 ratio were significantly lower in the DP group. The BDI scores significantly positively correlated with events and dysfunctional scores, and significantly negatively correlated with QOL scores and CD4/CD8 ratio. High psychiatric morbidity was found in parents of children with cancer. The findings of altered immunity in DP provide further evidence that the physiological response to stress and depression may alter immune functions.

Acute manic episode is associated with an increased risk of lower limb edema.

OBJECTIVE: Lower limb edema (LLE) was suggested to be associated with the use of psychotropic drugs among patients suffering from severe mental illnesses; however no direct mechanism was found. Therefore, we examined the association between the occurrence of LLE and acute untreated episode leading to hospitalization. METHODS: A retrospective cross-sectional study was conducted using medical charts of 2529 patients admitted to Geha Mental Health Center between 2002 and 2012. Incident cases of LLE, demographic and clinical data were retrieved. Admission clinical status was modeled as three non-overlapping groups of patients: (i) Patients with a non-affective psychosis (NAP) episode (n = 1563), (ii) patients with a manic episode (n = 366), and (iii) patients with a depressive episode (n = 600). We performed a logistic regression analysis with LLE as the dependent variable controlling for the demographic and clinical variables that may be associated with LLE. RESULTS: LLE was diagnosed in 3.8% (n = 95) of the study population. The rate of LLE was 3-fold higher (χ(2) = 51.9, df = 2, p<0.001) in patients admitted with a manic episode (n = 38; 10.4%) compared to patients admitted with a NAP episode (n = 41; 2.6%) and patients admitted with a depressive episode (n = 16; 2.7%). Manic episode was associated with an increased risk for LLE compared to depressive episode (OR 8.72, 95% CI: 3.53-21.52, p<0.001) or NAP episode (OR 3.96, 95% CI: 2.16-7.26, p<0.001) after controlling for relevant confounders. CONCLUSION: Acute manic episode, leading to hospitalization, is associated with an increased risk of LLE, compared to NAP or depressive episode, suggesting causal relationship between mood and fluid imbalance. Yet, future prospective studies are needed to rule out the contribution of physical agitation and lithium treatment.

Antipsychotic monotherapy and adjuvant psychotropic therapies in schizophrenia patients: effect on time to readmission.

This study assessed the relationship between pharmacological regimens at hospital discharge and hospital readmission among schizophrenia patients. The records reviewed were all consecutive admissions (N=720) from a specific catchment area during the period 1991-2005. Two main groups were selected for analysis: the first group (N=537) included patients discharged with first-generation antipsychotics (FGA), and the second group (N=183) included patients with second-generation antipsychotics (SGA). Data on clinical and demographic characteristics at discharge, including a brief psychiatric rating scale and pharmacological treatment, were collected. The rate of readmission within 12 months was analyzed in relation to the specific pharmacological treatment at discharge. There was no significant difference in the risk of readmission in patients treated with SGA compared with FGA. Adjuvant psychotropic medications to either FGA or SGA did not attenuate the risk of readmission. The readmission rate in patients treated with clozapine (N=74) was significantly lower in comparison with depot FGA (N=293) medications (P=0.016). There was no advantage of SGA over FGA, with or without adjuvant psychotropic treatment, with regard to rehospitalization risk during the 12-month follow-up. Clozapine was found to reduce the risk for readmission in comparison with depot FGA.