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Background: Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medication discontinuation is still unresolved. We aimed to compare time to all-cause discontinuation in patients randomly allocated to long-acting injectable (LAI) versus oral medication. Methods: EULAST was a pragmatic, randomised, open-label trial conducted at 50 general hospitals and psychiatric specialty clinics in 15 European countries and Israel. Patients aged 18 years and older, with DSM-IV schizophrenia (as confirmed by the Mini International Neuropsychiatric Interview 5 plus) and having experienced their first psychotic episode from 6 months to 7 years before screening, were randomly allocated (1:1:1:1) using block randomisation to LAI paliperidone, LAI aripiprazole, or the respective oral formulations of these antipsychotics. Randomisation was stratified by country and duration of illness (6 months up to 3 years vs 4 to 7 years). Patients were followed up for up to 19 months. The primary endpoint was discontinuation, regardless of the reason, during 19 months of treatment. We used survival analysis to assess the time until all-cause discontinuation in the intention-to-treat (ITT) group, and per protocol analyses were also done. This trial is registered with ClinicalTrials.gov, NCT02146547, and is complete. Findings: Between Feb 24, 2015, and Dec 15, 2018, 533 individuals were recruited and assessed for eligibility. The ITT population included 511 participants, with 171 (33%) women and 340 (67%) men, and a mean age of 30·5 (SD 9·6) years. 410 (80%) of 511 participants were White, 35 (7%) were Black, 20 (4%) were Asian, and 46 (9%) were other ethnicity. In the combined oral antipsychotics treatment group of 247 patients, 72 (29%) patients completed the study and 175 (71%) met all-cause discontinuation criteria. In the combined LAI treatment arm of 264 patients, 95 (36%) completed the study and 169 (64%) met the all-cause discontinuation criteria. Cox regression analyses showed that treatment discontinuation for any cause did not differ between the two combined treatment groups (hazard ration [HR] 1·16, 95% CI 0·94–1·43, p=0·18). No significant difference was found in the time to all-cause discontinuation between the combined oral and combined LAI treatment groups (log rank test χ 2=1·87 [df 1]; p=0·17). During the study, 121 psychiatric hospitalisations occurred in 103 patients, and one patient from each of the LAI groups died; the death of the patient assigned to paliperidone was assessed to be unrelated to the medication, but the cause of other patient's death was not shared with the study team. 86 (25%) of 350 participants with available data met akathisia criteria and 70 (20%) met parkinsonism criteria at some point during the study. Interpretation: We found no substantial advantage for LAI antipsychotic treatment over oral treatment regarding time to discontinuation in patients with early-phase schizophrenia, indicating that there is no reason to prescribe LAIs instead of oral antipsychotics if the goal is to prevent discontinuation of antipsychotic medication in daily clinical practice. Funding: Lundbeck and Otsuka.

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 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

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 evalua...

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

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.

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.

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.

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 18 weeks and had low levels of vitamin D ( 70 (to ascertain the presence of residual symptoms). Patients were randomly allocated to either weekly oral drops of vitamin D (14,000 IU) 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 ± 9.6 years, 75% males) and the other 23 patients to the placebo arm (aged 42.5 ± 11.2 years, 60.9% males). After eight weeks, the vitamin D group exhibited a significant increase in vitamin D levels (31.4 vs − 0.4 nmol/l, p, Highlights • This is the first study to explore the effects of vitamin D supplementation in chronic schizophrenia patients on clozapine • In this randomized double-blind study, patients received supplement vitamin D (14,000 IU weekly) or placebo for eight weeks • There was no difference between vitamin D and placebo with regards to severity of psychopathology or metabolic status • There was a trend towards improved cognition following the effect of vitamin D specifically in attention and delayed recall About third of schizophrenia patients do not respond to common antipsychotics and require a clozapine trial. Insufficient levels of serum Vitamin D, the sunshine hormone, were found to be very prevalent among schizophrenia patients. The vitamin has a potent active metabolite with specific receptors in the brain. We investigated the psychiatric, metabolic and cognitive effects of vitamin D supplementation in comparison to placebo in clozapine-treated chronic schizophrenia patients with residual psychotic symptoms. Vitamin D addition was not superior to placebo in reducing psychiatric symptoms or improving the metabolic parameters. However, vitamin D administration was associated with a trend towards improvement in cognitive performance.

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.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).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.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.

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

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.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.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, p0.001) 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, p0.001) or NAP episode (OR 3.96, 95% CI: 2.16-7.26, p0.001) after controlling for relevant confounders.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.

Marked gender differences have been identified in cigarette smoking. In this study, we aimed to identify the gender-specific emotional and behavioral disorders among adolescent smokers and their consequent utilization of mental health services. We performed a nationwide survey study of an Israeli representative sample of 906 adolescents and their mothers. Mental disorders were assessed using the Development and Well-Being Assessment (DAWBA) Inventory. Levels of emotional and behavioral difficulties were evaluated using the Strengths and Difficulties Questionnaire (SDQ). Mental health services use and smoking habits were also assessed. Among non-smoker adolescents there were significant gender differences in almost all SDQ scales: emotional problems, pro-social, hyperactivity/inattention and conduct problems, whereas in the smoker group there was a difference only in the SDQ emotional problems scale (both self- and maternal-rated, P < 0.001 and P = 0.002, respectively). Only marginal difference was noted between males and females in help-seeking for emotional or behavioral problems. Over 50% of both male and female smokers in the study had untreated mental disorders (non-significant gender difference). The well-established gender differences in psychiatric symptomatology narrowed markedly in adolescent smokers; the typical gender difference in disruptive behaviors was lost in the adolescent smoking population. The implications of these findings are particularly relevant to developing more effective gender-specific programs to prevent youth smoking, to facilitate quitting and prepare primary care practitioners to identify mental disorders and behavioral problems in adolescents with a smoking history.

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.

PurposeTo compare the readmission and the mortality rates of schizophrenia patients who were discharged against medical advice (AMA) and patients who were discharged by physician recommendation.MethodsThe records (1984–2005) of all consecutive admissions (n= 12,937) of schizophrenia patients (n= 8,052) were reviewed. Out of this group, 673 (8.3%) refused to remain in the hospital and signed a hospital form for discharge AMA. Their records were analyzed for rates of re-hospitalization and mortality at study closure. The records of AMA patients were compared to those of patients with regular discharge (n= 1345).ResultsAMA patients were younger at admission (PPPPPPPConclusionThe schizophrenia patients discharged AMA have a higher readmission rate and a higher mortality rate due to suicide and accidents compared to non-AMA discharged patients. Patients with AMA discharge warrant special community surveillance to improve outcome.

Background Compulsory admission is practiced around the world with legislative variations. The legal status during compulsory hospitalization might be changed to consent or the patient might be discharged against medical advice (AMA), if he no longer poses a risk. Objective In the present study, we investigated the outcome of compulsory admitted patients who left the hospital after commitment period despite request by the treating psychiatrist to remain in the hospital (AMA) vs those who agreed to prolong their hospitalization. Results Of 320 patients with schizophrenia admitted involuntarily, 157 (49%) were discharged without converting to consent, and 163 (51%) agreed to stay in the hospital. There was no difference in baseline clinical and demographic characteristics and outcome measures (rate of readmission, legal status of next admission, and length of stay in the next admission) between the 2 groups. Conclusions Prolongation of length of stay in compulsorily psychiatrist-ordered schizophrenia patients did not affect their rate of rehospitalizations or the length of next admission compared with those who left the hospital immediately after the change in their legal status AMA.

Objective The aim of this study was to investigate the relationship between 2 psychological profiles: ( a ) the intrapersonal profile , involving self-critical depression, self-oriented perfectionism, and narcissism, and ( b ) the interpersonal profile , involving dependent depression and socially prescribed perfectionism, and the association of these 2 profiles with suicidal behavior among adolescent inpatients. Methods One hundred adolescents, admitted to a university-affiliated psychiatric adolescent inpatient unit in Israel, completed the Depressive Experience Questionnaire for Adolescents, the Child and Adolescent Perfectionism Scale, and the Narcissistic Personality Inventory. The Suicidal Potential Interview was used to evaluate suicidal behavior and separate them into low-risk and high-risk groups. Results Dependent depression correlated positively and significantly with severity of suicidal behavior. Adolescent inpatients with high levels of suicidal behavior (n = 54) were more dependent in terms of depression and were more inclined to socially prescribed perfectionism compared with adolescent inpatients with low levels of suicidal behavior (n = 45). The components of the intrapersonal profile did not correlate with severity of suicidal behavior; however, low narcissism scores characterized the psychological function that strongly predicted severe suicidal behavior. Conclusions The findings indicated that the conceptualization of 2 broad intrapersonal and interpersonal profiles in adolescent inpatients may have some validity in terms of the interpersonal dimension. The components of the interpersonal profile related to severe suicidal behavior and may be important in planning treatment strategy.

Clozapine has superior efficacy for treating patients with schizophrenia. Its discontinuation could have detrimental consequences. We attempted to identify the clinical parameters that could predict clozapine discontinuation in patients diagnosed as having schizophrenia by conducting a retrospective analysis of all of those who started on clozapine treatment during their hospitalization in our institution between 2002 and 2008 (n=100). Demographic and clinical parameters were analyzed and compared between the 58 patients who continued and the 42 who discontinued clozapine treatment during a follow-up period of 8.1 years. Twenty of the latter patients (47.6%) discontinued clozapine because of nonadherence and 11 (26.2%) because of side effects. Thirty-three of them (78.6%) stopped taking clozapine during the first year of treatment. The duration of clozapine use correlated significantly with the time to readmission (P

Background McGurk effect is a perceptual phenomenon that reflects the integration of visual and auditory information during speech perception. Using McGurk effect, the authors examined the audiovisual integration in adolescents and adults with schizophrenia as compared with healthy volunteers. Sampling and Methods Thirty hospitalized patients with schizophrenia and 20 age-matched healthy controls were examined for perception of ambiguous audiovisual stimuli. Results The mean of McGurk-positive responses was significantly lower in adolescent patients with schizophrenia than in healthy adolescents (3.13 ± 2.09 vs 5.60 ± 0.7, respectively; t = 3.591, P = .001). The McGurk-positive responses were significantly higher in healthy adolescents than in healthy adults (5.60 ± 0.7 vs 3.60 ± 1.43, respectively; t = 3.974, P = .001). No significant difference in McGurk-positive responses was found between adults with schizophrenia and healthy adult individuals, or between adolescent and adults with schizophrenia. Duration of schizophrenia, soft sign status, type of symptoms, and type of antipsychotic medication showed no influence on the audiovisual integration ability. Conclusions (I) Age effect: It seems that the audiovisual integrative function increases from childhood to adolescence and decreases from adolescence to early adulthood. (II) Schizophrenia: Audiovisual integration is poor in adolescent and adult patients with schizophrenia. Thus, it seems that schizophrenia is associated with early and persistent impairment in the development of the audiovisual integration ability. (III) Reliance on visual cue stimuli: Although several previous investigations concluded that patients with schizophrenia rely less on visual cue stimuli than healthy controls, our data suggest that this is true only for specific types of visual cue stimuli.

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.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.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 (p0.05) 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, p0.05) and male gender (OR 3.23, 95% CI: 1.08-9.65, p0.05), but not with comorbidity of substance use disorder (OR 1.79, 95% CI: 0.71-4.50, p=0.24).Seasonal psychological/environmental factors contributing to the emergent of mood episodes could not be ruled out.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.

Nineteen female adolescent inpatients diagnosed with anorexia nervosa, restricting type (AN-R) and 16 non-eating disordered (ED) controls were assessed for plasma dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulphate (DHEA-S), and cortisol levels, and for eating-related and non-eating-related psychopathology. AN-R patients were assessed at admission, 1 month and 4 months following hospitalization. The non-ED controls were assessed once. No baseline between-group differences were found in plasma cortisol, DHEA, and DHEA-S levels, whereas the patient group had a significantly lower Cortisol/DHEA-S ratio and elevated scores on most psychopathological parameters. A significant increase was found in the body mass index of the AN-R patients at 4 months post-hospitalization, accompanied by a decrease in plasma cortisol levels and a trend towards decreased Cortisol/DHEA and Cortisol/DHEA-S ratios, whereas no change occurred in psychopathology. The difference in Cortisol/DHEA-S ratio between AN-R patients and non-ED controls, and the different patterns of change in cortisol vs. DHEA(-S) levels following weight restoration, may in part account for the feeding difficulties in AN, particularly during refeeding.

Brain neurosteroids modulate gamma-aminobutyric acid type A (GABAA) receptor activity, thereby playing a role in mood disorders. Alterations in 17beta-estradiol (E2) and progesterone (P) are also known to play a significant role in psychopathology in women. The aim of the present study was to evaluate the synthesis of dihydroprogesterone (DHP), tetrahydroprogesterone (THP), and the activity of 5alpha-reductase (5alphaR) which regulates the reduction of P to DHP on exposure to supraphysiological levels of E2 in vitro (C6 glioma cells) and in vivo (mouse brain). The results showed that supraphysiological levels of E2 induced a decrease in the accumulation of both neurosteroids, probably by decreasing the activity of 5alphaR. We hypothesize that the high levels of E2 in pregnancy attenuate the increase in the conversion of P to THP in the brain and that the ratio of E2/P modulates the sedative effect of THP. This process may be relevant to psychopathological disorders that are ascribed to drastic alterations in estrogen levels, such as premenstrual syndrome, pregnancy-related mental disorders, and postpartum "blues".

Clozapine is a dibenzodiazepine neuroleptic with atypical pharmacological and clinical profiles. Treatment with this drug may be complicated with agranulocytosis (AGR). It is likely that defective oxidative mechanism may be the cause of AGR. A candidate gene, dihydronicotinamide riboside (NRH) quinone oxidoreductase 2 (NQO2), which is involved in detoxification of drugs, was selected. This gene has been mapped to the short arm of chromosome six. The gene was studied by single-strand conformation polymorphism analysis and direct sequencing in 98 schizophrenic patients that were treated with clozapine. Eighteen of these patients developed AGR. Ten polymorphisms in the coding regions, in intron 1, and in the promoter region were found, two of which were novel. Comparisons of the polymorphisms in the first intron in AGR patients and controls suggested that this site might be connected with AGR. Quantitative reverse transcriptase-polymerase chain reaction analysis showed that the level of NQO2 mRNA is low in AGR patients compared with the control group. Such a reduction in message suggests that the NQO2 gene may be involved in the development of clozapine-induced AGR.

Vesicular monoamine transporter (VMAT2) plays a major role in the synaptic accumulation and release of monoamines. In the present study, we assessed high affinity [(3)H]dihydrotetrabenazine binding to platelet VMAT2 in a group of treated (n = 9) and untreated (n = 4) patients with schizophrenia and age- and sex-matched controls. Significantly elevated platelet VMAT2 density (B(max)) (53%, P0.0001) was observed in the mixed population of schizophrenia patients. The affinity of the ligand (K(d)) to platelet VMAT2 was similar in both groups. The increased platelet VMAT2 density may indicate a schizophrenia-related hyperactivity of the monoaminergic system or an adaptive response to chronic drug treatment.

The beneficial effect of atypical antipsychotic drugs (APDs) in treatment-resistant schizophrenia patients has been attributed, mostly, to their relatively high serotonergic (5-HT) 2 to dopaminergic (D) 2 receptor blockade ratio. We hypothesized that a combination of typical APDs (D 2 antagonists) and mianserin, a potent 5-HT 2 antagonist, might also exert superior efficacy in this population. Eighteen inpatients with treatment-resistant schizophrenia who had an acute psychotic exacerbation of the disorder received, in a double-blind design, 30 mg/day mianserin (n = 9) or placebo (n = 9) in conjunction with typical neuroleptics [haloperidol (n = 9) or perphenazine (n = 9)]. Clinical status was evaluated before, during, and at the end of 6 weeks of combined treatment with the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms and Hamilton Rating Scale for Depression. The typical APD/mianserin group exhibited significantly greater improvement in total BPRS scores (17.6% versus 5.5%; P = 0.03) and a trend towards greater improvement in SAPS scores (35.3% versus 13.0%; P= 0.07). Our study indicates that patients with chronic treatment-resistant schizophrenia who have an acute psychotic exacerbation ('acute-on-chronic') may benefit from the addition of a potent 5-HT 2 blocker, such as mianserin, to typical antipsychotics. Our findings may further emphasize the contribution of enhanced 5-HT 2 blockade to the 'atypicality' of the atypical APDs and to their greater efficacy in alleviating symptoms of chronic treatment-resistant schizophrenia.

Eight patients (6 men and 2 women) with chronic post-traumatic stress disorder (PTSD) were treated with naltrexone 100-200 mg/day. Seven patients completed 2 weeks of treatment. A subtle and clinically insignificant improvement was noted in intrusive and hyperarousal symptoms (p < 0.05 for both), but not in avoidance symptoms. All patients demonstrated side effects which limited the targeted dose. It is suggested that the subtle positive effect of naltrexone and the hypersensitivity of these patients to its side effects do not encourage the use of naltrexone in the treatment of PTSD patients.

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 β-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.

Schizophrenia patients may develop various thermoregulatory disturbances. We hypothesized that a standardized exercise-heat tolerance test [two 50-min bouts of walking a motor-driven treadmill at 40 degrees C (relative humidity=40%)] would reveal abnormal thermoregulation in drug-free schizophrenia patients. Six drug-free schizophrenia outpatients and seven healthy comparison subjects participated in this study. The schizophrenia patients exhibited significantly higher baseline and exertion-related rectal temperature. The relevance of these findings to the pathophysiology of schizophrenia-related thermoregulatory disorders is as yet unclear.

The present study describes two patients, both of Yemenite origin, with catatonic schizophrenia who responded to treatment with risperidone. One had a long history of psychiatric disorder, whereas the other was a first-episode, drug-naive patient. Our observation agrees with previous reports on the use of risperidone and other novel neuroleptic agents in the treatment of catatonia of different etiologies.

Psychopharmacological interventions for managing aggression in schizophrenia have thus far yielded inconsistent results. This study evaluates the antiaggressive efficacy of combined haloperidol-propranolol treatment. Thirty-four newly admitted schizophrenic patients were studied in a controlled double-blind trial. Following a 3-day drug-free period and 7 days of haloperidol treatment, patients were randomly assigned to receive either haloperidol-propranolol or haloperidol-placebo for eight consecutive weeks. Doses of medications were adjusted as necessary; biperiden was administered if required. Rating scales were applied to assess aggression, anger, psychosis, depression, anxiety and extrapyramidal symptoms. The mean daily dose of haloperidol was 21 mg (SD = 6.4) in the research group and 29 mg (SD = 6.9) in the controls. Mean and maximal daily doses of propranolol were 159 mg (SD = 61) and 192 mg (SD = 83), and of placebo, 145 mg (SD = 50) and 180 mg (SD = 70), respectively. Compared with the controls, the scores for the research patients decreased significantly from baseline, particularly after 4 weeks of treatment, for some dimensions of anger, psychosis, anxiety, and neuroleptic-induced parkinsonism. A tendency for reduced aggression was shown in the combined haloperidol-propranolol group for some dimensions but not others. These patients also required significantly less biperiden. The tendency toward elevated antiaggressive effect of combined haloperidol-propranolol treatment compared to haloperidol alone may be explained by a simultaneous decrease in aggression, psychotic symptomatology, and anxiety.

Elevated serum creatine phosphokinase (CPK)MM level is frequently found in acute psychosis. Theories relate this CPKemia to psychomotor agitation and medication. We hypothesized that psychosis-related CPKemia observed in individual patients is relatively consistent.Ninety psychotic patients were studied; 83% were schizophrenics (Brief Psychiatric Rating Scale scoresor = 40) whose serum CPKMM levels were recorded during two or more different acute psychoses. The serum CPKMM levels used were the maximal levels monitored during the beginning of each hospitalization. The last CPK measurement in a circumscribed period was defined as the index serum CPK level (IndCPK). The mean of all other individual maximal CPK measurements during other psychotic episodes was defined as the average CPK (AvgCPK).Multiple linear regression analysis showed a significant correlation of natural logarithm (Ln) of (IndCPK with Ln(AvgCPK), as well as with gender (coefficient = .65 and .63, p.0001 and p.01, respectively). There were significantly higher IndCPK levels among male patients than among female patients (por = .001). A relatively consistent individual pattern of serum CPKMM levels during repeated acute psychotic episodes was observed.Serum CPKMM levels and gender were found to be good predictors of maximal serum CPKMM levels during every repeated acute psychotic episode. High IndCPK levels are probably risk factors for neuroleptic malignant syndrome.

Neural network processed 41 variables of 289 psychiatric inpatients and successfully converged (97% correlation between output and target signals) on a good 8-week outcome. The sensitivity of each parameter was calculated by ditherring the input signals one by one at 1 % signal increase and computing the corresponding output. Fifteen parameters were predictors of good outcome and 17 parameters were predictors of bad outcome. The most sensitive good outcomes were ECT, group, behavioral and dynamic psychotherpeutic approaches, clozapine administration, noradrenergic antidepressant treatment, schizopositive symptoms, and being of high socioeconomic level. The most sensitive bad outcomes were long duration of the last in-hospital stay or last remission, suffering from OCD or resistant depression, being treated with low potency neuroleptic drugs, and having community support. Sensitivity detection by neural network is a new approach in psychiatry. A 70% concordance level was found with outcome measures reported in literature and that have been traditionally calculated. The fact that the system converged in spite of the wide spectrum of input signals means that underlying interconnections were detected by the neural network.

Neuroleptic malignant syndrome (NMS) is a potentially lethal antipsychotic drug (APD)-induced thermoregulatory disturbance. We hypothesized that several precautionary measures taken after administeration of APDs might prevent progression to definite NMS. The study group included 657 consecutively admitted drug-free schizophrenia inpatients who received various typical APDs for 28 days. Specific predefined precautionary measures were employed for this group. The comparison group (n=192) consisted of typical APD-treated schizophrenia inpatients in whom such precautionary measures were not imposed. The study group exhibited a significantly lower incidence of definite NMS (1/657=0.2% versus 4/192=2.1%; P=0.01, odds ratio=13.96; 95% confidence interval 1.55-125.63). Antipsychotics were discontinued in 28 patients (28/657=4.3%) from the study group due to NMS (n=1) or early detection of potential NMS-related signs (probable abortive NMS) (n=27). Our findings suggest that specific precautionary measures can effectively reduce the incidence of definite NMS by approximately one order in newly medicated schizophrenia inpatients.

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.

The aim of this study was to identify environmental factors that might correlate with the admission rate of patients with major psychiatric disorders. During the years 1988-90, 393 consecutive admissions (119 unipolar depressed patients, 211 schizophrenic patients, and 63 bipolar depressed patients) were monitored. Correlations were calculated between the mean daily admission rate for each month and monthly photoperiod, rate of change in photoperiod, mean temperature, mean relative humidity, and mean barometric pressure. It was found that the admission rate of bipolar depressed patients negatively correlated with monthly photoperiod, which means that during winter the admission rate of these patients increased.

A computerized psychiatric clinical application based on CLICKS program was developed, consisting of a network of 34 personal computers, run by Novell Netware version 3.11. It includes all clinical records and covers most of the administrative needs of the department; it may be used also in the outpatient clinics. Implementation of the system followed the stages of planning, record structuring, record programming, practice and operation. The system is favorably accepted by the patients, has several important advantages over pencil and paper record keeping, and although it is slightly more time-consuming, it improves record quality and departmental efficiency.

SummarySerotonin uptake by platelets was determined in 11 patients suffering from carcinoma of the pancreas, eleven patients hospitalized for chronic physical disease, 19 patients suffering from major depression unipolar type, and 19 healthy volunteers. The Vmax values of serotonin uptake were significantly lower in patients suffering from carcinoma of the pancreas (F = 18.6, df = 28, Ρ < 0.001) and chronic physical disease (F = 21.3, df = 28, Ρ < 0.0001) than in healthy volunteers. The Vmax values of the depressed patients were also significantly lower (F = 4.27, df = 36, Ρ < 0.05) than those in the control group. No difference was found between the carcinomatous and the chronically ill patients. Km values of serotonin uptake by platelets were significantly decreased in both groups of patients with organic disease (F = 5.91, df = 28, Ρ < 0.025; F = 4.44, df = 28, Ρ < 0.045 respectively) as compared to the control group, but were similar in the depressed and the control groups (F = 0.42, df = 20, P = 0.52). Since the patients with chronic disease were chronically medicated, the decreased serotonin uptake may not be disease-dependent but rather associated with medication. However, the carcinomatous patients were drug-free and in this group the decreased uptake and serotonin transporter hypersensitivity may have been disease-dependent. These results suggest the involvement of the presynaptic serotonergic system in the susceptibility of pancreatic carcinomatous patients to prodromal depression.

Objective To assess whether or not pyrimethamine (PMT) can be used to enhance β-hexosaminidase A activity (HexA) in subjects with Late Onset Tay Sachs (LOTS), we studied the effect of incremental doses of PMT in vivo in 9 LOTS patients carrying the αG269S/c.1278insTACT mutations. Methods PMT treatment was initiated at a dose of 6.25mg, increasing gradually up to a maximal allowable dose of 75mg daily at 4–6weeks intervals for a total of up 10months. Mean patients' age was 37.9±16.1yrs (range 20–67years). Results Lymphocyte HexA activity rose in all subjects, peaking at 78±30% over baseline activity (mean±SD; range 36–114%). The optimal PMT dose varied considerably, averaging at 30±24.1mg (range—6.25–75mg, daily). Further increase in PMT beyond the optimal dose was associated with gradual loss of effect on lymphocyte HexA. Improvement in speech was seen within several weeks in 4 out of 9 subjects, mostly paralleling the initial increment in HexA. Mood stabilization was also perceived in 3 subjects, but this was more difficult to assess due to the concomitant use of psychotropic/mood stabilizing agents. Reversible decline in motor activity manifesting predominantly in more frequent falls was seen in 3 subjects when the PMT dose was increased beyond the peak effect generating dose. Conclusions PMT therapy can increase HexA activity in LOTS in vivo . Optimal doses should be tailored individually to avoid loss of biochemical effects. Clear cut neurological and psychiatric effects are difficult to discern at this time, mostly due to short term study follow up and large inter-individual variability.

Blood levels of melatonin, serotonin, cortisol, prolactin, and serotonin uptake by platelets were measured at 08:00, 14:00, 20:00, 02:00, and 08:00 hours in 10 healthy men who ranged in age from 27 to 35 years. The Km values of serotonin active transport by platelets were significantly correlated with melatonin blood levels. There were no other significant correlations. The secretion of steroid hormones and prolactin showed an increase at 02:00 hours; levels of prolactin decreased at 08:00 hours, but steroid levels continued to rise. This finding suggests either a direct effect of melatonin on serotonin active transport or the influence of the suprachiasmatic nucleus on serotonin uptake by platelets. It is also possible that there is a simultaneous decrease in serotonin uptake and decline from peak levels of melatonin due to the rise in steroid secretion.

The effect of a single dose (10 mg P.O.) of trihexyphenidyl (THP) on plasma cortisol, growth hormone (GH), and immunoreactive beta-endorphin (ir-beta-EP) was studied in seven major depressed patients and seven controls. GH secretion was suppressed (34-41%) by THP in both groups. THP did not affect cortisol secretion in depressed patients and controls. An increase (18%; p less than 0.05) in plasma ir-beta-EP levels was detected in the healthy subjects only. The results of this study do not support the hypothesized altered responsiveness to anticholinergic provocation in major depression. The inhibitory activity of THP on GH secretion indicates the involvement of the cholinergic system in the regulation of GH release in humans.

Objective: To identify factors influencing the course of anorexia nervosa (AN) over time. Method: Former female patients with AN (36 remitted and 24 nonremitted) and 31 healthy females responded to standardized interviews and self-rating questionnaires. Remitted patients maintained normal eating, normal weight, and regular menses for the past 12 months. Patients not fulfilling these criteria were considered nonremitted. Results: Using logistic regression, we identified that number of hospitalizations, duration of ambulatory treatment, past vegetarianism, past anxiety, and childhood sexual abuse differentiated remitted from nonremitted patients, predicting nonremission. A similar analysis identified that elevated follow-up vegetarianism and eating-related concerns and lower body mass index (BMI) differentiated remitted from nonremitted patients, contributing to nonremission. Univariate analyses identified that remitted patients had elevated anxiety and eating-related obsessionality compared with the controls, suggesting these variables to potentially predispose to AN. Discussion: Elevated anxiety and eating-related obsessionality may increase the risk for the development of AN and for nonremission. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2009

Introduction Preliminary point-prevalent data suggest that drug-free schizophrenia patients may exhibit increased body/corneal temperature, that antipsychotic drugs (APDs) may decrease body/core temperature and that patients' mental status might be associated with their body/corneal temperature. Hence, we hypothesized that treatment-resistant psychotic APD-treated schizophrenia patients' mental status may correlate with their corneal temperature during a continuous 6-week period. Methods Corneal temperature of 12 treatment-resistant schizophrenia inpatients and 16 healthy volunteers was evaluated 2–3 times a week during 6 consecutive weeks using a flir thermal imaging camera. Results A significant and substantial correlation was found between inpatients' mean weekly Positive and Negative Syndrome Scale (PANSS)'s total scores and their mean weekly corneal temperature during the 6-week study period ( r = 0.82; n = 6 weeks; p = 0.043). There was no significant difference in mean 6-week corneal temperature between the patient group and the healthy subjects (34.25 ± 0.64 °C vs. 34.39 ± 0.69 °C, respectively; t = 1.127, df = 131, p = 0.26). Conclusions This study indicates that treatment-resistant overtly psychotic schizophrenia inpatients' mental status (as assessed by the PANSS) correlates with their corneal temperature. The relevance of these phenomena to the pathophysiology of schizophrenia, the biological mechanism underlying corneal temperature alterations and the possible role of temperature-modulating drugs (neuroleptics or non-neuroleptics) on schizophrenic psychosis merits further large-scale investigation in both medicated- and drug-free schizophrenia patients compared to matched controls.