Social affective context reveals altered network dynamics in schizophrenia patients.

Impairments in social cognition and interactions are core psychopathologies in schizophrenia, often manifesting as an inability to appropriately relate to the intentions and feelings of others. Neuroimaging has helped to demarcate the dynamics of two distinct functional connectivity circuits underlying the social-affective processes related to mentalization (known as Theory of Mind, ToM) and somatic-affiliation (known as Embodied Simulation, ES). While evidence points to abnormal activation patterns within these networks among those suffering from schizophrenia, it is yet unclear however, if these patients exhibit this abnormal functional connectivity in the context of social-affective experiences. The current fMRI study, investigated functional connectivity dynamics within ToM and ES networks as subjects experienced evolving cinematic portrayals of fear. During scanning, schizophrenia patients and healthy controls passively watched a cinematic scene in which a mother and her son face various threatening events. Participants then provided a continuous and retrospective report of their fear intensity during a second viewing outside the scanner. Using network cohesion index (NCI) analysis, we examined modulations of ES-related and ToM-related functional connectivity dynamics and their relation to symptom severity and the continuous emotional ratings of the induced cinematic fear. Compared to patients, healthy controls showed higher ES-NCI and marginally lower ToM-NCI during emotional peaks. Cross-correlation analysis revealed an intriguing dynamic between NCI and the inter-group difference of reported fear. Schizophrenia patients rated their fear as lower relative to healthy controls, shortly after exhibiting lower ES connectivity. This increased difference in rating was also followed by higher ToM connectivity among schizophrenia patients. The clinical relevance of these findings is further highlighted by the following two results: (a) ToM-NCI was found to have a strong correlation with the severity of general symptoms during one of the two main emotional peaks (Spearman R = 0.77); and (b) k-mean clustering demonstrated that the networks' NCI dynamic during the social-affective context reliably differentiated between patients and controls. Together, these findings point to a possible neural marker for abnormal social-affective processing in schizophrenia, manifested as the disturbed balance between two functional networks involved in social-affective affiliation. This in turn suggests that exaggerated mentalization over somatic-affiliative processing, in response to another's' distress may underlie social-affective deficits in schizophrenia.

Abnormal neural hierarchy in processing of verbal information in patients with schizophrenia.

Previous research indicates abnormal comprehension of verbal information in patients with schizophrenia. Yet the neural mechanism underlying the breakdown of verbal information processing in schizophrenia is poorly understood. Imaging studies in healthy populations have shown a network of brain areas involved in hierarchical processing of verbal information over time. Here, we identified critical aspects of this hierarchy, examining patients with schizophrenia. Using functional magnetic resonance imaging, we examined various levels of information comprehension elicited by naturally presented verbal stimuli; from a set of randomly shuffled words to an intact story. Specifically, patients with first episode schizophrenia (N = 15), their non-manifesting siblings (N = 14) and healthy controls (N = 15) listened to a narrated story and randomly scrambled versions of it. To quantify the degree of dissimilarity between the groups, we adopted an inter-subject correlation (inter-SC) approach, which estimates differences in synchronization of neural responses within and between groups. The temporal topography found in healthy and siblings groups were consistent with our previous findings - high synchronization in responses from early sensory toward high order perceptual and cognitive areas. In patients with schizophrenia, stimuli with short and intermediate temporal scales evoked a typical pattern of reliable responses, whereas story condition (long temporal scale) revealed robust and widespread disruption of the inter-SCs. In addition, the more similar the neural activity of patients with schizophrenia was to the average response in the healthy group, the less severe the positive symptoms of the patients. Our findings suggest that system-level neural indication of abnormal verbal information processing in schizophrenia reflects disease manifestations.

ErbB signaling antagonist ameliorates behavioral deficit induced by phencyclidine (PCP) in mice, without affecting metabolic syndrome markers.

Schizophrenia is a severe syndrome that affects about 1% of the world population. Since the mid-1950s, antipsychotics have been used to treat schizophrenia with preference for treating positive symptoms; however, their tolerance level is low, there are numerous side effects, and only some patients respond to the treatment. Antipsychotic medications that are more effective, better tolerated, and with fewer adverse effects are urgently needed. Given the accumulating evidence of the role filled by the ErbB signaling network in the biology of the dopamine, GABA, and glutamate systems, and in the etiology of schizophrenia, we hypothesized that the ErbB network is a candidate for development of a novel agent through which various symptoms of schizophrenia and other psychiatric disorders might be treated. Herein, we studied, in mice, the capability of blocking the ErbB signaling, in comparison with the atypical antipsychotic drug clozapine, to counter schizophrenia-like behavior induced by acute and sub-chronic phencyclidine (PCP), and determined whether inhibition of the ErbB networks induced weight gain and affected social and exploratory behavior, and metabolic syndrome markers. We demonstrated that administration of the pan-ErbB inhibitor JNJ28871063 (JNJ) reduced the level of activity in the open field induced by an acute injection of PCP. Moreover, the ability of JNJ to attenuate the effect of PCP is as effective as clozapine. In addition and like clozapine, JNJ normalized social behavior impairment induced by sub-chronic PCP and stress. Adult JNJ-treated mice displayed normal sociability and exploratory behavior, and their serum cholesterol, LDL, and HDL levels were lower than in the saline-treated mice. Sub-chronic treatment did not affect weight gain, glucose levels, and the activity of hepatic enzymes catalase and SOD. These data suggest that treatment with JNJ attenuates abnormal behaviors induced by PCP, and has similar effects as the antipsychotic drug clozapine, with no adverse effects. Thus, the ErbB signaling can serve as a new starting point for non-dopaminergic-based drug development of schizophrenia.

Behavioral characterization of blocking the ErbB signaling during adolescent and adulthood in reward-liking (preference) and reward-related learning.

Adolescence is a critical period in brain development. During this critical period the seeking for hedonic activities is increased, and their activity signals are stronger than the regulatory signals of judgment and reasoning. We recently reported that alteration of ErbB signaling during this period led to elevated striatal dopamine levels and reduced preference for sweetness without affecting locomotor activity and exploratory behavior. In the current study, we extend our findings and explore whether inhibition of the ErbB pathway during adolescence or adulthood also affects alcohol preference (hedonic "liking"), avoidance learning, and motivational reward "wanting". We demonstrated that chronic administration of the pan-ErbB kinase inhibitor JNJ28871063 (JNJ) to adolescent mice, but not to adult mice, reduced alcohol preference compared with the saline-injected group, without affecting avoidance learning as measured by increasing concentrations of quinine in the bitter avoidance test. Adolescent JNJ-treated mice continue to demonstrate less alcohol preference in adulthood compared with their saline-injected controls. In addition, adolescent JNJ-treated mice and their saline-injected controls did not differ in the time they spent in the food-condition chamber, and in their preference for social odor. In contrast to adolescent JNJ- treated mice, blocking the pathway during adulthood alter the preference to natural reward. These data support our initial findings that interruption of the ErbB pathway during adolescence emerges in a reduced hedonic capacity that persists into adulthood, without disturbing avoidance and reward learning. In addition, this paper provides a further behavioral role of the ErbB signaling pathway in the reward system, and suggests a different time period for the involvement of the pathway in the "liking" and the "wanting" components of the system.

Decoding emotion of the other differs among schizophrenia patients and schizoaffective patients: A pilot study.

The deficit in ability to attribute mental states such as thoughts, beliefs, and intentions of another person is a key component in the functional impairment of social cognition in schizophrenia. In the current study, we compared the ability of persons with first episode schizophrenia (FE-SZ) and individuals with schizophrenia displaying symptomatic remission (SZ-CR) to decode the mental state of others with healthy individuals and schizoaffective patients. In addition, we analyzed the effect of dopamine-related genes polymorphism on the ability to decode the mental state of another, and searched for different genetic signatures. Our results show that overall, individuals with schizophrenia performed worse in the "Reading the Mind in the Eyes" (eyes) test, a simple well-defined task to infer the mental state of others than healthy individuals. Within the schizophrenia group, schizoaffective scored significantly higher than FE-SZ, SZ-CR, and healthy individuals. No difference was observed in performance between FE-SZ and SZ-CR subjects. Interestingly, FE-SZ and SZ-CR, but not schizoaffective individuals, performed worse in decoding negative and neutral emotional valance than the healthy control group. At the genetic level, we observed a significant effect of the DAT genotype, but not D4R genotype, on the eyes test performance. Our data suggest that understanding the mental state of another person is a trait marker of the illness, and might serve as an intermediate phenotype in the diagnostic process of schizophrenia disorders, and raise the possibility that DA-related DAT gene might have a role in decoding the mental state of another person.

Disruption of the ErbB signaling in adolescence increases striatal dopamine levels and affects learning and hedonic-like behavior in the adult mouse.

The ErbB signaling pathway has been genetically and functionally implicated in schizophrenia. Numerous findings support the dysregulation of Neuregulin (NRG) and epidermal growth factor (EGF) signaling in schizophrenia. However, it is unclear whether alterations of these pathways in the adult brain or during development are involved in the pathophysiology of schizophrenia. Herein we characterized the behavioral profile and molecular changes resulting from pharmacologically blocking the ErbB signaling pathway during a critical period in the development of decision making, planning, judgments, emotions, social cognition and cognitive skills, namely adolescence. We demonstrate that chronic administration of the pan-ErbB kinase inhibitor JNJ-28871063 (JNJ) to adolescent mice elevated striatal dopamine levels and reduced preference for sucrose without affecting locomotor activity and exploratory behavior. In adulthood, adolescent JNJ-treated mice continue to consume less sucrose and needed significantly more correct-response trials to reach the learning criterion during the discrimination phase of the T-maze reversal learning task than their saline-injected controls. In addition, JNJ mice exhibited deficit in reference memory but not in working memory as measured in the radial arm maze. Inhibition of the pathway during adolescence did not affect exploratory behavior and locomotor activity in the open field, social interaction, social memory, and reversal learning in adult mice. Our data suggest that alteration of ErbB signaling during adolescence resulted in changes in the dopaminergic systems that emerge in pathological learning and hedonic behavior in adulthood, and pinpoints the possible role of the pathway in the development of cognitive skills and motivated behavior.

The Effects of Acupuncture Treatment on Sleep Quality and on Emotional Measures among Individuals Living with Schizophrenia: A Pilot Study.

Purpose. To examine the effects of acupuncture on sleep quality and on emotional measures among patients with schizophrenia. Methods. Twenty patients with schizophrenia participated in the study. The study comprised a seven-day running-in no-treatment period, followed by an eight-week experimental period. During the experimental period, participants were treated with acupuncture twice a week. During the first week (no-treatment period) and the last week of the experimental period, participants filled out a broad spectrum of questionnaires and their sleep was continuously monitored by wrist actigraph. Results. A paired-sample t-test was conducted comparing objective and subjective sleep parameters manifested by participants before and after sequential acupuncture treatment. A significant effect of acupuncture treatment was observed for seven objective sleep variables: sleep onset latency, sleep percentage, mean activity level, wake time after sleep onset, mean number of wake episodes, mean wake episode and longest wake episode. However, no significant effects of acupuncture treatment were found for subjective sleep measures. Likewise, the results indicate that acupuncture treatment improved psychopathology levels and emotional measures, that is, depression level and anxiety level. Conclusions. Overall, the findings of this pilot study suggest that acupuncture has beneficial effects as a treatment for insomnia and psychopathology symptoms among patients with schizophrenia.

A randomized add-on trial of high-dose D-cycloserine for treatment-resistant depression.

Antagonism of N-methyl-D-aspartate glutamatergic receptors (NMDAR) may represent an effective antidepressant mechanism. D-cycloserine (DCS) is a partial agonist at the NMDAR-associated glycine modulatory site that at high doses acts as a functional NMDAR antagonist. Twenty-six treatment-resistant major depressive disorder patients participated in a double blind, placebo-controlled, 6-wk parallel group trial with a gradually titrated high dose (1000 mg/d) of DCS added to their antidepressant medication. DCS treatment was well tolerated, had no psychotomimetic effects and led to improvement in depression symptoms as measured by Hamilton Depression Rating Scale (HAMD; p = 0.005) and Beck Depression Inventory (p = 0.046). Of the 13 subjects treated with DCS, 54% had a ≥ 50% HAMD score reduction vs. 15% of the 13 patients randomized to placebo (p = 0.039). A significant (p = 0.043) treatment× pre-treatment glycine serum levels interaction was registered. These findings indicate that NMDAR glycine site antagonism may be a cost-effective target for development of mechanistically novel antidepressants. Larger-sized DCS trials are warranted.

Epigenetic and genetic factors predict women's salivary cortisol following a threat to the social self.

Evidence suggests that the reactivity of the Hypothalamus-Pituitary-Adrenal axis (HPAA) is modulated by both genetic and environmental variables. Of special interest are the underlying molecular mechanisms driving gender differences to psychosocial stressors. Epigenetic mechanisms that sculpt the genome are ideal candidates for mediating the effects of signals on the HPAA. In the current study, we analyzed by pyrosequencing, bisulfite-treated buccal DNA from male and female university students who participated in the Trier Social Stress Test (TSST). A linear regression model was used to ascertain the effects of sex, CpG methylation and genes on stress response. Total cortisol output (area under the curve, AUC) was significantly predicted by glucocorticoid receptor (NR3C1) exon 1F methylation (averaged across 39 CpG sites) solely in female subjects. A single CpG site located in the exon 1F noncanonical nerve growth factor-inducible protein A (NGFI-A) transcription factor was a highly significant predictor of AUC in female subjects. Additionally, variations in the estrogen receptor alpha (ESR1) and the serotonin transporter promoter (5-HTTLPR) genes were independent additive predictors of AUC. The full model accounted for half of the variance (50.06%) in total cortisol output. Notably, this is the first demonstration that epigenetic changes at the GR exon 1F correlate with HPAA reactivity. These findings have important implications for understanding the molecular mechanisms underlying gender differences in stress-related disorders and underscore the unique value of modeling both epigenetic and genetic information in conferring vulnerability to stress.

The effects of music relaxation and muscle relaxation techniques on sleep quality and emotional measures among individuals with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD), an anxiety disorder with lifetime prevalence of 7.8%, is characterized by symptoms that develop following exposure to traumatic life events and that cause an immediate experience of intense fear, helplessness or horror. PTSD is marked by recurrent nightmares typified by the recall of intrusive experiences and by extended disturbance throughout sleep. Individuals with PTSD respond poorly to drug treatments for insomnia. The disadvantages of drug treatment for insomnia underline the importance of non-pharmacological alternatives. Thus, the present study had three aims: first, to compare the efficiency of two relaxation techniques (muscular relaxation and progressive music relaxation) in alleviating insomnia among individuals with PTSD using both objective and subjective measures of sleep quality; second, to examine whether these two techniques have different effects on psychological indicators of PTSD, such as depression and anxiety; and finally, to examine how initial PTSD symptom severity and baseline emotional measures are related to the efficiency of these two relaxation methods. Thirteen PTSD patients with no other major psychiatric or neurological disorders participated in the study. The study comprised one seven-day running-in, no-treatment period, followed by two seven-day experimental periods. The treatments constituted either music relaxation or muscle relaxation techniques at desired bedtime. These treatments were randomly assigned. During each of these three experimental periods, subjects' sleep was continuously monitored with a wrist actigraph (Ambulatory Monitoring, Inc.), and subjects were asked to fill out several questionnaires concerned with a wide spectrum of issues, such as sleep, depression, and anxiety. Analyses revealed a significant increase in objective and subjective sleep efficiency and a significant reduction in depression level following music relaxation. Moreover, following music relaxation, a highly significant negative correlation was found between improvement in objective sleep efficiency and reduction in depression scale. The study's findings provide evidence that music relaxation at bedtime can be used as treatment for insomnia among individuals with PTSD.

D-serine adjuvant treatment alleviates behavioural and motor symptoms in Parkinson's disease.

Parkinson's disease (PD) manifestations include motor symptoms and behavioural deficits that resemble schizophrenia negative symptoms. The N-methyl-D-aspartate subtype of glutamate receptor (NMDAR) represents a novel pharmacological target in PD. D-serine (DSR) allosterically modulates in-vivo NMDAR-mediated neurotransmission and has been shown to improve negative and antipsychotic drug-induced parkinsonian symptoms in schizophrenia patients. This pilot study assessed DSR effects in ten PD patients who completed a 6-wk double-blind, placebo-controlled, crossover adjuvant treatment trial with 30 mg/kg.d DSR. Primary outcome analyses consisted of separate repeated-measures multivariate analyses of variance for Unified Parkinson's Disease Rating Scale (UPDRS), Simpson-Angus Scale for Extrapyramidal Symptoms (SAS), Abnormal Involuntary Movement Scale (AIMS), and Positive and Negative Syndrome Scale (PANSS) scores. DSR treatment was well tolerated and resulted in increased DSR serum levels (p=0.001) and significantly reduced UPDRS (p=0.02), SAS (p=0.009) and PANSS (0.05) total scores. These preliminary findings suggest that DSR treatment may be beneficial in PD. Larger-sized studies with optimized DSR dosages are warranted.

The effects of music relaxation on sleep quality and emotional measures in people living with schizophrenia.

The aim of the present study was to examine the effects of music relaxation on insomnia and emotional measures in people living with schizophrenia. Twenty-four people living with schizophrenia participated in the study. The study involved a 7-day running-in no-treatment period, followed by a 7-day experimental period. Treatment consisted of music relaxation played at bedtime. During each of these periods, participants' sleep was continuously monitored with a wrist actigraph, and participants completed a wide spectrum of questionnaires. Results showed an improvement in sleep latency and sleep efficiency after the music relaxation was played. Likewise, music relaxation was shown to improve participants' total psychopathology score (PANSS) as well as their level of depression. Moreover, a significant correlation was found between reduction in level of situational anxiety and improvement in sleep efficiency. The findings suggest the beneficial effect of music relaxation as a treatment both for insomnia and for emotional measures in people living with schizophrenia.

Preliminary effects of bupropion and the promoter region (HTTLPR) serotonin transporter (SLC6A4) polymorphism on smoking behavior in schizophrenia.

In the current study, we investigated how individual variants in the serotonin promoter gene, previously associated with smoking cessation and linked to anxiety-related personality traits, were associated with individual differences in responsiveness to bupropion and cognitive behavioral therapy (CBT) in a clinical population. We hypothesize that subjects with the long allele may be less responsive to treatment. Altogether 61 schizophrenic patients (46 M, 15 F) on stable neuroleptic medication were initially enrolled in a smoking reduction program (prospective, double-blind, placebo-controlled) including cognitive behavioral therapy plus placebo or CBT plus bupropion. Additionally, subjects were genotyped for a polymorphism in the serotonin transporter (SLC6A4). Thirty-two subjects (23 M, 9 F) completed a 14-week course of treatment. While both groups of subjects demonstrated significant reductions in smoking behavior due to CBT, subjects receiving bupropion did not show significant differences in smoking behavior when compared to placebo. In addition, analysis by SPSS repeated measures multivariate showed a significant sex by SLC6A4 genotype interaction on the number of cigarettes smoked. Only male subjects with at least one short promoter region allele (short/short and short/long combined) showed a reduction in cigarette consumption as a result of treatment. This study provides preliminary evidence of how polymorphisms in the serotonin transporter can be informative in predicting individual responses to smoking reduction therapy.

The rate of consanguineous marriages among parents of schizophrenic patients in the Arab Bedouin population in Southern Israel.

Consanguinity may contribute to the incidence of schizophrenia in offspring despite the usually accepted polygenic model of schizophrenia inheritance. Bedouin Arab families in southern Israel have a high rate of cousin marriages as do families throughout most Arab societies. We studied consanguinity in the parents of schizophrenic patients admitted in a defined catchment area of southern Israel, compared to a control group of parents of all infants born to Bedouin mothers in this catchment area. There was a small but significant increase in the rate of cousin marriages among the parents of schizophrenia patients compared to parents of infant controls. These results are consistent with claims that inbreeding can contribute to the incidence of schizophrenia even as a polygenic illness. However, the absence of a better matched control group limits confidence in the results.

Pilot controlled trial of D-serine for the treatment of post-traumatic stress disorder.

Enhancement of neurotransmission mediated at N-methyl-D-aspartate subtype of glutamate receptors (NMDAR) may be beneficial in post-traumatic stress disorder (PTSD). d-serine (DSR) is an endogenous full agonist at the NMDAR-associated glycine modulatory site. Twenty-two chronic PTSD outpatients were randomly assigned to participate in a 6-wk double-blind, placebo-controlled, crossover trial with 30 mg/kg x d DSR used as monotherapy or add-on pharmacotherapy. Outcome was assessed using the Clinician-Administered PTSD scale (CAPS), Hamilton Anxiety (HAMA) and Depression (HAMD) scales and the civilian version of the Mississippi Scale for Combat-Related PTSD (MISS). DSR treatment was well tolerated and resulted in significantly (p=0.03) increased DSR serum levels. Compared with placebo administration, DSR treatment resulted in significantly reduced HAMA (p=0.007) and MISS (p=0.001) scores and a trend (p=0.07) towards improved CAPS total scores. These preliminary findings indicate that NMDAR glycine site-based pharmacotherapy may be effective in PTSD and warrant larger-sized clinical trials with optimized DSR dosages.

Self-monitoring in anorexia nervosa.

BACKGROUND: A possible connection between Mark Snyder's concept of self-monitoring and anorexia nervosa (AN) has not previously been examined. AIMS: We hypothesized that AN symptomatology correlates positively with the Other-Directedness aspect of Snyder's self-monitoring construct and negatively with its Extraversion aspect. METHOD: 194 women with a history of AN were classified as currently ill (n = 17), partially recovered (n = 106) and recovered (n = 71).These women and 100 female controls with no history of an eating disorder completed Snyder's Self-Monitoring Scale (SMS) and the Eating Attitudes Test-26 (EAT-26). ;Other-Directedness' and ;Acting and Extraversion'subscales were derived from an exploratory factor analysis of the Hebrew version of the SMS. Mean total and subscale scores were compared across groups, and correlations were calculated between EAT-26 scores and SMS total and subscale scores. RESULTS: Both subscales of the SMS correlated significantly with total scores but not with one another. As expected, AN symptomatology and EAT-26 scores were associated positively with Other-Directedness yet negatively with Acting and Extraversion, rendering the correlation with total SMS scores insignificant. CONCLUSION: Different aspects of Snyder's self-monitoring construct correlate in opposite directions with eating pathology and AN symptomatology. AN appears to be associated with high Other-Directedness but low Acting and Extroversion.

Treatment lag on the way to the mental health clinic among Arab- and Jewish-Israeli patients.

BACKGROUND: The early recognition and timely treatment of psychiatric disorders helps reduce suffering, prevents mental disabilities and makes interventions more cost-effective. OBJECTIVE: To examine treatment lag among Arab- and Jewish-Israelis applying to psychiatric clinics for the first time, and the association of this lag with selected socio-demographic and mental health-related variables. METHODS: 251 adult outpatients making their first-ever visit to a psychiatric clinic completed a self-administered questionnaire, including questions on the time elapsed since the onset of the current disorder, reasons for the treatment lag, source of referral, main complaints, current psychiatric problems (self-diagnosis), attitudes to psychiatric disorders and treatment, pathways to care, and standard sociodemographic information. Univariate and multivariate analyses were performed to compare Arab- and Jewish-Israelis on parameters of interest. RESULTS: Compared with their Jewish counterparts, Arab-Israeli patients showed a two-fold delay in initial treatment contact (X2 = 4.00, df = 1, p < 0.05). Logistic regression analysis showed that this delay was associated with lower schooling, other-than-psychiatric attribution of mental symptoms, and a more pessimistic attitude to the successful treatment of mental disorders in general and for oneself in particular. CONCLUSIONS: Since longer treatment delay was mostly associated with potentially modifiable knowledge and attitudes on mental disorders and treatment, educational programs targeting specific community sectors and community agents should be promoted to shorten this lag.

Emotional distress among first-time patients attending outpatient mental health clinics in Israel: an Arab-Jewish comparative study.

BACKGROUND: Few studies have focused specifically on the role of ethnicity in emotional distress and symptoms among first-time psychiatric outpatients. METHODS: 251 first-time patients, aged 18-72 years, attending three outpatient mental health clinics in Israel, were surveyed. Three methods of case detection were used: a GHQ-12 score (equal or >3), self-reported symptoms (using a checklist) and a psychiatrist's provisional ICD-10 diagnosis. In addition, self-efficacy and perceived social support were measured using standardized self-report questionnaires. Univariate and multivariate analyses compared the two ethnic groups: Israeli Arabs and Israeli Jews. RESULTS: Compared to Jewish patients, Israeli Arab patients had a higher "distress caseness" rate based on GHQ-12 score (70.8% versus 41.2%) and a higher rate of psychiatrist-detected ICD-10 stress-related disorders (46.7% versus 23.3%), but a lower rate of self-reported emotional distress (36% versus 54.3%) and symptoms of mood disturbances (38.7% versus 64.7%). The Israeli Arabs also had lower mean scores on measures of self-efficacy (2.0 versus 2.4) and perceived social support from friends (12.2 versus 17.6) and significant others (16.7 versus 20.0). In a parsimonious regression model, the best predictors of emotional distress had low self-efficacy and social support from significant others, and, being Arab, these variables accounted for 27.1%, 7.2% and 8.8%, respectively, of the total variance in GHQ distress scores. CONCLUSION: The results suggest that the detection of emotional distress and symptoms varies markedly by patients' ethnic background. These variations can be predicted by a lower sense of self-efficacy and social support among Israeli Arabs as compared to Israeli Jews.

Mitochondrial DNA HV lineage increases the susceptibility to schizophrenia among Israeli Arabs.

Haplotypes and haplogroups are linked sets of common DNA variants, acting as susceptibility or protective factors to complex disorders. Growing evidence suggests that dysfunction of mitochondrial bioenergetics contributes to the schizophrenia phenotype. We studied mitochondrial DNA haplogroups in schizophrenia patients. Since mitochondria are inherited from the mothers, we used healthy fathers as an ideal case-control group. Analysis of the distribution of mitochondrial haplogroups in schizophrenia patients compared to their healthy fathers (202 pairs) resulted in an over-representation of the mtDNA lineage cluster, HV, in the patients (p=0.01), with increased relative risk (odds ratio) of 1.8. Since mitochondrial DNA is small relative to nuclear DNA, a total mitochondrial genome analysis was possible in a hypothesis-free manner. However, mitochondrial DNA haplogroups are highly variable in human population and it will be necessary to replicate our results in other human ethnic groups.