Ilan Treves

A Double-Blind, Randomized Study of Minocycline for the Treatment of Negative and Cognitive Symptoms in Early-Phase Schizophrenia

BACKGROUND Current antipsychotics have only a limited effect on 2 core aspects of schizophrenia: negative symptoms and cognitive deficits. Minocycline is a second-generation tetracycline that has a beneficial effect in various neurologic disorders. Recent findings in animal models and human case reports suggest its potential for the treatment of schizophrenia. These findings may be linked to the effect of minocycline on the glutamatergic system, through inhibition of nitric oxide synthase and blocking of nitric oxide-induced neurotoxicity. Other proposed mechanisms of action include effects of minocycline on the dopaminergic system and its inhibition of microglial activation. OBJECTIVE To examine the efficacy of minocycline as an add-on treatment for alleviating negative and cognitive symptoms in early-phase schizophrenia. METHOD A longitudinal double-blind, randomized, placebo-controlled design was used, and patients were followed for 6 months from August 2003 to March 2007. Seventy early-phase schizophrenia patients (according to DSM-IV) were recruited and 54 were randomly allocated in a 2:1 ratio to minocycline 200 mg/d. All patients had been initiated on treatment with an atypical antipsychotic < or = 14 days prior to study entry (risperidone, olanzapine, quetiapine, or clozapine; 200-600 mg/d chlorpromazine-equivalent doses). Clinical, cognitive, and functional assessments were conducted, with the Scale for the Assessment of Negative Symptoms (SANS) as the primary outcome measure. RESULTS Minocycline was well tolerated, with few adverse events. It showed a beneficial effect on negative symptoms and general outcome (evident in SANS, Clinical Global Impressions scale). A similar pattern was found for cognitive functioning, mainly in executive functions (working memory, cognitive shifting, and cognitive planning). CONCLUSIONS Minocycline treatment was associated with improvement in negative symptoms and executive functioning, both related to frontal-lobe activity. Overall, the findings support the beneficial effect of minocycline add-on therapy in early-phase schizophrenia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00733057.

Mental pain and its communication in medically serious suicide attempts : An impossible situation

BACKGROUND The study of near-fatal suicide attempters may provide insight into the minds of suicidal subjects. Our aim is to test the hypothesis that mental pain is a general risk factor for suicidal behavior and communication difficulties are a particular risk factor for medically serious suicidal behavior. METHODS Thirty five subjects who made medically serious suicide attempts were compared with 67 medically not serious suicide attempters and 71 healthy controls. All were interviewed with the SCID-I and completed questionnaires covering mental pain, communication difficulties and seriousness of suicide attempt. RESULT Variables from the mental pain domain (e.g. depression) predicted the presence of suicidal behavior, and variables from the communication difficulties domain (e.g., self-disclosure) predicted the lethality and seriousness of the suicide attempts. LIMITATIONS Relatively small number of patients with medically serious suicide attempt and the relatively large number of questionnaires which may to some extent have diminished informant reliability. CONCLUSIONS Problems with sharing of feelings with others are an important risk factor for near-lethal suicide, over and above the contribution of psychiatric illness and mental pain, including depression and hopelessness.

The effect of Ondansetron on memory in schizophrenic patients

It has been well established that patients with schizophrenia have impaired cognitive function on neuropsychological tasks related to memory. Previous studies also suggest serotonins central role in memory. This double-blind crossover study aimed to explore the effect of Ondansetron, a selective serotonin 3 receptor (5-HT(3)) antagonist, on a variety of memory tasks in schizophrenic patients. Clozapine-treated schizophrenic patients in remission (N=21) were randomly treated with Ondansetron or placebo and then evaluated at three consecutive points. These evaluations included clinical measures (including Positive and Negative Syndrome Scale for Schizophrenia, Clinical Global Impression and Extrapyramidal Symptoms Rating Scale) and neuropsychological measures (including Digit Span, Paired Association, Rey-Osterich Complex Figure Test, Digit Symbol and the Rivermead Behavioral Memory Tests). Ondansetron, when compared with placebo, did not affect the above clinical measures and most of the neuropsychological tests. Short-term administration of Ondansetron, however, was associated with significantly improved visuo-spatial memory as measured by the Rey-Osterich Complex Figure Test. These preliminary results suggest Ondansetrons possible role in enhancement of memory function in schizophrenia.

Effect of L-tryptophan on Memory in patients with schizophrenia

It has been well established that patients with schizophrenia have impaired cognitive abilities on neuropsychological tasks related to memory. Previous studies also suggest a central role for serotonin in memory. This double-blind crossover study aimed to explore the effect of l-tryptophan, a serotonin precursor, on a variety of memory tasks in schizophrenic patients. Antipsychotic-treated schizophrenic patients in remission (N = 21) were randomly treated with l-tryptophan or placebo and then evaluated at three consecutive points on clinical measures (including Positive and Negative Syndrome Scale for Schizophrenia, Clinical Global Impression, and Extrapyramidal Symptoms Rating Scale) and by neuropsychological tests (including Digit-Span, Paired Association, Rey-Osterich Complex Figure Test, Digit Symbol, Number Facility Test, and the Rivermead Behavioral Memory Tests. Compared with placebo, l-tryptophan had a beneficial effect on memory functions but not on the patients’ psychotic state or on the side effects of medications. These preliminary results suggest the possibility of using serotonin precursor to enhance memory function in schizophrenia.

Group interpersonal psychotherapy for patients with major depression disorder - pilot study

BACKGROUND This study evaluated the effectiveness of group interpersonal psychotherapy (IPT-G) for patients suffering from moderate to severe major depressive disorder (MDD), and who responded to antidepressant drugs during the acute phase treatment. METHODS Subjects were allocated into two groups: in the study group subjects entered IPT-G while in the comparison group subjects continued with standard treatment. All subjects were assessed five times during and 6 months after the termination of the IPT-G in a double-blind, matched-control design. RESULTS Subjects who participated in the IPT-G demonstrated significant improvement of their depressive symptoms compared to those who received the standard treatment both during the group therapy and in a 6-month follow-up period. CONCLUSIONS Our preliminary results suggest that IPT in a group setting might be effective for a subset of patients who respond to antidepressant medication. LIMITATIONS Small group of patients, lack of different types of treatment as control groups.

Aggression-impulsivity, mental pain, and communication difficulties in medically serious and medically non-serious suicide attempters

BACKGROUND Unbearable mental pain, depression, and hopelessness have been associated with suicidal behavior in general, while difficulties with social communication and loneliness have been associated with highly lethal suicide attempts in particular. The literature also links aggression and impulsivity with suicidal behavior but raises questions about their influence on the lethality and outcome of the suicide attempt. OBJECTIVES To evaluate the relative effects of aggression and impulsivity on the lethality of suicide attempts we hypothesized that impulsivity and aggression differentiate between suicide attempters and non-attempters and between medically serious and medically non-serious suicide attempters. METHOD The study group included 196 participants divided into four groups: 43 medically serious suicide attempters; 49 medically non-serious suicide attempters, 47 psychiatric patients who had never attempted suicide; and 57 healthy control subjects. Data on sociodemographic parameters, clinical history, and details of the suicide attempts were collected. Participants completed a battery of instruments for assessment of aggression-impulsivity, mental pain, and communication difficulties. RESULTS The medically serious and medically non-serious suicide attempters scored significantly higher than both control groups on mental pain, depression, and hopelessness (p<.001 for all) and on anger-in, anger-out, violence, and impulsivity (p<.05 for all), with no significant difference between the two suicide attempter groups. Medically serious suicide attempters had significantly lower self-disclosure (p<.05) and more schizoid tendencies (p<.001) than the other three groups and significantly more feelings of loneliness than the medically non-serious suicide attempters and nonsuicidal psychiatric patients (p<.05). Analysis of aggression-impulsivity, mental pain, and communication variables with suicide lethality yielded significant correlations for self-disclosure, schizoid tendency, and loneliness. The interaction between mental pain and schizoid traits explained some of the variance in suicide lethality, over and above the contribution of each component alone. CONCLUSIONS Aggression-impulsivity and mental pain are risk factors for suicide attempts. However, only difficulties in communication differentiate medically serious from medically non-serious suicide attempters. The combination of unbearable mental pain and difficulties in communication has a magnifying effect on the risk of lethal suicidal behavior.

Mental Pain, Communication Difficulties, and Medically Serious Suicide Attempts: A Case-Control Study

Medical severe suicide attempts (MSSA) are epidemiologically very similar to individuals who complete suicide. Thus the investigation of individuals who have made MSSAs may add to our understanding of the risk factors for completed suicide. The aim of this study was to assess the role of mental pain and communication difficulties in MSSA. A total of 336 subjects were divided into 4 groups: 78 meeting criteria for MSSA compared with116 subjects who made a medically non-serious suicide attempt (MNSSA), 47 psychiatric controls with no history of suicidal behavior, and 95 healthy controls. Mental pain variants (e.g., hopelessness), facets of communication difficulties (e.g., self-disclosure), as well as socio-demographic and clinical characteristics were assessed. The MSSA had significantly higher communication difficulties than the other 3 groups. Moreover, the interaction between mental pain and communication difficulties explained some of the variance in suicide lethality, above and beyond the contribution of each component alone. This report underlines the importance of mental pain for suicide attempts in general while difficulties in communication abilities play a critical role in differentiating MSSA from MNSSA. The co-existence of unbearable mental pain with difficulties in communication significantly enhances the risk for more lethal forms of suicidal behavior.

Perception of ill spouse and dyadic relationship in couples with affective disorder and those without

BACKGROUND This study compares the perception of spouses and the quality of the dyadic relationship of patients with severe affective disorders in remission with healthy couples. METHOD The sample included spouses of patients between the ages of 20 and 65 who had been hospitalized with severe affective illness and who were currently in remission (depressive, n=23; bipolar, n=11) and a control group matched by socioeconomic status. Both groups completed three instruments measuring the quality of the dyadic relationship, attributed characteristics of the spouse and non-formal social support. RESULTS The spouses of patients, as compared to spouses of controls, scored lower on consensus, unity and expressions of affection in their marital relationship, ranked their ill spouses lower on the positive qualities and higher on the negative qualities and reported receiving less emotional and practical support. LIMITATIONS The limitations of the study are the small sample size and cross sectional design. CONCLUSIONS The results suggest that severe affective disorders are associated with marital dysfunction, even during periods of symptom remission.

Perception of dyadic relationship and emotional states in patients with affective disorder.

BACKGROUND Previous research has shown that interpersonal processes play a significant role in the development and maintenance of affective disorders. In this study, this claim was further investigated by comparing the perception of the dyadic relationship and judgment of others emotions in affective disorder patients. METHOD The sample included 39 couples (n=39 couples) with one of the partners suffering from an affective disorder and currently either in an acute or remitted depressive state. All participants completed four instruments, measuring the perceived quality of the dyadic relationship and the perception of others emotions as reflected by judgments of facial expressions line drawings. RESULTS While the level of marital satisfaction was found to be lower in the acute than in the remitted group both for ill partners and their spouses, spouses in both the acute and remitted group tended to be more critical of their ill partners. Patients who were depressed judged facial expressions significantly less positively than did remitted patients. Judgments of negative emotions were highly correlated between partners in the acute group, but uncorrelated in the remitted group. Acutely depressed patients were less sensitive to invitation than remitted patients, while their spouses displayed the opposite pattern. CONCLUSION The present results shed further light on the interpersonal dynamics between depressed patients and their spouses by underscoring differences between couples with a remitted vs. acutely depressed partner in their perception of the dyadic unit and their judgments of facial emotions. LIMITATIONS Longitudinal research is needed, in which the same patients are tested during periods of remission and acute episodes, as well as research investigating the role of patient gender in the perception of facial expressions of emotions.

Predictive value of psychological characteristics and suicide history on medical lethality of suicide attempts: A follow-up study of hospitalized patients

BACKGROUND This study examined the role of mental pain, communication difficulties, and suicide history in predicting the medical severity of follow-up suicide attempts. METHODS The cohort included 153 consecutive psychiatric in-patients who participated in earlier studies 1-9 years previously. Fifty-three had a history of a medically serious suicide attempt (MSSA), 64 had a history of a medically non-serious suicide attempt (MNSSA), and 36 had no history of suicide. A MSSA was defined as a suicide attempt that warranted hospitalization for at least 24h and extensive medical treatment. Participants completed a battery of instruments measuring mental pain and communication difficulties. Findings were analyzed in relation to follow-up suicide attempts and their severity. RESULTS Fifty-three patients (35.5%) had attempted suicide: 15 (9.9%) a MSSA (including 5 fatalities) and 38 (25%) a MNSSA. The medical severity of the index attempt and level of hopelessness at the index attempt were significantly correlated with medical severity of the follow-up attempt. In younger patients, high levels of depression and self-disclosure predicted the medical severity of the follow-up attempt. In patients with relatively low hopelessness, the medical severity of the attempt increased with the level of self-disclosure. LIMITATIONS (i) Possibly incomplete patient information, as some of the patients who participated in the index studies could not be located. (ii) Relatively small group of patients with an index MSSA. CONCLUSIONS Patients who have made a suicide attempt should be assessed for medical severity of the attempt, hopelessness, and communication difficulties, which are important factors in follow-up attempts.