Lessons learned from a comparison of evidence-based research in pregnant opioid-dependent women.

OBJECTIVES: Lessons learned in research and treatment of opioid dependence demonstrate the need to include pregnant women in clinical trials. METHODS: Two double-blind, double-dummy, randomized controlled trials (Pilot study, European sample(†) of MOTHER-trial) comparing buprenorphine and methadone in opioid-dependent pregnant women were conducted. In both studies, participants received voucher-based incentives for attendance and completion of study assessments. In the MOTHER trial, participants additionally received escalating voucher incentives for drug-free urine samples. Neonatal abstinence syndrome was treated with oral morphine solution based on standardized modified Finnegan scores. RESULTS: After a mean treatment period of 13.79 weeks in the Pilot study (PS, n = 18) and 20.78 weeks in the MOTHER-trial (MT, n = 41), respectively (p < 0.001), PS patients delivered at mean doses of 14.00 mg buprenorphine/52.50 mg methadone and MT participants at 13.44 mg buprenorphine/63.68 mg methadone. Nonsignificant differences regarding dropout rates were found (22% in PS versus 10% in MT), but dropout was significantly earlier in the MT (p = 0.013). Significantly higher rates of concomitant consumption of opioids and benzodiazepines occurred in the PS compared with the MT (p < 0.001), however, with no significant differences in neonatal data between both settings. CONCLUSIONS: Early treatment enrolment combined with contingency management contributes to reduced illicit drug use throughout pregnancy, surprisingly without influencing neonatal outcome parameters.

Suicide mortality among physicians, dentists, veterinarians, and pharmacists as well as other high-skilled occupations in Austria from 1986 through 2020.

Some evidence puts health professionals at increased risk of suicide, especially females, whereas other research suggests a lower risk in high-skilled occupations. This study investigated the suicide risk of four health professions (physicians, dentists, veterinarians, pharmacists) and three other high-skilled occupations (notaries, lawyers, tax advisors/public accountants) in Austria compared to the general population, and analyzed suicide methods across occupations. Data was collected from professional associations and Austrian cause-of-death statistics to determine suicide cases. Gender-specific standardized mortality ratios (SMRs), crude and age-adjusted suicide rates and frequencies for suicide methods were calculated for each profession (maximum time span 1986-2020). Among males, only veterinarians had a significantly elevated suicide risk compared to the general population. Physicians and tax advisors/public accountants had a significantly lower suicide risk. Among females, the veterinarians, physicians, and pharmacists had a significantly elevated suicide risk; for dentists, it was also elevated, though non-significantly. Age-adjusted suicide rates showed a smaller gap between men and women in all professions compared to the general population. Poisoning was the predominant suicide method among health professions, except dentists. These findings are consistent with some of the prior literature and call for specific suicide prevention efforts in health professions, focusing on women.

Influence of site differences between urban and rural American and Central European opioid-dependent pregnant women and neonatal outcome characteristics.

BACKGROUND: Multi-center trials enable the recruitment of larger study samples, although results might be influenced by site-specific factors. METHODS: Site differences of a multi-center prospective double-blind, double-dummy randomized controlled trial (7 centers: Central Europe (Vienna)/USA (3 urban/3 rural centers)) comparing safety and efficacy of methadone and buprenorphine in pregnant opioid-dependent women and their neonates. RESULTS: Urban US women had the highest rate of concomitant opioid (p = 0.050) and cocaine consumption (p = 0.003), the highest dropout rate (p = 0.001), and received the lowest voucher sums (p = 0.001). Viennese neonates had significantly higher Apgar scores 1 min (p = 0.001) and 5 min after birth (p < 0.001) and were more often born by cesarean section (p = 0.024). Rural US newborns had a significantly shorter neonatal abstinence syndrome treatment duration compared to Viennese and urban US sites (p = 0.006), in addition to other site-specific differences, suggesting a more severely affected group of women in the urban US sites. CONCLUSION: This clinical trial represents a role model for pharmacological treatment in this unique sample of pregnant women and demonstrates the clinical importance of considering site-specific factors in research and clinical practice.

Lithium in drinking water and suicide mortality.

BACKGROUND: There is some evidence that natural levels of lithium in drinking water may have a protective effect on suicide mortality. AIMS: To evaluate the association between local lithium levels in drinking water and suicide mortality at district level in Austria. METHOD: A nationwide sample of 6460 lithium measurements was examined for association with suicide rates per 100,000 population and suicide standardised mortality ratios across all 99 Austrian districts. Multivariate regression models were adjusted for well-known socioeconomic factors known to influence suicide mortality in Austria (population density, per capita income, proportion of Roman Catholics, as well as the availability of mental health service providers). Sensitivity analyses and weighted least squares regression were used to challenge the robustness of the results. RESULTS: The overall suicide rate (R(2) = 0.15, ß = -0.39, t = -4.14, P = 0.000073) as well as the suicide mortality ratio (R(2) = 0.17, ß = -0.41, t = -4.38, P = 0.000030) were inversely associated with lithium levels in drinking water and remained significant after sensitivity analyses and adjustment for socioeconomic factors. CONCLUSIONS: In replicating and extending previous results, this study provides strong evidence that geographic regions with higher natural lithium concentrations in drinking water are associated with lower suicide mortality rates.

Retention rate and side effects in a prospective trial on hepatitis C treatment with pegylated interferon alpha-2a and ribavirin in opioid-dependent patients.

Hepatitis C viral (HCV) infection is present in 30 to 98% of intravenous drug users. Intravenous substance abuse represents the main route of HCV transmission in industrialized countries. A multi-centre, randomized, controlled, prospective study assessed sustained virological response (SVR), adverse events such as depressive episodes and retention rate of HCV treatment in opioid-dependent patients. Stabilized, opioid-dependent patients with chronic HCV infection (genotype 2 or 3) received pegylated interferon alpha-2a in combination with ribavirin 800 mg/day (Group A) or 400 mg/day (Group B). Participants were randomized, blocked and stratified by genotype and viral load. A standardized psychiatric assessment, Beck Depression Inventory (BDI) and Van Zerssen's list of complaints were administered at each study visit. In 31 months, 300 opioid-dependent patients were screened; 190 (63.3%) were hepatitis C antibody positive. According to study protocol, out of 75 'potential-to-treat' patients with genotype 2 or 3, 17 stable patients (22.6%) were included in the study. All participants completed the study. Significant haemoglobin decreases occurred in both Groups A (P = 0.001) and B (P = 0.011). All the patients had an end-of-treatment (week 24) HCV RNA negativity. Fifteen (88.2%) achieved SVR at week 48. Overall, 52.9% developed depressive symptoms during treatment. Because of the prompt initiation of antidepressant medication at first appearance of depressive symptoms, no severe depressive episodes occurred. Our data show a high retention rate and reliability, and good viral response for both treatments. Hepatitis C treatment in stable opioid-dependent patients was efficacious, suggesting that addiction clinics can offer antiviral therapy in combination with agonistic treatment as part of multi-disciplinary treatment.

Association between prenatal tobacco exposure and outcome of neonates born to opioid-maintained mothers. Implications for treatment.

BACKGROUND: Prenatal nicotine exposure is associated with increased neonatal mortality, low birth weight, and smaller head circumference. Opioid-dependent pregnant women show a particularly high prevalence of tobacco smoking and are at greater risk for additional adverse events. However, little is known about the impact of tobacco smoking on opioid-maintained pregnant women and neonatal outcomes. PATIENTS AND METHODS: This study examined the effect of cigarette smoking on 139 opioid-maintained pregnant women and their neonates. Forty-five percent of the participants were maintained on slow-release oral morphine (SROM), 39% received methadone maintenance, and 16% received buprenorphine. Participants were divided into two groups: (1) women who reported a low cigarette consumption of < or =10 cigarettes/day (56.8%) and (2) those reporting heavy consumption of > or =20 cigarettes/day (43.2%). Neonatal outcome measures were assessed, and a standardized Finnegan score was applied to determine the neonatal abstinence syndrome (NAS). RESULTS: Fifty-two percent of the newborns did not require treatment for NAS (54% of neonates born to methadone-maintained mothers, 30% born to SROM-maintained mothers, and 95% born to buprenorphine-maintained mothers; p < 0.001). Heavy cigarette consumption was associated with significantly lower neonatal birth weight (p < 0.001), smaller birth length (p = 0.017) as well as with the severity of NAS (p = 0.03). With regard to concomitant consumption of opioids (p = 0.54), cocaine (p = 0.25), amphetamines (p = 0.90) or benzodiazepines (p = 0.09), no significant differences between heavy or low nicotine consumption were noted. CONCLUSION: Heavy tobacco smoking in opioid-maintained pregnant women is associated with adverse medical and developmental consequences for the newborn. Future treatment programs for this target group should focus on an individualized approach to opioid maintenance therapy in addition to offering specially tailored counseling for smoking cessation.

Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence: a knowledge synthesis for better treatment for women and neonates.

AIMS: Through a novel synthesis of the literature and our own clinical experience, we have derived a set of evidence-based recommendations for consideration as guidance in the management of opioid-dependent pregnant women and infants. METHODS: PubMed literature searches were carried out to identify recent key publications in the areas of pregnancy and opioid dependence, neonatal abstinence syndrome (NAS) prevention and treatment, multiple substance abuse and psychiatric comorbidity. RESULTS: Pregnant women dependent on opioids require careful treatment to minimize harm to the fetus and neonate and improve maternal health. Applying multi-disciplinary treatment as early as possible, allowing medication maintenance and regular monitoring, benefits mother and child both in the short and the long term. However, there is a need for randomized clinical trials with sufficient sample sizes. RECOMMENDATIONS: Opioid maintenance therapy is the recommended treatment approach during pregnancy. Treatment decisions must encompass the full clinical picture, with respect to frequent complications arising from psychiatric comorbidities and the concomitant consumption of other drugs. In addition to standardized approaches to pregnancy, equivalent attention must be given to the treatment of NAS, which occurs frequently after opioid medication. CONCLUSION: Methodological flaws and inconsistencies confound interpretation of today's literature. Based on this synthesis of available evidence and our clinical experience, we propose recommendations for further discussion.

Breath alcohol level and plasma amino acids: a comparison between older and younger chronic alcohol-dependent patients.

AIM: The aim of the present study is to examine the distribution of plasma excitatory and inhibitory amino acids, according to the age and current breath alcohol levels (BrAl+/-), of alcohol-dependent patients. PARTICIPANTS AND METHODS: 78 alcohol-dependent patients (mean age=46.2+/-11 years, men/women=54/24) were clinically tested, including the determination of the major excitatory as well as inhibitory amino acids. The independent variables were gender, age and current alcohol consumption measured with the breath alcohol level (BrAl+/-status). RESULTS: In comparison to BrAl negatives, BrAl positives had higher plasma levels of glutamic acid (P=0.01) and proline (P=0.026), and lower levels of aminobutyric acid (P=0.002), serine (P=0.031) and urea (P=0.01). In the BrAl positives, no age effect was found related to the plasma amino acids. In contrast, the BrAl negatives displayed age-related differences. The older (>or=50 years) BrAl negative patients had higher plasma levels of cystine, tyrosine, citrulline and urea, and lower histidine levels, compared to the younger group (<50 years). In general, differences in plasma levels of certain amino acids were dependent on gender, BrAl status, age and biochemical markers (GGT, MCV) of alcohol abuse. CONCLUSIONS: Abstaining patients (BrAl-/) display age-related differences in AAs' distribution, while active drinking (BrAl+/) seems to even out those differences, underpinning the hypothesis that drinking mimics changes seen with advanced age.

Quality of life in patients receiving opioid maintenance therapy. A comparative study of slow-release morphine versus methadone treatment.

BACKGROUND/AIMS: In recent years, quality of life (QoL) assessments have proved useful for evaluating and comparing drug treatment programs. To compare QoL of patients maintained on methadone versus slow-release morphine, a prospective, randomized, double-blind, double-dummy, cross-over study was conducted. METHODS: Over two 7-week study phases, participants received either oral slow-release morphine capsules followed by methadone oral solution or vice versa. QoL status was assessed at baseline, week 7, and week 14 using the German version of the Lancashire Quality of Life Profile. RESULTS: No statistically significant difference was found between methadone and slow-release morphine in any QoL domain. A significant time effect for nearly all QoL domains was observed after 14 weeks of opioid medication, independent of the chosen drug (general well-being, p < 0.001; mental health, p = 0.001; general state of health, p = 0.018; leisure time at home, p = 0.034; leisure time out of the home, p = 0.008). Furthermore, this study revealed that even short-term maintenance yields significantly higher QoL scores in the important domain of general well-being. CONCLUSION: These results indicate that slow-release morphine has effects comparable to methadone on patient-reported QoL data and is thus a promising option for treatment of opioid-dependent subjects.

Mortality in opioid-maintained patients after release from an addiction clinic.

AIM: To investigate the mortality rate in a cohort of 269 opioid-dependent patients and the outcome of survivors meeting DSM-IV criteria for opioid dependence. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients enrolled in synthetic opioid maintenance therapy during a time frame from 1998 to 1999 originally at the Addiction Clinic and then discharged to general practitioners. METHODS: Structured interviews (Europ-ASI), urinalysis at time of interview as well as autopsy findings from deceased patients. RESULTS: After six mailings, information from 147 (54.6%) patients was gained. 85 patients (31.6%) were interviewed. From these 76.5% (n = 65) were still enrolled in maintenance therapy, 18.8% (n = 16) were drug-free and 4.7% (n = 4) relapsed. From 29 fatalities, 37.9% died of intoxication with illicit substances, 34.5% related to AIDS and 27.6% of somatic complications. The Standardized Mortality Ratio (SMR) was 29.13 (95% CI = 19.27-44.04). A higher lifetime frequency of hospitalization, less working days and a lack of social relationships were factors associated with high mortality. CONCLUSIONS: The study confirms the high mortality rate in this patient group and supports the importance of maintenance therapy. Although great efforts were undertaken in locating patients, about 45% of the target group could not be located.

No strong evidence for abnormal levels of dysfunctional attitudes, automatic thoughts, and emotional information-processing biases in remitted bipolar I affective disorder.

INTRODUCTION: Beck extended his original cognitive theory of depression by suggesting that mania was a mirror image of depression characterized by extreme positive cognition about the self, the world, and the future. However, there were no suggestions what might be special regarding cognitive features in bipolar patients (Mansell & Scott, 2006). We therefore used different indicators to evaluate cognitive processes in bipolar patients and healthy controls. METHODS: We compared 19 remitted bipolar I patients (BPs) without any Axis I comorbidity with 19 healthy individuals (CG). All participants completed the Beck Depression Inventory, the Dysfunctional Attitude Scale, the Automatic Thoughts Questionnaire, the Emotional Stroop Test, and an incidental recall task. RESULTS: No significant group differences were found in automatic thinking and the information-processing styles (Emotional Stroop Test, incidental recall task). Regarding dysfunctional attitudes, we obtained ambiguous results. CONCLUSIONS: It appears that individuals with remitted bipolar affective disorder do not show cognitive vulnerability as proposed in Beck's theory of depression if they only report subthreshold levels of depressive symptoms. Perhaps, the cognitive vulnerability might only be observable if mood induction procedures are used.

[123I]-beta-CIT SPECT imaging shows reduced thalamus-hypothalamus serotonin transporter availability in 24 drug-free obsessive-compulsive checkers.

Numerous findings indicate alterations in brain serotonin systems in obsessive-compulsive disorder (OCD). We investigated the in vivo availability of thalamus-hypothalamus serotonin transporters (SERT) in patients with DSM-IV OCD who displayed prominent behavioral checking compulsions (OC-checkers). Four hours after injection of [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT), single photon emission computed tomography (SPECT) scans were performed in 24 medication-free non-depressed OC-checkers and 24 age- and gender-matched healthy controls. For quantification of brain serotonin transporter availability, a ratio of specific to non-displaceable [(123)I]-beta-CIT brain binding was used (V''(3)=(thalamus and hypothalamus-cerebellum)/cerebellum). Drug-free non-depressed OC-checkers showed an 18% reduced brain serotonin transporter availability in the thalamus and hypothalamus, as compared with healthy control subjects (1.38+/-0.19 vs 1.69+/-0.21; p<0.001). There was a strong negative correlation between severity of OC symptomatology (Y-BOCS scores) and SERT availability (r=-0.80; p<0.001). Moreover, we found a significant positive correlation between illness duration and serotonin transporter availability (r=0.43; p<0.05). This first report of significantly reduced [(123)I]-beta-CIT binding in the thalamus-hypothalamus region in OC-checkers suggests reduced brain serotonin transporter availability, which is more pronounced with increased severity of OC symptomatology and short duration of illness. The results provide direct evidence for an involvement of the serotonergic system in the pathophysiology of OCD.

Management of neonatal abstinence syndrome in neonates born to opioid maintained women.

Neonates born to opioid-maintained mothers are at risk of developing neonatal abstinence syndrome (NAS), which often requires pharmacological treatment. This study examined the effect of opioid maintenance treatment on the incidence and timing of NAS, and compared two different NAS treatments (phenobarbital versus morphine hydrochloride). Fifty-three neonates born to opioid-maintained mothers were included in this study. The mothers received methadone (n=22), slow-release oral morphine (n=17) or buprenorphine (n=14) throughout pregnancy. Irrespective of maintenance treatment, all neonates showed APGAR scores comparable to infants of non-opioid dependent mothers. No difference was found between the three maintenance groups regarding neonatal weight, length or head circumference. Sixty percent (n=32) of neonates required treatment for NAS [68% in the methadone-maintained group (n=15), 82% in the morphine-maintained group (n=14), and 21% in the buprenorphine-maintained group (n=3)]. The mean duration from birth to requirement of NAS treatment was 33 h for the morphine-maintained group, 34 h for the buprenorphine-maintained group and 58 h for the methadone-maintained group. In neonates requiring NAS treatment, those receiving morphine required a significantly shorter mean duration of treatment (9.9 days) versus those treated with phenobarbital (17.7 days). Results suggest that morphine hydrochloride is preferable for neonates suffering NAS due to opioid withdrawal.

Multiple substance use among young males.

Neurobiological studies hypothesize a common final pathway of addictive behavior in the mesolimbic dopaminergic system. Nicotine has been shown to sensitize the reward pathway, thereby causing increased drug-seeking behavior. Since there is evidence to suggest that nicotine, alcohol and other psychoactive substances act on the same final pathway and seem to augment their effects in animal subjects, drug intake behavior of humans would likely be reflected in increased substance use of nicotine-dependent persons. We used biological markers of substance use as well as questionnaires to assess the levels of psychoactive substance use among 18-year-old males in a naturalistic cross-sectional setting. We found that increasing levels of nicotine dependence were related to higher levels of alcohol abuse and dependence. Furthermore, higher levels of nicotine dependence were associated with elevated levels of recent cannabinoid use.

Substance abuse in patients with schizophrenia.

The comorbidity of schizophrenia and substance abuse has attracted increasing attention in the past years, with multiple potential links, including genetic vulnerability, neurobiological aspects, side effects of medications, and psychosocial factors being under discussion. The link between the use of substances and the development of psychoses is demonstrated by the high prevalence of substance abuse in schizophrenia. Apart from alcohol misuse, substances commonly abused in this patient group include nicotine, cocaine, and cannabis. In particular, heavy cannabis abuse has been reported to be a stressor eliciting relapse in schizophrenic patients. In general, substance use in psychosis is associated with poorer outcomes, including increased psychotic symptoms and poorer treatment compliance. Since both disorders have been observed to be closely interdependent, a particular treatment for schizophrenic patients with comorbidity of substance abuse is needed in order to provide more effective care. In this article, we discuss various potential modes of interaction and interdependence, and the possibility of embarking on new therapeutic paths for treating this particular population.

[Cocaine abuse in Vienna and European cities--a multi-center study]. / Kokainmissbrauch in Wien und in europäischen Metropolen--eine multizentrische Studie.

INTRODUCTION: As cocaine consumption seems to have increased over the last decades, the EU has funded this multi-center, cross-sectional survey to investigate cocaine consumption in three different target groups. The study was conducted by the Addiction Clinic, Department of Psychiatry, Medical University Vienna and other nine European cities. METHODS: Data were collected by structured face-to-face interviews. The sample was composed of 211 cocaine abusers out of three target groups: (1) treatment group undergoing opioid maintenance therapy, (2) marginalized scene group and (3) integrated party group. Sociodemographic data such as age, education, employment, monthly expenses on cocaine/crack, data on consumption patterns, physical and mental health and personal needs regarding cocaine consumption were evaluated. Urine toxicology results for cocaine in the treatment group completed the analysis. RESULTS: The marginalized scene group was the oldest with a mean age of 29.35 years, with the highest unemployment rate (mean 25.11 days) and the longest duration of cocaine consumption (mean 5.80 years). They had the highest cocaine consumption pattern with a mean of 22.32 days within the last month. On average 1969 Euros/months was spent for their addiction. The treatment group had the lowest school education with a mean of 10.36 years, but showed a sufficient insight in their cocaine problem. However, the party group (with the lowest mean age, 25.64 years) highly underestimated their drug problem, the mean amount of money they spent for their addiction was 588.99 Euro/months. Structured urine toxicology between 1996 and 2002 in patients undergoing opioid maintenance therapy ("treatment group") revealed a significant increase of concomitant cocaine consumption (1996: 33.1%; 2002: 40.2%; p = 0.044). DISCUSSION: The European trend of increased cocaine use could also be observed in Vienna. One of the greatest barriers for establishing adequate treatment settings for this target group is the difficulty to reach this population. In addition, multiple substance abuse seems to be one of the predominating patterns of cocaine consumption and this aspect should be integrated within treatment (in the treatment and scene groups additional heroin and benzodiapzepines abuse is observed, in the party group intensive alcohol consumption). The Viennese results are in line with those of the other European cities; however, it could not be confirmed that consumption of crack cocaine and binge play a similarly significant role as in cities such as Hamburg or London.

Diencephalic serotonin transporter availability predicts both transporter occupancy and treatment response to sertraline in obsessive-compulsive checkers.

BACKGROUND: To our knowledge, no studies have investigated the predictive value of central serotonin transporter (SERT) availability for treatment response to serotonin reuptake inhibitors (SSRIs) in patients with obsessive-compulsive disorder (OCD). This study used brain imaging to examine the relationship between pretreatment SERT availability and transporter occupancy as well as treatment response by sertraline in patients displaying prominent behavioral checking compulsions (OC checkers). METHODS: Single photon emission computed tomography (SPECT) was used to measure thalamic-hypothalamic SERT availability with [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane in 28 nondepressed OC checkers at baseline and after 14 weeks of treatment with sertraline (175 mg daily). SERT availability was correlated with OC severity and treatment response as assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Associations between individual transporter occupancies and clinical parameters were investigated. RESULTS: 1) Correlation analyses between thalamic-hypothalamic SERT availability and OC severity showed significant negative associations at baseline and after treatment with sertraline. 2) Pretreatment SERT availability correlated significantly with both transporter occupancy and treatment response; in addition, a positive association was found between transporter occupancy and treatment response directly. 3) Using multivariate statistical models, the data demonstrated that higher pretreatment SERT availability significantly predicted higher occupancy rates as well as better treatment response 14 weeks later. CONCLUSIONS: Higher pretreatment thalamic-hypothalamic SERT availability may predict both higher occupancy rates and better treatment response to sertraline. The data suggest a strong connection between transporter occupancy and treatment response.

Changes in thalamus-hypothalamus serotonin transporter availability during clomipramine administration in patients with obsessive-compulsive disorder.

To the authors' knowledge there is as of yet no study demonstrating in vivo alterations in human serotonin transporters (SERT) during clomipramine treatment in patients with obsessive-compulsive disorder. The only study in which SERT binding has been investigated in obsessive-compulsive disorder (OCD) patients before and after treatment is a small pilot study by Stengler-Wenzke et al (2006), who treated five OCD patients with citalopram. In the study at hand, we measured transporter availability in the thalamus-hypothalamus with [(123)I] beta-CIT single photon emission computed tomography (SPECT) in 24 patients with DSM-IV OCD. All patients displayed prominent behavioral checking compulsions (OC-checkers). At baseline and upon medication after 12 weeks of treatment with clomipramine (150 mg daily) 24 non-depressed OC-checkers underwent a SPECT measurement of brain SERT availability using [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane. For quantification of brain serotonin transporter availability, a ratio of specific to non-displaceable [(123)I] beta-CIT brain binding was used (BP(ND)=(thalamus and hypothalamus-cerebellum)/cerebellum). The SERT availability was compared between baseline and after treatment and correlated with severity of OC symptomatology and treatment response as assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). After treatment with clomipramine patients showed a 48% reduced brain serotonin transporter availability in the thalamus-hypothalamus, as compared with values at baseline (0.72+/-0.12 vs 1.39+/-0.18, p<0.001). Correlations between brain SERT availability and OC symptomatology (Y-BOCS scores) revealed significantly negative associations both at baseline and after treatment (r=-0.46; p<0.05 and r=-0.53; p<0.01 respectively). These data suggest that the SERT availability values could be considered a biological indicator of disease severity. Moreover, in search of predictors we found that higher pretreatment SERT availability significantly predicted better treatment response 12 weeks later (B=14.145+/-4.514; t=3.133; p=0.005). These results provide further support for an important role of alterations in serotonergic neurons in the pathophysiology of OCD.

Glutamic acid in withdrawal and weaning in patients classified according to Cloninger's and Lesch's typologies.

AIMS: Though glutamic acid is well known as a working excitatory in the CNS, its impact on the modulation of alcohol withdrawal symptoms and withdrawal fits are not yet clear. The study has been undertaken to examine the levels of glutamic acid in chronic alcohol-dependent patients at different stages of alcohol withdrawal and weaning and to examine any existence of any differences according to Cloninger's and Lesch's typologies. PATIENTS AND METHODS: One hundred and fifty-nine alcohol-dependent patients were assessed according to Cloninger's and Lesch's typologies and related to abstinence duration, age, and gender. Blood samples were taken for mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT) and glutamic acid, in order to find primarily any differences in glutamic acid according to the typologies, age, abstinence duration, and liver damage. RESULTS: There was no significant association between Cloninger's and Lesch's typologies. Cloninger's types 1 and 2 had an equal distribution of GGT and duration of abstinence, while Lesch's type I had more patients with high GGT, and more patients who were sober for a maximum of 2 days. Unlike in Lesch's types, glutamic acid levels did not differ according to Cloninger's types, as significantly higher glutamic acid values were found in Lesch's types I and IV. Glutamic acid values did not differ significantly in different age groups. CONCLUSIONS: Our study findings of varying glutamic acid levels seen in Lesch's typology, higher in types I and IV than in types II and III, are of significant clinical value and can be interpreted differently, as in type I high levels of glutamic acid is seen as a kindling phenomenon, while in type IV elevated levels might be related to either compulsivity of frequent repetition of drinking or withdrawal.