Adrian P. Mundt

Lesions of dopaminergic neurons in the substantia nigra pars compacta and in the ventral tegmental area enhance depressive-like behavior in rats

Depression is the most common psychiatric complication in Parkinsons disease (PD). The pathophysiological events leading to PD-associated depression, however, remain largely unknown. The present study tested the differential implication of dopaminergic systems in depressive-like behavior in rats and its response to l-Dopa and the selective serotonin reuptake inhibitor citalopram. The learned helplessness model was used as a behavioral paradigm. Rats were lesioned in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) and assigned to subgroups with respect to the stereologically verified extent of the nigral and/or VTA degeneration. Both lesions increased depressive-like behavior in rats, which was reduced by both citalopram and l-Dopa treatment. We conclude that dopaminergic lesions of either the SNc or the VTA contribute to the manifestation of depressive-like behavior in rats. The effects of citalopram administration on depressive behavior induced by lesions of dopaminergic brain regions furthermore suggest an involvement of serotonergic pathways in dopaminergic cell loss-induced depression.

High frequency stimulation and temporary inactivation of the subthalamic nucleus reduce quinpirole-induced compulsive checking behavior in rats

Obsessive-compulsive disorder (OCD) represents a highly prevalent and impairing psychiatric disorder. Functional and structural imaging studies implicate the involvement of basal ganglia-thalamo-cortical circuits in the pathophysiology of this disorder. In patients remaining resistant to pharmaco- and behavioral therapy, modulation of these circuits may consequently reverse clinical symptoms. High frequency stimulation (HFS) of the subthalamic nucleus (STN), an important station of the basal ganglia-thalamo-cortical circuits, has been reported to reduce obsessive-compulsive symptoms in a few Parkinsons disease patients with comorbid OCD. The present study tested the effects of bilateral HFS of the STN and of bilateral pharmacological inactivation of the STN (via intracranial administration of the GABA agonist muscimol) on checking behavior in the quinpirole rat model of OCD. We demonstrate that both HFS and pharmacological inactivation of the STN reduce quinpirole-induced compulsive checking behavior. We conclude that functional inhibition of the STN can alleviate compulsive checking, and suggest the STN as a potential target structure for HFS in the treatment of OCD.

High-frequency stimulation of the nucleus accumbens core and shell reduces quinpirole-induced compulsive checking in rats

Electrical deep brain stimulation (DBS) is currently studied in the treatment of therapy‐refractory obsessive compulsive disorders (OCDs). The variety of targeted brain areas and the inconsistency in demonstrating anti‐compulsive effects, however, highlight the need for better mapping of brain regions in which stimulation may produce beneficial effects in OCD. Such a goal may be advanced by the assessment of DBS in appropriate animal models of OCD. Currently available data on DBS of the nucleus accumbens (NAc) on OCD‐like behavior in rat models of OCD are contradictory and partly in contrast to clinical data and theoretical hypotheses about how the NAc might be pathophysiologically involved in the manifestation of OCD. Consequently, the present study investigates the effects of DBS of the NAc core and shell in a quinpirole rat model of OCD. The study demonstrates that electrical modulation of NAc core and shell activity via DBS reduces quinpirole‐induced compulsive checking behavior in rats. We therefore conclude that both, the NAc core and shell constitute potential target structures in the treatment of OCD.

Reduced availability of serotonin transporters in obsessive-compulsive disorder correlates with symptom severity – a [11C]DASB PET study

SummaryReduced availability of brainstem serotonin transporters (5-HTT) has been observed in vivo in obsessive-compulsive disorder (OCD). However, results vary and may be influenced by competition with endogenous serotonin. Using positron emission tomography (PET) and [11C]DASB, a specific 5-HTT ligand that showed no competition with serotonin for 5-HTT binding in vitro, we tested the hypothesis that 5-HTT availability is reduced in OCD patients and correlated with OCD severity. Methods. 5-HTT availability in the thalamus and the midbrain was measured in nine drug-free OCD patients and compared with 19 healthy controls, matched for the individual combination of 5-HTT genotype, gender and smoking status. OCD severity was assessed with the Yale-Brown obsessive compulsive scale (Y-BOCS). Results. 5-HTT availability was significantly reduced in the thalamus and midbrain of OCD patients. Age and 5-HTT in the thalamus explained 83% of OCD severity in patients that were drug-free for at least 1 year. Conclusion. This PET study confirms a central role of the serotonergic system, particularly the thalamus in the pathogenesis of obsessive compulsive disorder.

Changes in the Provision of Institutionalized Mental Health Care in Post-Communist Countries

Background General psychiatric and forensic psychiatric beds, supported housing and the prison population have been suggested as indicators of institutionalized mental health care. According to the Penrose hypothesis, decreasing psychiatric bed numbers may lead to increasing prison populations. The study aimed to assess indicators of institutionalized mental health care in post-communist countries during the two decades following the political change, and to explore whether the data are consistent with the Penrose hypothesis in that historical context. Methodology/Principal Findings General psychiatric and forensic psychiatric bed numbers, supported housing capacities and the prison population rates were collected in Azerbaijan, Belarus, Croatia, Czech Republic, East Germany, Hungary, Kazakhstan, Latvia, Poland, Romania, Russia and Slovenia. Percentage change of indicators over the decades 1989–1999, 1999–2009 and the whole period of 1989–2009 and correlations between changes of different indicators were calculated. Between 1989 and 2009, the number of general psychiatric beds was reduced in all countries. The decrease ranged from −11% in Croatia to −51% in East Germany. In 2009, the bed numbers per 100,000 population ranged from 44.7 in Azerbaijan to 134.4 in Latvia. Forensic psychiatric bed numbers and supported housing capacities increased in most countries. From 1989–2009, trends in the prison population ranged from a decrease of −58% in East Germany to an increase of 43% in Belarus and Poland. Trends in different indicators of institutionalised care did not show statistically significant associations. Conclusions/Significance After the political changes in 1989, post-communist countries experienced a substantial reduction in general psychiatric hospital beds, which in some countries may have partly been compensated by an increase in supported housing capacities and more forensic psychiatric beds. Changes in the prison population are inconsistent. The findings do not support the Penrose hypothesis in that historical context as a general rule for most of the countries.

Psychiatric hospital beds and prison populations in South America since 1990: does the Penrose hypothesis apply?

IMPORTANCE In 1939, English mathematician, geneticist, and psychiatrist Lionel Sharples Penrose hypothesized that the numbers of psychiatric hospital beds and the sizes of prison populations were inversely related; 75 years later, the question arises as to whether the hypothesis applies to recent developments in South America. OBJECTIVE To explore the possible association of changes in the numbers of psychiatric hospital beds with changes in the sizes of prison populations in South America since 1990. DESIGN, SETTING, AND PARTICIPANTS We searched primary sources for the numbers of psychiatric hospital beds in South American countries since 1990 (the year that the Latin American countries signed the Caracas Declaration) and compared these changes against the sizes of prison populations. The associations between the numbers of psychiatric beds and the sizes of prison populations were tested using fixed-effects regression of panel data. Economic variables were considered as covariates. Sufficiently reliable and complete data were obtained from 6 countries: Argentina, Bolivia, Brazil, Chile, Paraguay, and Uruguay. MAIN OUTCOMES AND MEASURES The numbers of psychiatric beds and the sizes of prison populations. RESULTS Since 1990, the numbers of psychiatric beds decreased in all 6 countries (ranging from -2.0% to -71.9%), while the sizes of prison populations increased substantially (ranging from 16.1% to 273.0%). Panel data regression analysis across the 6 countries showed a significant inverse relationship between numbers of psychiatric beds and sizes of prison populations. On average, the removal of 1 bed was associated with 5.18 more prisoners (95% CI, 3.10-7.26; P = .001), which was reduced to 2.78 prisoners (95% CI, 2.59-2.97; P < .001) when economic growth was considered as a covariate. The association between the numbers of psychiatric beds and the sizes of prison populations remained practically unchanged when income inequality was considered as a covariate (-4.28 [95% CI, -5.21 to -3.36]; P < .001). CONCLUSIONS AND RELEVANCE Since 1990, the numbers of psychiatric beds have substantially decreased in South America, while the sizes of the prison populations have increased against a background of strong economic growth. The changes appear to be associated because the numbers of beds decreased more extensively when and where the sizes of prison populations increased. These findings are consistent with and specify the assumption of an association between the numbers of psychiatric beds and the sizes of prison populations. More research is needed to understand the drivers of the capacities of psychiatric hospitals and prisons and to explore reasons for their association.

A method to assess biochemical activity of liver cells during clinical application of extracorporeal hybrid liver support.

Biochemical activity of a hybrid liver support system based on porcine liver cells was investigated in patients suffering from acute liver failure, coma stage III-IV. Patient plasma was drawn systemically and after circulation through the bioreactor at four hour intervals. A method is used that takes into account the rate of plasma flow and the differences in plasma concentration systemically and after circulation through the liver support system to determine the net release or uptake of metabolites such as ammonia, urea and glucose. Urea release (mean 2.28 ± 0.37 μmol/h/g cells) and ammonia uptake (mean 0.17 ± 0.11 μmol/h/g cells) was seen during treatment, an active role of the system in glucose metabolism was observed. All patients were bridged successfully to liver transplantation.

Prevalence rates of mental disorders in Chilean prisons

Objective High rates of mental disorders have been reported for prison populations worldwide, particularly in low- and middle-income countries (LMICs). The present study aimed to establish prevalence rates of mental disorders in Chilean prisoners. Method A nationwide random sample of 1008 prisoners was assessed in 7 penal institutions throughout Chile. Twelve-month prevalence rates were established using the Composite International Diagnostic Interview (CIDI) and compared to the prevalence rates previously published for the general population. Results Prevalence rates were 12.2% (95% CI, 10.2-14.1) for any substance use disorder, 8.3% (6.6-10.0) for anxiety disorders, 8.1% (6.5-9.8) for affective disorders, 5.7% (4.4-7.1) for intermittent explosive disorders, 2.2% (1.4-3.2) for ADHD of the adult, and 0.8% (0.3-1.3) for non-affective psychoses. Significantly higher prevalence rates among prisoners as compared to the general population in Chile were seen for major depression (6.1% vs. 3.7% males, Z=2.58, p<0.05) and illicit drug use (3.3% vs. 0.6% males with drug abuse, Z=2.04, p<0.05; 2.6% vs. 0.1% females with drug abuse, Z=5.36, p<0.001; 3.4% vs. 1.1% males with drug dependence, Z=3.70; p<0.001). Dysthymia (6.5% vs. 15.6%, Z=-2.39, p<0.05), simple (3.3% vs. 11.5%, Z=-3.13, p<0.001) and social phobias (3.9% vs. 9.7%, Z=2.38, p<0.05) were significantly less frequent in the female prison population than in the general population. One-year prevalence rates of alcohol abuse (2.3% vs. 3.9%; Z=-2.04; p<0.05) and dependence (2.7% vs. 8.2%; Z=-5.24; p<0.001) were less prevalent in the male prison population than in the general population. Conclusions Service provision for prison populations in Chile should acknowledge high rates of depression and illicit drug use. Overall prevalence rates are lower than reported in other LMICs. Previous research in prison populations in LMICs might have overestimated prevalence rates of mental disorders.

Treating substance abuse is not enough: comorbidities in consecutively admitted female prisoners.

INTRODUCTION Several studies have pointed to high rates of substance use disorders among female prisoners. The present study aimed to assess comorbidities of substance use disorders with other mental disorders in female prisoners at admission to a penal justice system. METHODS A sample of 150 female prisoners, consecutively admitted to the penal justice system of Berlin, Germany, was interviewed using the Mini-International Neuropsychiatric Interview (MINI). The presence of borderline personality disorder was assessed using the Structured Clinical Interview II for DSM-IV. Prevalence rates and comorbidities were calculated as percentage values and 95% confidence intervals (CIs). RESULTS Ninety-three prisoners (62%; 95% CI: 54-70) had substance use disorders; n=49 (33%; 95% CI: 24-42) had alcohol abuse/dependence; n=76 (51%; 95% CI: 43-59) had illicit drug abuse/dependence; and n=53 (35%; 95% CI: 28-44) had opiate use disorders. In the group of inmates with substance use disorders, 84 (90%) had at least one other mental disorder; n=63 (68%) had comorbid affective disorders; n=45 (49%) had borderline or antisocial personality disorders; and n=41 (44%) had comorbid anxiety disorders. CONCLUSIONS Female prisoners with addiction have high rates of comorbid mental disorders at admission to the penal justice system, ranging from affective to personality and anxiety disorders. Generic and robust interventions that can address different comorbid mental health problems in a flexible manner may be required to tackle widespread addiction and improve mental health of female prisoners.

Socio-economic status and emotional distress of female Turkish immigrants and native German women living in Berlin

BACKGROUND Many immigrants face more economic strains and hardship than non-immigrants. Income inequality and an increasing social gap between immigrants and non-immigrants in Europe warrant further studies on the impact of socioeconomic factors on health in immigrant groups. The purpose of this study was to examine the association of socioeconomic status (SES) and emotional distress in women of Turkish descent and in women of German descent. METHODS AND SUBJECTS A total of 405 women of German or Turkish descent residing in Berlin were interviewed. Emotional distress was assessed by the General Health Questionnaire-28 (GHQ-28), and SES was examined by level of education, employment status, and income. The associations of emotional distress and SES were estimated in multivariate linear regression analyses. RESULTS Unemployment was associated with increased levels of emotional distress in all women, with the highest level of distress in the group of unemployed Turkish women. The overall SES level was related to a greater level of emotional distress in Turkish women, but not in German women (-3.2, 95%CI -5.9 - -.5; p=.020 vs. -.8, 95%CI -2.7 - 1.2; p=.431). Further stratified analyses by relationship status revealed that the association of SES and emotional distress only remained significant among single women. CONCLUSION The impact of socioeconomic hardship appears to be complicated by social roles and expectations related to these. Further in-depth study of the complex nature of the interaction of social roles and socioeconomic position in female Turkish immigrants in Germany is needed to better understand differing risk patterns for emotional distress.