Pattern of brain atrophy in elderly patients with depression revealed by voxel-based morphometry.

In this study, we explored to what extent brain abnormalities can be identified in specific brain structures of patients suffering from late onset depression. We examined the structural difference in regional gray and white matter volume between 14 community-dwelling patients suffering from geriatric depression and 20 age-matched non-depressed normal subjects by voxel-based morphometry (VBM) based on magnetic resonance imaging. All subjects also underwent an extensive neuropsychological assessment. Compared with control subjects, patients with depression were impaired in measures of verbal and visual memory, construction, executive ability, and information-processing speed. VBM of gray matter revealed a significant decrease of volume in the right rostral hippocampus, in the right amygdala and in the medial orbito-frontal cortex (gyrus rectus) bilaterally. In the correlation analysis of gray matter volume with the score of the geriatric depression scale, we observed a negative correlation with the medial orbito-frontal cortex (gyrus rectus) bilaterally. There were no differences in white matter volumes between patients with depression and healthy control subjects. The most important limitation of this study was sample size. A larger sample size may have improved detection of changes not reaching significance. Furthermore, our results may not be generalizable across depression severity or to hospitalized patients. The findings are consistent with our hypothesis that depression in the elderly is associated with local gray matter dysfunction.

Age and gender effects on olanzapine and risperidone plasma concentrations in children and adolescents.

BACKGROUND: Risperidone and olanzapine are second-generation antipsychotics that are increasingly used in child and adolescent psychiatry. So far, little is known about plasma concentrations and concentration-to-dose (C/D) ratios of these agents in children and adolescents compared to adults. METHOD: This study investigated whether age and gender influence risperidone and olanzapine plasma concentration by determining risperidone and olanzapine plasma levels by tandem mass spectrometry in 162 Caucasian patients (98 risperidone and 64 olanzapine). RESULTS: For risperidone and 9-hydroxyrisperidone, the C(total)/D ratio was almost identical in both age groups (10-18 and 19-45 years, respectively). In the younger age group, females exhibited significantly higher total plasma levels than males while receiving similar doses of risperidone. For olanzapine, in adolescents significantly higher C/D ratios were detected by an average of 43% (after adjustment for weight: 34%) compared to adults. CONCLUSION: This study demonstrates an age effect for olanzapine but not for risperidone resulting in higher olanzapine plasma levels in younger patients. For risperidone, we found a gender effect as female adolescent patients had significantly higher risperidone plasma concentrations than male adolescent patients. Future prospective studies are necessary to clarify whether the prescribed dosage should be different in young and older patients.

Influence of age, gender, body weight and valproate comedication on quetiapine plasma concentrations.

Quetiapine is a second-generation antipsychotic with a favourable risk/benefit profile that is increasingly used in psychiatric patients. Similar to other antipsychotics, the efficacy and adverse effects of quetiapine depend much more on the actual plasma concentration of the active drug than on the prescribed dose. The present study investigated whether age, gender, body weight or certain comedications influence quetiapine plasma concentration by determining quetiapine plasma levels by tandem mass spectrometry in 94 (36 male and 58 female) patients aged 42.2 +/- 20.0 years. Older age was a significant predictor of a higher quetiapine plasma concentration, with a mean increase of weight-corrected concentration/dose ratio of 11% per 10 years of age (P = 0.003). In females, the concentration/dose (C/D) ratio was 35.4% higher than in males (adjusted mean 0.144 ng/ml/mg for males versus 0.195 ng/ml/mg for females, respectively; P = 0.035). However, after correction for weight, the gender difference in C/D ratio dropped to 22% and significance was lost (P = 0.133). Valproate comedication was associated with a 77% increase in quetiapine plasma levels (P = 0.016). In conclusion, older age, body weight and comedication with valproate have to be considered when prescribing quetiapine. Higher plasma levels in female patients need to be replicated in larger samples.

Measurement of thirteen biological markers in CSF of patients with Alzheimer's disease and other dementias.

Cerebrospinal fluid (CSF) biological markers may be of valuable help in the diagnosis of dementia. The aim of the present study was to evaluate CSF levels of 13 potential biomarkers in patients with Alzheimer's disease (AD), frontotemporal lobe dementia, alcohol dementia, major depression and control patients without any neuropsychiatric disease. The study was performed using beta-amyloid 1-42 (Abeta42), total tau and phosphorylated tau-181 (P-tau181) as core markers. The ratio P-tau181/Abeta42 could significantly distinguish AD patients from all other diagnostic subgroups. CSF levels of 5 growth factors (HGF, GDNF, VEGF, BDNF, FGF-2) and 3 cytokines/chemokines (TNF-alpha, TGF-beta1, MIP-1alpha) did not significantly differentiate between the studied groups. However, depending on the degree of neurodegeneration (as expressed by the ratio P-tau181/Abeta42), patients with AD displayed significantly increased CSF levels of nerve growth factor (NGF) as compared to healthy controls. CSF levels of monocyte chemoattractant protein 1 (MCP-1) were found to be significantly increased with age in all groups but did not distinguish AD patients from healthy controls. The results confirmed the suitability of the ratio P-tau181/Abeta42 for the diagnosis of AD, while CSF levels of NGF and MCP-1 are less specific and reliable for AD. It is suggested that the increase in NGF depends on the extent of neurodegeneration of the AD type and the increase in MCP-1 on age.

Longitudinal volumetric MRI study in first- and multiple-episode male schizophrenia patients.

In this longitudinal study we compared brain volume changes in first- and multiple-episode patients with schizophrenia to normal aging changes observed in healthy control subjects scanned at comparable times. Two to four years after an initial examination including MRI volumetry, we followed up 21 first episode patients, 17 patients after multiple episodes of schizophrenia, and 20 healthy controls. Volumetric measurements of left and right hemispheres, total brain volume, lateral ventricles, hippocampus and amygdala as well as a clinical evaluation were performed. Patients with schizophrenia showed significant ventricular enlargement and volume reduction of the hippocampus-amygdala complex compared with healthy control subjects both at baseline and follow-up. While there were no differences between patients and controls with respect to mean annual volume changes in the measured regions, patients with schizophrenia showed higher between-subject variability in ventricular volume change. These data are consistent with cross-sectional studies demonstrating ventricular enlargement and hippocampal volume deficits in schizophrenia. However, we were not able to demonstrate a difference in the rate of volume changes over time that distinguished patients with schizophrenia from healthy controls for any of the brain structures measured. Drawbacks of the study are that the follow-up was done after a relatively short interval and that there was a difference in time to follow-up and age between patients and controls. Our results do not support the hypothesis that schizophrenia leads to progressive volume reduction in these areas, although there may be a subset of patients with morphologically visible disease progression.

Trends in the pharmacological treatment of patients with schizophrenia over a 12 year observation period.

In this study we evaluated whether our efforts to promote evidence-based guidelines for the psychopharmacological treatment of patients with schizophrenia have led to measurable changes of treatment practice in our hospital by investigating three primary hypotheses: 1) Polypharmacy has become less common in recent years, 2) Conventional neuroleptics have been replaced by second generation antipsychotics; and 3) Dosing regimes have changed towards lower doses. We have therefore collected data from the clinical records of all in-patients with ICD-9/ICD-10 diagnoses of schizophrenia hospitalized at the Department of Psychiatry of the Medical University Innsbruck in the years 1989, 1995, 1998 and 2001. Data from 1989 to 1998 showed a significant decrease in the use of two or more antipsychotics given simultaneously. Contrary to our hypothesis, there was a significant increase in polypharmacy between 1998 and 2001. The predominant use of second generation antipsychotics became standard in schizophrenia treatment. In this context the decrease of concomitant anticholinergic medication is notable. Doses of conventional antipsychotics like haloperidol as well as doses of risperidone decreased whereas doses of other second generation antipsychotics increased. All in all, the pharmacological management of schizophrenia patients is increasingly in tune with current treatment guidelines.

Childhood body-focused behaviors and social behaviors as risk factors of eating disorders.

BACKGROUND: The risk factors for adolescent eating disorders are poorly understood. It is generally agreed, however, that interactions with one's body and interactions with others are two important features in the development of anorexia and bulimia nervosa. Therefore, we assessed a variety of childhood body-focused behaviors and childhood social behaviors in eating-disordered patients as compared to non-eating-disordered subjects. METHOD: We compared 50 female inpatients with eating disorders (anorexia or bulimia nervosa), 50 female inpatients with polysubstance dependence, and 50 nonpatient female control subjects with no history of eating or substance abuse disorders (all defined by DSM-IV criteria), using a semi-structured interview of our own design. We asked questions about (1) childhood body-focused behaviors (e.g. thumb-sucking) and body-focused family experiences (e.g. bodily caresses), and (2) childhood social behaviors (e.g. numbers of close friends) and family social styles (e.g. authoritarian upbringing). RESULTS: Many body-focused measures, such as feeding problems, auto-aggressive behavior, lack of maternal caresses, and family taboos regarding nudity and sexuality, characterized eating-disordered patients as opposed to both comparison groups, as did several social behaviors, such as adjustment problems at school and lack of close friends. However, nail-biting, insecure parental bonding, and childhood physical and sexual abuse were equally elevated in both psychiatric groups. CONCLUSION: It appears that eating-disordered patients, as compared to substance-dependent patients and healthy controls, show a distinct pattern of body-focused and social behaviors during childhood, characterized by self-harm, a rigid and 'body-denying' family climate, and lack of intimacy.

Influence of age and gender on risperidone plasma concentrations.

There is limited information on gender- and age-specific effects on plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone. The present study investigated dose- and weight-adjusted plasma concentrations of risperidone and its metabolite in three age groups (45 years, 45-60 years, over 60 years). Gender-specific differences were examined in the whole sample and for the premenopausal subgroup. One hundred and twenty-nine patients (18-93 years) were included in the study, 52 (40%) male and 77 (60%) female. Concentrations of risperidone and 9-hydroxyrisperidone were measured at steady-state by high-performance liquid chromatography with electrochemical detection (HPLC-ED). When total plasma concentrations (risperidone plus 9-hydroxyrisperidone) were adjusted for daily maintenance dose (ng/mL/mg C/D ratio), significant differences between all age groups were found. We found a mean increase of the C/D ratio by 34.8% per decade in patients older than 42 years. No significant sex-related differences in the average plasma concentrations were observed for the whole sample and for the premenopausal subgroup. This study shows clear evidence of higher risperidone total plasma concentrations for patients over 40 years of age. This linear increase (over 30% per decade) may then lead to an increased incidence of adverse effects in elderly patients.

Measurement of tryptophan, kynurenine and neopterin in women with and without postpartum blues.

BACKGROUND: Activation of the tryptophan-degrading enzyme indoleamine (2,3)-dioxygenase was demonstrated to be critically involved in tolerance induction to prevent fetal rejection. Our study was designed to examine alterations of tryptophan and its catabolic product kynurenine in the postpartum period and to compare them to neopterin as an immunological marker. METHODS: 95 healthy women delivering without complications provided blood during labour, and 2 and 4 days after birth. The blood samples were analysed for concentrations of tryptophan, kynurenine and neopterin. Women were asked to perform the Edinburgh Postnatal Depression Scale (EPDS) on days 2 and 4. RESULTS: In women without blues symptoms (n=86) tryptophan concentrations increased within 2 days after birth, whereas they did not change in women with postpartum blues (n=9; 9.5%). The group difference reached statistical significance (p<0.05). The change of the kynurenine to tryptophan ratio (kyn/trp), which estimates the degree of tryptophan degradation, was also different between the two groups at days 0 and 2 (p<0.05). Neopterin concentrations decreased between days 2 and 4 (p<0.05), but there were no differences between the two groups. LIMITATIONS: Our study population had a low prevalence of postpartum blues symptoms. CONCLUSION: Low postpartal mood is associated with continuously low serum tryptophan after delivery due to an increased degradation to kynurenine, but is independent of the postpartal course of neopterin.

Olfactory functions and volumetric measures of orbitofrontal and limbic regions in schizophrenia.

OBJECTIVE: Olfactory deficits in schizophrenia patients have been suggested to reflect medial temporal and/or prefrontal brain abnormalities. In this study, we examined the relationship between different olfactory functions and volumes of the hippocampus-amygdala complex (HAC) and the orbitofrontal brain region using magnetic resonance imaging (MRI). METHODS: Thirty-three young men with schizophrenia (DSM-IV) and 40 healthy controls performed unirhinal olfactory assessment including the main olfactory functions (threshold, discrimination, and identification), and odor judgements (intensity, edibility, familiarity, and pleasantness). Volumes of regions in the medial temporal lobe (hippocampus and amygdala) and the prefrontal region (orbitofrontal gray and white matter) were measured on MRI scans. RESULTS: Compared with controls, patients showed bilaterally impaired thresholds, quality discrimination and identification, as well as edibility judgements. Olfactory deficits were not attributable to smoking, premorbid intelligence, or impaired thresholds. Relative to controls, patients had bilateral reduced hippocampus and amygdala volumes. In patients, smaller hippocampus volumes were associated with poorer olfactory discrimination ability. CONCLUSIONS: Olfactory deficits in schizophrenia appear to be associated with morphometric abnormalities in the medial temporal rather than the orbitofrontal region (OFR). These results indicate that olfactory quality discrimination deficits are related to structural hippocampus abnormalities. Future studies of genetic and behavioral high-risk samples seem warranted.

Body-image dissatisfaction in gay versus heterosexual men: is there really a difference?

BACKGROUND: Gay men are thought to experience body-image concerns or disorders more frequently than heterosexual men. It is unclear, however, whether these putative concerns are due to unrealistic body ideals (aspiring to a body shape that is difficult or impossible to attain), body-image distortion (misperceiving the actual shape of one's body), or both. METHOD: We administered a well-established computerized body-image test, the "somatomorphic matrix," to 37 gay men recruited from the community in April 1999 and compared the results with previous data from 49 community-recruited heterosexual comparison men and 24 clinic-recruited heterosexual men with eating disorders. RESULTS: Gay men were indistinguishable from the community-recruited heterosexual comparison men on measures of both body ideals and body-image distortion. By contrast, eating-disordered men were significantly distinguishable from both other groups on body-image distortion. The lack of differences between community gay and heterosexual men on body-image indices seems unlikely to represent a type II error, since the somatomorphic matrix showed ample power to detect abnormalities in the eating-disordered men, despite the smaller sample size of the latter group. CONCLUSION: Contrary to our hypotheses, gay men did not differ significantly from heterosexual men on measures of body image. These unexpected findings cast doubt on the widespread belief that gay men experience greater body-image dissatisfaction than heterosexual men. If our findings are valid, it follows that some previous studies of body image in gay men may possibly have been influenced by selection bias.

Efficacy of donepezil treatment in Alzheimer patients with and without subcortical vascular lesions.

In a pilot study designed as a case control study the efficacy of donepezil treatment was investigated in patients with Alzheimer's disease (AD). Patients were stratified according to radiological criteria into patients without (AD group) and with subcortical vascular lesions (AD+SVD group). Changes in cognition were assessed as the primary outcome measurement after 6 and 18 months of treatment by the Mini-Mental Status Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery. After 6 months, patients had improved from baseline by 0.7 points in MMSE score in the AD group and by 1.8 in the AD+SVD group. After 18 months of treatment, the AD+SVD group performed significantly worse in one CERAD subscore, whereas a deterioration in two subscores was observed in the AD group. A comparison between the 2 groups revealed that treatment did not lead to statistically significant differences between the AD and AD+SVD groups in any of CERAD parameters following 6 or 18 months of treatment. These data support previous observations that donepezil therapy is effective in AD patients with and without subcortical vascular lesions.

Body fat perception in eating-disordered men.

OBJECTIVE: We sought to assess the relative roles of body fat ideals and body fat perception in men with eating disorders. METHOD: We compared 27 men meeting criteria for a current eating disorder (17 with anorexia nervosa and 10 with bulimia nervosa), 21 male mountain climbers, and 21 control men, using a computerized test of body image, the "somatomorphic matrix." RESULTS: When asked to choose the body that they "ideally would like to have," men with eating disorders selected an image with body fat closely comparable to that chosen by the control men. On perceived body fat, however, the groups differed dramatically. The eating-disordered men perceived themselves to be almost twice as fat as they actually were, whereas the control subjects showed virtually no such distortion. These findings resemble those of a previous study of women, which found that women dieters showed abnormal body fat perception, but not body fat ideals, when compared with non-dieters. CONCLUSION: These observations suggest that distorted body perception, rather than body ideal, may be central to eating disorders in men. This distinction may be important for both research and therapy.