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Recent Articles in BMC Psychiatry

Rapeli P, Kivisaari R, Autti T, K�hk�nen S, Puuskari V, Jokela O, Kalska H
Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls.
BMC Psychiatry. 2006;69.
BACKGROUND: Individuals with opioid dependence have cognitive deficits during abuse period in attention, working memory, episodic memory, and executive function. After protracted abstinence consistent cognitive deficit has been found only in executive function. However, few studies have explored cognitive function during first weeks of abstinence. The purpose of this study was to study cognitive function of individuals with opioid dependence during early abstinence. It was hypothesized that cognitive deficits are pronounced immediately after peak withdrawal symptoms have passed and then partially recover. METHODS: Fifteen patients with opioid dependence and fifteen controls matched for, age, gender, and verbal intelligence were tested with a cognitive test battery When patients performed worse than controls correlations between cognitive performance and days of withdrawal, duration of opioid abuse, duration of any substance abuse, or opioid withdrawal symptom inventory score (Short Opiate Withdrawal Scale) were analyzed. RESULTS: Early abstinent opioid dependent patients performed statistically significantly worse than controls in tests measuring complex working memory, executive function, and fluid intelligence. Their complex working memory and fluid intelligence performances correlated statistically significantly with days of withdrawal. CONCLUSION: The results indicate a rather general neurocognitive deficit in higher order cognition. It is suggested that cognitive deficit during early abstinence from opioid dependence is related to withdrawal induced neural dysregulation in the prefrontal cortex and is partly transient. [Abstract/Link to Full Text]

Ascher-Svanum H, Zhu B, Faries D, Landbloom R, Swartz M, Swanson J
Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia.
BMC Psychiatry. 2006;68.
BACKGROUND: There is an ongoing debate over whether atypical antipsychotics are more effective than typical antipsychotics in the treatment of schizophrenia. This naturalistic study compares atypical and typical antipsychotics on time to all-cause medication discontinuation, a recognized index of medication effectiveness in the treatment of schizophrenia. METHODS: We used data from a large, 3-year, observational, non-randomized, multisite study of schizophrenia, conducted in the U.S. between 7/1997 and 9/2003. Patients who were initiated on oral atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone) or oral typical antipsychotics (low, medium, or high potency) were compared on time to all-cause medication discontinuation for 1 year following initiation. Treatment group comparisons were based on treatment episodes using 3 statistical approaches (Kaplan-Meier survival analysis, Cox Proportional Hazards regression model, and propensity score-adjusted bootstrap resampling methods). To further assess the robustness of the findings, sensitivity analyses were performed, including the use of (a) only 1 medication episode for each patient, the one with which the patient was treated first, and (b) all medication episodes, including those simultaneously initiated on more than 1 antipsychotic. RESULTS: Mean time to all-cause medication discontinuation was longer on atypical (N = 1132, 256.3 days) compared to typical antipsychotics (N = 534, 197.2 days; p < .01), and longer on atypicals compared to typicals of high potency (N = 320, 187.5 days; p < .01), medium potency (N = 140, 213.5 days; p < .01), and low potency (N = 74, 208.7 days; p < .01). Among the atypicals, only clozapine, olanzapine, and risperidone had significantly longer time to all-cause medication discontinuation compared to typicals, regardless of potency level, and compared to haloperidol with prophylactic anticholinergic treatment. When compared to perphenazine, a medium-potency typical antipsychotic, only clozapine and olanzapine had a consistently and significantly longer time to all-cause medication discontinuation. Results were confirmed by sensitivity analyses. CONCLUSION: In the usual care of schizophrenia patients, time to medication discontinuation for any cause appears significantly longer for atypical than typical antipsychotics regardless of the typical antipsychotic potency level. Findings were primarily driven by clozapine and olanzapine, and to a lesser extent by risperidone. Furthermore, only clozapine and olanzapine therapy showed consistently and significantly longer treatment duration compared to perphenazine, a medium-potency typical antipsychotic. [Abstract/Link to Full Text]

Oades RD, Wild-Wall N, Juran SA, Sachsse J, Oknina LB, R�pcke B
Auditory change detection in schizophrenia: sources of activity, related neuropsychological function and symptoms in patients with a first episode in adolescence, and patients 14 years after an adolescent illness-onset.
BMC Psychiatry. 2006;67.
BACKGROUND: The event-related brain response mismatch negativity (MMN) registers changes in auditory stimulation with temporal lobe sources reflecting short-term echoic memory and frontal sources a deviance-induced switch in processing. Impairment, controversially present at the onset of schizophrenia, develops rapidly and can remain independent of clinical improvement. We examined the characteristics of the scalp-recorded MMN and related these to tests of short-term memory and set-shifting. We assessed whether the equivalent dipole sources are affected already at illness-onset in adolescence and how these features differ after a 14-year course following an adolescent onset. The strength, latency, orientation and location of frontal and temporal lobe sources of MMN activity early and late in the course of adolescent-onset schizophrenia are analysed and illustrated. METHODS: MMN, a measure of auditory change-detection, was elicited by short deviant tones in a 3-tone oddball-presentation and recorded from 32 scalp electrodes. Four dipole sources were placed following hypothesis-led calculations using brain electrical source analysis on brain atlas and MR-images. A short neuropsychological test battery was administered. We compared 28 adolescent patients with a first episode of schizophrenia and 18 patients 14 years after diagnosis in adolescence with two age-matched control groups from the community (n = 22 and 18, respectively). RESULTS: MMN peaked earlier in the younger than the older subjects. The amplitude was reduced in patients, especially the younger group, and was here associated with negative symptoms and slow set-shifting. In first-episode patients the temporal lobe sources were more ventral than in controls, while the left cingular and right inferior-mid frontal sources were more caudal. In the older patients the left temporal locus remained ventral (developmental stasis), the right temporal locus extended more antero-laterally (illness progression), and the right frontal source moved antero-laterally (normalised). CONCLUSION: From the start of the illness there were differences in the dipole-model between healthy and patient groups. Separate characteristics of the sources of the activity differences showed an improvement, stasis or deterioration with illness-duration. The precise nature of the changes in the sources of MMN activity and their relationship to selective information processing and storage depend on the specific psychopathology and heterogeneous course of the illness. [Abstract/Link to Full Text]

Araj�rvi R, Ukkola J, Haukka J, Suvisaari J, Hintikka J, Partonen T, L�nnqvist J
Psychosis among "healthy" siblings of schizophrenia patients.
BMC Psychiatry. 2006;66.
BACKGROUND: Schizophrenia aggregates in families and accurate diagnoses are essential for genetic studies of schizophrenia. In this study, we investigated whether siblings of patients with schizophrenia can be identified as free of any psychotic disorder using only register information. We also analyzed the emergence of psychotic disorders among siblings of patients with schizophrenia during seven to eleven years of follow-up. METHODS: A genetically homogenous population isolate in north-eastern Finland having 365 families with 446 patients with a diagnosis of schizophrenia was initially identified in 1991 using four nationwide registers. Between 1998 and 2002, 124 patients and 183 siblings in 110 families were contacted and interviewed using SCID-I, SCID-II and SANS. We also compared the frequency of mental disorders between siblings and a random population comparison group sample. RESULTS: Thirty (16%) siblings received a diagnosis of psychotic disorder in the interview. 14 siblings had had psychotic symptoms already before 1991, while 16 developed psychotic symptoms during the follow-up. Over half of the siblings (n = 99, 54%) had a lifetime diagnosis of any mental disorder in the interview. CONCLUSION: Register information cannot be used to exclude psychotic disorders among siblings of patients with schizophrenia. The high rate of emergence of new psychotic disorders among initially healthy siblings should be taken into account in genetic analysis. [Abstract/Link to Full Text]

Paul I, Bott C, Wienbruch C, Elbert TR
Word Processing differences between dyslexic and control children.
BMC Psychiatry. 2006;65.
BACKGROUND: The aim of this study was to investigate brain responses triggered by different wordclasses in dyslexic and control children. The majority of dyslexic children have difficulties to phonologically assemble a word from sublexical parts following grapheme-to-phoneme correspondences. Therefore, we hypothesised that dyslexic children should mainly differ from controls processing low frequent words that are unfamiliar to the reader. METHODS: We presented different wordclasses (high and low frequent words, pseudowords) in a rapid serial visual word (RSVP) design and performed wavelet analysis on the evoked activity. RESULTS: Dyslexic children had lower evoked power amplitudes and a higher spectral frequency for low frequent words compared to control children. No group differences were found for high frequent words and pseudowords. Control children had higher evoked power amplitudes and a lower spectral frequency for low frequent words compared to high frequent words and pseudowords. This pattern was not present in the dyslexic group. CONCLUSION: Dyslexic children differed from control children only in their brain responses to low frequent words while showing no modulated brain activity in response to the three word types. This might support the hypothesis that dyslexic children are selectively impaired reading words that require sublexical processing. However, the lacking differences between word types raise the question if dyslexic children were able to process the words presented in rapid serial fashion in an adequate way. Therefore the present results should only be interpreted as evidence for a specific sublexical processing deficit with caution. [Abstract/Link to Full Text]

Serretti A, Olgiati P, Colombo C
Influence of postpartum onset on the course of mood disorders.
BMC Psychiatry. 2006;64.
BACKGROUND: To ascertain the impact of postpartum onset (PPO) on the subsequent time course of mood disorders. METHODS: This retrospective study compared per year rates of excited (manic or mixed) and depressive episodes between fifty-five women with bipolar (N = 22) or major depressive (N = 33) disorders with first episode occurring postpartum (within four weeks after childbirth according to DSM-IV definition) and 218 non-postpartum onset (NPPO) controls. Such patients had a traceable illness course consisting of one or more episodes alternating with complete symptom remission and no additional diagnoses of axis I disorders, mental retardation or brain organic diseases. A number of variables reported to influence the course of mood disorders were controlled for as possible confounding factors RESULTS: Bipolar women with postpartum onset disorder had fewer excited episodes (p = 0.005) and fewer episodes of both polarities (p = 0.005) compared to non-postpartum onset subjects. No differences emerged in the rates of depressive episodes. All patients who met criteria for rapid cycling bipolar disorder (7 out of 123) were in the NPPO group. Among major depressives, PPO patients experienced fewer episodes (p = 0.016). With respect to clinical and treatment features, PPO-MDD subjects had less personality disorder comorbidity (p = 0.023) and were less likely to be on maintenance treatment compared to NPPO comparison subjects (p = 0.002) CONCLUSION: Such preliminary findings suggest that PPO mood disorders may be characterized by a less recurrent time course. Future research in this field should elucidate the role of comorbid personality disorders and treatment. Moreover it should clarify whether PPO disorders are also associated with a more positive outcome in terms of social functioning and quality of life. [Abstract/Link to Full Text]

Rossi A, Daneluzzo E, Tomassini A, Struglia F, Cavallaro R, Smeraldi E, Stratta P
The effect of verbalization strategy on Wisconsin Card Sorting Test performance in schizophrenic patients receiving classical or atypical antipsychotics.
BMC Psychiatry. 2006;63.
BACKGROUND: A number of reports showed en encouraging remediation in some patients' executive deficits thanks to the use of 'information processing strategies'. Moreover the impact of antipsychotics on cognitive functions of the schizophrenics is an important issue, especially if an integrated psychosocial treatment is needed. The aim of this paper is to evaluate different executive performance and response to verbalization, a strategy of the Wisconsin Card Sorting Test (WCST) remediation, in subjects on classical vs atypical antipsychotic (AP) treatment. METHODS: Sixty-three schizophrenic subjects undertook the WCST under standard and modified (verbalization) administration. Subjects were stratified by the kind of WCST response (i.e. good, poor and remediable) and AP treatment (i.e. atypical vs. classical). RESULTS: Subjects on atypical APs showed a better performance than those on classical ones. More poor performers who did not remediate were seen in the sample with classical Aps while subjects who remediated the performance were seen in the subgroup with atypical APs only. An increase of perseverative and total errors was seen in poor performers subjects on classical APs. CONCLUSION: Subjects on atypicals showed a better cognitive pattern in terms of WCST performance. Since the naturalistic assignment of medication we cannot draw conclusions about its effect on cognitive performance and its interaction with cognitive remediation potential. However the data lead us to hypothesize that subjects with potential room for remediation did so with the atypical APs. [Abstract/Link to Full Text]

Pedersen CB, Mortensen PB
Urbanization and traffic related exposures as risk factors for schizophrenia.
BMC Psychiatry. 2006;62.
BACKGROUND: Urban birth or upbringing increase schizophrenia risk. Though unknown, the causes of these urban-rural differences have been hypothesized to include, e.g., infections, diet, toxic exposures, social class, or an artefact due to selective migration. METHODS: We investigated the hypothesis that traffic related exposures affect schizophrenia risk and that this potential effect is responsible for the urban-rural differences. The geographical distance from place of residence to nearest major road was used as a proxy variable for traffic related exposures. We used a large population-based sample of the Danish population (1.89 million people) including information on all permanent addresses linked with geographical information on all roads and house numbers in Denmark. Schizophrenia in cohort members (10,755 people) was identified by linkage with the Danish Psychiatric Central Register. RESULTS: The geographical distance from place of residence to nearest major road had a significant effect. The highest risk was found in children living 500-1000 metres from nearest major road (RR = 1.30 (95% Confidence Interval: 1.17-1.44). However, when we accounted for the degree of urbanization, the geographical distance to nearest major road had no significant effect. CONCLUSION: The cause(s) or exposure(s) responsible for the urban-rural differences in schizophrenia risk were closer related to the degree of urbanization than to the geographical distance to nearest major road. Traffic related exposures might thus be less likely explanations for the urban-rural differences in schizophrenia risk. [Abstract/Link to Full Text]

Delorme R, Bille A, Betancur C, Mathieu F, Chabane N, Mouren-Simeoni MC, Leboyer M
Exploratory analysis of obsessive compulsive symptom dimensions in children and adolescents: a prospective follow-up study.
BMC Psychiatry. 2006;61.
BACKGROUND: Recent statistical approaches based on factor analysis of obsessive compulsive (OC) symptoms in adult patients have identified dimensions that seem more effective in symptom-based taxonomies and appear to be more stable over time. Although a phenotypic continuum from childhood to adulthood has been hypothesized, no factor analytic studies have been performed in juvenile patients, and the stability of OC dimensions in children and adolescents has not been assessed. METHODS: This study was designed to perform an exploratory factor analysis of OC symptoms in a sample of children and adolescents with OC disorder (OCD) and to investigate the course of factors over time (mean follow-up period: four years). RESULTS: We report for the first time that four symptom dimensions, remarkably similar to those previously described in adults, underlined the heterogeneity of OC symptoms in children and adolescents. Moreover, after follow-up, the symptom dimensions identified remained essentially unmodified. The changes observed concerned the intensity of dimensions rather than shifts from one dimension to another. CONCLUSION: These findings reinforce the hypothesis of a phenotypic continuum of OC symptoms from childhood to adulthood. They also strengthen the interest for investigating the clinical, neurobiological and genetic heterogeneity of OCD using a dimension-based approach. [Abstract/Link to Full Text]

Lindberg N, Holi MM, Tani P, Virkkunen M
Looking for pyromania: characteristics of a consecutive sample of Finnish male criminals with histories of recidivist fire-setting between 1973 and 1993.
BMC Psychiatry. 2005;547.
BACKGROUND: As pyromania is a rare diagnosis with questionable validity, we aimed to describe a forensic psychiatric population of arson recidivists. METHODS: The medical records as well as the forensic psychiatric examination statements of 90 arson recidivists referred for pretrial psychiatric assessment in Helsinki University Hospital Department of Forensic Psychiatry between 1973 and 1993 were reviewed. RESULTS: The most important diagnostic categories of arson recidivists were personality disorders, psychosis and mental retardation, often with comorbid alcoholism. In all, 68% of arsonists were under alcohol intoxication during the index crime. Psychotic as well as mentally retarded persons with repeated fire-setting behaviour were mostly "pure arsonists"--persons guilty only of arsons during their criminal careers. Arson recidivists with personality disorder, in contrast, often exhibited various types of criminal behaviour and arson appeared to be only one expression of a wide range of criminal activity. Comorbid alcoholism was apparently a more rarely observed phenomenon among pure arsonists than in "nonpure arsonists". We found only three subjects fulfilling the present diagnostic criteria for pyromania. CONCLUSION: Using the criteria of the DSM-IV-TR, pyromania must be regarded as an extremely rare phenomenon. Especially the question of substance intoxication as an exclusion criterion for pyromania should be reconsidered. [Abstract/Link to Full Text]

Olss�n I, Mykletun A, Dahl AA
The Hospital Anxiety and Depression Rating Scale: a cross-sectional study of psychometrics and case finding abilities in general practice.
BMC Psychiatry. 2005;546.
BACKGROUND: General practitioners' (GPs) diagnostic skills lead to underidentification of generalized anxiety disorders (GAD) and major depressive episodes (MDE). Supplement of brief questionnaires could improve the diagnostic accuracy of GPs for these common mental disorders. The aims of this study were to examine the usefulness of The Hospital Anxiety and Depression Rating Scale (HADS) for GPs by: 1) Examining its psychometrics in the GPs' setting; 2) Testing its case-finding properties compared to patient-rated GAD and MDE (DSM-IV); and 3) Comparing its case finding abilities to that of the GPs using Clinical Global Impression-Severity (CGI-S) rating. METHODS: In a cross-sectional survey study 1,781 patients in three consecutive days in September 2001 attended 141 GPs geographically spread in Norway. Sensitivity, specificity, optimal cut off score, and Area under the curve (AUC) for the HADS and the CGI-S were calculated with Generalized Anxiety Questionnaire (GAS-Q) as reference standard for GAD, and Depression Screening Questionnaire (DSQ) for MDE. RESULTS: The HADS-A had optimal cut off > or =8 (sensitivity 0.89, specificity 0.75), AUC 0.88 and 76% of patients were correctly classified in relation to GAD. The HADS-D had by optimal cut off > or =8 (sensitivity 0.80 and specificity 0.88) AUC 0.93 and 87% of the patients were correctly classified in relation to MDE. Proportions of the total correctly classified at the CGI-S optimal cut-off > or =3 were 83% of patients for GAD and 81% for MDE. CONCLUSION: The results indicate that addition of the patients' HADS scores to GPs' information could improve their diagnostic accuracy of GAD and MDE. [Abstract/Link to Full Text]

Hesse M, Schliewe S, Thomsen RR
Rating of personality disorder features in popular movie characters.
BMC Psychiatry. 2005;545.
BACKGROUND: Tools for training professionals in rating personality disorders are few. We present one such tool: rating of fictional persons. However, before ratings of fictional persons can be useful, we need to know whether raters get the same results, when rating fictional characters. METHOD: Psychology students at the University of Copenhagen (N = 8) rated four different movie characters from four movies based on three systems: Global rating scales representing each of the 10 personality disorders in the DSM-IV, a criterion list of all criteria for all DSM-IV personality disorders in random order, and the Ten Item Personality Inventory for rating the five-factor model. Agreement was estimated based on intraclass-correlation. RESULTS: Agreement for rating scales for personality disorders ranged from 0.04 to 0.54. For personality disorder features based on DSM-IV criteria, agreement ranged from 0.24 to 0.89, and agreement for the five-factor model ranged from 0.05 to 0.88. The largest multivariate effect was observed for criteria count followed by the TIPI, followed by rating scales. Raters experienced personality disorder criteria as the easiest, and global personality disorder scales as the most difficult, but with significant variation between movies. CONCLUSION: Psychology students with limited or no clinical experience can agree well on the personality traits of movie characters based on watching the movie. Rating movie characters may be a way to practice assessment of personality. [Abstract/Link to Full Text]

Loving RT, Kripke DF, Knickerbocker NC, Grandner MA
Bright green light treatment of depression for older adults [ISRCTN69400161].
BMC Psychiatry. 2005;542.
BACKGROUND: Bright white light has been successfully used for the treatment of depression. There is interest in identifying which spectral colors of light are the most efficient in the treatment of depression. It is theorized that green light could decrease the intensity duration of exposure needed. Late Wake Treatment (LWT), sleep deprivation for the last half of one night, is associated with rapid mood improvement which has been sustained by light treatment. Because spectral responsiveness may differ by age, we examined whether green light would provide efficient antidepressant treatment in an elder age group. METHODS: We contrasted one hour of bright green light (1,200 Lux) and one hour of dim red light placebo (<10 Lux) in a randomized treatment trial with depressed elders. Participants were observed in their homes with mood scales, wrist actigraphy and light monitoring. On the day prior to beginning treatment, the participants self-administered LWT. RESULTS: The protocol was completed by 33 subjects who were 59 to 80 years old. Mood improved on average 23% for all subjects, but there were no significant statistical differences between treatment and placebo groups. There were negligible adverse reactions to the bright green light, which was well tolerated. CONCLUSION: Bright green light was not shown to have an antidepressant effect in the age group of this study, but a larger trial with brighter green light might be of value. [Abstract/Link to Full Text]

Loving RT, Kripke DF, Elliott JA, Knickerbocker NC, Grandner MA
Bright light treatment of depression for older adults [ISRCTN55452501].
BMC Psychiatry. 2005;541.
BACKGROUND: The incidence of insomnia and depression in the elder population is significant. It is hoped that use of light treatment for this group could provide safe, economic, and effective rapid recovery. METHODS: In this home-based trial we treated depressed elderly subjects with bright white (8,500 Lux) and dim red (<10 Lux) light for one hour a day at three different times (morning, mid-wake and evening). A placebo response washout was used for the first week. Wake treatment was conducted prior to the initiation of treatment, to explore antidepressant response and the interaction with light treatment. Urine and saliva samples were collected during a 24-hour period both before and after treatment and assayed for aMT6s and melatonin respectively to observe any change in circadian timing. Subjects wore a wrist monitor to record light exposure and wrist activity. Daily log sheets and weekly mood (GDS) and physical symptom (SAFTEE) scales were administered. Each subject was given a SCID interview and each completed a mood questionnaire (SIGH-SAD-SR) before and after treatment. Also, Hamilton Depression Rating (SIGH-SAD version) interviews were conducted by a researcher who was blind to the treatment condition. A control group of healthy, age-matched, volunteers was studied for one day to obtain baseline data for comparison of actigraphy and hormone levels. RESULTS: Eighty-one volunteers, between 60 and 79 years old, completed the study. Both treatment and placebo groups experienced mood improvement. Average GDS scores improved 5 points, the Hamilton Depression Rating Scale (HDRS) 17 scores (extracted from the self-rated SIGH-SAD-SR) improved 6 points. There were no significant treatment effects or time-by-treatment interactions. No significant adverse reactions were observed in either treatment group. The assays of urine and saliva showed no significant differences between the treatment and placebo groups. The healthy control group was active earlier and slept earlier but received less light than the depressed group at baseline. CONCLUSION: Antidepressant response to bright light treatment in this age group was not statistically superior to placebo. Both treatment and placebo groups experienced a clinically significant overall improvement of 16%. [Abstract/Link to Full Text]

Jorm AF, Kitchener BA, Mugford SK
Experiences in applying skills learned in a Mental Health First Aid training course: a qualitative study of participants' stories.
BMC Psychiatry. 2005;543.
BACKGROUND: Given the high prevalence of mental disorders and the comparatively low rate of professional help-seeking, it is useful for members of the public to have some skills in how to assist people developing mental disorders. A Mental Health First Aid course has been developed to provide these skills. Two randomized controlled trials of this course have shown positive effects on participants' knowledge, attitudes and behavior. However, these trials have provided limited data on participants' subsequent experiences in providing first aid. To remedy this, a study was carried out gathering stories from participants in one of the trials, 19-21 months post-training. METHODS: Former course participants were contacted and sent a questionnaire either by post or via the internet. Responses were received from 94 out of the 131 trainees who were contacted. The questionnaire asked about whether the participant had experienced a post-training situation where someone appeared to have a mental health problem and, if so, asked questions about that experience. RESULTS: Post-training experiences were reported by 78% of respondents. Five key points emerged from the qualitative data: (1) the majority of respondents had had some direct experience of a situation where mental health issues were salient and the course enabled them to take steps that led to better effects than otherwise might have been the case; (2) positive effects were experienced in terms of increased empathy and confidence, as well as being better able to handle crises; (3) the positive effects were experienced by a wide range of people with varied expectations and needs; (4) there was no evidence of people over-reaching themselves because of over-confidence and (5) those who attended were able to identify quite specific benefits and many thought the course not only very useful, but were keen to see it repeated and extended. CONCLUSION: The qualitative data confirm that most members of the public who receive Mental Health First Aid training subsequently provide support to people with mental health problems and that this support generally has positive effects. [Abstract/Link to Full Text]

Kuntsi J, Andreou P, Ma J, B�rger NA, van der Meere JJ
Testing assumptions for endophenotype studies in ADHD: reliability and validity of tasks in a general population sample.
BMC Psychiatry. 2005;540.
BACKGROUND: Advances in both genetic and cognitive-experimental studies on attention deficit hyperactivity disorder (ADHD) have opened new opportunities for cognitive endophenotype research. In such genetic designs the focus is on individual differences in characteristics, associated with ADHD, that can be measured reliably over time. Genetic studies that take a 'quantitative trait loci' approach hypothesise that multiple susceptibility genes contribute to a continuous dimension of ADHD symptoms. As an important initial step, we aimed to investigate the underlying assumptions that (1) key cognitive-experimental tasks indicate adequate test-retest reliability and (2) ADHD symptom scores in a general population sample are associated with performance on these tasks. METHODS: Forty-nine children were assessed on a go/no-go task and a reaction time task (the 'fast task') that included manipulations with event rate and incentives. The children were assessed twice, with a test-retest interval of two weeks. RESULTS: The majority of the task variables demonstrated moderate-to-good test-retest reliability. The correlations between teacher ratings of ADHD symptoms and key task variables were .4-.6: ADHD symptoms were associated with poor performance (especially high reaction time variability) in a slow baseline condition, whereas there was low or no association in conditions with a faster event rate or incentives. In contrast, no clear pattern of findings emerged based on parent ratings of ADHD symptoms. CONCLUSION: The data support the usefulness of the go/no-go and fast tasks for genetic studies, which require reliable and valid indices of individual differences. The overall pattern of associations between teacher ratings of ADHD symptoms and task variables is consistent with effects of event rate and incentives on performance, as predicted by the model of activation and arousal regulation. The lack of a clear pattern of findings with parent ratings of ADHD symptoms warrants further study. [Abstract/Link to Full Text]

Gold C, Rolvsjord R, Aaro LE, Aarre T, Tjemsland L, Stige B
Resource-oriented music therapy for psychiatric patients with low therapy motivation: protocol for a randomised controlled trial [NCT00137189].
BMC Psychiatry. 2005;539.
BACKGROUND: Previous research has shown positive effects of music therapy for people with schizophrenia and other mental disorders. In clinical practice, music therapy is often offered to psychiatric patients with low therapy motivation, but little research exists about this population. The aim of this study is to examine whether resource-oriented music therapy helps psychiatric patients with low therapy motivation to improve negative symptoms and other health-related outcomes. An additional aim of the study is to examine the mechanisms of change through music therapy. METHODS: 144 adults with a non-organic mental disorder (ICD-10: F1 to F6) who have low therapy motivation and a willingness to work with music will be randomly assigned to an experimental or a control condition. All participants will receive standard care, and the experimental group will in addition be offered biweekly sessions of music therapy over a period of three months. Outcomes will be measured by a blind assessor before and 1, 3, and 9 months after randomisation. DISCUSSION: The findings to be expected from this study will fill an important gap in the knowledge of treatment effects for a patient group that does not easily benefit from treatment. The study's close link to clinical practice, as well as its size and comprehensiveness, will make its results well generalisable to clinical practice. [Abstract/Link to Full Text]

Ubhi K, Price J
Expression of POU-domain transcription factor, Oct-6, in schizophrenia, bipolar disorder and major depression.
BMC Psychiatry. 2005;538.
BACKGROUND: The POU-domain transcription factor Oct-6 has been reported to be differentially expressed between schizophrenic and control post-mortem brains. In this study, we attempted to replicate this finding and to discover whether Oct-6 was also dysregulated in bipolar disorder and major depression. METHODS: Oct-6 mRNA and protein expression were determined by in-situ hybridization and immunohistochemistry respectively in sections of post-mortem brain. RESULTS: We did not observe any differences in Oct-6 expression between any of the groups under study. Oct-6 mRNA and protein was identically expressed in the hippocampal and cortical regions of most specimens in all groups, including controls. CONCLUSION: Oct-6 is, therefore, unlikely to be a specific marker for any psychological disorder; rather its expression in controls suggests that it is normally expressed in most adult brains. [Abstract/Link to Full Text]

Bruwer BR, Stein DJ
A survey of participants in two internet support groups for people with hair-pulling.
BMC Psychiatry. 2005;537.
BACKGROUND: A substantial number of patients suffering from psychological problems or psychiatric disorders have turned to internet support groups for help. This paper reports on the perceived effectiveness of trichotillomania (TTM) internet support groups for people suffering from hair-pulling. METHODS: A questionnaire was sent via e-mail to all subscribers of two mailing lists devoted to TTM, each of which takes a somewhat different approach to the condition. The questionnaire addressed the possible benefits and problems associated with belonging to a TTM virtual support group. RESULTS: Subscribers had similar demographic features as clinical samples of trichotillomania patients. Subscribers to both internet lists found them helpful in terms of feeling supported and in obtaining information. The different approaches to TTM on the two lists were associated with differences in treatments attempted by participants. CONCLUSION: Internet support groups can potentially contribute to increasing awareness about and knowledge of psychiatric disorders such as TTM, as well as to their management. Nevertheless, additional effort is required to ensure that subscribers are able to make informed, evidence-based decisions. [Abstract/Link to Full Text]

St�ber G, Kohlmann B, Iekiera M, Rubie C, Gawlik M, M�ller-Ehrlich K, Meitinger T, Bettecken T
Systematic mutation analysis of KIAA0767 and KIAA1646 in chromosome 22q-linked periodic catatonia.
BMC Psychiatry. 2005;536.
BACKGROUND: Periodic catatonia is a familial subtype of schizophrenia characterized by hyperkinetic and akinetic episodes, followed by a catatonic residual syndrome. The phenotype has been evaluated in two independent genome-wide linkage scans with evidence for a major locus on chromosome 15q15, and a second independent locus on chromosome 22qtel. METHODS: In the positional and brain-expressed candidate genes KIAA0767 and KIAA1646, we searched for variants in the complete exons and adjacent splice-junctions as well as in parts of the 5'- and 3'-untranslated regions by means of a systematic mutation screening in individuals from chromosome 22q-linked pedigrees. RESULTS: The mutation scan revealed 24 single nucleotide polymorphisms, among them two rare codon variants (KIAA0767: S159I; KIAA1646: V338G). However, both were neither found segregating with the disease in the respective pedigree nor found at a significant frequency in a case-control association sample. CONCLUSION: Starting from linkage signals at chromosome22qtel in periodic catatonia, we screened two positional brain-expressed candidate genes for genetic variation. Our study excludes genetic variations in the coding and putative promoter regions of KIAA0767 and KIAA1646 as causative factors for periodic catatonia. [Abstract/Link to Full Text]

Faul T, Gawlik M, Bauer M, Jung S, Pfuhlmann B, Jabs B, Knapp M, St�ber G
ZDHHC8 as a candidate gene for schizophrenia: analysis of a putative functional intronic marker in case-control and family-based association studies.
BMC Psychiatry. 2005;535.
BACKGROUND: The chromosome 22q11 region is proposed as a major candidate locus for susceptibility genes to schizophrenia. Recently, the gene ZDHHC8 encoding a putative palmitoyltransferase at 22q11 was proposed to increase liability to schizophrenia based on both animal models and human association studies by significant over-transmission of allele rs175174A in female, but not male subjects with schizophrenia. METHODS: Given the genetic complexity of schizophrenia and the potential genetic heterogeneity in different populations, we examined rs175174 in 204 German proband-parent triads and in an independent case-control study (schizophrenic cases: n = 433; controls: n = 186). RESULTS: In the triads heterozygous parents transmitted allele G preferentially to females, and allele A to males (heterogeneity chi2 = 4.43; p = 0.035). The case-control sample provided no further evidence for overall or gender-specific effects regarding allele and genotype frequency distributions. CONCLUSION: The findings on rs175174 at ZDHHC8 are still far from being conclusive, but evidence for sexual dimorphism is moderate, and our data do not support a significant genetic contribution of rs175174 to the aetiopathogenesis of schizophrenia. [Abstract/Link to Full Text]

Kar N
Chronic koro-like symptoms - two case reports.
BMC Psychiatry. 2005;534.
BACKGROUND: Koro is a culture bound syndrome, which has been reported usually from Asian countries. It has been described as an acute, brief lasting illness, which often occurs in epidemics. There is no description in literature of a chronic form of this syndrome. CASE PRESENTATION: Two sporadic cases with koro-like symptoms from East India are presented where the illness had a chronic course with durations spanning more than ten years. In contrast to acute, good prognosis, psycho-education responsive form that is usually seen in epidemics; the chronic form, appeared to be associated with greater morbidity and poorer response to interventions. CONCLUSION: There is a possibility of a chronic form of koro syndrome. [Abstract/Link to Full Text]

Nakane Y, Jorm AF, Yoshioka K, Christensen H, Nakane H, Griffiths KM
Public beliefs about causes and risk factors for mental disorders: a comparison of Japan and Australia.
BMC Psychiatry. 2005;533.
BACKGROUND: Surveys of the public in a range of Western countries have shown a predominant belief in social stressors as causes of mental disorders. However, there has been little direct cross-cultural comparison. Here we report a comparison of public beliefs about the causes of mental disorders in Japan and Australia. METHODS: Surveys of the public were carried out in each country using as similar a methodology as feasible. In both countries, household interviews were carried out concerning beliefs about causes and risk factors in relation to one of four case vignettes, describing either depression, depression with suicidal thoughts, early schizophrenia or chronic schizophrenia. In Japan, the survey involved 2000 adults aged between 20 and 69 from 25 regional sites spread across the country. In Australia, the survey involved a national sample of 3998 adults aged 18 years or over. RESULTS: In both countries, both social and personal vulnerability causes were commonly endorsed across all vignettes. The major differences in causal beliefs were that Australians were more likely to believe in infection, allergy and genetics, while Japanese were more likely to endorse "nervous person" and "weakness of character". For risk factors, Australians tended to believe that women, the young and the poor were more at risk of depression, but these were not seen as higher risk groups by Japanese. CONCLUSION: In both Japan and Australia, the public has a predominant belief in social causes and risk factors, with personal vulnerability factors also seen as important. However, there are also some major differences between the countries. The belief in weakness of character as a cause, which was stronger in Japan, is of particular concern because it may reduce the likelihood of seeking professional help and support from others. [Abstract/Link to Full Text]

Pirkola S, Sohlman B, Wahlbeck K
The characteristics of suicides within a week of discharge after psychiatric hospitalisation - a nationwide register study.
BMC Psychiatry. 2005;532.
BACKGROUND: The characteristics of victims of immediate post-discharge suicides are not well known. We explored these characteristics for the purposes of better recognition and preventive efforts of potential immediate post-discharge suicides. METHODS: Suicides from a Finnish nationwide register were linked with preceding periods of psychiatric inpatient treatment. Characteristics of suicides within a week of discharge were compared to those occurring later after discharge. RESULTS: Compared to other previously hospitalised suicide victims, those committing suicide within a week of discharge were more often female, unmarried, had a higher grade of education and a diagnosis of schizophrenia spectrum or affective disorder, tended to use more drowning and jumping from heights as the methods for suicide and had gained a smaller improvement in psychological functioning during hospitalization. CONCLUSION: These characteristics indicate a more severe psychopathology, relatively poorer level of functioning, less global response to hospitalisation, and a more frequent choice of lethal and easily available method for suicide. Potentially suicidal psychiatric patients should be better recognized and an immediate follow-up arranged if it is decided they be discharged. [Abstract/Link to Full Text]

Vythilingum B, Hugo CJ, Maritz JS, Pienaar W, Stein DJ
Pharmacological challenge with a serotonin 1D agonist in alcohol dependence.
BMC Psychiatry. 2005;531.
BACKGROUND: Both animal and clinical studies have implicated serotonergic dysfunction in the pathogenesis of alcohol abuse and dependence. However the exact mechanisms involved remain unknown. Theoretically, low serotonin promotes alcohol seeking behavior. Sumatriptan is a serotonin1D agonist. It is postulated that sumatriptan's agonism at this terminal autoreceptor increases negative feedback, creating a net effect of decreased serotonergic neurotransmission. Administration of sumatriptan should therefore produce a craving for alcohol and the desire to drink. METHODS: Fifteen patients with alcohol dependence who had undergone detoxification were recruited. Sumatriptan (100 mg) and placebo was administered in cross-over fashion on 2 separate days 72 hours apart. Both patients and raters were blind to all treatments. Patients were assessed on the following scales at -30, 0, 30, 90, 150 and 210 minutes: A 6-item scale designed to rate the patient's intention to drink; The Sensation Scale; a 13-item affect analog scale designed to rate the pattern and extent of emotional changes; and an 8-item scale designed to rate the patient's craving for alcohol. RESULTS: No significant differences were found between the placebo and sumatriptan groups and no significant cross over effects were found. CONCLUSION: The general lack of efficacy of sumatriptan in producing alcohol-like symptoms or a desire to drink alcohol may suggest that the 5HT1D receptor plays little role in the pathophysiology of alcoholism. [Abstract/Link to Full Text]

Takriti Y, El-Sayeh HG, Adams CE
Internet-based search of randomised trials relevant to mental health originating in the Arab world.
BMC Psychiatry. 2005;530.
BACKGROUND: The internet is becoming a widely used source of accessing medical research through various on-line databases. This instant access to information is of benefit to busy clinicians and service users around the world. The population of the Arab World is comparable to that of the United States, yet it is widely believed to have a greatly contrasting output of randomised controlled trials related to mental health. This study was designed to investigate the existence of such research in the Arab World and also to investigate the availability of this research on-line. METHODS: Survey of findings from three internet-based potential sources of randomised trials originating from the Arab world and relevant to mental health care. RESULTS: A manual search of an Arabic online current contents service identified 3 studies, MEDLINE, EMBASE, and PsycINFO searches identified only 1 study, and a manual search of a specifically indexed, study-based mental health database, PsiTri, revealed 27 trials. CONCLUSION: There genuinely seem to be few trials from the Arab world and accessing these on-line was problematic. Replication of some studies that guide psychiatric/psychological practice in the Arab world would seem prudent. [Abstract/Link to Full Text]

Wienbruch C, Paul I, Bauer S, Kivelitz H
The influence of methylphenidate on the power spectrum of ADHD children - an MEG study.
BMC Psychiatry. 2005;529.
BACKGROUND: The present study was dedicated to investigate the influence of Methylphenidate (MPH) on cortical processing of children who were diagnosed with different subtypes of Attention Deficit Hyperactivity Disorder (ADHD). As all of the previous studies investigating power differences in different frequency bands have been using EEG, mostly with a relatively small number of electrodes our aim was to obtain new aspects using high density magnetoencephalography (MEG). METHODS: 35 children (6 female, 29 male) participated in this study. Mean age was 11.7 years (+/- 1.92 years). 17 children were diagnosed of having an Attention-Deficit/Hyperactivity Disorder of the combined type (ADHDcom, DSM IV code 314.01); the other 18 were diagnosed for ADHD of the predominantly inattentive type (ADHDin, DSM IV code 314.0). We measured the MEG during a 5 minute resting period with a 148-channel magnetometer system (MAGNES 2500 WH, 4D Neuroimaging, San Diego, USA). Power values were averaged for 5 bands: Delta (D, 1.5-3.5 Hz), Theta (T, 3.5-7.5 Hz), Alpha (A, 7.5-12.5 Hz), Beta (B, 12.5-25 Hz) and Global (GL, 1.5-25 Hz).). Additionally, attention was measured behaviourally using the D2 test of attention with and without medication. RESULTS: The global power of the frequency band from 1.5 to 25 Hz increased with MPH. Relative Theta was found to be higher in the left hemisphere after administration of MPH than before. A positive correlation was found between D2 test improvement and MPH-induced power changes in the Theta band over the left frontal region. A linear regression was computed and confirmed that the larger the improvement in D2 test performance, the larger the increase in Theta after MPH application. CONCLUSION: Main effects induced by medication were found in frontal regions. Theta band activity increased over the left hemisphere after MPH application. This finding contradicts EEG results of several groups who found lower levels of Theta power after MPH application. As relative Theta correlates with D2 test improvement we conclude that MEG provide complementary and therefore important new insights to ADHD. [Abstract/Link to Full Text]

Tamayo JM, Rom�n K, Fumero JJ, Rivas M
The level of recognition of physical symptoms in patients with a major depression episode in the outpatient psychiatric practice in Puerto Rico: an observational study.
BMC Psychiatry. 2005;528.
BACKGROUND: This study was designed to evaluate the psychiatrists' level of recognition of somatic symptoms associated to a major depressive episode (MDE) (DSM-IV-TR criteria) and the impact of those somatic symptoms on the treatment effectiveness. METHODS: This non-interventional study was conducted in 25 medical offices in Puerto Rico from February to December 2003. It had 2 visits separated by 8 weeks. The level of recognition was determined by: the correlation between the physician clinical evaluation and their patients' self-evaluations through different validated instruments using kappa statistics. Chi-square test was used to evaluate the impact of somatic symptoms on treatment antidepressants' effectiveness. RESULTS: All the 145 recruited patients reported the presence of at least one somatic symptom associated with their current MDE. In the two visits covered by the study, a fair agreement between the psychiatrists' and the patients' reports was noted for headache, abdominal pain and upper limb pains (0.4003 <or= kappa >or= 0.6594). For other painful symptoms and painless somatic symptoms, the Kappa values obtained were non-significant. Slight but significant reductions in depression and painful symptoms severity were observed after 8 weeks of treatment. A proportional relationship between the pain and depression severity was observed (p < 0.0001). CONCLUSION: The study results show that somatic symptoms: are very common in depressed Puerto Rican patients; are significant under-reported by psychiatrists; and have a significant impact on the antidepressant effectiveness. [Abstract/Link to Full Text]

Momeni N, Nordstr�m BM, Horstmann V, Avarseji H, Sivberg BV
Alterations of prolyl endopeptidase activity in the plasma of children with autistic spectrum disorders.
BMC Psychiatry. 2005;527.
BACKGROUND: Prolyl Endopeptidase (PEP, EC 3.4.21.26), a cytosolic endopeptidase, hydrolyses peptide bonds on the carboxyl side of proline residue in proteins with a relatively small molecular weight. It has been shown that altered PEP activity is associated with various psychological diseases such as schizophrenia, mania and depression. Autistic Spectrum Disorders (ASD) are neuropsychiatric and behavioural syndromes affecting social behaviours and communication development. They are classified as developmental disorders. The aim of this study was to examine the hypothesis that PEP activity is also associated with ASDs. METHODS: Fluorometric assay was used to measure PEP activity in EDTA plasma in children with ASD (n = 18) aged 4-12 years (mean +/- SD: 7.9 +/- 2.5). These results were then compared to PEP activity in a control group of non-ASD children (n = 15) aged 2-10 years (mean +/- SD: 6.4 +/- 2.2). RESULTS: An alteration in PEP activity was found in the children with ASD compared to the control group. There was much greater variation of PEP activity in the group of ASD children when compared to the controls (SD= 39.9 and SD 9.6, respectively). This variation was significant (p < 0.0005), although the mean level of PEP activity in the group of ASD children was slightly higher than in the control group (124.4 and 134.1, respectively). CONCLUSION: Our preliminary finding suggests a role for PEP enzyme in the pathophysiology of autism but further research should be conducted to establish its role in the aetiology of psychiatric and neurological disorders, including autism and related spectrum disorders. [Abstract/Link to Full Text]

Faries D, Ascher-Svanum H, Zhu B, Correll C, Kane J
Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics.
BMC Psychiatry. 2005;526.
BACKGROUND: Antipsychotic monotherapy is recognized as the treatment of choice for patients with schizophrenia. Simultaneous treatment with multiple antipsychotics (polypharmacy) is suggested by some expert consensus guidelines as the last resort after exhausting monotherapy alternatives. This study assessed the annual rate and duration of antipsychotic monotherapy and its inverse, antipsychotic polypharmacy, among schizophrenia patients initiated on commonly used atypical antipsychotic medications. METHODS: Data were drawn from a large prospective naturalistic study of patients treated for schizophrenia-spectrum disorders, conducted 7/1997-9/2003. Analyses focused on patients (N = 796) who were initiated during the study on olanzapine (N = 405), quetiapine (N = 115), or risperidone (N = 276). The percentage of patients with monotherapy on the index antipsychotic over the 1-year post initiation, and the cumulative number of days on monotherapy were calculated for all patients and for each of the 3 atypical antipsychotic treatment groups. Analyses employed repeated measures generalized linear models and non-parametric bootstrap re-sampling, controlling for patient characteristics. RESULTS: During the 1-year period, only a third (35.7%) of the patients were treated predominately with monotherapy (> 300 days). Most patients (57.7%) had at least one prolonged period of antipsychotic polypharmacy (> 60 consecutive days). Patients averaged 195.5 days on monotherapy, 155.7 days on polypharmacy, and 13.9 days without antipsychotic therapy. Olanzapine-initiated patients were significantly more likely to be on monotherapy with the initiating antipsychotic during the 1-year post initiation compared to risperidone (p = .043) or quetiapine (p = .002). The number of monotherapy days was significantly greater for olanzapine than quetiapine (p < .001), but not for olanzapine versus risperidone, or for risperidone versus quetiapine-initiated patients. CONCLUSION: Despite guidelines recommending the use of polypharmacy only as a last resort, the use of antipsychotic polypharmacy for prolonged periods is very common during the treatment of schizophrenia patients in usual care settings. In addition, in this non-randomized naturalistic observational study, the most commonly used atypical antipsychotics significantly differed on the rate and duration of antipsychotic monotherapy. Reasons for and the impact of the predominant use of polypharmacy will require further study. [Abstract/Link to Full Text]

Khademi A, Alleyassin A, Aghahosseini M, Ramezanzadeh F, Abhari AA
Pretreatment Beck Depression Inventory score is an important predictor for post-treatment score in infertile patients: a before-after study.
BMC Psychiatry. 2005;525.
BACKGROUND: The experience of infertility can be extremely stressful. Some of the risk factors for depression in infertility are being female, repeated unsuccessful treatment cycles or a 2 to 3 year history of infertility, low socioeconomic status, foreign nationality, lack of partner support, life events and previous depression. In this study, we analyzed the Beck Depression Inventory score at the beginning and the end of infertility treatment, to determine which factors may influence the BDI score after treatment of infertility. METHODS: In a before-after study, in a university-affiliated teaching hospital, 251 women who had been visited for assisted reproductive technology infertility treatment participated in the study. BDI score was assessed before and after treatment of infertility. RESULTS: The mean BDI score rose after unsuccessful treatment and dropped after successful treatment. Those with lower education levels had a higher BDI score before treatment. BDI score after treatment was positively correlated with pretreatment BDI scoreand duration of infertility. CONCLUSION: BDI score after treatment was strongly connected to the BDI score before treatment, the result of therapy and to the duration of infertility. The influence of duration of infertility on BDI score after treatment of infertility is weak. So a simple method to screen patients at risk of depression after infertility treatment is determining pretreatment BDI score and predicting the result of infertility treatment by other risk factors. [Abstract/Link to Full Text]

Recent Articles in Annals of General Hospital Psychiatry

No recent articles are currently available.

Recent Articles in Journal of Psychiatry & Neuroscience

Dongier M
What are the treatment options for comorbid alcohol abuse and depressive disorders?
J Psychiatry Neurosci. 2005 May;30(3):224. [Abstract/Link to Full Text]

Lee TW, Yu YW, Chen TJ, Tsai SJ
Loudness dependence of the auditory evoked potential and response to antidepressants in Chinese patients with major depression.
J Psychiatry Neurosci. 2005 May;30(3):202-5.
OBJECTIVE: To investigate the loudness dependence of the auditory evoked potential (LDAEP) in predicting response to treatment for major depression. METHODS: One hundred patients of Chinese ethnicity with major depression were divided into 2 groups, having strong or weak pretreatment LDAEP; the cutoff was the median of the LDAEP slope (for amplitude as a function of intensity). There were no between-group differences before treatment in terms of score on the Hamilton Depression Rating Scale (HDRS), age or sex distribution. The LDAEP for 4 intensity levels (60, 70, 80 and 90 dB) was recorded before treatment. Each patient then received fluoxetine 20 mg per day for 4 weeks. The response to treatment was evaluated by means of the HDRS. RESULTS: At week 4, the HDRS score had declined by 44.3; for the group with strong LDAEP and by 34.4% for the group with weak LDAEP (t for mean difference = 2.584, p = 0.011). CONCLUSION: Strong pretreatment LDAEP predicted a favourable response to treatment with a selective serotonin reuptake inhibitor in patients with major depression. [Abstract/Link to Full Text]

Kolla N, Wei Z, Richardson JS, Li XM
Amitriptyline and fluoxetine protect PC12 cells from cell death induced by hydrogen peroxide.
J Psychiatry Neurosci. 2005 May;30(3):196-201.
OBJECTIVE: To investigate the potential protective effects of amitriptyline and fluoxetine in a catecholamine cell model. METHODS: Cultured rat pheochromocytoma (PC12) cells were pretreated with amitriptyline or fluoxetine for 24 or 48 hours and were then subjected to neurotoxic insult (200 micromol/L hydrogen peroxide). Cell viability was determined by measurement of the reduction product of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). The enzyme activity of superoxide dismutase (SOD) was determined by a commercial SOD assay kit. RESULTS: The decrease in cell viability induced by hydrogen peroxide was attenuated in PC12 cells pretreated with 100 micromol/L amitriptyline for 24 hours or with 50 micromol/L amitriptyline or 50 micromol/L fluoxetine for 48 hours. Pretreatment with either amitriptyline or fluoxetine was associated with increased SOD activity in PC12 cells. Inhibition of SOD activity with diethyldithiocarbamic acid reduced the cytoprotective action of fluoxetine. CONCLUSIONS: These data suggest that the neuroprotective actions of some antidepressants include the upregulation of SOD activity. [Abstract/Link to Full Text]

Bottas A, Cooke RG, Richter MA
Comorbidity and pathophysiology of obsessive-compulsive disorder in schizophrenia: is there evidence for a schizo-obsessive subtype of schizophrenia?
J Psychiatry Neurosci. 2005 May;30(3):187-93.
Epidemiologic and neurobiologic evidence suggests that patients with comorbid obsessive-compulsive disorder (OCD) and schizophrenia may represent a special category among patients with schizophrenia. Efforts to examine the neurobiology of this group have focused on neuroimaging studies and neuropsychologic testing. Convergent evidence suggests that there may be a specific pattern of neurobiologic dysfunction in this subgroup of patients accounting for symptom co-expression. This review indicates that future studies should distinguish among (1) apparent obsessive-compulsive symptoms (OCS) that occur only in the context of psychosis and that may overlap with psychotic phenomenology, representing a forme fruste of psychosis; (2) OCS occurring only in the prodromal phase of schizophrenia; (3) neuroleptic-induced OCS or OCD; and (4) OCS or frank OCD occurring concurrently with schizophrenia. We examine the evidence for a putative schizo-obsessive disorder and outline suggestions for identifying OCS in the presence of psychosis. [Abstract/Link to Full Text]

Konarski JZ, McIntyre RS, Grupp LA, Kennedy SH
Is the cerebellum relevant in the circuitry of neuropsychiatric disorders?
J Psychiatry Neurosci. 2005 May;30(3):178-86.
Contemporary mechanistic models of several psychiatric disorders propose abnormalities in the structure and function of distinct neural networks. The cerebellum has both anatomic and functional connections to the prefrontal cortex, the subcortical limbic structures and monoamine-producing brainstem nuclei. Conspicuously, however, the cerebellum has been underemphasized in neuropsychiatric research. A growing confluence of scientific data indicate that the cerebellum may not be irrelevant, which suggests that an integrated model of neuropsychiatric disorders should include a role for the cerebellum and its relevant neural connections. This review summarizes the published data describing and characterizing the putative role of the cerebellum in normal and abnormal mood regulation, with specific attention to states of psychosis, depression and mania. The available evidence suggests that a functional role for the cerebellum should be considered in future neuropsychiatric studies. [Abstract/Link to Full Text]

Zwanzger P, Rupprecht R
Selective GABAergic treatment for panic? Investigations in experimental panic induction and panic disorder.
J Psychiatry Neurosci. 2005 May;30(3):167-75.
gamma-Aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the central nervous system (CNS). It exerts its rapid inhibitory action mostly through GABA(A) receptors, which are targets for benzodiazepines, barbiturates, neuroactive steroids and distinct anticonvulsive agents. There is considerable evidence that dysfunction of GABA(A) receptors or dysregulation of GABA concentrations in the CNS (or both) plays an important role in the pathophysiology of panic disorder. Currently, benzodiazepines are the only drugs directly targeting the GABA(A) receptors that are approved for the treatment of anxiety disorders. Because of their well-known anxiolytic effects, they are widely used in this setting, but side effects limit their use in long-term treatment. The question of whether drugs that selectively increase GABA concentrations in the CNS could improve symptoms of anxiety has been discussed. Recent investigations by our group have demonstrated that enhancement of endogenous GABA (through blockade of GABA transaminase by vigabatrin or through inhibition of GABA transporters by tiagabine) exerts anxiolytic effects on experimentally induced panic. Our studies in healthy volunteers have shown that both compounds lead to a significant reduction in panic symptoms elicited by cholecystokinin-tetrapeptide. Moreover, benzodiazepine-like effects on the activity of the hypothalamic-pituitary-adrenal axis have been observed in association with vigabatrin treatment. Small open studies in patients with panic disorder also showed an improvement in panic and anxiety with both compounds. This review summarizes our recent research on the effects of selective GABAergic treatment in experimentally induced panic and outlines the possible role of compounds targeting the GABA binding site of the GABA(A)-benzodiazepine receptor for the treatment of panic and anxiety. [Abstract/Link to Full Text]

Young SN
Universities, governments and industry: can the essential nature of universities survive the drive to commercialize?
J Psychiatry Neurosci. 2005 May;30(3):160-3. [Abstract/Link to Full Text]

Le Mell�do JM, Perez J
Selective serotonin reuptake inhibitors (SSRIs) and depression after myocardial infarction (MI).
J Psychiatry Neurosci. 2005 Mar;30(2):152. [Abstract/Link to Full Text]

G�rker I, T�z�n U
Autistic-like findings associated with a urea cycle disorder in a 4-year-old girl.
J Psychiatry Neurosci. 2005 Mar;30(2):133-5.
A 4-year-old girl presented at our clinic with autistic-like symptoms, aggressivity and occasional hyperactivity. She had no history of neurologic or physical symptoms. Her condition was diagnosed as pervasive developmental disorder not otherwise specified, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). She received pharmacologic (thioridazine), educational and speech therapy. During this process, a urea cycle disorder was also identified, namely, ornithine transcarbamylase deficiency and arginase deficiency, because of the high level of ammonia in the patient's bloodstream, the high level of organic acids in the 24-hour urine collection and the constant presence of slow multifocal epileptic discharges on the electroencephalograms. The patient's protein intake was restricted, and she was treated with sodium benzoate and arginine. After 1 year of treatment, the autistic-like findings and hyperactivity were no longer apparent. [Abstract/Link to Full Text]

Centonze D, Palmieri MG, Boffa L, Pierantozzi M, Stanzione P, Brusa L, Marciani M, Siracusano A, Bernardi G, Caramia M
Cortical hyperexcitability in post-traumatic stress disorder secondary to minor accidental head trauma: a neurophysiologic study.
J Psychiatry Neurosci. 2005 Mar;30(2):127-32.
OBJECTIVE: We applied paired transcranial magnetic stimulation (pTMS) to patients with post-traumatic stress disorder (PTSD) secondary to minor accidental head trauma. Our purpose was to determine the potential abnormality of motor cortex excitability in this pathologic condition. METHODS: pTMS stimulation, according to the conditioning-test paradigm employing interstimulus intervals (ISIs) of 1-6 ms, was used to investigate intracortical inhibition in control subjects and patients with PTSD. The study population consisted of 14 patients who had developed PTSD following minor head trauma, 12 healthy volunteers without a clinical history of head trauma and 11 healthy subjects who had reported accidental minor head trauma 1-4 months before the study. This clinical electrophysiologic study was performed at the Department of Neuroscience, University of Rome "Tor Vergata." RESULTS: All patients with PTSD exhibited a significantly lower motor evoked potential (MEP) inhibition than controls at 2 ms, 3 ms and 4 ms ISI. The statistical analysis of the pTMS protocol showed a significant effect (F2,36 = 25.63, p < 0.001) of the factor "group," because patients with PTSD showed a mean conditioned MEP amplitude higher than that observed in both control groups for all 6 ISIs analyzed. The "ISI" factor was also significant (F5,180 = 89.85, Greenhouse-Geisser epsilon = 0.35; p < 0.001), with the mean conditioned MEP amplitude increasing from 22.5% to 127.8% as the ISI increased from 1 ms to 6 ms. Finally, the interaction of group with ISI was also significant (F10,180 = 8.97, p < 0.001), showing that the condition of PTSD secondary to head trauma was able to affect the MEP amplitude at different ISIs. CONCLUSIONS: Our results demonstrate that PTSD can give rise to abnormalities in intracortical inhibition. Our results provide further evidence that alterations in cortical inhibitory circuits may underlie specific forms of neuroticism in humans. [Abstract/Link to Full Text]

Ben Amor L, Grizenko N, Schwartz G, Lageix P, Baron C, Ter-Stepanian M, Zappitelli M, Mbekou V, Joober R
Perinatal complications in children with attention-deficit hyperactivity disorder and their unaffected siblings.
J Psychiatry Neurosci. 2005 Mar;30(2):120-6.
OBJECTIVES: Genetic and nonshared environmental factors (experienced by 1 family member to the exclusion of the others) have been strongly implicated in the causes of attention-deficit hyperactivity disorder (ADHD). Pregnancy, labour/delivery and neonatal complications (PLDNC) have often been associated with ADHD; however, no investigations aimed at delineating the shared or nonshared nature of these factors have been reported. We aimed to identify those elements of the PLDNC that are more likely to be of a nonshared nature. METHODS: We used an intrafamily study design, comparing the history of PLDNC between children diagnosed with ADHD, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and their unaffected siblings. Children with ADHD were recruited from the outpatient, day-treatment program of the Child Psychiatry Department, Douglas Hospital, Montreal. The unaffected sibling closest in age to the child with ADHD was used as a control. The history of PLDNC was assessed using the Kinney Medical and Gynecological Questionnaire and the McNeil-Sjostrom Scale for both children with ADHD and their siblings. Seventy children with ADHD along with 50 of their unaffected siblings agreed to participate in the study. Child Behavior Checklist (CBCL), Continuous Performance Test (CPT) and Restricted Academic Situation Scale (RASS) scores were also used as measures of ADHD symptoms in children with ADHD. RESULTS: The children with ADHD had significantly higher rates of neonatal complications compared with their unaffected siblings (F4,196 = 3.67, p < 0.006). Furthermore, neonatal complications in the children with ADHD were associated with worse CBCL total and externalizing scores and with poorer performance on the CPT. CONCLUSIONS: These results suggest that neonatal complications are probably a nonshared environmental risk factor that may be pathogenic in children with ADHD. [Abstract/Link to Full Text]

Le Saux M, Di Paolo T
Changes in 5-HT1A receptor binding and G-protein activation in the rat brain after estrogen treatment: comparison with tamoxifen and raloxifene.
J Psychiatry Neurosci. 2005 Mar;30(2):110-7.
OBJECTIVE: It is thought that an imbalance in serotonergic neurotransmission may underlie many affective disorders. Thus, the serotonin-1A (5-HT1A) receptor is a target for antidepressant and neuroleptic drugs. It has been reported that estrogens modulate serotonergic neurotransmission. Therefore, we investigated the effect of long-term ovariectomy on 5-HT1A receptor-specific binding and G-protein activation in the brain. Correction therapy with estradiol was compared with treatments using the selective estrogen receptor modulators tamoxifen and raloxifene. METHODS: Four months after ovariectomy, Sprague-Dawley rats were treated with vehicle, 17beta-estradiol (80 microg/kg), tamoxifen (1 mg/kg) or raloxifene (1 mg/kg) subcutaneously for 2 weeks. Specific binding to 5-HT1A receptors was assessed by autoradiography of brain sections using the 5-HT1A agonist [3H]8-OH-DPAT. 5-HT1A receptor stimulation was measured using R-(+)-8-OH-DPAT-stimulated [35S]GTPgammaS-binding autoradiography. RESULTS: Ovariectomy decreased uterine weight, which was corrected by estradiol; tamoxifen and raloxifene partially corrected this decrease. Hormonal withdrawal and replacement left [3H]8-OH-DPAT-specific binding unchanged in the cortex. In contrast, ovariectomy induced a decrease in R-(+)-8-OH-DPAT-stimulated [35S]GTPgammaS-specific binding in the cortex; this was corrected by estradiol but was not corrected significantly by tamoxifen or raloxifene. In the hippocampus, ovariectomy had no effect on [3H]8-OH-DPAT-specific binding, whereas only 17beta-estradiol treatment decreased this binding in a subregion of the CA3. Ovariectomy increased R-(+)-8-OH-DPAT-stimulated [35S]GTPgammaS-specific binding in the dentate gyrus (but not in the CA1 or CA3); this was corrected by estradiol and raloxifene, but not by tamoxifen. In the dorsal raphe nucleus, ovariectomy increased [3H]8-OH-DPAT-specific binding and R-(+)-8-OH-DPAT-stimulated [35S]GTPgammaS-specific binding; estradiol corrected this increase, but this was not corrected significantly by tamoxifen or raloxifene. CONCLUSIONS: An overall stimulation by estradiol of 5-HT1A receptor-specific binding and coupling was observed, decreasing raphe somatodendritic receptors and increasing cortical postsynaptic receptors. [Abstract/Link to Full Text]

Gagnon B, Low G, Schreier G
Methylphenidate hydrochloride improves cognitive function in patients with advanced cancer and hypoactive delirium: a prospective clinical study.
J Psychiatry Neurosci. 2005 Mar;30(2):100-7.
OBJECTIVE: To investigate the clinical improvement observed in patients with advanced cancer and hypoactive delirium after the administration of methylphenidate hydrochloride. METHODS: Fourteen patients with advanced cancer and hypoactive delirium were seen between March 1999 and August 2000 at the Palliative Care Day Hospital and the inpatient Tertiary Palliative Care Unit of Montreal General Hospital, Montreal. They were chosen for inclusion in a prospective clinical study on the basis of (1) cognitive failure documented by the Mini-Mental State Examination (MMSE), (2) sleep-wake pattern disturbances, (3) psychomotor retardation, (4) absence of delusions or hallucinations, and (5) absence of an underlying cause to explain the delirium. All patients were treated with methylphenidate, and changes in their cognitive function were measured using the MMSE. RESULTS: All 14 patients showed improvement in their cognitive function as documented by the MMSE. The median pretreatment MMSE score (maximum score 30) was 21 (mean 20.9, standard deviation [SD] 4.9), which improved to a median of 27 (mean 24.9, SD 4.7) after the first dose of methylphenidate (p < 0.001, matched, paired Wilcoxon signed rank test). One patient died before reaching a stable dose of methylphenidate. In the other 13 patients, the median MMSE score further improved to 28 (mean 27.8, SD 2.4) (p = 0.02 compared with the median MMSE score documented 1 hour after the first dose of methylphenidate). All patients showed an improvement in psychomotor activities. CONCLUSIONS: Hypoactive delirium that cannot be explained by an underlying cause (metabolic or drug-induced) in patients with advanced cancer appears to be a specific syndrome that could be improved by the administration of methylphenidate. [Abstract/Link to Full Text]

Schutter DJ, van Honk J
A framework for targeting alternative brain regions with repetitive transcranial magnetic stimulation in the treatment of depression.
J Psychiatry Neurosci. 2005 Mar;30(2):91-7.
It has been argued that clinical depression is accompanied by reductions in cortical excitability of the left prefrontal cortex (PFC). In support of this, repetitive transcranial magnetic stimulation (rTMS), which is a method of enhancing cortical excitability, has shown antidepressant efficacy when applied over the left PFC, although the overall therapeutic effects remain inconclusive. The cerebral pathophysiology of depression is, however, not limited to dysfunctions in the PFC, thus, targeting alternative brain regions with rTMS may provide new therapeutic windows in the treatment of depression. Evidence from electroencephalography and lesion studies suggests that not only is the left PFC involved in depression but also the parietal cortex and cerebellum. Furthermore, rTMS over the parietal cortex and the cerebellum has been found to improve mood and emotional functioning, at least in healthy volunteers. We have integrated these findings in an rTMS-oriented theoretical framework for the neurobiology of low mood and depression. To establish the possible therapeutic efficacy of this model, whereby, for example, the application of slow rTMS over the right parietal cortex and fast rTMS over the cerebellum may be beneficial in different subtypes of depression, clinical rTMS studies that target the parietal cortex and cerebellum are warranted. [Abstract/Link to Full Text]

Daskalakis ZJ
Repetitive transcranial magnetic stimulation for the treatment of depression: to stimulate or not to stimulate?
J Psychiatry Neurosci. 2005 Mar;30(2):81-2. [Abstract/Link to Full Text]

Couturier JL
Efficacy of rapid-rate repetitive transcranial magnetic stimulation in the treatment of depression: a systematic review and meta-analysis.
J Psychiatry Neurosci. 2005 Mar;30(2):83-90.
OBJECTIVE: To systematically review the literature pertaining to rapid-rate repetitive transcranial magnetic stimulation (rTMS) compared with sham therapy for the treatment of a major depressive episode in order to arrive at qualitative and quantitative conclusions about the efficacy of rapid-rate rTMS. METHODS: MEDLINE, the Cochrane Library, the metaRegister of Controlled Trials and abstracts from scientific meetings were searched for the years 1966 until July 2003. The search terms "transcranial magnetic stimulation" and "transcranial magnetic stimulation AND depression" were used. Eighty-seven randomized controlled trials investigating the efficacy of rTMS were referenced on MEDLINE. Nineteen of these involved treatment of a major depressive episode, and these were reviewed. Six met more specific inclusion criteria including the use of rapid-rate stimulation, application to the left dorsolateral prefrontal cortex, evaluation with the 21-item Hamilton Rating Scale for Depression (HAM-D) and use of an intent-to-treat analysis. Scores on the 21-item HAM-D after treatment and standard deviations were extracted from each article for treatment and control subjects. A random-effects model was chosen for the meta-analysis, and the weighted mean difference was used as a summary measure. RESULTS: Six studies that met the inclusion criteria were identified and included in the meta-analysis. Two of these reported a significantly greater improvement in mood symptoms in the treatment versus the sham group. When combined in the meta-analysis, the overall weighted mean difference was -1.1 (95% confidence interval -4.5 to 2.3), and the results of a test for heterogeneity were not significant (chi2(5) = 5.81, p = 0.33). CONCLUSIONS: This meta-analysis suggests that rapid-rate rTMS is no different from sham treatment in major depression; however, the power within these studies to detect a difference was generally low. Randomized controlled trials with sufficient power to detect a clinically meaningful difference are required. [Abstract/Link to Full Text]

Fregni F, Pascual-Leone A
Repetitive transcranial magnetic stimulation for the treatment of depression.
J Psychiatry Neurosci. 2005 Nov;30(6):434; author reply 434-5. [Abstract/Link to Full Text]

Levitan RD
What is the optimal implementation of bright light therapy for seasonal affective disorder (SAD)?
J Psychiatry Neurosci. 2005 Jan;30(1):72. [Abstract/Link to Full Text]

Ramaswamy S, Siddiqui Z, Saharan S, Gabel TL, Bhatia SC
Quetiapine-induced hypothyroidism.
J Psychiatry Neurosci. 2005 Jan;30(1):57. [Abstract/Link to Full Text]

Aleman A, de Haan EH, Kahn RS
Object versus spatial visual mental imagery in patients with schizophrenia.
J Psychiatry Neurosci. 2005 Jan;30(1):53-6.
OBJECTIVE: Recent research has revealed a larger impairment of object perceptual discrimination than of spatial perceptual discrimination in patients with schizophrenia. It has been suggested that mental imagery may share processing systems with perception. We investigated whether patients with schizophrenia would show greater impairment regarding object imagery than spatial imagery. METHODS: Forty-four patients with schizophrenia and 20 healthy control subjects were tested on a task of object visual mental imagery and on a task of spatial visual mental imagery. Both tasks included a condition in which no imagery was needed for adequate performance, but which was in other respects identical to the imagery condition. This allowed us to adjust for nonspecific differences in individual performance. RESULTS: The results revealed a significant difference between patients and controls on the object imagery task (F(1,63) = 11.8, p = 0.001) but not on the spatial imagery task (F(1,63) = 0.14, p = 0.71). To test for a differential effect, we conducted a 2 (patients v. controls) small ha, Cyrillic 2 (object task v. spatial task) analysis of variance. The interaction term was statistically significant (F(1,62) = 5.2, p = 0.026). CONCLUSIONS: Our findings suggest a differential dysfunction of systems mediating object and spatial visual mental imagery in schizophrenia. [Abstract/Link to Full Text]

Spalletta G, Romeo E, Bonaviri G, Bernardi G, Caltagirone C, di Michele F
Preliminary evidence for an association between aggressive and hostile behaviour and 3alpha,5alpha-tetrahydroprogesterone plasma levels in schizophrenia.
J Psychiatry Neurosci. 2005 Jan;30(1):49-52.
OBJECTIVE: Because it has been suggested that agents acting on the gamma-aminobutyric acid-A (GABA(A)) receptor complex, such as the neuroactive steroid 3!#!alpha;,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP), may be biologic modulators of aggression, we aimed to measure 3alpha,5alpha-THP plasma concentrations in subjects with schizophrenia in order to investigate a possible relation with aggressive and hostile behaviour. METHODS: Eight outpatients with schizophrenia diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), were included. Aggression and hostility were assessed using the Modified Overt Aggression Scale and the paranoid/belligerence symptom cluster of the Positive and Negative Syndrome Scale. Plasma samples were obtained 1 hour before psychometric assessment and were quantified for 3alpha,5alpha-THP using a highly sensitive and specific combined analysis by gas chromatography-mass spectrometry. RESULTS: Increased aggressiveness and hostility were associated with increased 3alpha,5alpha-THP plasma levels (Pearson r = 0.72, p = 0.043 and Pearson r = 0.72, p = 0.041, respectively). CONCLUSIONS: These preliminary results suggest that the neuroactive steroid 3alpha,5alpha-THP may affect aggression and hostility in humans. [Abstract/Link to Full Text]

Young SN, Shalchi M
The effect of methionine and S-adenosylmethionine on S-adenosylmethionine levels in the rat brain.
J Psychiatry Neurosci. 2005 Jan;30(1):44-8.
OBJECTIVE: S-Adenosylmethionine (SAMe) is a major methyl donor in the brain and is also an antidepressant with few reported side effects; however, SAMe is relatively expensive and unstable. Brain SAMe can be increased by giving methionine to rats, raising the possibility that methionine may be an antidepressant. We aimed to study whether SAMe and methionine, when given orally to rats, could raise levels of SAMe in the central nervous system (CNS). We also aimed to test the relative abilities of SAMe and methionine to increase tail-flick latency after a thermal stimulus. This test was used to measure changes in CNS function. METHODS: Rats were given SAMe and methionine orally at various doses, and biochemical and behavioural testing was carried out at intervals up to 6 hours later. RESULTS: Methionine raised SAMe levels in various regions of the CNS and increased tail-flick latency, both at lower doses than SAMe. CONCLUSION: Methionine should be tested for antidepressant properties in humans. [Abstract/Link to Full Text]

Ludewig S, Geyer MA, Ramseier M, Vollenweider FX, Rechsteiner E, Cattapan-Ludewig K
Information-processing deficits and cognitive dysfunction in panic disorder.
J Psychiatry Neurosci. 2005 Jan;30(1):37-43.
OBJECTIVE: The plasticity of the startle reflex, including prepulse inhibition (PPI) and habituation, provides operational measures of information processing that are abnormal in several neuropsychiatric disorders characterized by deficits in suppression or inhibition of intrusive or irrelevant stimuli. Clinically, patients with panic disorder (PD) have been described as having difficulties in the inhibition of their response to sensory and cognitive events. Because such difficulties may be the result of failures in early stages of information processing, we hypothesized that startle reactivity, PPI and habituation are deficient in unmedicated patients with PD. Moreover, we tested whether there was a relation between startle reflex measures and dysfunctional cognition. METHODS: Fourteen unmedicated patients with PD (7 men, 7 women) and 28 healthy comparison subjects (14 men, 14 women) were recruited. Acoustic startle reactivity, habituation and PPI (30-ms, 60-ms, 120-ms, 240-ms and 2000-ms interstimulus intervals) were assessed in the patients with PD and the age-matched and sex-matched healthy controls. These data for unmedicated patients with PD were compared with those for 24 medicated patients with PD. Moreover, dysfunctional cognition in patients with PD was measured using the Body Sensations Questionnaire. RESULTS: Unmedicated patients with PD exhibited increased startle reactivity, reduced habituation and significantly reduced PPI in the 30-ms, 60-ms, 120-ms and 240-ms prepulse conditions. Furthermore, in unmedicated patients with PD, increased startle response and decreased habituation were correlated significantly with higher cognitive dysfunction scores, but this was not the case for PPI. CONCLUSIONS: These data indicate that the early stages of sensory information processing are abnormal in patients with PD in the absence of medication. The observed deficits in PPI and habituation could reflect a more generalized difficulty in suppressing or gating information in PD. The correlation between cognitive symptoms and higher startle response and deficient habituation supports the hypothesis that subjects with PD have abnormalities in the early stages of information processing that lead to a cascade of downstream effects on cognition. [Abstract/Link to Full Text]

Kumperscak HG, Paschke E, Gradisnik P, Vidmar J, Bradac SU
Adult metachromatic leukodystrophy: disorganized schizophrenia-like symptoms and postpartum depression in 2 sisters.
J Psychiatry Neurosci. 2005 Jan;30(1):33-6.
We describe the cases of 2 sisters with adult metachromatic leukodystrophy (MLD). Whereas one sister presented with disorganized schizophrenia-like symptoms as the initial manifestation of MLD, the other remained symptom free except for a 4-week period of postpartum depression. In both patients, there was some residual activity of leukocyte arylsulfatase A (1.7% and 5.5% of normal), and a marked increase in urinary sulfatides was present, as measured by tandem mass spectrometry. An arylsulfatase A pseudodeficiency was therefore excluded. The most common mutations of the adult phenotype, Ile-179-Ser and Pro-426-Leu, were not found. In the literature, only 1 case of adult MLD manifesting as disorganized schizophrenia-like symptoms has been described, whereas postpartum depression has been so far unknown as a presenting symptom of MLD. [Abstract/Link to Full Text]

Riala K, Hakko H, Isohanni M, Pouta A, R�s�nen P
Is initiation of smoking associated with the prodromal phase of schizophrenia?
J Psychiatry Neurosci. 2005 Jan;30(1):26-32.
OBJECTIVE: Although the association between smoking and schizophrenia is well known, little attention has been paid to the time between initiation of smoking and onset of schizophrenia. Our goal was to study this putative temporal relation among patients with schizophrenia. METHODS: We used data from the Northern Finland 1966 Birth Cohort (n = 11,017) linked with the National Finnish Hospital Discharge Register to study age at initiation of smoking and age at onset of schizophrenia, and we examined associations between family and environmental factors and the retrospectively determined regular smoking among patients with schizophrenia. RESULTS: Our main finding was that the initiation of regular smoking was closely related to the onset of schizophrenia. The mean difference in time between the initiation of regular smoking and the onset of schizophrenia among patients (n = 30) was 2.3 (standard deviation [SD] 6.6) years, which was statistically significantly lower than that for subjects with other psychoses (n = 18) (8.6 [SD 6.3] yr) (p < 0.001). Among patients with schizophrenia, the increased likelihood of smoking was associated only with paternal smoking in the family environment, but not with any other background factors (odds ratio 3.5, 95; confidence interval 1.9-11.3). CONCLUSION: Smoking may be a sign of the prodromal phase of schizophrenia. [Abstract/Link to Full Text]

Fern�ndez A, Rodriguez-Palancas A, L�pez-Ibor M, Zuluaga P, Turrero A, Maest� F, Amo C, L�pez-Ibor JJ, Ortiz T
Increased occipital delta dipole density in major depressive disorder determined by magnetoencephalography.
J Psychiatry Neurosci. 2005 Jan;30(1):17-23.
OBJECTIVE: To test the hypothesis that there is increased low-frequency activity located predominantly in the frontal lobe in patients with major depressive disorder using magnetoencephalography. METHODS: We carried out an unmatched or separate sampling case-control study of 31 medication-free patients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria for major depressive disorder and were outpatients of the Hospital Central de la Defensa, Madrid, and 22 healthy control subjects with no history of mental illness. A logistic regression analysis was employed to examine the predictive value of magnetoencephalography dipole density scores in the diagnosis of depression. We attempted to locate generators of focal magnetic slow waves by employing a single moving dipole model and by calculating dipole densities in prefrontal, frontal, parietal, temporal and occipital areas. The study lasted from February 2001 to January 2003. RESULTS: Only 2 dipole density scores, right occipital delta and left temporal delta, were significantly related to depression. According to the comparison of univariate and multivariate models and odds ratios, the right occipital delta dipole density is the factor with the greatest predictive power for depression, and the only one to show a significant correlation with severity of depression. CONCLUSIONS: We did not find any frontal lobe functional alteration. Our study provides, to the best of our knowledge, the first evidence of abnormal focal magnetic low-frequency activity in the occipital lobe of untreated patients with depression. Increased occipital lobe delta dipole density seems to be a reliable risk factor for depression, which correlates with disease severity according to the Hamilton Rating Scale for Depression. [Abstract/Link to Full Text]

Shen J, Kennedy SH, Levitan RD, Kayumov L, Shapiro CM
The effects of nefazodone on women with seasonal affective disorder: clinical and polysomnographic analyses.
J Psychiatry Neurosci. 2005 Jan;30(1):11-6.
OBJECTIVE: To outline the clinical and polysomnographic changes induced by nefazodone in patients with seasonal affective disorder. METHODS: Twelve patients were enrolled, and 9 of them studied, in an open-label trial with objective and subjective measurements. The mean age of the studied patients was 45 (range 35-58) years. They met Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria for major depressive disorder and current major depressive episode with seasonal patterns. The patients' mean baseline score on the Seasonal Patterns Assessment Questionnaire (SPAQ) was 15.7 (standard deviation [SD] 5.3). The total nefazodone treatment period was 8 weeks, and the daily dosages were 100 mg in week 1, 200 mg in week 2, 300 mg in week 3, and up to 400 mg in weeks 4-8. Each patient received the 29-item version of the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A) and 2-night polysomnographic assessments on 3 occasions: before treatment (baseline, W0), at the end of week 4 (W4) and at the end of week 8 (W8). RESULTS: There were statistically significant improvements in depression, anxiety, sleep latency and sleep efficiency during the 8-week treatment protocol. Repeated-measures analysis of variance results indicated that nefazodone has a time-dependent effect on both HAM-D and HAM-A scores. After 8 weeks of nefazodone therapy, HAM-D scores decreased from 33.4 (SD 8.1) to 11.6 (SD 5.6) (F(2,14) = 13.68, p = 0.001) and HAM-A decreased from 26.6 (SD 7.0) to 11.5 (SD 11.1) (F(2,14) = 13.46, p = 0.001). The results of paired t tests show that, compared with baseline, HAM-D and HAM-A scores decreased at both W4 (p = 0.004 and p = 0.002, respectively) and W8 (p = 0.002 and p = 0.005, respectively). The time-dependent effects on stage 1 sleep (F(2,16) = 6.06, p = 0.011) and periodic leg movement index (F(2,16) = 4.31, p = 0.035) were also significant. The mean sleep latency of these patients decreased from 39.9 (SD 32.7) minutes at W0 to 16.6 (SD 15.3) minutes at W8 (p < 0.05). Sleep efficiency increased from 78.8% (SD 14.6%) at W0 to 91.5% (SD 5.5%) at W8 (p < 0.05). Stage 1 sleep decreased from 4.9% (SD 1.9%) at W0 to 3.4% (SD 2.6%) at W8 (p < 0.05). CONCLUSIONS: The results of this preliminary study indicate that nefazodone not only has favourable antidepressant and anxiolytic effects but also enhances sleep efficiency and sleep latency. [Abstract/Link to Full Text]

Joffe RT
Depression and multiple sclerosis: a potential way to understand the biology of major depressive illness.
J Psychiatry Neurosci. 2005 Jan;30(1):9-10. [Abstract/Link to Full Text]

Kanba S
Although antidepressants and anxiolytics are frequently used together to treat depression in the acute phase, how effective is the concomitant use of these drugs?
J Psychiatry Neurosci. 2004 Nov;29(6):485. [Abstract/Link to Full Text]

Ananth J, Burgoyne KS, Niz D, Smith M
Tardive dyskinesia in 2 patients treated with ziprasidone.
J Psychiatry Neurosci. 2004 Nov;29(6):467-9.
Ziprasidone is an atypical antipsychotic drug that is believed to have a low propensity for inducing extrapyramidal symptoms, including tardive dyskinesia (TD). Two of our patients developed TD after 23 months and 34 months of ziprasidone monotherapy, respectively. One of the patients had had earlier exposure to typical antipsychotic drugs, but no other predisposing factors for TD were noted. Therefore, patients on long-term therapy with atypical antipsychotic drugs should be screened periodically for TD. [Abstract/Link to Full Text]

Tringali G, Aubry JM, Moscianese K, Zamori C, Vairano M, Preziosi P, Navarra P, Pozzoli G
Valproic acid inhibits corticotropin-releasing factor synthesis and release from the rat hypothalamus in vitro: evidence for the involvement of GABAergic neurotransmission.
J Psychiatry Neurosci. 2004 Nov;29(6):459-66.
OBJECTIVE: Corticotropin-releasing factor (CRF), the major adrenocorticotropic hormone (ACTH) secretagogue, acts within the brain to integrate the stress responses of the central nervous, endocrine and immune systems. The involvement of this peptide in the origin and pathophysiology of various endocrine, neurologic, inflammatory and psychiatric diseases, particularly affective disorders, has also been suggested. The antiepileptic drug valproic acid is frequently used as a mood-stabilizing agent in patients with bipolar disorders; however, its mechanism of action for the latter indication is still poorly characterized. We investigated whether valproic acid can directly modulate CRF production by using the incubation of rat hypothalamic explants as an in-vitro model. We then studied the involvement of the gamma-aminobutyric acid (GABA) system as a putative mediator of the effects of valproic acid on CRF production. METHODS: Rat hypothalamic explants were incubated in a 24-well plate (2 hypothalami per well) at 37 degrees C in a humidified atmosphere (5; CO(2) and 95% O(2)) in incubation medium, 700 muL, then were treated with medium alone (control) or test substances, namely, valproic acid, KCI, bicuculline methiodide and muscimol. Released CRF was measured by radioimmunoassay. CRF mRNA was measured by RNase protection analysis. RESULTS: Incubation of the hypothalamic fragments with valproic acid, 100 mumol/L, resulted in a reduction of basal CRF secretion after 3 hours' treatment. The drug was also able to inhibit KCl-stimulated CRF release. Moreover, valproic acid, 100 mumol/L, significantly decreased CRF mRNA levels after 3 hours. A specific GABA(A) receptor antagonist, bicuculline methiodide, completely reversed the inhibition of CRF gene expression and peptide release induced by valproic acid; in this paradigm, the GABA(A)-specific agonist muscimol inhibited both CRF gene expression and peptide release in a concentration-dependent manner. CONCLUSIONS: These results suggest that valproic acid may exert part of its therapeutic effect as a mood-stabilizing drug via the modulation of CRF secretion from the hypothalamus. This action may be mediated in part by the activation of GABAergic neurotransmission. [Abstract/Link to Full Text]

Sattar SP, Bhatia SC, Petty F
Potential benefits of quetiapine in the treatment of substance dependence disorders.
J Psychiatry Neurosci. 2004 Nov;29(6):452-7.
OBJECTIVE: Some antipsychotic medications prescribed for the treatment of psychoses, mood disorders or post-traumatic stress disorder in patients with coexisting substance dependence disorders (SDD) have reduced substance dependence. We studied the potential benefits of quetiapine in the treatment of SDD. METHODS: We conducted a retrospective chart review of data for 9 patients who were admitted to a 28-day residential rehabilitation program designed for individuals with SDD during a 3-month period from January 2003 through March 2003 and treated with quetiapine for nonpsychotic anxiety. These patients also met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for alcohol, cocaine and/or methamphetamine dependence and substance-induced anxiety disorder. The patients were assessed using the Hamilton-D Rating Scale for Depression (Ham-D), a 10-point Likert scale to measure alcohol or drug cravings, and random Breathalyzer and urine drug screens. RESULTS: Quetiapine was generally well tolerated. Only 1 of the 9 patients stopped taking the medication because of increased anxiety. Other patients reported improvement in sleep and anxiety. The mean decrease in Ham-D score at discharge for the responders was 18.5 (p < 0.005). The biggest decreases on the Ham-D occurred on the subscales of insomnia, agitation, somatic anxiety, psychologic anxiety, hypochondriasis and obsessional symptoms. The mean decrease in the Likert 10-point craving scale was 5.9 for the responders (p < 0.005). These patients' periodic Breathalyzer and urine test results suggested that they remained abstinent from alcohol and other drug use. CONCLUSION: Quetiapine was beneficial in the treatment of SDD in patients with nonpsychotic anxiety. [Abstract/Link to Full Text]

Hermann D, Hewer W, Lederbogen F
Testing the association between thyroid dysfunction and psychiatric diagnostic group in an iodine-deficient area.
J Psychiatry Neurosci. 2004 Nov;29(6):444-9.
OBJECTIVE: To test the association between thyroid dysfunction and psychiatric diagnostic group in a large sample of consecutive patients, while controlling for the effects of age, sex, medication and concomitant medical conditions. METHODS: We compared the distribution of psychiatric diagnostic groups according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10), and of selected psychopathological symptoms in 100 newly admitted psychiatric patients who had genuine thyroid disease and 92 psychiatric patients who had nonspecific alterations of thyroid function with the corresponding items for the whole group of admitted patients (n = 1134) during the observation period. This analysis was then repeated using an age-matched and sex-matched comparison group selected from all admitted patients in a random order. RESULTS: When all admitted patients were considered, the presence of a genuine thyroid disorder was associated with the diagnosis of a mood disorder (ICD-10 category F3). This effect was no longer detectable when the age-matched and sex-matched comparison group was used, indicating a simple effect of these 2 variables. Nonspecific alterations of thyroid-stimulating hormone (TSH) were associated with the ICD-10 diagnostic group F4 (neurotic, stress-related and somatoform disorders), with demographic variables being similar in this subgroup to those of all admitted patients. These patients also tended to display more symptoms of a mild depressive syndrome. When only patients with nonspecifically decreased TSH concentrations were tested, these findings could not be reproduced. Nonspecifically decreased concentrations of thyroxine and free thyroxine index were found significantly more often in the diagnosis group F1 (mental disorder due to substance use), reflecting results for alcohol-dependent patients. This result could not be replicated using an age-matched and sex-matched control group. CONCLUSION: In newly admitted psychiatric patients with genuine thyroid disease, there was no notable association of thyroid disease and major psychiatric diagnostic groups according to ICD-10, especially depression. This argues against the hypothesis of thyroid disorders being a major risk factor for psychiatric illnesses. Nonspecific alterations of TSH were more frequently seen in patients of diagnostic group F4 and with mild depressive syndromes, possibly representing an altered influence of stress-regulating systems on thyroid function. [Abstract/Link to Full Text]

Kar S, Slowikowski SP, Westaway D, Mount HT
Interactions between beta-amyloid and central cholinergic neurons: implications for Alzheimer's disease.
J Psychiatry Neurosci. 2004 Nov;29(6):427-41.
Alzheimer's disease is an age-related neurodegenerative disorder that is characterized by a progressive loss of memory and deterioration of higher cognitive functions. The brain of an individual with Alzheimer's disease exhibits extracellular plaques of aggregated beta-amyloid protein (Abeta), intracellular neurofibrillary tangles that contain hyperphosphorylated tau protein and a profound loss of basal forebrain cholinergic neurons that innervate the hippocampus and the neocortex. Abeta accumulation may trigger or contribute to the process of neurodegeneration. However, the mechanisms whereby Abeta induces basal forebrain cholinergic cell loss and cognitive impairment remain obscure. Physiologically relevant concentrations of Abeta-related peptides have acute, negative effects on multiple aspects of acetylcholine (ACh) synthesis and release, without inducing toxicity. These data suggest a neuromodulatory influence of the peptides on central cholinergic functions. Long-term exposure to micromolar Abeta induces cholinergic cell toxicity, possibly via hyperphosphorylation of tau protein. Conversely, activation of selected cholinergic receptors has been shown to alter the processing of the amyloid precursor protein as well as phosphorylation of tau protein. A direct interaction between Abeta and nicotinic ACh receptors has also been demonstrated. This review addresses the role of Abeta-related peptides in regulating the function and survival of central cholinergic neurons and the relevance of these effects to cholinergic deficits in Alzheimer's disease. Understanding the functional interrelations between Abeta peptides, cholinergic neurons and tau phosphorylation will unravel the biologic events that precede neurodegeneration and may lead to the development of more effective pharmacotherapies for Alzheimer's disease. [Abstract/Link to Full Text]

Campbell S, Macqueen G
The role of the hippocampus in the pathophysiology of major depression.
J Psychiatry Neurosci. 2004 Nov;29(6):417-26.
Converging lines of research suggest that the hippocampal complex (HC) may have a role in the pathophysiology of major depressive disorder (MDD). Although postmortem studies show little cellular death in the HC of depressed patients, animal studies suggest that elevated glucocorticoid levels associated with MDD may negatively affect neurogenesis, cause excitotoxic damage or be associated with reduced levels of key neurotrophins in the HC. Antidepressant medications may counter these effects, having been shown to increase HC neurogenesis and levels of brain-derived neurotrophic factor in animal studies. Neuropsychological studies have identified deficits in hippocampus-dependent recollection memory that may not abate with euthymia, and such memory impairment has been the most reliably documented cognitive abnormality in patients with MDD. Finally, data from imaging studies suggest both structural changes in the volume of the HC and functional alterations in frontotemporal and limbic circuits that may be critical for mood regulation. The extent to which such functional and structural changes determine clinical outcome in MDD remains unknown; a related, but also currently unanswered, question is whether the changes in HC function and structure observed in MDD are preventable or modifiable with effective treatment for the depressive illness. [Abstract/Link to Full Text]

Le Mell�do JM, Mahil N, Baker GB
Nitric oxide: a key player in the relation between cardiovascular disease and major depressive disorder?
J Psychiatry Neurosci. 2004 Nov;29(6):414-6. [Abstract/Link to Full Text]